Clinical trial NCT04681170
Conditions: Homozygous Familial Hypercholesterolaemia (HoFH)
Sponsor: Amryt Pharma
Start date: 2020-12-14; Completion date: 2024-06-06
Enrollment: 46 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a single arm, open label, multi centre phase III study to evaluate the efficacy and long term safety of lomitapide in paediatric patients with HoFH receiving stable lipid lowering therapy (LLT) (including lipoprotein apheresis (LA), when applicable) comprising of the following phases:

* Screening Period (starting at Week 12, i.e. ≤12 weeks prior to Baseline for up to 6 weeks)
* Stratified Enrolment and Start of Run in Period (starting at minimum at Week 6, i.e., 6 weeks prior to Baseline for a minimum of 6 weeks):
* Efficacy Phase (starting at Baseline, i.e. Day \[D\] 0 for 24 weeks±3 days
* Safety Phase (starting at Week 24±3 days for 80±1 weeks)

Detailed description:
Lomitapide has been approved for use in adult patients with HoFH in the European Union (EU) and European Economic Area (EEA), United States of America (USA), Israel, Argentina, Canada, Colombia, and Japan. This study is designed to determine if lomitapide is effective and can be safely administered to paediatric patients with HoFH. If the efficacy and safety so far observed in adults is confirmed in paediatric patients, the potential exists to significantly lower low-density lipoprotein cholesterol (LDL-C) levels in paediatric patients with HoFH. Furthermore, the lower LDL-C levels may reduce atherosclerosis progression and would be expected to benefit these paediatric patients with HoFH.

A single arm, non comparator design has been selected due to the rarity of the disease and because the evaluation of safety variables such as growth and sexual maturation requires longer term observation than would be feasible in the context of a placebo controlled study.

To mitigate the disadvantages of a single arm design, the study includes a Run in Period of at least 6 weeks during which current lipid lowering therapy (LLT) (including lipoprotein apheresis (LA), when applicable) will be stabilised to establish baseline levels allowing each patient to serve as his/her own control. Patients will also remain on stable LLT (including LA, when applicable) during the Efficacy Phase of the study through Week 24±3 days.

Arms: arm 1: Lomitapide dosing commenced with 2mg at week 1 for 8 Weeks,then increased to 5mg at Week 8±3 days, 10 mg at Week 12±3 days to the maximum allowable dose of 20 mg by Week 16±3 days or the MTD by Week 20±3 days based upon acceptable safety and tolerability criteria in addition to LDL C values. arm 2: Lomitapide dosing commenced with 2mg at week 1 for 4 Weeks, then increased to 5mg at Week 4±3 days, 10 mg at Week 8±3 days, 20mg at Week 12±3 days to the maximum allowable dose of 40mg by Week 16±3 days or the MTD by Week 20±3 days based upon acceptable safety and tolerability criteria in addition to LDL C values. arm 3: Lomitapide dosing commenced with 5mg at week 1 for 4 Weeks, then increased to 10mg at Week 4±3 days, 20 mg at Week 8±3 days, 40mg at Week 12±3 days to the maximum allowable dose of 60mg by Week 16±3 days or the MTD by Week 20±3 days based upon acceptable safety and tolerability criteria in addition to LDL C values.
Interventions: intervention 1: Lomitapide
Intervention descriptions: intervention 1: 2mg,5mg, 10mg and 20mg capsules

Protocol documents:
SAP_002.pdf: 
Phase III, Single-arm, Open-label, International, Multi-
centre Study to Evaluate the Efficacy and Safety of 
Lomitapide in Paediatric Patients with Homozygous 
Familial Hypercholesterolaemia (HoFH) on Stable Lipid-
lowering Therapy
Amryt Pharma Study No: APH-19
SQN Clinical Study No:  OCH19003
Table, Figure and Listing Shells 
Version: Final 5.0
Date: 28 June 2024
Author
Approved By Amryt Pharma
Ruth Nallen
Associate Director Clinical Operations
Zsuzsanna Tamas
Senior Director / Project Physician Leader
Global Rare Diseases


SQN Clinical study no: OCH19003
Amryt Pharma study no: APH-19
TABLE/FIGURE/LISTING CONTENTS
 
Table 14.1.1.1 Subject Disposition ............................................................................................ 11
Table 14.1.1.2 Subject Study Visits........................................................................................... 13
Table 14.1.2.1 Demography ...................................................................................................... 14
Table 14.1.2.2 Baseline Lipids .................................................................................................. 18
Table 14.1.2.3 Diagnosis of HoFH ............................................................................................ 22
Table 14.1.3.1 Medical History .................................................................................................. 24
Table 14.1.3.2 Cardiovascular History ...................................................................................... 25
Table 14.1.3.3 Cardiovascular Disease History at Screening ................................................... 26
Table 14.1.4.1 Prior and 'Run-in Medications' Medications ...................................................... 27
Table 14.1.4.2 Concomitant Medications .................................................................................. 28
Table 14.1.4.3 Lipid-Lowering-Therapy Medications ................................................................ 29
Table 14.1.4.5 Procedures ........................................................................................................ 31
Table 14.1.4.6 Days from most recent apheresis to the corresponding LDL-C primary efficacy 
assessment ............................................................................................................................... 32
Table 14.1.5.1 Study Drug Exposure and Dosing ..................................................................... 34
Table 14.1.5.2 Summary of Compliance to IMP ....................................................................... 43
Table 14.1.5.3 Time to Dose Reduction and Interruption ......................................................... 44
Table 14.1.5.4 Distribution of Achieved Doses ......................................................................... 45
Table 14.2.1.1 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks ........ 46
Table 14.2.1.2 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks 
(Supplementary analysis - per protocol set) .............................................................................. 51
Table 14.2.1.3 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks 
(Supplementary analysis - completer analysis set) ................................................................... 52
Table 14.2.1.4 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 1 - Age groups) .......................................................................................... 53
Table 14.2.1.5 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 2 - Documented cardiovascular disease history) ...................................... 57
Table 14.2.1.6 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 3 -  Established cardiovascular disease history (defined as aortic valve 
disease and/or coronary atherosclerosis)) ................................................................................ 61
Table 14.2.1.7 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 4 - Concomitant LLT medications/procedures) ......................................... 66
Table 14.2.1.8 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 5 - Dose reductions / dose interruptions) .................................................. 70
Table 14.2.1.9 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 6 - Reached MTD for age group/ did not reach MTD for age group) ........ 74
Table 14.2.1.10 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 7 - Sex) ...................................................................................................... 78
Table 14.2.1.11 Lipid parameter: LDL-C (mg/dL) Responder Analysis (Supplementary 
analysis) .................................................................................................................................... 82
Table 14.2.2.1 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks 
(Secondary analysis) ................................................................................................................. 83
Table 14.2.2.2 Lipid parameter: Non-HDL-C (mg/dL)and change from baseline at 24 weeks 
(Supplementary analysis - per protocol set) .............................................................................. 84
Table 14.2.2.3 Lipid parameter: Non-HDL-C value (mg/dL) change from baseline at 24 weeks 
(Supplementary analysis - completer analysis set) ................................................................... 85
Table 14.2.2.4 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 1 - Age groups) .......................................................................................... 86
Table 14.2.2.5 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 2 - Documented cardiovascular disease history) ...................................... 87
Table 14.2.2.6 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 3 -  Established cardiovascular disease history (defined as aortic valve 
disease and/or coronary atherosclerosis)) ................................................................................ 88
Table 14.2.2.7 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 4 - Concomitant LLT medications/procedures) ......................................... 89


SQN Clinical study no: OCH19003
Amryt Pharma study no: APH-19
Table 14.2.2.8 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 5 - Dose reductions / dose interruptions) .................................................. 90
Table 14.2.2.9 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 6 - Reached MTD for age group/ did not reach MTD for age group) ........ 91
Table 14.2.2.10 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 7 - Sex) ...................................................................................................... 92
Table 14.2.2.11 Lipid parameter: Non-HDL-C (mg/dL) Responder Analysis (Supplementary 
analysis) .................................................................................................................................... 93
Table 14.2.3.1 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks 
(Secondary analysis) ................................................................................................................. 94
Table 14.2.3.2 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks 
(Supplementary analysis - per protocol set) .............................................................................. 95
Table 14.2.3.3 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks 
(Supplementary analysis - completer analysis set) ................................................................... 96
Table 14.2.3.4 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Subgroup 
analysis 1 - Age groups) ............................................................................................................ 97
Table 14.2.3.5 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Subgroup 
analysis 2 - Documented cardiovascular disease history) ........................................................ 98
Table 14.2.3.6 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Subgroup 
analysis 3 -  Established cardiovascular disease history (defined as aortic valve disease and/or 
coronary atherosclerosis)) ......................................................................................................... 99
Table 14.2.3.7 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Subgroup 
analysis 4 - Concomitant LLT medications/procedures) ......................................................... 100
Table 14.2.3.8 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Subgroup 
analysis 5 - Dose reductions / dose interruptions) .................................................................. 101
Table 14.2.3.9 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Subgroup 
analysis 6 - Reached MTD for age group/ did not reach MTD for age group) ........................ 102
Table 14.2.3.10 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 7 - Sex) .................................................................................................... 103
Table 14.2.3.11 Lipid parameter: TC (mg/dL) Responder Analysis (Supplementary 
analysis) .................................................................................................................................. 104
Table 14.2.4.1 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks 
(Secondary analysis) ............................................................................................................... 105
Table 14.2.4.2 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks 
(Supplementary analysis - per protocol set) ............................................................................ 106
Table 14.2.4.3 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks 
(Supplementary analysis - completer analysis set) ................................................................. 107
Table 14.2.4.4 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 1 - Age groups) ........................................................................................ 108
Table 14.2.4.5 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 2 - Documented cardiovascular disease history) .................................... 109
Table 14.2.4.6 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 3 -  Established cardiovascular disease history (defined as aortic valve 
disease and/or coronary atherosclerosis)) .............................................................................. 110
Table 14.2.4.7 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 4 - Concomitant LLT medications/procedures) ....................................... 111
Table 14.2.4.8 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 5 - Dose reductions / dose interruptions) ................................................ 112
Table 14.2.4.9 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 6 - Reached MTD for age group/ did not reach MTD for age group) ...... 113
Table 14.2.4.10 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 7 - Sex) .................................................................................................... 114
Table 14.2.4.11 Lipid parameter: VLDL-C (mg/dL) Responder Analysis (Supplementary 
analysis) .................................................................................................................................. 115
Table 14.2.5.1 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks 
(Secondary analysis) ............................................................................................................... 116
Table 14.2.5.2 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks 
(Supplementary analysis - per protocol set) ............................................................................ 117
Table 14.2.5.3 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks 
(Supplementary analysis - completer analysis set) ................................................................. 118


SQN Clinical study no: OCH19003
Amryt Pharma study no: APH-19
Table 14.2.5.4 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 1 - Age groups) ........................................................................................ 119
Table 14.2.5.5 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 2 - Documented cardiovascular disease history) .................................... 120
Table 14.2.5.6 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 3 -  Established cardiovascular disease history (defined as aortic valve 
disease and/or coronary atherosclerosis)) .............................................................................. 121
Table 14.2.5.7 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 4 - Concomitant LLT medications/procedures) ....................................... 122
Table 14.2.5.8 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 5 - Dose reductions / dose interruptions) ................................................ 123
Table 14.2.5.9 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 6 - Reached MTD for age group/ did not reach MTD for age group) ...... 124
Table 14.2.5.10 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 7 - Sex) .................................................................................................... 125
Table 14.2.5.11 Lipid parameter: Apo B (mg/dL) Responder Analysis (Supplementary 
analysis) .................................................................................................................................. 126
Table 14.2.6.1 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks 
(Secondary analysis) ............................................................................................................... 127
Table 14.2.6.2 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks 
(Supplementary analysis - per protocol set) ............................................................................ 128
Table 14.2.6.3 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks 
(Supplementary analysis - completer analysis set) ................................................................. 129
Table 14.2.6.4 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Subgroup 
analysis 1 - Age groups) .......................................................................................................... 130
Table 14.2.6.5 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Subgroup 
analysis 2 - Documented cardiovascular disease history) ...................................................... 131
Table 14.2.6.6 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Subgroup 
analysis 3 -  Established cardiovascular disease history (defined as aortic valve disease and/or 
coronary atherosclerosis)) ....................................................................................................... 132
Table 14.2.6.7 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Subgroup 
analysis 4 - Concomitant LLT medications/procedures) ......................................................... 133
Table 14.2.6.8 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Subgroup 
analysis 5 - Dose reductions / dose interruptions) .................................................................. 134
Table 14.2.6.9 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Subgroup 
analysis 6 - Reached MTD for age group/ did not reach MTD for age group) ........................ 135
Table 14.2.6.10 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 7 - Sex) .................................................................................................... 136
Table 14.2.6.11 Lipid parameter: TG (mg/dL) Responder Analysis (Supplementary 
analysis) .................................................................................................................................. 137
Table 14.2.7.1 Lipid parameter: Lp(a) and change from baseline at 24 weeks (Secondary 
analysis) .................................................................................................................................. 138
Table 14.2.7.2 Lipid parameter: LP(a) and change from baseline at 24 weeks (Supplementary 
analysis - per protocol set) ...................................................................................................... 139
Table 14.2.7.3 Lipid parameter: LP(a) and change from baseline at 24 weeks (Supplementary 
analysis - completer analysis set) ........................................................................................... 140
Table 14.2.7.4 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 1 - Age groups) ........................................................................................ 141
Table 14.2.7.5 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 2 - Documented cardiovascular disease history) .................................... 142
Table 14.2.7.6 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 3 -  Established cardiovascular disease history (defined as aortic valve 
disease and/or coronary atherosclerosis)) .............................................................................. 143
Table 14.2.7.7 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 4 - Concomitant LLT medications/procedures) ....................................... 144
Table 14.2.7.8 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 5 - Dose reductions / dose interruptions) ................................................ 145
Table 14.2.7.9 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 6 - Reached MTD for age group/ did not reach MTD for age group) ...... 146
Table 14.2.7.10 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks 
(Subgroup analysis 7 - Sex) .................................................................................................... 147


SQN Clinical study no: OCH19003
Amryt Pharma study no: APH-19
Table 14.2.7.11 Lipid parameter: LP(a) (mg/dL) Responder Analysis (Supplementary 
analysis) .................................................................................................................................. 148
Table 14.2.8.1 Lipid parameter: LDL-C (mg/dL) and change from Baseline to EOT / Week 104 
by age group (Summary Measures) ........................................................................................ 149
Table 14.2.8.2 Lipid parameter: Non-HDL-C (mg/dL) and change from Baseline to EOT / Week 
104 by age group (Summary Measures) ................................................................................. 152
Table 14.2.8.3 Lipid parameter: TC (mg/dL) and change from Baseline to EOT / Week 104 by 
age group (Summary Measures)............................................................................................. 153
Table 14.2.8.4 Lipid parameter: VLDL-C (mg/dL) and change from Baseline to EOT / Week 
104 by age group (Summary Measures) ................................................................................. 154
Table 14.2.8.5 Lipid parameter: Apo B (g/L)  and change from Baseline to EOT / Week 104 by 
age group (Summary Measures)............................................................................................. 155
Table 14.2.8.6 Lipid parameter: TG (mg/dL) and change from Baseline to EOT / Week 104 by 
age group (Summary Measures)............................................................................................. 156
Table 14.2.8.7 Lipid parameter: Lp(a) and change from Baseline to EOT / Week 104 by age 
group (Summary Measures) .................................................................................................... 157
Table 14.2.8.8 Lipid parameter: TC/HDL-C ratio and change from Baseline to EOT / Week 104 
by age group (Summary Measures) ........................................................................................ 158
Table 14.2.9.1 Lipid parameter: LDL-C (mg/dL) and change from Baseline to EOT / Week 104 
(Mixed Model Repeated Measures analysis) .......................................................................... 159
Table 14.2.9.2 Lipid parameter: Non-HDL-C (mg/dL) and change from Baseline to EOT / Week 
104 (Mixed Model Repeated Measures analysis) ................................................................... 160
Table 14.2.9.3 Lipid parameter: TC (mmol/L) and change from Baseline to EOT / Week 104 
(Mixed Model Repeated Measures analysis) .......................................................................... 161
Table 14.2.9.4 Lipid parameter: VLDL-C (mg/dL) and change from Baseline to EOT / Week 
104 (Mixed Model Repeated Measures analysis) ................................................................... 162
Table 14.2.9.5 Lipid parameter: Apo B (g/L) and change from Baseline to EOT / Week 104 
(Mixed Model Repeated Measures analysis) .......................................................................... 163
Table 14.2.9.6 Lipid parameter: TG (mg/dL) and change from Baseline to EOT / Week 104 
(Mixed Model Repeated Measures analysis) .......................................................................... 164
Table 14.2.9.7 Lipid parameter: LP(a) and change from Baseline to EOT / Week 104 (Mixed 
Model Repeated Measures analysis) ...................................................................................... 165
Table 14.2.9.8 Lipid parameter: TC/HDL-C ratio and change from Baseline to EOT / Week 104 
(Mixed Model Repeated Measures analysis) .......................................................................... 166
Table 14.2.10.1 Treated with standard Lipid Lowering Therapy (LLT) (including Lipoprotein 
Apheresis (LA) ......................................................................................................................... 167
Table 14.2.10.2 Reduction in dose of standard Lipid Lowering Therapy (LLT) / Reduced need 
for Lipoprotein Apheresis (LA) compared to Week 24 (end of Efficacy Phase) ...................... 168
Table 14.2.10.3 Discontinue standard Lipid Lowering Therapy (LLT) / Discontinue need for 
Lipoprotein Apheresis (LA) compared to Week 24 (end of Efficacy Phase) ........................... 169
Table 14.2.10.4 Increase dose of standard Lipid Lowering Therapy (LLT) / Increased need for 
Lipoprotein Apheresis (LA) compared to Week 24 (end of Efficacy Phase) ........................... 170
Table 14.2.11.1 Recommended target of LDL-C of <135 mg/dL (i.e. 3.5 mmol/L) - EAS 
recommendation ...................................................................................................................... 171
Table 14.2.11.2 Recommended target of LDL-C of <135 mg/dL (i.e. 3.5 mmol/L) by age group 
and Lomitapide dose - EAS recommendation ......................................................................... 172
Table 14.2.11.3 Recommended targets of LDL-C - Exploratory endpoints ............................ 173
Table 14.2.11.4 Recommended targets of LDL-C by age group and Lomitapide dose - 
Exploratory endpoints .............................................................................................................. 174
Table 14.2.12.1 Lipid parameter: HDL-C (mg/dL) and change from Baseline to EOT / Week 
104 by age group (Summary Measures) ................................................................................. 175
Table 14.2.12.2 Lipid parameter: HDL-C (mg/dL) and change from Baseline to EOT / Week 
104 (Mixed Model Repeated Measures analysis) ................................................................... 176
Table 14.3.1.1 Summary of Treatment-Emergent Adverse Events ........................................ 178
Table 14.3.1.2 Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term ....................................................................................................... 180
Table 14.3.1.3 Summary of Serious Adverse Events (SAEs) by MedDRA System Organ Class 
and Preferred Term ................................................................................................................. 181
Table 14.3.1.4 Summary of Treatment-Emergent Adverse Events by MedDRA Preferred 
Term 182
Table 14.3.1.5 Summary of Serious Adverse Events (SAEs) by MedDRA Preferred Term... 183


SQN Clinical study no: OCH19003
Amryt Pharma study no: APH-19
Table 14.3.1.6 Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class, Preferred Term and Severity ........................................................................................ 184
Table 14.3.1.7 Summary of Serious Adverse Events (SAEs) by MedDRA System Organ Class, 
Preferred Term and Severity ................................................................................................... 185
Table 14.3.1.8 Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class, Preferred Term and Relationship to Study Treatment ................................................. 186
Table 14.3.1.9 Summary of Serious Adverse Events (SAEs) by MedDRA System Organ Class, 
Preferred Term and Relationship to Study Treatment ............................................................ 187
Table 14.3.1.10 Summary of Adverse Events of Special Interest (AESI) by AESI Category, 
MedDRA System Organ Class and Preferred Term ............................................................... 188
Table 14.3.1.11 Summary of Gastrointestinal (GI) Adverse Events by MedDRA System Organ 
Class and Preferred Term ....................................................................................................... 189
Table 14.3.1.12 Summary of Most Frequent Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term ............................................................................... 190
Table 14.3.1.13 Time to First Gastrointestinal Treatment-Emergent Adverse Events ........... 191
Table 14.3.1.14 Time to First Hepatic Treatment-Emergent Adverse Events ........................ 192
Table 14.3.1.15 Summary of Treatment-Emergent Adverse Events, by Sex ......................... 193
Table 14.3.1.16 Summary of Adverse Events of Special Interest (AESI) by AESI Category, 
MedDRA System Organ Class and Preferred Term, by Sex .................................................. 194
Table 14.3.1.17 Summary of Elevation in Serum Transaminases Related Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and Preferred Term, by Country ............ 195
Table 14.3.2.1 Haematology Values and Change from Baseline over Time .......................... 196
Table 14.3.2.2 Clinical Significance of Haematology Values over Time ................................. 197
Table 14.3.2.3 Shift in Haematology Values over Time .......................................................... 198
Table 14.3.3.1 Serum Clinical Chemistry Values and Change from Baseline over Time ....... 199
Table 14.3.3.2 Clinical Significance of Serum Clinical Chemistry Values over Time ............. 200
Table 14.3.3.3 Shift in Clinical Chemistry Values over Time .................................................. 201
Table 14.3.3.4 Summary of Maximum Clinical Chemistry Values .......................................... 202
Table 14.3.3.5 Summary of Subjects Exceeding Hepatotoxicity Thresholds over Time ........ 204
Table 14.3.3.6 Time to Onset of Liver Function Test Abnormality .......................................... 205
Table 14.3.4.1 Urinalysis Values and Change from Baseline over Time ................................ 206
Table 14.3.4.2 Clinical Significance of Urinalysis Values over Time ...................................... 207
Table 14.3.4.3 Shift in Urinalysis Values over Time................................................................ 208
Table 14.3.5.1 Vital Signs and Change from Baseline over Time .......................................... 209
Table 14.3.6.1 Summary of Overall ECG Interpretation over Time ........................................ 212
Table 14.3.6.2 Shift in Overall ECG Interpretation over Time ................................................. 213
Table 14.3.7.1 Summary of Echocardiography (Standard of Care) over Time ....................... 214
Table 14.3.7.2 Summary of Subjects with Worsening in Echocardiography over Time ......... 219
Table 14.3.8.1.1 Summary of Lipid Accumulation in the Liver over Time ............................... 220
Table 14.3.8.1.2 Summary of Lipid Accumulation in the Liver over Time (Sensitivity Analysis -
Excluding Site 12) ................................................................................................................... 221
Table 14.3.8.2.1 Shift in Lipid Accumulation in the Liver over Time ....................................... 222
Table 14.3.8.2.2 Shift in Lipid Accumulation in the Liver over Time (Sensitivity Analysis - 
Excluding Site 12) ................................................................................................................... 223
Table 14.3.8.3.1 Summary of Lipid Accumulation in the Liver over Time ............................... 224
Table 14.3.8.3.2 Summary of Lipid Accumulation in the Liver over Time ............................... 225
Table 14.3.8.4.1 Summary of Lipid Accumulation Increase over Time................................... 226
Table 14.3.8.4.2 Summary of Lipid Accumulation Increase over Time................................... 227
Table 14.3.9.1 Summary of Tanner Staging over Time .......................................................... 228
..... 229
Table 14.3.9.3 Shift in Tanner Staging Over Time .................................................................. 230
Table 14.3.10.1 Summary of Pulmonary Function Test (PFT) Parameters and Change from 
Baseline over Time .................................................................................................................. 231
Table 14.3.11.1 Summary of Xanthoma Assessment over Time ............................................ 232
Table 14.3.11.2 Changes to pre-existing Xanthoma over Time .............................................. 233
Table 14.3.11.3 Summary of new xanthomas over Time ....................................................... 238
Table 14.3.11.4 Cumulative changes to pre-existing Xanthoma over Time ........................... 242
Table 14.3.12.1 Carotid Intima-Media Thickness and Flow-mediated Dilation Summary and 
Percentage Change from Baseline over Time ........................................................................ 246
Table 14.3.13.1 Summary of Palatability over Time ............................................................... 247
Table 14.3.14.1 Summary of Diet Compliance over Time ...................................................... 249


SQN Clinical study no: OCH19003
Amryt Pharma study no: APH-19
Listing 16.2.1.1 Subject Completions and Withdrawals .......................................................... 251
Listing 16.2.2.1 Eligibility ......................................................................................................... 252
Listing 16.2.2.2 Protocol Deviations ........................................................................................ 253
Listing 16.2.2.3 COVID-19 Protocol Deviations ...................................................................... 254
Listing 16.2.3.1 Analysis Sets ................................................................................................. 255
Listing 16.2.4.1 Demography .................................................................................................. 256
Listing 16.2.4.2 Diagnosis of HoFH ......................................................................................... 258
Listing 16.2.4.3 Medical History .............................................................................................. 259
Listing 16.2.4.4 Cardiovascular Medical History ..................................................................... 260
Listing 16.2.4.5 Prior/Run-in/Concomitant Medications .......................................................... 261
Listing 16.2.4.6 Lipid-lowering-therapy (LLT) Medications ..................................................... 263
Listing 16.2.4.7 Prior/Run-in/Concomitant Procedures ........................................................... 264
Listing 16.2.5.1 IMP Administration ......................................................................................... 265
Listing 16.2.6.1 Lipoprotein Apheresis (LA) History ................................................................ 268
Listing 16.2.6.2 Lipoprotein Apheresis (LA) Treatment ........................................................... 269
Listing 16.2.7.1 Adverse Events .............................................................................................. 270
Listing 16.2.7.2 Serious Adverse Events ................................................................................ 273
Listing 16.2.8.1 Serum Clinical Chemistry (Fasting Lipid Panel) Values ................................ 274
Listing 16.2.8.2 Serum Clinical Chemistry (Metabolic Panel) Values ..................................... 277
Listing 16.2.8.3 Serum Clinical Chemistry (Liver Function Tests) Values .............................. 279
Listing 16.2.8.4 Serum Clinical Chemistry (Essential Fatty Acids) Values ............................. 280
Listing 16.2.8.5 Serum Clinical Chemistry (Fat Soluble Vitamin Levels) Values .................... 282
Listing 16.2.8.6 Serum Clinical Chemistry (Hormones) Values .............................................. 283
Listing 16.2.8.7 Serum Clinical Chemistry (Sex Hormones) Values ....................................... 284
Listing 16.2.8.8 Serum Clinical Chemistry (Serum Lipase) Values ......................................... 285
Listing 16.2.8.9 Serum Haematology Values .......................................................................... 286
Listing 16.2.8.10 Urinalysis Values ......................................................................................... 287
Listing 16.2.9.1 Vital Signs ...................................................................................................... 288
Listing 16.2.10.1 ECG Results ................................................................................................ 289
Listing 16.2.11.1 Echocardiography Results ........................................................................... 290
Listing 16.2.12.1 Lipid Accumulation in the Liver Results ....................................................... 293
Listing 16.2.13.1 Physical Examination ................................................................................... 294
Listing 16.2.13.2 Tanner Staging ............................................................................................ 295
Listing 16.2.14.1 Pulmonary Function Test ............................................................................. 296
Listing 16.2.15.1 Pregnancy Test ............................................................................................ 297
Listing 16.2.16.1 Visit Dates .................................................................................................... 298
Listing 16.2.17.1 Xanthoma Examination ................................................................................ 301
Listing 16.2.17.2 Carotid Intima-Media Thickness (CIMT) ...................................................... 303
Listing 16.2.17.3 Flow-mediated Dilation (FMD) ..................................................................... 304
Listing 16.2.17.4 Palatability .................................................................................................... 305
Listing 16.2.19.1 Diet and Dietary Supplement Compliance ................................................... 307
Figure 14.1.5.1 Kaplan-Meier Plot of Time to Dose Reduction ............................................... 308
Figure 14.1.5.2 Kaplan-Meier Plot of Time to Dose Interruption ............................................. 309
Figure 14.2.1.1 Waterfall Plot of Percentage Change (%) from Baseline in Fasting Lipid Panel 
at Week 24 by age group ........................................................................................................ 310
Figure 14.2.1.2 Forest Plot of Sub-group analysis for primary end point (percentage change at 
week 24) .................................................................................................................................. 311
Figure 14.2.1.3 Profile Plot of LSMeans percentage change from baseline over time in Fasting 
Lipid Panel ............................................................................................................................... 312
Figure 14.2.1.4 Forest Plot of Sub-group analysis for key secondary endpoint: Non-HDL-C 
(percentage change at week 24) ............................................................................................. 313
Figure 14.2.1.5 Forest Plot of Sub-group analysis for key secondary endpoint: TC (percentage 
change at week 24) ................................................................................................................. 314
Figure 14.2.1.6 Forest Plot of Sub-group analysis for key secondary endpoint: VLDL-C 
(percentage change at week 24) ............................................................................................. 315
Figure 14.2.1.7 Forest Plot of Sub-group analysis for key secondary endpoint: Apo B 
(percentage change at week 24) ............................................................................................. 316
Figure 14.2.1.8 Forest Plot of Sub-group analysis for key secondary endpoint: TG (percentage 
change at week 24) ................................................................................................................. 317
Figure 14.2.1.9 Forest Plot of Sub-group analysis for key secondary endpoint: Lp(a) 
(percentage change at week 24) ............................................................................................. 318


SQN Clinical study no: OCH19003
Amryt Pharma study no: APH-19
Figure 14.2.1.10 Profile Plot of percentage change from baseline over time in Fasting Lipid 
Panel 319
Figure 14.3.2.1 Cumulative distribution function (CDF) plot of LDL-C at Week 24 ................ 320
Figure 14.3.2.2 Cumulative distribution function (CDF) plot of LDL-C over time .................... 321
Figure 14.3.2.3 Cumulative distribution function (CDF) plot of percentage change in LDL-C at 
Week 24 .................................................................................................................................. 322
Figure 14.3.2.4 Cumulative distribution function (CDF) plot of lowest percentage change in 
LDL-C from Week 8 ................................................................................................................. 323
Figure 14.3.1.1 Subject profile for distribution of Treatment-Emergent adverse events and dose 
at time of event ........................................................................................................................ 324
Figure 14.3.1.2 Age profile for distribution of Treatment-Emergent adverse events and 
MTD 
325
Figure 14.3.1.3 Histogram of Time to First Gastrointestinal Treatment-Emergent Adverse 
Event 326
Figure 14.3.1.4 Histogram of Time to First Hepatic Treatment-Emergent Adverse Event ..... 327
Figure 14.3.3.1 Individual subject profiles of liver function data ............................................. 328
Figure 14.3.3.2 AST profiles over time, by subject age .......................................................... 329
Figure 14.3.3.3 ALT profiles over time, by subject age ........................................................... 330
Figure 14.3.3.4 AST profiles over time, by subject MTD ........................................................ 331
Figure 14.3.3.5 ALT profiles over time, by subject MTD ......................................................... 332
Figure 14.3.3.6 Individual subject profiles of LDL-C data ....................................................... 333
Figure 14.3.3.7 LDL-C profiles over time, by subject age ....................................................... 334
Figure 14.3.3.8 LDL-C profiles over time, by subject MTD ..................................................... 335
Figure 14.3.3.9 Spaghetti plot of lipid profiles over time ......................................................... 336
Figure 14.3.3.10 eDISH plot of Maximum Post-Baseline ALT by Maximum Post-Baseline Total 
Bilirubin .................................................................................................................................... 337
Figure 14.3.3.11 eDISH plot of Maximum Post-Baseline AST by Maximum Post-Baseline Total 
Bilirubin .................................................................................................................................... 338
Figure 14.3.3.12 Subject profile for distribution of Liver Function Test Abnormalities and dose 
at time of event ........................................................................................................................ 339
Figure 14.3.5.1 Boxplot of Observed Vital Signs over Time ................................................... 340
Figure 14.3.5.2 Boxplot of Change from Baseline Vital Signs over Time ............................... 341
Figure 14.3.5.3 Waterfall plot of change in BMI at Week 24, 56 and 104, by patient sex ...... 342
Figure 14.3.8.1 Scatter plot of change in hepatic fat up with change in BMI Z score up to week 
56 and 104, by subject age ..................................................................................................... 343
Figure 14.3.8.2 Scatter plot of change in hepatic fat with change in BMI Z score up to week 56 
and 104, by subject MTD ........................................................................................................ 344
Figure 14.3.8.3 Scatter plot of change in hepatic fat up to week 56 and 104 and time fom 
Lomitapide administration, by subject age .............................................................................. 345
Figure 14.3.8.4 Scatter plot of change in hepatic fat up to week 56 and 104 and time from 
Lomitapide administration, by subject MTD ............................................................................ 346
Figure 14.3.8.5 Cumulative distribution function (CDF) plot of percentage change in hepatic fat 
over time .................................................................................................................................. 347
Figure 14.3.8.6 Scatter plot of ALT vs hepatic fat over time ................................................... 348
Figure 14.3.8.7 Scatter plot of AST vs hepatic fat over time ................................................... 349
Figure 14.3.9.1 Waterfall plot of change in BMI Z score at Week 24, 56 and 104, by patient 
age 
350
Figure 14.3.9.2 Waterfall plot of change in BMI Z score at Week 24, 56 and 104, by patient 
sex 
351
Figure 14.3.9.3 Spaghetti plot of BMI Z score over time, by patient age and sex .................. 352
Figure 14.3.9.4 Spaghetti plot of BMI absolute value over time, by patient age and sex ....... 353
Figure 14.3.9.5 Spaghetti plot of weight absolute value over time, by patient age and sex ... 354
Figure 14.3.9.6 Spaghetti plot of sexual maturation development over time .......................... 355
Figure 14.3.9.7 Spaghetti plot of growth development over time ............................................ 356
Figure 14.3.9.8 Waterfall plot of change in BMI Z-score at Week 24, 56 and 104, by baseline 
BMI for Age Z-score ................................................................................................................ 357
Figure 14.3.9.9 Spaghetti plot of BMI Z-score over time, by baseline BMI for Age Z-score... 358
Figure 14.3.9.10 Individual spaghetti plot of weight and Z scores over time .......................... 359
Figure 14.3.9.11 Waterfall plot of change from baseline to maximum weight loss ................. 360
Figure 14.3.9.12 Waterfall plot of change from baseline to minimum BMI z-score change.... 361


SQN Clinical study no: OCH19003
Amryt Pharma study no: APH-19
1   
 
Summary statistics  for quantitative data will be recorded as n, mean, standard 
deviation, minimum, median and maximum, 25th & 75th percentile (as specified in 
shell).  For categorical data, a frequency table (showing n and %) will replace this 
summary. 
Data manipulations will be detailed as appropriate in the SAS code.  Derived database 
(DDB) specifications will be created and maintained by Veristat. 
All tables, listings and figures will use recommended ICH numbering. 
Complex manipulations should be detailed in the body of the SAP text or as 
programming notes  on the table shells. 
 
Decimal places will be as follows (where applicable), where x is the precision of the raw 
data: 
 
x +2 (standard errors, standard deviations, CV%). 
 
x +1 (means, medians, confidence intervals). 
 
x (min and max). 
 
1 decimal place (percentages).  Percentages will not be displayed where n=0.
Percentages will be based on the number of subjects in the analysis set/population, for 
the relevant treatment group (regardless of time point), unless otherwise stated. 
The missing  category, where used, will not include subjects who have withdrawn at 
earlier visits. Subjects with missing results or assessment not done at visit x will be 
included in the missing category only if they have a visit x or a visit greater than x in the 
visit date listing. 
Page set-up specifications for the SAS output TFLs: 
 
Word document landscape 
 
Word document margins set to: 
o top = 2.54 cm 
o bottom = 1.5 cm 
o left = 2 cm 
o right = 2 cm 
o gutter = 0 cm 
o header = 1.25 cm 
o footer = 1.25 cm 
 
Word document font: Courier New, 8pt 
 
SAS output options ls=141 ps=52 
 
All output will be provided as individual and collated .rtf files. 
The sponsor study number and sponsor name will be displayed in the top left hand side 
of the TFLs and page numbers will be displayed in the top right hand side of the TFLs.


SQN Clinical study no: OCH19003
Amryt Pharma study no: APH-19
For each listing, only the visits/time points where the data was collected will be listed, 
including unscheduled assessments where applicable. Tables will show results for all 
visits and time points where data was collected, unless specified otherwise within the 
shell (see programming notes). 
Other standards and conventions: 
 
General: 
o UK spelling used in all tables, listings and figures. 
o Output spans entire width of page (where possible). 
o Top line spanning output but no line at bottom. 
o Numeric results aligned by decimal place. 
 
Listings only: 
o Ordered by age group (5-10,11-15 and 16-<=17), visit and subject 
number (as applicable). 
o All dates will be displayed as DDMONYYYY. Missing days will be 
displayed in the listings as UK , missing months as UNK  and missing 
years as UKUK . Add footnote UK/UNK = Unknown.  where required.
o Data will be presented in date order. 
o Leave all footnote decodes such as L = 
, H = 
. even if not actually 
within data listed. 
o Where adding a footnote for decodes such as Route/Frequency, add all 
possible values from CRF rather than just those in the data. 
o Where one row per subject  no break lines. Where more than one row 
per subject  break after subject/visit/time point as applicable. 
 
Tables only: 
o Remove percentages when count is zero. 
o All results should be aligned. For example, numbers from summary 
statistics should align with results from frequency counts. 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.1.1 Subject Disposition 
(Enrolled Set) 
 
 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
Screen Failures, n 
XX 
XX 
XX 
Enrolled Set [1], n (%)* 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Run-in Failures, n (%)* 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Completed Run-In Period, n (%)* 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Safety Set (SAF) [2], n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Full Analysis Set (FAS) [3], n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Completers Analysis Set (CAS) [4], n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Per Protocol Set (PPS) [5], n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Subjects who completed the Safety Phase (week 104) of the 
study, n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Subjects who prematurely discontinued study, n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Reason for study withdrawal n (%) 
 
 
 
  Adverse Event 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Discontinuation of the study by sponsor 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Lost to follow-up 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Non-compliance 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Pregnancy 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Protocol Deviation 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Voluntary Withdrawal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  COVID-19 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Death 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects enrolled. n = the number of subjects meeting the criterion. 
[*] Percentages based off the Enrolled Set. All other percentages based off the Safety Analysis Set. 
[**] The calculation of study duration excludes screen failure patients. 
[1] The Enrolled Set includes all subjects who pass screening and enter into the run-in period, irrespective of whether they receive the 
study treatment. 
[2] The Safety Analysis Set includes all subjects who are treated with at least one dose of the IMP. 
[3] The Full Analysis Set includes all subjects who receive at least one dose of the IMP and who have a baseline and at least one post-
baseline measurement of LDL-C. 
[4] The Completers Analysis Set includes all subjects from the FAS who have not discontinued the Efficacy Phase (up to Week 24) of the study 
early irrespective of the reason for discontinuation. 
[5] The Per Protocol Set includes all patients from the FAS who reasonably adhere to all protocol conditions (i.e. who have met the 
eligibility criteria and receive planned study medication without important protocol deviations considered to have a serious impact on the 
efficacy results within the Efficacy Phase of the trial).
Source: Listing 16.2.1.1 and Listing 16.2.3.1
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.1.1 Subject Disposition 
(Enrolled Set) 
 
 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
Study duration (weeks)** 
 
 
 
  n 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX.X 
XX.X 
XX.X 
  Median 
XX.X 
XX.X 
XX.X 
  Maximum 
XX.X 
XX.X 
XX.X 
 
 
 
 
Treatment duration (weeks) 
 
 
 
  n 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX.X 
XX.X 
XX.X 
  Median 
XX.X 
XX.X 
XX.X 
  Maximum 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
N = the number of subjects enrolled. n = the number of subjects meeting the criterion. 
[*] Percentages based off the Enrolled Set. All other percentages based off the Safety Analysis Set. 
[**] The calculation of study duration excludes screen failure patients. 
[1] The Enrolled Set includes all subjects who pass screening and enter into the run-in period, irrespective of whether they receive the 
study treatment. 
[2] The Safety Analysis Set includes all subjects who are treated with at least one dose of the IMP. 
[3] The Full Analysis Set includes all subjects who receive at least one dose of the IMP and who have a baseline and at least one post-
baseline measurement of LDL-C. 
[4] The Completers Analysis Set includes all subjects from the FAS who have not discontinued the Efficacy Phase (up to Week 24) of the study 
early irrespective of the reason for discontinuation. 
[5] The Per Protocol Set includes all patients from the FAS who reasonably adhere to all protocol conditions (i.e. who have met the 
eligibility criteria and receive planned study medication without important protocol deviations considered to have a serious impact on the 
efficacy results within the Efficacy Phase of the trial). 
Source: Listing 16.2.1.1 and Listing 16.2.3.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.1.2 Subject Study Visits 
(Enrolled Set) 
 
 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
Run-in period: 
 
 
 
Visit 2 (Enrolment), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 3 (Compliance), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Efficacy Phase: 
 
 
 
Visit 4 (Week 0 / Day 0), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 5 (Week 4 / Day 28), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 6 (Week 8 / Day 56), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 7 (Week 12 / Day 84), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 8 (Week 16 / Day 112), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 9 (Week 20 / Day 140), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 10 (Week 24 / Day 168), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Safety Phase: 
 
 
 
Visit 11 (Week 28 / Day 196), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 12 (Week 32 / Day 224), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 13 (Week 36 / Day 252), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 14 (Week 40 / Day 280), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 15 (Week 44 / Day 308), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 16 (Week 48 / Day 336), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 17 (Week 52 / Day 364), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 18 (Week 56 / Day 392), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 19 (Week 68 / Day 479), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 20 (Week 80 / Day 560), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Visit 21 (Week 92 / Day 644), n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
End Of Treatment: 
 
 
 
Visit 22 (EOT / Week 104) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Follow-up: 
 
 
 
Visit 23 (Week 108) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects enrolled. n = the number of subjects meeting the criterion. 
Percentages based off the Enrolled Set. 
Source: Listing 16.2.16.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.2.1 Demography 
(Safety Analysis Set) 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Sex, n (%) 
Male 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Female 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Unknown 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
Age (years) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Race, n (%) 
Black or African American 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
American Indian or Alaska Native 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Asian 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Native Hawaiian or other Pacific 
Islander 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Arabic 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
White 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
Ethnicity, n (%) 
Hispanic or Latino 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Not Hispanic or Latino 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Not Reported 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Unknown 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
[1] BMI = {weight(kg) / height(m)^2} 
[2] BSA  (m^2) = [{height(cm) x weight(kg)} / 3600]   [Mosteller formula] 
[3] z scores and percentiles calculated using the WHO growth reference indicators for children aged 5 to 19 years 
Source: Listing 16.2.4.1, Listing 16.2.4.2, Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
NOTES:
Age is calculated in years = [full age in month (months + years) / 12]


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.2.1 Demography 
(Safety Analysis Set) 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Country, n (%) 
Germany 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Spain 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Italy 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Saudi Arabia 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Tunisia 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Israel 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height (cm) at Baseline 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Weight (kg) at Baseline 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
[1] BMI = {weight(kg) / height(m)^2} 
[2] BSA  (m^2) = [{height(cm) x weight(kg)} / 3600]   [Mosteller formula] 
[3] z scores and percentiles calculated using the WHO growth reference indicators for children aged 5 to 19 years 
Source: Listing 16.2.4.1, Listing 16.2.4.2, Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
NOTES:
Age is calculated in years = [full age in month (months + years) / 12]


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.2.1 Demography 
(Safety Analysis Set) 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Body mass index (kg/m^2) at 
Baseline [1] 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Body surface area (BSA) at Baseline 
[2] 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Height percentile [3] 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
[1] BMI = {weight(kg) / height(m)^2} 
[2] BSA  (m^2) = [{height(cm) x weight(kg)} / 3600]   [Mosteller formula] 
[3] z scores and percentiles calculated using the WHO growth reference indicators for children aged 5 to 19 years 
Source: Listing 16.2.4.1, Listing 16.2.4.2, Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX
NOTES:
Age is calculated in years = [full age in month (months + years) / 12]


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.2.1 Demography 
(Safety Analysis Set) 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Height Z Score [3] 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
BMI percentile [3] 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
BMI Z Score [3] 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
[1] BMI = {weight(kg) / height(m)^2} 
[2] BSA  (m^2) = [{height(cm) x weight(kg)} / 3600]   [Mosteller formula] 
[3] z scores and percentiles calculated using the WHO growth reference indicators for children aged 5 to 19 years 
Source: Listing 16.2.4.1, Listing 16.2.4.2, Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
NOTES:
Age is calculated in years = [full age in month (months + years) / 12]


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.2.2 Baseline Lipids 
(Safety Analysis Set) 
 
 
 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
LDL-C (mg/dL) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Non-HDL-C (mg/dL) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Total Cholesterol (TC) (mg/dL) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. 
LDL-C, Non-HDL-C, Cholesterol, VLDL-C, Apo B, Triglycerides, HDL-C, Apo A1 summarised using Central Lab values. 
Lp(a) summarised using Local Lab values. 
Source: Listing 16.2.4.1, Listing 16.2.4.2, Listing 16.2.8.1 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.2.2 Baseline Lipids 
(Safety Analysis Set) 
 
 
 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
VLDL-C (mg/dL) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Apo B (mg/dL) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Triglycerides (TG) (mg/dL) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. 
LDL-C, Non-HDL-C, Cholesterol, VLDL-C, Apo B, Triglycerides, HDL-C, Apo A1 summarised using Central Lab values. 
Lp(a) summarised using Local Lab values. 
Source: Listing 16.2.4.1, Listing 16.2.4.2, Listing 16.2.8.1 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.2.2 Baseline Lipids 
(Safety Analysis Set) 
 
 
 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Apo A1 (mg/dL) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
HDL-C (mg/dL) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Lp(a) (mg/dL) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. 
LDL-C, Non-HDL-C, Cholesterol, VLDL-C, Apo B, Triglycerides, HDL-C, Apo A1 summarised using Central Lab values. 
Lp(a) summarised using Local Lab values. 
Source: Listing 16.2.4.1, Listing 16.2.4.2, Listing 16.2.8.1 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.2.2 Baseline Lipids 
(Safety Analysis Set) 
 
 
 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Lp(a) (nmol/L) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
TC/HDL-C 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX.X 
XX.X 
XX.X 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX.X 
XX.X 
XX.X 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. 
LDL-C, Non-HDL-C, Cholesterol, VLDL-C, Apo B, Triglycerides, HDL-C, Apo A1 summarised using Central Lab values. 
Lp(a) summarised using Local Lab values. 
Source: Listing 16.2.4.1, Listing 16.2.4.2, Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.2.3 Diagnosis of HoFH 
(Safety Analysis Set) 
 
 
 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Duration of HoFH diagnosis (weeks) 
[1] 
 
 
 
 
 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Genetic confirmation of 2 mutant 
alleles, n (%) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
Type of mutant allele, n (%) 
LDLR gene locus 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Apo B gene locus 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
PCSK9 gene locus 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
LDLRAP1 gene locus 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Unknown 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
LDL receptor function mutation 
LDLR-deficient mutation 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
LDLR-defective mutation 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
[1] Duration of diagnosis is defined as the time in weeks from diagnosis to baseline. 
Source: Listing 16.2.4.2 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.2.3 Diagnosis of HoFH 
(Safety Analysis Set) 
 
 
 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
An untreated LDL-C >500mg/dL 
(13mmol/L) or treated LDLC 
300mg/dL (8mmol/L) AND cutaneous 
or tendon xanthoma before age of 10 
years? n (%) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
An untreated LDL-C >500mg/dL 
(13mmol/L) or treated LDLC 
300mg/dL (8mmol/L) AND untreated 
LDL-C levels consistent with HoFH 
in both parents? n (%) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
[1] Duration of diagnosis is defined as the time in weeks from diagnosis to baseline. 
Source: Listing 16.2.4.2 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.3.1 Medical History 
(Safety Analysis Set) 
 
Ongoing conditions 
 
 
 
System organ class 
   Preferred term 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
Subjects with any medical history 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
System organ class 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
System organ class 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Etc
 
 
 
 
 
Medical history events were coded using the MedDRA Dictionary, version xx.x. 
System organ classes (SOC) are ordered in decreasing frequency of the total number of subjects with medical histories reported in each SOC 
and preferred terms are ordered within a SOC in decreasing frequency of the total number of subjects with each medical history. 
N = the number of subjects in the analysis set. n = the number of subjects with medical history. (%) = n/N*100. 
Source: Listing 16.2.4.3 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for 'Previous conditions'. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.3.2 Cardiovascular History 
(Safety Analysis Set) 
 
Ongoing conditions 
 
 
 
System organ class 
   Preferred term 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
Subjects with any cardiovascular history 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
System organ class 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
System organ class 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Preferred term 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Etc
 
 
 
 
 
Cardiovascular history events were coded using the MedDRA Dictionary, version xx.x. 
System organ classes (SOC) are ordered in decreasing frequency of the total number of subjects with cardiovascular histories reported in each 
SOC and preferred terms are ordered within a SOC in decreasing frequency of the total number of subjects with each cardiovascular history. 
N = the number of subjects in the analysis set. n = the number of subjects with medical history. (%) = n/N*100. 
Cardiovascular History will be identified using pre-specified SOC and PT terms. 
Source: Listing 16.2.4.4 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for 'Previous conditions'. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.3.3 Cardiovascular Disease History at Screening 
(Safety Analysis Set) 
 
 
 
 
 
Type of cardiovascular disease 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
Subjects with cardiovascular history at 
screening, n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Valvular disease, n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Coronary artery disease, n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Other, n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Cardiovascular disease ongoing, n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Duration of cardiovascular disease (months)* 
 
 
 
  n 
XX 
XX 
XX 
  Mean 
XX.X 
XX.X 
XX.X 
  SD 
XX.XX 
XX.XX 
XX.XX 
  Minimum 
XX 
XX 
XX 
  Median 
XX.X 
XX.X 
XX.X 
  Maximum 
XX 
XX 
XX 
  25th percentile 
XX.X 
XX.X 
XX.X 
  75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = m/n*100. 
* Duration of cardiovascular disease (months). For those with ongoing CVD, duration is calculated up to date of screening visit. 
Source: Listing 16.2.4.4 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.4.1 Prior and 'Run-in Medications' Medications 
(Safety Analysis Set) 
 
 
 
 
 
Medication class 
   Standardised medication name 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
Subjects with any prior and/or 'Run-in' 
medication 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Medication class 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Medication class 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Etc
 
 
 
 
 
Medications were coded using WHO Drug Dictionary, version xxx. 
Medication classes and standardised medication names are ordered by descending frequency. 
Prior medications / procedures are defined as those that started and ended prior to the enrolment date visit (visit 2) (i.e. start of the 
'run-in period'). 
Run-in period' medications / procedures are defined as those that are ongoing at the time of starting the run-in  period (i.e. Visit 2) or 
started after the start of the run-in  period, but before the time of first administration of study treatment. 
N = the number of subjects in the analysis set receiving the treatment. n = the number of subjects taking a prior/'run-in' medication. (%) = 
n/N*100. 
[*] Indicates prior medication only. 
Source: Listing 16.2.4.5 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Please flag (*) medications that are prior only medications. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.4.2 Concomitant Medications 
(Safety Analysis Set) 
 
 
 
 
 
Medication class 
   Standardised medication name 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
Subjects with any concomitant medication 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Medication class 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Medication class 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Etc
 
 
 
 
 
Medications were coded using WHO Drug Dictionary, version xxx. 
Medication classes and standardised medication names are ordered by descending frequency. 
Concomitant medications / procedures are defined as those that are ongoing at the time of first administration of study treatment or started 
on or after the time of first administration of study treatment or started prior to the end / last dose of study treatment. If medication / 
procedure dates are incomplete and it is not clear whether the medication / procedure was concomitant, it will be assumed to be concomitant. 
N = the number of subjects in the analysis set receiving the treatment. n = the number of subjects taking a concomitant medication. (%) = 
n/N*100. 
Source: Listing 16.2.4.5 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.4.3 Lipid-Lowering-Therapy Medications 
(Safety Analysis Set) 
 
Prior and 'Run-in' LLT medications 
 
 
 
Medication class 
   Standardised medication name 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
Subjects with any prior and/or 'run-in' LLT 
medication 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Subjects with >= 2 run-in  LLT medications 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Subjects with >= 3 run-in  LLT medications 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Medication class 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Medication class 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Standardised medication name 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Etc
 
 
 
 
 
Medications were coded using WHO Drug Dictionary, version xxx. 
Medication classes and standardised medication names are ordered by descending frequency. 
Prior Lipid-lowering therapy medications and procedures are defined as those that started and ended prior to the enrolment visit (visit 2) 
date (i.e. start of the run-in period ). 
Run-in' periord Lipid-lowering therapy medications and procedures are defined as any lipid-lowering therapy or procedure that are ongoing at 
the enrolment visit (visit 2) date (i.e. start of the run-in period ) and / or started after the start of the run-in period , but before the 
time of first administration of study treatment. 
N = the number of subjects in the analysis set receiving the treatment. n = the number of subjects with a prior and/or 'run-in' medication. 
(%) = n/N*100. 
[*] Indicates prior medication only. 
Source: Listing 16.2.4.6 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX
NOTES:
Repeat for Concomitant LLT medications (efficacy phase); Concomitant LLT medications (safety phase).
Update first row table text and footnotes accordingly.
Please flag (*) medications that are prior only medications.


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.4.5 Procedures 
(Safety Analysis Set) 
 
 
 
 
 
Procedure category 
  Indication 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
Subjects with any procedure 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Procedure category 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Indication 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Indication 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Indication 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Indication 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Procedure category 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Indication 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Indication 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Indication 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Indication 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Etc
 
 
 
 
 
Procedures were coded using the MedDRA Dictionary, version xx.x. 
N = the number of subjects in the analysis set receiving the treatment. n = the number of subjects with procedure. (%) = n/N*100. 
Source: Listing 16.2.4.7 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.4.6 Days from most recent apheresis to the corresponding LDL-C primary efficacy assessment 
(Safety Analysis Set) 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
 
 
 
 
Established regimen during run-in 
Twice a week 
XX (XX.X) 
XX (XX.X) 
 
Weekly 
XX (XX.X) 
XX (XX.X) 
 
Every two weeks 
XX (XX.X) 
XX (XX.X) 
 
Other 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Weighted average number of days from previous LA 
during run-in (days) [1] 
n 
XX 
XX 
 
Mean 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
 
Median 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
Days from most recent apheresis to LDL-C 
assessment on [2]: 
 
 
 
 
Baseline  
n 
XX 
XX 
 
Mean 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
 
Median 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
 
 
 
 
Week 24/LOCF  
n 
XX 
XX 
 
Mean 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
 
Median 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
Only subjects on apheresis at baseline are presented.
[1] Established apheresis regimen during run-in in days. The weighted average number of days is summarised.
[2] Days from most recent apheresis to baseline LDL-C assessment and to Week 24 are summarised. For subjects discontinuing before Week 24, 
the duration between the most recent apheresis and the LDL-C assessment that was carried forward is presented.
N = the number of subjects in the analysis set receiving the treatment. n = the number of subjects with procedure. (%) = n/N*100.


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Source: Listing 16.2.6.2, Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: For discontinued subjects, note the Week number used for the LOCF in the footnotes. 
Add categories for established regimen as applicable. 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.5.1 Study Drug Exposure and Dosing 
(Safety Analysis Set) 
 
Study Phase 
 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Exposure (weeks) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Exposure (mg / day) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Maximum Tolerated Dose (mg), n (%) 
5mg 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
10mg 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
20mg 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
30mg 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
40mg 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
60mg 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
Exposure to maintenance dose (weeks) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
25th percentile
XX.X
XX.X
XX.X
75th percentile
XX.X
XX.X
XX.X
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100.


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
[1] Subject compliant for IMP dosing has been medically reviewed on a patient level basis. Subjects will be considered compliant if 80% to 
100% of IMP doses have been taken. 
Source: Listing 16.2.5.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Additional doses may be added to Maximum Tolerated Dose as appropriate. 
 
Subject percentage compliance for dosing as per protocol (Efficacy Phase) - Use post-baseline study visits Week 4 to Week 24 
inclusive 
 
Subject percentage compliance for dosing as per protocol (Safety Phase) - Use post-baseline study visits Week 28 to Week 104 
inclusive 
 
Subject percentage compliance for dosing as per protocol (Overall) - Use post-baseline study visits Week 4 to Week 104 inclusive 
 
If a subject discontinues early during the efficacy phase, Use post-baseline study visits Week 4 to Week 24 and EOT/Week 104, as 
appropriate. 
 
For the compliant with IMP dosing present only the corresponding to the study phase. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.5.1 Study Drug Exposure and Dosing 
(Safety Analysis Set) 
 
Study Phase 
 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Number of Doses Received 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Number of Dose Increases 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Number of Dose Reductions 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
[1] Subject compliant for IMP dosing has been medically reviewed on a patient level basis. Subjects will be considered compliant if 80% to 
100% of IMP doses have been taken. 
Source: Listing 16.2.5.1 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX
NOTES:
Additional doses may be added to Maximum Tolerated Dose as appropriate.
Subject percentage compliance for dosing as per protocol (Efficacy Phase) - Use post-baseline study visits Week 4 to Week 24 
inclusive


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
 
Subject percentage compliance for dosing as per protocol (Safety Phase) - Use post-baseline study visits Week 28 to Week 104 
inclusive 
 
Subject percentage compliance for dosing as per protocol (Overall) - Use post-baseline study visits Week 4 to Week 104 inclusive 
 
If a subject discontinues early during the efficacy phase, Use post-baseline study visits Week 4 to Week 24 and EOT/Week 104, as 
appropriate. 
 
For the compliant with IMP dosing present only the corresponding to the study phase. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.5.1 Study Drug Exposure and Dosing 
(Safety Analysis Set) 
 
Study Phase 
 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Number of Dose Interruptions 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Number of Dose Reductions due to concomitant 
medication 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Number of Dose Reductions due to adverse events 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
[1] Subject compliant for IMP dosing has been medically reviewed on a patient level basis. Subjects will be considered compliant if 80% to 
100% of IMP doses have been taken. 
Source: Listing 16.2.5.1 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX
NOTES:
Additional doses may be added to Maximum Tolerated Dose as appropriate.


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
 
Subject percentage compliance for dosing as per protocol (Efficacy Phase) - Use post-baseline study visits Week 4 to Week 24 
inclusive 
 
Subject percentage compliance for dosing as per protocol (Safety Phase) - Use post-baseline study visits Week 28 to Week 104 
inclusive 
 
Subject percentage compliance for dosing as per protocol (Overall) - Use post-baseline study visits Week 4 to Week 104 inclusive 
 
If a subject discontinues early during the efficacy phase, use post-baseline study visits Week 4 to Week 24 and EOT/Week 104, as 
appropriate. 
 
For the compliant with IMP dosing present only the corresponding to the study phase. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.5.1 Study Drug Exposure and Dosing 
(Safety Analysis Set) 
 
Study Phase 
 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Number of Dose Interruptions due to concomitant 
medication 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Number of Dose Interruptions due to adverse events 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Number of Drug Discontinuations due to adverse 
events 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
[1] Subject compliant for IMP dosing has been medically reviewed on a patient level basis. Subjects will be considered compliant if 80% to 
100% of IMP doses have been taken. 
Source: Listing 16.2.5.1
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX
NOTES:
Additional doses may be added to Maximum Tolerated Dose as appropriate.


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
 
Subject percentage compliance for dosing as per protocol (Efficacy Phase) - Use post-baseline study visits Week 4 to Week 24 
inclusive 
 
Subject percentage compliance for dosing as per protocol (Safety Phase) - Use post-baseline study visits Week 28 to Week 104 
inclusive 
 
Subject percentage compliance for dosing as per protocol (Overall) - Use post-baseline study visits Week 4 to Week 104 inclusive 
 
If a subject discontinues early during the efficacy phase, use post-baseline study visits Week 4 to Week 24 and EOT/Week 104, as 
appropriate. 
 
For the compliant with IMP dosing present only the corresponding to the study phase. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.5.1 Study Drug Exposure and Dosing 
(Safety Analysis Set) 
 
Study Phase 
 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Dose at Drug Discontinuation due to adverse events 
(mg), n (%) 
2mg 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
5mg 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
10mg 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
20mg 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
30mg 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
40mg 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
60mg 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
Subject compliant with IMP dosing, n (%) [1] 
(Efficacy Phase) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
Subject compliant with IMP dosing, n (%) [1] 
(Safety Phase) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
[1] Subject compliant for IMP dosing has been medically reviewed on a patient level basis. Subjects will be considered compliant if 80% to 
100% of IMP doses have been taken. 
Source: Listing 16.2.5.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Additional doses may be added to Maximum Tolerated Dose as appropriate. 
 
Subject percentage compliance for dosing as per protocol (Efficacy Phase) - Use post-baseline study visits Week 4 to Week 24 
inclusive 
 
Subject percentage compliance for dosing as per protocol (Safety Phase) - Use post-baseline study visits Week 28 to Week 104 
inclusive 
 
Subject percentage compliance for dosing as per protocol (Overall) - Use post-baseline study visits Week 4 to Week 104 inclusive 
 
If a subject discontinues early during the efficacy phase, use post-baseline study visits Week 4 to Week 24 and EOT/Week 104, as 
appropriate. 
 
For the compliant with IMP dosing present only the corresponding to the study phase. 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.5.2 Summary of Compliance to IMP 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
m1 
5 to 10 years 
(N=XX) 
m2 
11 to 17 years 
(N=XX) 
m 
Overall 
(N=XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 4 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
Week 8 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
Week 12 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
Week 16 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Week 104 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. mx = number of subjects attending the 
visit. (%) = n/mx*100.  
Subject compliant for IMP dosing has been medically reviewed on a patient level basis. Subjects will be considered compliant if 80% to 100% 
of IMP doses have been taken. 
Source: Listing 16.2.5.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.5.3 Time to Dose Reduction and Interruption 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
 
 
 
Number of subjects with dose reduction, n (%) 
XX (XX.X) 
XX (XX.X) 
Number of subjects censored, n (%) 
XX (XX.X) 
XX (XX.X) 
 
 
 
Kaplan-Meier estimates of time to dose reduction 
(weeks) 
 
 
  25th percentile 
XX.X 
XX.X 
  95% CI [1] 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
  Median 
XX.X 
XX.X 
  95% CI [1] 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
  75th percentile 
XX.X 
XX.X 
  95% CI [1] 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
 
 
 
Number of subjects with dose interruption, n (%) 
XX (XX.X) 
XX (XX.X) 
Number of subjects censored, n (%) 
XX (XX.X) 
XX (XX.X) 
 
 
 
Kaplan-Meier estimates of time to dose interruption 
(weeks) 
 
 
  25th percentile 
XX.X 
XX.X 
  95% CI [1] 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
  Median 
XX.X 
XX.X 
  95% CI [1] 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
  75th percentile 
XX.X 
XX.X 
  95% CI [1] 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
 
Time to dose reduction is defined as the time (weeks) from the date of the start of the respective phase to the time of first dose reduction, 
if any. For the safety phase, subjects who do not enter the safety phase will be censored at time 0. If a patient discontinues study drug 
they will be counted as an event at the time of study discontinuation. If a patient has not had a dose reduction and is still on study drug, 
they will be censored at their last visit assessment date. 
Time to dose interruption is defined as the time (weeks) from the date of the start of the respective phase to the time of first dose 
interruption, if any. For the safety phase, subjects who do not enter the safety phase will be censored at time 0. If a patient discontinues 
study drug they will be counted as an event at the time of study discontinuation. If a patient has not had a dose interruption and is still 
on study drug, they will be censored at their last visit assessment date. 
[1] 95% Confidence Interval for Kaplan-Meier estimate. 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. 
(%) = n/N*100. 
Source: Listing 16.2.5.1
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX
NOTES:
Repeat for Safety Phase and Overall.


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.1.5.4 Distribution of Achieved Doses 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
Dose 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
 
 
 
 
Week 24 
5 mg 
XX (XX.X) 
XX (XX.X) 
 
10 mg 
XX (XX.X) 
XX (XX.X) 
 
20 mg 
XX (XX.X) 
XX (XX.X) 
 
30 mg 
XX (XX.X) 
XX (XX.X) 
 
40 mg 
XX (XX.X) 
XX (XX.X) 
 
60 mg 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Week 56 
5 mg 
XX (XX.X) 
XX (XX.X) 
 
10 mg 
XX (XX.X) 
XX (XX.X) 
 
20 mg 
XX (XX.X) 
XX (XX.X) 
 
30 mg 
XX (XX.X) 
XX (XX.X) 
 
40 mg 
XX (XX.X) 
XX (XX.X) 
 
60 mg 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Week 104 
5 mg 
XX (XX.X) 
XX (XX.X) 
 
10 mg 
XX (XX.X) 
XX (XX.X) 
 
20 mg 
XX (XX.X) 
XX (XX.X) 
 
30 mg 
XX (XX.X) 
XX (XX.X) 
 
40 mg 
XX (XX.X) 
XX (XX.X) 
 
60 mg 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
Source: Listing 16.2.5.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Add or remove dose categories as applicable. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.1 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Overall 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
Baseline 
n 
XX 
 
 
 
Mean 
XX.X 
 
 
 
SD 
XX.XX 
 
 
 
Minimum 
XX 
 
 
 
Median 
XX.X 
 
 
 
Maximum 
XX 
 
 
 
25th percentile 
XX.X 
 
 
 
75th percentile 
XX.X 
 
 
 
 
 
 
 
Efficacy Week 24 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Efficacy Week 24 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4).
N = the number of subjects in the analysis set. n = the number of subjects with a measurement.
[1] 95% confidence interval for mean percentage change.
[*] Null hypothesis of 0% change. One-sample t-test or Wilcoxon Signed-Rank test.


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
[**] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[***] Missing data has been imputed using Baseline Observation Carried Forward (BOCF). 
[****] Sensitivity analysis: Mixed Model Repeated Measures model with missing at random assumption. Model includes visit as a categorical 
fixed effect. An unstructured covariance will be used initially. The Akaike Information Criterion (AIC) used to assess model fit for 
covariance structures. 
Percentage change from baseline is interpreted clinically as the greater the negative percentage change from baseline the greater the 
absolute clinical percentage change (i.e. percentage change of -48.5% is interpreted clinically as a 48.5% decrease from baseline). 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.1 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Overall 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
Efficacy Week 24 (LOCF)** 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Efficacy Week 24 (LOCF)** 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
[1] 95% confidence interval for mean percentage change. 
[*] Null hypothesis of 0% change. One-sample t-test or Wilcoxon Signed-Rank test. 
[**] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[***] Missing data has been imputed using Baseline Observation Carried Forward (BOCF). 
[****] Sensitivity analysis: Mixed Model Repeated Measures model with missing at random assumption. Model includes visit as a categorical 
fixed effect. An unstructured covariance will be used initially. The Akaike Information Criterion (AIC) used to assess model fit for 
covariance structures. 
Percentage change from baseline is interpreted clinically as the greater the negative percentage change from baseline the greater the 
absolute clinical percentage change (i.e. percentage change of -48.5% is interpreted clinically as a 48.5% decrease from baseline).
Source: Listing 16.2.8.1
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.1 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Overall 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
Efficacy Week 24 (BOCF)*** 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
Efficacy Week 24 (BOCF)*** 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
[1] 95% confidence interval for mean percentage change. 
[*] Null hypothesis of 0% change. One-sample t-test or Wilcoxon Signed-Rank test. 
[**] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[***] Missing data has been imputed using Baseline Observation Carried Forward (BOCF). 
[****] Sensitivity analysis: Mixed Model Repeated Measures model with missing at random assumption. Model includes visit as a categorical 
fixed effect. An unstructured covariance will be used initially. The Akaike Information Criterion (AIC) used to assess model fit for 
covariance structures. 
Percentage change from baseline is interpreted clinically as the greater the negative percentage change from baseline the greater the 
absolute clinical percentage change (i.e. percentage change of -48.5% is interpreted clinically as a 48.5% decrease from baseline).
Source: Listing 16.2.8.1
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.1 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Overall 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
Primary Analysis  
(Analysis Study Week 24) 
Mean percentage change                                  
95% Confidence Interval[1] 
 
 
XX.X 
(X.XXXX, X.XXXX) 
 
P-Value* 
 
 
X.XXXX 
 
 
 
 
 
Sensitivity Analysis (Wilcoxon 
signed rank)(LOCF) 
P-Value* 
 
 
X.XXXX 
 
 
 
 
 
Sensitivity Analysis (Nominal 
Study Visit 10) 
Mean percentage change                                  
95% Confidence Interval[1] 
 
 
XX.X 
(X.XXXX, X.XXXX) 
 
P-Value* 
 
 
X.XXXX 
 
 
 
 
 
Sensitivity Analysis (MMRM)**** 
Mean percentage change                                  
95% Confidence Interval[1] 
 
 
XX.X 
(X.XXXX, X.XXXX) 
 
P-Value* 
 
 
X.XXXX 
 
 
 
 
 
Sensitivity Analysis (BOCF)*** 
Mean percentage change                                  
95% Confidence Interval[1] 
 
 
XX.X 
(X.XXXX, X.XXXX) 
 
P-Value* 
 
 
X.XXXX 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
[1] 95% confidence interval for mean percentage change. 
[*] Null hypothesis of 0% change. One-sample t-test or Wilcoxon Signed-Rank test. 
[**] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[***] Missing data has been imputed using Baseline Observation Carried Forward (BOCF). 
[****] Sensitivity analysis: Mixed Model Repeated Measures model with missing at random assumption. Model includes visit as a categorical 
fixed effect. An unstructured covariance will be used initially. The Akaike Information Criterion (AIC) used to assess model fit for 
covariance structures. 
Percentage change from baseline is interpreted clinically as the greater the negative percentage change from baseline the greater the 
absolute clinical percentage change (i.e. percentage change of -48.5% is interpreted clinically as a 48.5% decrease from baseline).
Source: Listing 16.2.8.1
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.2 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Supplementary analysis - per protocol set) 
(Per Protocol Set) 
 
 
 
 
 
Repeat of Table 14.2.1.1 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.1 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.3 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Supplementary analysis - completer analysis set) 
(Completers Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.1 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.1 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.4 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 1 - Age groups) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
5 to 10 years 
(N=XX) 
 
11 to 17 years 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Baseline 
n 
XX 
 
 
 
XX 
 
 
 
Mean 
XX.X 
 
 
 
XX.X 
 
 
 
SD 
XX.XX 
 
 
 
XX.XX 
 
 
 
Minimum 
XX 
 
 
 
XX 
 
 
 
Median 
XX.X 
 
 
 
XX.X 
 
 
 
Maximum 
XX 
 
 
 
XX 
 
 
 
25th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
75th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4).
N = the number of subjects in the analysis set.
Analysis of Covariance (ANCOVA) model with age group as a categorical fixed effect.
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF).


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.4 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 1 - Age groups) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
5 to 10 years 
(N=XX) 
 
11 to 17 years 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with age group as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.4 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 1 - Age groups) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
5 to 10 years 
(N=XX) 
 
11 to 17 years 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Analysis Study Week 24 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
Nominal Study Visit 10 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with age group as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.5 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 2 - Documented cardiovascular disease 
history) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Documented cardiovascular disease 
history at screening 
(N=XX) 
 
No documented cardiovascular 
disease history at screening 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Baseline 
n 
XX 
 
 
 
XX 
 
 
 
Mean 
XX.X 
 
 
 
XX.X 
 
 
 
SD 
XX.XX 
 
 
 
XX.XX 
 
 
 
Minimum 
XX 
 
 
 
XX 
 
 
 
Median 
XX.X 
 
 
 
XX.X 
 
 
 
Maximum 
XX 
 
 
 
XX 
 
 
 
25th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
75th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X
XX.X
XX.X
 
XX.X
XX.X
XX.X
75th percentile
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4).
N = the number of subjects in the analysis set.


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Analysis of Covariance (ANCOVA) model with classification of documented cardiovascular disease history as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.5 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 2 - Documented cardiovascular disease 
history) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Documented cardiovascular disease 
history at screening 
(N=XX) 
 
No documented cardiovascular 
disease history at screening 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with classification of documented cardiovascular disease history as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change.
Source: Listing 16.2.8.1
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.5 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 2 - Documented cardiovascular disease 
history) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Documented cardiovascular disease 
history at screening 
(N=XX) 
 
No documented cardiovascular 
disease history at screening 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Analysis Study Week 24 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
Nominal Study Visit 10 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with classification of documented cardiovascular disease history as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.6 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 3 -  Established cardiovascular disease 
history (defined as aortic valve disease and/or coronary atherosclerosis)) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Established cardiovascular disease 
history (defined as aortic valve 
disease and/or coronary 
atherosclerosis) at screening 
(N=XX) 
 
No established cardiovascular 
disease history (defined as aortic 
valve disease and/or coronary 
atherosclerosis) at screening 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Baseline 
n 
XX 
 
 
 
XX 
 
 
 
Mean 
XX.X 
 
 
 
XX.X 
 
 
 
SD 
XX.XX 
 
 
 
XX.XX 
 
 
 
Minimum 
XX 
 
 
 
XX 
 
 
 
Median 
XX.X 
 
 
 
XX.X 
 
 
 
Maximum 
XX 
 
 
 
XX 
 
 
 
25th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
75th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
Maximum
XX
XX
XX
XX
XX
XX
25th percentile
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
75th percentile
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with classification of established cardiovascular disease history (defined as aortic valve disease 
and/or coronary atherosclerosis) as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.6 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 3 -  Established cardiovascular disease 
history (defined as aortic valve disease and/or coronary atherosclerosis)) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Established cardiovascular disease 
history (defined as aortic valve 
disease and/or coronary 
atherosclerosis) at screening 
(N=XX) 
 
No established cardiovascular 
disease history (defined as aortic 
valve disease and/or coronary 
atherosclerosis) at screening 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with classification of established cardiovascular disease history (defined as aortic valve disease 
and/or coronary atherosclerosis) as a categorical fixed effect.
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF).
[1] Mean percentage change at week 24 from baseline
[2] 95% confidence interval for mean percentage change.
Source: Listing 16.2.8.1


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.6 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 3 -  Established cardiovascular disease 
history (defined as aortic valve disease and/or coronary atherosclerosis)) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Established cardiovascular disease 
history (defined as aortic valve 
disease and/or coronary 
atherosclerosis) at screening 
(N=XX) 
 
No established cardiovascular 
disease history (defined as aortic 
valve disease and/or coronary 
atherosclerosis) at screening 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Analysis Study Week 24 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
Nominal Study Visit 10 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with classification of established cardiovascular disease history (defined as aortic valve disease 
and/or coronary atherosclerosis) as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.7 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 4 - Concomitant LLT 
medications/procedures) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Had concomitant LLT 
medications/procedures excluding LA 
(N=XX) 
 
Had concomitant LLT 
medications/procedures including LA 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Baseline 
n 
XX 
 
 
 
XX 
 
 
 
Mean 
XX.X 
 
 
 
XX.X 
 
 
 
SD 
XX.XX 
 
 
 
XX.XX 
 
 
 
Minimum 
XX 
 
 
 
XX 
 
 
 
Median 
XX.X 
 
 
 
XX.X 
 
 
 
Maximum 
XX 
 
 
 
XX 
 
 
 
25th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
75th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X
XX.X
XX.X
 
XX.X
XX.X
XX.X
75th percentile
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4).
N = the number of subjects in the analysis set.


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Analysis of Covariance (ANCOVA) model with classification of concomitant LLT medications/procedures as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.7 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 4 - Concomitant LLT 
medications/procedures) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Had concomitant LLT 
medications/procedures excluding LA 
(N=XX) 
 
Had concomitant LLT 
medications/procedures including LA 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with classification of concomitant LLT medications/procedures as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change.
Source: Listing 16.2.8.1
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.7 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 4 - Concomitant LLT 
medications/procedures) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Had concomitant LLT 
medications/procedures excluding LA 
(N=XX) 
 
Had concomitant LLT 
medications/procedures including LA 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Analysis Study Week 24 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
Nominal Study Visit 10 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with classification of concomitant LLT medications/procedures as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.8 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 5 - Dose reductions / dose 
interruptions) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
No dose reductions 
(N=XX) 
 
At least one dose reduction 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Baseline 
n 
XX 
 
 
 
XX 
 
 
 
Mean 
XX.X 
 
 
 
XX.X 
 
 
 
SD 
XX.XX 
 
 
 
XX.XX 
 
 
 
Minimum 
XX 
 
 
 
XX 
 
 
 
Median 
XX.X 
 
 
 
XX.X 
 
 
 
Maximum 
XX 
 
 
 
XX 
 
 
 
25th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
75th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
75th percentile
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4).
N = the number of subjects in the analysis set.
Analysis of Covariance (ANCOVA) model with classification of dose reduction as a categorical fixed effect.


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.8 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 5 - Dose reductions / dose 
interruptions) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
No dose reductions 
(N=XX) 
 
At least one dose reduction 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with classification of dose reduction as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.8 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 5 - Dose reductions / dose 
interruptions) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
No dose reductions 
(N=XX) 
 
At least one dose reduction 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Analysis Study Week 24 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
Nominal Study Visit 10 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with classification of dose reduction as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.9 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 6 - Reached MTD for age group/ did not 
reach MTD for age group) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Reached MTD for age group 
(N=XX) 
 
Did not reach MTD for age group 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Baseline 
n 
XX 
 
 
 
XX 
 
 
 
Mean 
XX.X 
 
 
 
XX.X 
 
 
 
SD 
XX.XX 
 
 
 
XX.XX 
 
 
 
Minimum 
XX 
 
 
 
XX 
 
 
 
Median 
XX.X 
 
 
 
XX.X 
 
 
 
Maximum 
XX 
 
 
 
XX 
 
 
 
25th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
75th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
75th percentile
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4).
N = the number of subjects in the analysis set.
Analysis of Covariance (ANCOVA) model with classification of dose reduction as a categorical fixed effect.


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.9 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 6 - Reached MTD for age group/ did not 
reach MTD for age group) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Reached MTD for age group 
(N=XX) 
 
Did not reach MTD for age group 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with classification of dose reduction as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.9 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 6 - Reached MTD for age group/ did not 
reach MTD for age group) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Reached MTD for age group 
(N=XX) 
 
Did not reach MTD for age group 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Analysis Study Week 24 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
Nominal Study Visit 10 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with classification of dose reduction as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.10 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 7 - Sex) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Male 
(N=XX) 
 
Female 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Baseline 
n 
XX 
 
 
 
XX 
 
 
 
Mean 
XX.X 
 
 
 
XX.X 
 
 
 
SD 
XX.XX 
 
 
 
XX.XX 
 
 
 
Minimum 
XX 
 
 
 
XX 
 
 
 
Median 
XX.X 
 
 
 
XX.X 
 
 
 
Maximum 
XX 
 
 
 
XX 
 
 
 
25th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
75th percentile 
XX.X 
 
 
 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4).
N = the number of subjects in the analysis set.
Analysis of Covariance (ANCOVA) model with sex as a categorical fixed effect.
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF).


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.10 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 7 - Sex) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Male 
(N=XX) 
 
Female 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Analysis Study Week 24) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Efficacy Week 24 
(LOCF)** 
(Nominal Study Visit 10) 
n 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with sex as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.10 Lipid parameter: LDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 7 - Sex) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
Male 
(N=XX) 
 
Female 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
Analysis Study Week 24 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
Nominal Study Visit 10 
Mean percentage change [1] 
 
 
XX.X 
 
 
 
XX.X 
 
95% Confidence Interval[2] 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
(X.XXXX, 
X.XXXX) 
 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. 
Analysis of Covariance (ANCOVA) model with sex as a categorical fixed effect. 
[*] Missing data has been imputed using Last Observation Carried Forward (LOCF). 
[1] Mean percentage change at week 24 from baseline 
[2] 95% confidence interval for mean percentage change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.1.11 Lipid parameter: LDL-C (mg/dL) Responder Analysis (Supplementary analysis) 
(Full Analysis Set) 
 
 
 
 
 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Number of subjects achieving a reduction in 
LDL-C at Week 24 of: 
 
 
 
 
    >15% 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    >25% 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    >50% 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
Number of subjects achieving a reduction in 
LDL-C at any time from Week 8 of: 
 
 
 
 
    >15% 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    >25% 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    >50% 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Subjects that discontinued study medication early will be considered a non-responder. 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.2.1 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks (Secondary analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.1 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Replace Primary Analysis with Secondary Analysis and exclude Sensitivity Analysis (MMRM) 
 
Footnotes as per Table 14.2.1.1 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.2.2 Lipid parameter: Non-HDL-C (mg/dL)and change from baseline at 24 weeks (Supplementary analysis - per protocol set) 
(Per Protocol Set) 
 
 
 
 
 
Repeat of Table 14.2.1.2 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.2 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.2.3 Lipid parameter: Non-HDL-C value (mg/dL) change from baseline at 24 weeks (Supplementary analysis - completer analysis set) 
(Completers Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.3 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.3 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.2.4 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 1 - Age groups) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.4 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.4 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.2.5 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 2 - Documented cardiovascular 
disease history) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.5 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.5 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.2.6 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 3 -  Established cardiovascular 
disease history (defined as aortic valve disease and/or coronary atherosclerosis)) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.6 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.6 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.2.7 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 4 - Concomitant LLT 
medications/procedures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.7 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.7 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.2.8 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 5 - Dose reductions / dose 
interruptions) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.8 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.8 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.2.9 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 6 - Reached MTD for age group/ did 
not reach MTD for age group) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.9 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.9 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.2.10 Lipid parameter: Non-HDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 7 - Sex) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.10 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.10 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.2.11 Lipid parameter: Non-HDL-C (mg/dL) Responder Analysis (Supplementary analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.11 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.11 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.3.1 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Secondary analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.1 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.1 (as applicable) 
 
Replace Primary Analysis with Secondary Analysis and exclude Sensitivity Analysis (MMRM) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.3.2 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Supplementary analysis - per protocol set) 
(Per Protocol Set) 
 
 
 
 
 
Repeat of Table 14.2.1.2 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.2 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.3.3 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Supplementary analysis - completer analysis set) 
(Completers Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.3 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.3 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.3.4 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 1 - Age groups) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.4 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.4 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.3.5 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 2 - Documented cardiovascular disease 
history) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.5 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.5 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.3.6 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 3 -  Established cardiovascular disease 
history (defined as aortic valve disease and/or coronary atherosclerosis)) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.6 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.6 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.3.7 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 4 - Concomitant LLT 
medications/procedures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.7 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.7 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.3.8 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 5 - Dose reductions / dose interruptions) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.8 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.8 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.3.9 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 6 - Reached MTD for age group/ did not 
reach MTD for age group) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.9 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.9 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.3.10 Lipid parameter: TC (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 7 - Sex) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.10 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.10 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.3.11 Lipid parameter: TC (mg/dL) Responder Analysis (Supplementary analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.11 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.11 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.4.1 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks (Secondary analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.1 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.1 (as applicable) 
 
Replace Primary Analysis with Secondary Analysis and exclude Sensitivity Analysis (MMRM) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.4.2 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks (Supplementary analysis - per protocol set) 
(Per Protocol Set) 
 
 
 
 
 
Repeat of Table 14.2.1.2 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.2 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.4.3 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks (Supplementary analysis - completer analysis set) 
(Completers Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.3 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.3 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.4.4 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 1 - Age groups) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.4 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.4 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.4.5 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 2 - Documented cardiovascular disease 
history) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.5 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.5 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.4.6 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 3 -  Established cardiovascular 
disease history (defined as aortic valve disease and/or coronary atherosclerosis)) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.6 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.6 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.4.7 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 4 - Concomitant LLT 
medications/procedures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.7 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.7 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.4.8 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 5 - Dose reductions / dose 
interruptions) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.8 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.8 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.4.9 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 6 - Reached MTD for age group/ did not 
reach MTD for age group) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.9 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.9 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.4.10 Lipid parameter: VLDL-C (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 7 - Sex) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.10 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.10 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.4.11 Lipid parameter: VLDL-C (mg/dL) Responder Analysis (Supplementary analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.11 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.11 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.5.1 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks (Secondary analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.1 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.1 (as applicable) 
 
Replace Primary Analysis with Secondary Analysis and exclude Sensitivity Analysis (MMRM) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.5.2 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks (Supplementary analysis - per protocol set) 
(Per Protocol Set) 
 
 
 
 
 
Repeat of Table 14.2.1.2 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.2 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.5.3 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks (Supplementary analysis - completer analysis set) 
(Completers Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.3 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.3 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.5.4 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 1 - Age groups) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.4 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.4 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.5.5 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 2 - Documented cardiovascular disease 
history) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.5 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.5 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.5.6 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 3 -  Established cardiovascular disease 
history (defined as aortic valve disease and/or coronary atherosclerosis)) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.6 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.6 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.5.7 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 4 - Concomitant LLT 
medications/procedures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.7 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.7 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.5.8 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 5 - Dose reductions / dose 
interruptions) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.8 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.8 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.5.9 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 6 - Reached MTD for age group/ did not 
reach MTD for age group) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.9 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.9 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.5.10 Lipid parameter: Apo B (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 7 - Sex) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.10 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.10 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.5.11 Lipid parameter: Apo B (mg/dL) Responder Analysis (Supplementary analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.11 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.11 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.6.1 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Secondary analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.1 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.1 (as applicable) 
 
Replace Primary Analysis with Secondary Analysis and exclude Sensitivity Analysis (MMRM) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.6.2 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Supplementary analysis - per protocol set) 
(Per Protocol Set) 
 
 
 
 
 
Repeat of Table 14.2.1.2 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.2 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.6.3 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Supplementary analysis - completer analysis set) 
(Completers Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.3 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.3 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.6.4 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 1 - Age groups) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.4 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.4 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.6.5 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 2 - Documented cardiovascular disease 
history) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.5 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.5 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.6.6 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 3 -  Established cardiovascular disease 
history (defined as aortic valve disease and/or coronary atherosclerosis)) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.6 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.6 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.6.7 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 4 - Concomitant LLT 
medications/procedures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.7 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.7 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.6.8 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 5 - Dose reductions / dose interruptions) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.8 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.8 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.6.9 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 6 - Reached MTD for age group/ did not 
reach MTD for age group) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.9 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.9 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.6.10 Lipid parameter: TG (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 7 - Sex) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.10 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.10 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.6.11 Lipid parameter: TG (mg/dL) Responder Analysis (Supplementary analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.11 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.11 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.7.1 Lipid parameter: Lp(a) and change from baseline at 24 weeks (Secondary analysis) 
(Full Analysis Set) 
 
<Unit> 
 
 
 
Repeat of Table 14.2.1.1 separately by unit 
 
 
Results are based on local labs rather than central labs. 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.1 (as applicable) 
 
Replace Primary Analysis with Secondary Analysis and exclude Sensitivity Analysis (MMRM) 
 
Add a combined p-value using Fisher's method. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.7.2 Lipid parameter: LP(a) and change from baseline at 24 weeks (Supplementary analysis - per protocol set) 
(Per Protocol Set) 
 
 
 
 
 
Repeat of Table 14.2.1.2 
 
 
Results are based on local labs rather than central labs. 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.2 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.7.3 Lipid parameter: LP(a) and change from baseline at 24 weeks (Supplementary analysis - completer analysis set) 
(Completers Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.3 
 
 
Results are based on local labs rather than central labs. 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.3 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.7.4 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 1 - Age groups) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.4 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.4 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.7.5 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 2 - Documented cardiovascular disease 
history) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.5 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.5 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.7.6 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 3 -  Established cardiovascular disease 
history (defined as aortic valve disease and/or coronary atherosclerosis)) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.6 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.6 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.7.7 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 4 - Concomitant LLT 
medications/procedures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.7 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.7 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.7.8 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 5 - Dose reductions / dose 
interruptions) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.8 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.8 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.7.9 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 6 - Reached MTD for age group/ did not 
reach MTD for age group) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.9 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.9 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.7.10 Lipid parameter: LP(a) (mg/dL) and change from baseline at 24 weeks (Subgroup analysis 7 - Sex) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.10 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.10 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
 Table 14.2.7.11 Lipid parameter: LP(a) (mg/dL) Responder Analysis (Supplementary analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.1.11 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.2.1.11 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.8.1 Lipid parameter: LDL-C (mg/dL) and change from Baseline to EOT / Week 104 by age group (Summary Measures) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statisti
cs 
5 to 10 years 
(N=XX) 
 
11 to 17 years 
(N=XX) 
 
Overall 
(N=XX) 
Dose 
Observe
d 
value 
Change 
from 
baselin
e 
% 
Change 
from 
baselin
e 
Dose 
Observe
d 
value 
Change 
from 
baselin
e 
% 
Change 
from 
baselin
e 
Dose 
Observe
d 
value 
Change 
from 
baselin
e 
% 
Change 
from 
baselin
e 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
Baselin
e 
n 
XX 
XX 
 
 
 XX 
XX 
 
 
 XX 
XX 
 
 
 
Mean 
XX.X 
XX.X 
 
 
 
XX.X 
XX.X 
 
 
 
XX.X 
XX.X 
 
 
 
SD 
XX.X
X 
XX.X
X 
 
 
 
XX.X
X 
XX.X
X 
 
 
 
XX.X
X 
XX.X
X 
 
 
 
Minimum 
XX 
XX 
 
 
 XX 
XX 
 
 
 XX 
XX 
 
 
 
Median 
XX.X 
XX.X 
 
 
 
XX.X 
XX.X 
 
 
 
XX.X 
XX.X 
 
 
 
Maximum 
XX 
XX 
 
 
 XX 
XX 
 
 
 XX 
XX 
 
 
 
25th 
percenti
le 
XX.X 
XX.X 
 
 
 
XX.X 
XX.X 
 
 
 
XX.X 
XX.X 
 
 
 
75th 
percenti
le 
XX.X 
XX.X 
 
 
 
XX.X 
XX.X 
 
 
 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
XXX 
n 
XX 
XX 
XX 
XX 
 XX 
XX 
XX 
XX 
 XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX.X
X 
XX.X
X 
XX.X
X 
XX.X
X 
 
XX.X
X 
XX.X
X 
XX.X
X 
XX.X
X 
 
XX.X
X 
XX.X
X 
XX.X
X 
XX.X
X 
 
Minimum 
XX 
XX 
XX 
XX 
 XX 
XX 
XX 
XX 
 XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
 XX 
XX 
XX 
XX 
 XX 
XX 
XX 
XX 
 
25th 
percenti
le 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
75th 
percenti
le 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4).
N = the number of subjects in the analysis set. n = the number of subjects with a measurement.
Source: Listing 16.2.8.1


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.8.1 Lipid parameter: LDL-C (mg/dL) and change from Baseline to EOT / Week 104 by age group (Summary Measures) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Statistic
s 
5 to 10 years 
(N=XX) 
 
11 to 17 years 
(N=XX) 
 
Overall 
(N=XX) 
Dose 
Observe
d 
value 
Change 
from 
baselin
e 
% 
Change 
from 
baselin
e 
Dose 
Observe
d 
value 
Change 
from 
baselin
e 
% 
Change 
from 
baselin
e 
Dose 
Observe
d 
value 
Change 
from 
baselin
e 
% 
Change 
from 
baselin
e 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
Etc
..
. 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
EOT / 
Week 
104 
n 
XX 
XX 
XX 
XX 
 XX 
XX 
XX 
XX 
 XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX.X
X 
XX.X
X 
XX.X
X 
XX.X
X 
 
XX.X
X 
XX.X
X 
XX.X
X 
XX.X
X 
 
XX.X
X 
XX.X
X 
XX.X
X 
XX.X
X 
 
Minimum 
XX 
XX 
XX 
XX 
 XX 
XX 
XX 
XX 
 XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
 XX 
XX 
XX 
XX 
 XX 
XX 
XX 
XX 
 
25th 
percentil
e 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
75th 
percentil
e 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
XX.X 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.8.2 Lipid parameter: Non-HDL-C (mg/dL) and change from Baseline to EOT / Week 104 by age group (Summary Measures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.8.1 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.8.3 Lipid parameter: TC (mg/dL) and change from Baseline to EOT / Week 104 by age group (Summary Measures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.8.1 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.8.4 Lipid parameter: VLDL-C (mg/dL) and change from Baseline to EOT / Week 104 by age group (Summary Measures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.8.1 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.8.5 Lipid parameter: Apo B (g/L)  and change from Baseline to EOT / Week 104 by age group (Summary Measures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.8.1 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.8.6 Lipid parameter: TG (mg/dL) and change from Baseline to EOT / Week 104 by age group (Summary Measures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.8.1 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.8.7 Lipid parameter: Lp(a) and change from Baseline to EOT / Week 104 by age group (Summary Measures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.8.1 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.8.8 Lipid parameter: TC/HDL-C ratio and change from Baseline to EOT / Week 104 by age group (Summary Measures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.8.1 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.9.1 Lipid parameter: LDL-C (mg/dL) and change from Baseline to EOT / Week 104 (Mixed Model Repeated Measures analysis) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Overall 
(N=XX) 
Least Square Means 
Estimate[1] 
Standard Error 
95% Confidence 
Interval 
P-Value* 
 
 
 
 
 
 
 
 
 
 
Week 4 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 8 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 12 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 16 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 20 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 24 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 28 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 32 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 36 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 40 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 44 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 48 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 52 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 56 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 68 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 80 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
Week 92 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
EOT / Week 104 
XX.X 
XX.XX 
(X.XXXX, X.XXXX) 
X.XXXX 
 
 
 
 
 
 
N = the number of subjects in the analysis set. 
Mixed Model Repeated Measures model with missing at random assumption. Model includes visit as a categorical fixed effect. An unstructured 
covariance will be used initially. The Alkaike Information Criterion (AIC) used to assess model fit for covariance structures. 
[1] Mean percentage change from baseline 
[*] Null hypothesis of 0% change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.9.2 Lipid parameter: Non-HDL-C (mg/dL) and change from Baseline to EOT / Week 104 (Mixed Model Repeated Measures analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.9.1 
 
 
N = the number of subjects in the analysis set. 
Mixed Model Repeated Measures model with missing at random assumption. Model includes visit as a categorical fixed effect, baseline as a 
covariate and subject as a random effect. An unstructured covariance will be used initially. The Alkaike Information Criterion (AIC) used to 
assess model fit for covariance structures. 
[1] Mean percentage change from baseline 
[*] Null hypothesis of 0% change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.9.3 Lipid parameter: TC (mmol/L) and change from Baseline to EOT / Week 104 (Mixed Model Repeated Measures analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.9.1 
 
 
N = the number of subjects in the analysis set. 
Mixed Model Repeated Measures model with missing at random assumption. Model includes visit as a categorical fixed effect, baseline as a 
covariate and subject as a random effect. An unstructured covariance will be used initially. The Alkaike Information Criterion (AIC) used to 
assess model fit for covariance structures. 
[1] Mean percentage change from baseline 
[*] Null hypothesis of 0% change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.9.4 Lipid parameter: VLDL-C (mg/dL) and change from Baseline to EOT / Week 104 (Mixed Model Repeated Measures analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.9.1 
 
 
N = the number of subjects in the analysis set. 
Mixed Model Repeated Measures model with missing at random assumption. Model includes visit as a categorical fixed effect, baseline as a 
covariate and subject as a random effect. An unstructured covariance will be used initially. The Alkaike Information Criterion (AIC) used to 
assess model fit for covariance structures. 
[1] Mean percentage change from baseline 
[*] Null hypothesis of 0% change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.9.5 Lipid parameter: Apo B (g/L) and change from Baseline to EOT / Week 104 (Mixed Model Repeated Measures analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.9.1 
 
 
N = the number of subjects in the analysis set. 
Mixed Model Repeated Measures model with missing at random assumption. Model includes visit as a categorical fixed effect, baseline as a 
covariate and subject as a random effect. An unstructured covariance will be used initially. The Alkaike Information Criterion (AIC) used to 
assess model fit for covariance structures. 
[1] Mean percentage change from baseline 
[*] Null hypothesis of 0% change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.9.6 Lipid parameter: TG (mg/dL) and change from Baseline to EOT / Week 104 (Mixed Model Repeated Measures analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.9.1 
 
 
N = the number of subjects in the analysis set. 
Mixed Model Repeated Measures model with missing at random assumption. Model includes visit as a categorical fixed effect, baseline as a 
covariate and subject as a random effect. An unstructured covariance will be used initially. The Alkaike Information Criterion (AIC) used to 
assess model fit for covariance structures. 
[1] Mean percentage change from baseline 
[*] Null hypothesis of 0% change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.9.7 Lipid parameter: LP(a) and change from Baseline to EOT / Week 104 (Mixed Model Repeated Measures analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.9.1 
 
 
N = the number of subjects in the analysis set. 
Mixed Model Repeated Measures model with missing at random assumption. Model includes visit as a categorical fixed effect, baseline as a 
covariate and subject as a random effect. An unstructured covariance will be used initially. The Alkaike Information Criterion (AIC) used to 
assess model fit for covariance structures. 
[1] Mean percentage change from baseline 
[*] Null hypothesis of 0% change. 
Results are based on local labs rather than central labs. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.9.8 Lipid parameter: TC/HDL-C ratio and change from Baseline to EOT / Week 104 (Mixed Model Repeated Measures analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.9.1 
 
 
N = the number of subjects in the analysis set. 
Mixed Model Repeated Measures model with missing at random assumption. Model includes visit as a categorical fixed effect, baseline as a 
covariate and subject as a random effect. An unstructured covariance will be used initially. The Alkaike Information Criterion (AIC) used to 
assess model fit for covariance structures. 
[1] Mean percentage change from baseline 
[*] Null hypothesis of 0% change. 
Results are based on local labs rather than central labs. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.10.1 Treated with standard Lipid Lowering Therapy (LLT) (including Lipoprotein Apheresis (LA) 
(Full Analysis Set) 
 
 
 
 
 
Visit 
 Number 
attending visit 
(m) 
 
LLT 
 
LA 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
 
 
 
 
Baseline 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 4 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 8 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 12 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 16 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 20 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 24 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 28 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 32 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 36 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 40 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 44 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 48 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 52 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 56 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 68 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 80 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 92 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
EOT / 
Week 104 
XX 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
N = the number of subjects in the analysis set. m = number of subjects attending visit. n = the number of subjects meeting the criterion. (%) 
= n/m*100. 
Source: Lising 16.2.4.6 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.10.2 Reduction in dose of standard Lipid Lowering Therapy (LLT) / Reduced need for Lipoprotein Apheresis (LA) compared to Week 24 
(end of Efficacy Phase) 
(Full Analysis Set) 
 
 
 
Visit 
LLT 
 
LA 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
 
 
Number of 
patients treated 
with LLT / LA at 
Week 24 (m) 
XX 
XX 
XX 
 
XX 
XX 
XX 
Week 28 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   High LDL-C 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Low LDL-C 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   
 
 
 
 
 
 
 
 
Week 32 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   High LDL-C 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Low LDL-C 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = the number of subjects in the analysis set. m = number of patients treated with LLT (including LA) at Week 24. n = the number of subjects 
meeting the criterion. (%) = n/m*100. 
Source: Lising 16.2.4.6 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.10.3 Discontinue standard Lipid Lowering Therapy (LLT) / Discontinue need for Lipoprotein Apheresis (LA) compared to Week 24 (end 
of Efficacy Phase) 
(Full Analysis Set) 
 
 
Visit 
LLT 
 
LA 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
 
 
Number of 
patients treated 
with LLT / LA at 
Week 24 (m) 
XX 
XX 
XX 
 
XX 
XX 
XX 
Week 28 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   High LDL-C 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Low LDL-C 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   
 
 
 
 
 
 
 
 
Week 32 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   High LDL-C 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Low LDL-C 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = the number of subjects in the analysis set. m = number of patients treated with LLT (including LA) at Week 24. n = the number of subjects 
meeting the criterion. (%) = n/m*100. 
Source: Lising 16.2.4.6 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.10.4 Increase dose of standard Lipid Lowering Therapy (LLT) / Increased need for Lipoprotein Apheresis (LA) compared to Week 24 
(end of Efficacy Phase) 
(Full Analysis Set) 
 
 
Visit 
LLT 
 
LA 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
 
 
Number of 
patients treated 
with LLT / LA at 
Week 24 (m) 
XX 
XX 
XX 
 
XX 
XX 
XX 
Week 28 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   High LDL-C 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Low LDL-C 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   
 
 
 
 
 
 
 
 
Week 32 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   High LDL-C 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Low LDL-C 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = the number of subjects in the analysis set. m = number of patients treated with LLT (including LA) at Week 24. n = the number of subjects 
meeting the criterion. (%) = n/m*100. 
Source: Lising 16.2.4.6 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.11.1 Recommended target of LDL-C of <135 mg/dL (i.e. 3.5 mmol/L) - EAS recommendation 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Number 
attending 
visit (m) 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Baseline 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 4 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 8 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 12 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 16 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 20 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 24 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 28 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 32 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 36 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 40 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 44 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 48 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 52 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 56 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 68 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 80 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 92 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
EOT / Week 104 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
Anytime up to Week 24 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Anytime up to Week 104 
XX 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
N = the number of subjects in the analysis set. m = number of patients attending the study visit. n = the number of subjects meeting the 
criterion. (%) = n/m*100. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.11.2 Recommended target of LDL-C of <135 mg/dL (i.e. 3.5 mmol/L) by age group and Lomitapide dose - EAS recommendation 
(Full Analysis Set) 
 
Age Group = 5 to 10 years 
 
 
 
Visit 
Number 
attending 
visit (m) 
 
Lomitapide dose at time when LDL-C < 135 mg/dL 
2mg 
 
5mg 
 
10mg 
 
20mg 
 
30mg 
40mg 
 
60mg 
 
 
 
 
 
 
 
 
 
 
Baseline 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 4 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 8 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 12 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 16 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 20 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 24 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 28 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 32 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 36 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 40 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 44 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 48 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 52 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 56 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 68 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 80 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 92 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
EOT / Week 104 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
m = number of patients attending the study visit. n = the number of subjects meeting the criterion. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for Age Group = 11 to 17 years. 
 
Only include applicable Lomitapide doses applicable for age group 
 
Additional doses may be added in to Lomitapide dose at time when LDL-C < 135 mg/dL as appropriate 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.11.3 Recommended targets of LDL-C - Exploratory endpoints 
(Full Analysis Set) 
 
 
 
 
 
Visit 
Number 
attending 
visit (m) 
Recommended target 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
Baseline 
XX 
< 115 mg/dL 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
< 110 mg/dL 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 4 
XX 
< 115 mg/dL 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
< 110 mg/dL 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 8 
XX 
< 115 mg/dL 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
< 110 mg/dL 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
EOT / Week 104 
XX 
< 115 mg/dL 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
< 110 mg/dL 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
Anytime up to Week 24 
XX 
< 115 mg/dL 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
< 110 mg/dL 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Anytime up to Week 104 
XX 
< 115 mg/dL 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
< 110 mg/dL 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects in the analysis set. m = number of patients attending the study visit. n = the number of subjects meeting the 
criterion. (%) = n/m*100. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for each visit 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.11.4 Recommended targets of LDL-C by age group and Lomitapide dose - Exploratory endpoints 
(Full Analysis Set) 
 
Age Group = 5 to 10 years 
 
 
 
Visit 
Number 
attending 
visit (m) 
Recommended 
target 
 
Lomitapide dose at time when LDL-C recommended target was reached 
2mg 
 
5mg 
 
10mg 
 
20mg 
 
30mg 
 
40mg 
 
60mg 
 
 
 
 
 
 
 
 
 
 
 
Baseline 
XX 
< 115 mg/dL 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
< 110 mg/dL 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 4 
XX 
< 115 mg/dL 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
< 110 mg/dL 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Week 8 
XX 
< 115 mg/dL 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
< 110 mg/dL 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
EOT / Week 
104 
XX 
< 115 mg/dL 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
< 110 mg/dL 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
m = number of patients attending the study visit. n = the number of subjects meeting the criterion. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for Age Group = 11 to 17 years. 
 
Only include applicable Lomitapide doses applicable for age group 
 
Additional doses may be added in to Lomitapide dose at time as appropriate 
 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.2.12.1 Lipid parameter: HDL-C (mg/dL) and change from Baseline to EOT / Week 104 by age group (Summary Measures) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.8.1 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
 
Table 14.2.12.2 Lipid parameter: HDL-C (mg/dL) and change from Baseline to EOT / Week 104 (Mixed Model Repeated Measures analysis) 
(Full Analysis Set) 
 
 
 
 
 
Repeat of Table 14.2.9.1 
 
 
N = the number of subjects in the analysis set. 
Mixed Model Repeated Measures model with missing at random assumption. Model includes visit as a categorical fixed effect, baseline as a 
covariate and subject as a random effect. An unstructured covariance will be used initially. The Alkaike Information Criterion (AIC) used to 
assess model fit for covariance structures. 
[1] Mean percentage change from baseline 
[*] Null hypothesis of 0% change. 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.1 Summary of Treatment-Emergent Adverse Events 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Events 
Subjects (%) 
Events 
Subjects (%) 
Events 
Subjects (%) 
 
 
 
 
 
 
 
Total number of TEAEs 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Total number of Non-TEAEs 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Serious TEAEs 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Serious Related TEAEs [3] 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
TEAEs leading to study discontinuation 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Serious TEAEs leading to study discontinuation 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Related TEAEs leading to study discontinuation 
[3] 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Serious Related TEAEs leading to study 
discontinuation [3] 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
TEAEs leading to death 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Adverse Events of Special Interest (AESI) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
AESI leading to study discontinuation 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Study treatment-related AESI 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
NTEAEs leading to death 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Treatment emergent adverse events (TEAEs) are defined as an adverse event that started after administration of study drug. 
[1] If a subject experienced more than one TEAE, the subject is counted once at the most severe or most related event. 
[2] Unrelated adverse events are those classified as having a non-reasonable causal relationship to the study treatment. 
[3] Related adverse events are those classified as having a reasonable causal relationship to the study treatment. 
N = the number of subjects in the analysis set. (%) = Subjects/N*100.
*Major Adverse Cardiac Events are defined by the clinical team
Source: Listing 16.2.7.1 and Listing 16.2.7.2
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.1 Summary of Treatment-Emergent Adverse Events 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Events 
Subjects (%) 
Events 
Subjects (%) 
Events 
Subjects (%) 
 
 
 
 
 
 
 
Major Adverse Cardiac Events (MACE)* 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Severity [1] 
 
 
 
 
 
 
   Mild 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Moderate 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Severe 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Life Threatening 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Death 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Relationship to study treatment [1] 
 
 
 
 
 
 
   Related [3] 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Unrelated [2] 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Action taken with study treatment 
 
 
 
 
 
 
   Dose Decreased 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Dose not Changed 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Drug Withdrawn 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Not Applicable 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Unknown 
 
 
 
 
 
 
   Other 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment emergent adverse events (TEAEs) are defined as an adverse event that started after administration of study drug. 
[1] If a subject experienced more than one TEAE, the subject is counted once at the most severe or most related event. 
[2] Unrelated adverse events are those classified as having a non-reasonable causal relationship to the study treatment. 
[3] Related adverse events are those classified as having a reasonable causal relationship to the study treatment. 
N = the number of subjects in the analysis set. (%) = Subjects/N*100. 
*Major Adverse Cardiac Events are defined by the clinical team 
Source: Listing 16.2.7.1 and Listing 16.2.7.2 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.2 Summary of Treatment-Emergent Adverse Events by MedDRA System Organ Class and Preferred Term 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
System organ class 
   Preferred term 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Events 
Subjects (%) 
Events 
Subjects (%) 
Events 
Subjects (%) 
 
 
 
 
 
 
 
Total number of TEAEs 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
System organ class 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 2 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 3 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 4 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
System organ class 2 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 2 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 3 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 4 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Etc
 
 
 
 
 
 
 
 
Treatment emergent adverse events (TEAEs) are defined as an adverse event that started after administration of study drug. 
If a subject experienced more than one TEAE, the subject is counted once for each system organ class (SOC) and once for each preferred term 
(PT). 
SOCs are ordered in decreasing frequency of the total number of subjects with TEAEs reported in each SOC and PTs are ordered within a SOC in 
decreasing frequency of the total number of subjects with each TEAE. 
Adverse events were coded using the MedDRA Dictionary, version xx.x. 
N = the number of subjects in the analysis set. (%) = Subjects/N*100. 
Source: Listing 16.2.7.1 and Listing 16.2.7.2 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.3 Summary of Serious Adverse Events (SAEs) by MedDRA System Organ Class and Preferred Term 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
Repeat of Table 14.3.1.2 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.3.1.2 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.4 Summary of Treatment-Emergent Adverse Events by MedDRA Preferred Term 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
   Preferred term 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Events 
Subjects (%) 
Events 
Subjects (%) 
Events 
Subjects (%) 
 
 
 
 
 
 
 
Total number of TEAEs 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
   Preferred term 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 2 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 3 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 4 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Etc
 
 
 
 
 
 
 
 
Treatment emergent adverse events (TEAEs) are defined as an adverse event that started after administration of study drug. 
If a subject experienced more than one TEAE, the subject is counted once for each preferred term (PT). 
PTs are ordered in decreasing frequency of subject incidence. 
Adverse events were coded using the MedDRA Dictionary, version xx.x. 
N = the number of subjects in the analysis set. (%) = Subjects/N*100. 
Source: Listing 16.2.7.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.5 Summary of Serious Adverse Events (SAEs) by MedDRA Preferred Term 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
Repeat of Table 14.3.1.4 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.3.1.4 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.6 Summary of Treatment-Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Severity 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
System organ class 
   Preferred term 
Severity 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Events 
Subjects (%) 
Events 
Subjects (%) 
Events 
Subjects (%) 
 
 
 
 
 
 
 
 
Total number of TEAEs 
Overall 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Mild 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Moderate 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Severe 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Life-threatening 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Death 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
 
System organ class 1 
Overall 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Mild 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Moderate 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Severe 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Life-threatening 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Death 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
 
   Preferred term 1 
Overall 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Mild 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Moderate 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Severe 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Life-threatening 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Death 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
Etc
 
 
 
 
 
 
 
 
 
Treatment emergent adverse events (TEAEs) are defined as an adverse event that started after administration of study drug. 
If a subject experienced more than one TEAE, the subject is counted once for each system organ class (SOC) and once for each preferred term 
(PT) at the most severe. 
SOCs are ordered in decreasing frequency of the total number of subjects with TEAEs reported in each SOC and PTs are ordered within a SOC in 
decreasing frequency of the total number of subjects with each TEAE. 
Adverse events were coded using the MedDRA Dictionary, version xx.x. 
N = the number of subjects in the analysis set. (%) = Subjects/N*100. 
Source: Listing 16.2.7.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.7 Summary of Serious Adverse Events (SAEs) by MedDRA System Organ Class, Preferred Term and Severity 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
Repeat of Table 14.3.1.6 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.3.1.6 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.8 Summary of Treatment-Emergent Adverse Events by MedDRA System Organ Class, Preferred Term and Relationship to Study Treatment 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
System organ class 
   Preferred term 
Relationship to 
study treatment 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Events 
Subjects (%) 
Events 
Subjects (%) 
Events 
Subjects (%) 
 
 
 
 
 
 
 
 
Total number of TEAEs 
Overall 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Unrelated [1] 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Related [2] 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
 
System organ class 1 
Overall 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Unrelated [1] 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Related [2] 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
 
   Preferred term 1 
Overall 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Etc... 
 
 
 
 
 
 
Etc
 
 
 
 
 
 
 
 
 
Treatment emergent adverse events (TEAEs) are defined as an adverse event that started after administration of study drug. 
If a subject experienced more than one TEAE, the subject is counted once for each system organ class (SOC) and once for each preferred term 
(PT) using the most related event. 
SOCs are ordered in decreasing frequency of the total number of subjects with TEAEs reported in each SOC and PTs are ordered within a SOC in 
decreasing frequency of the total number of subjects with each TEAE. 
Adverse events were coded using the MedDRA Dictionary, version xx.x. 
[1] Unrelated adverse events are those classified as having no reasonable causal relationship to the study treatment. 
[2] Related adverse events are those classified as having a reasonable causal relationship to the study treatment. 
N = the number of subjects in the analysis set. (%) = Subjects/N*100. 
Source: Listing 16.2.7.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.9 Summary of Serious Adverse Events (SAEs) by MedDRA System Organ Class, Preferred Term and Relationship to Study Treatment 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
Repeat of Table 14.3.1.8 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.3.1.8 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.10 Summary of Adverse Events of Special Interest (AESI) by AESI Category, MedDRA System Organ Class and Preferred Term 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
System organ class 
   Preferred term 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Events 
Subjects (%) 
Events 
Subjects (%) 
Events 
Subjects (%) 
 
 
 
 
 
 
 
Total number of AESI 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
AESI category 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
System organ class 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 2 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 3 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 4 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
System organ class 2 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 2 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 3 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 4 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Etc
 
 
 
 
 
 
 
 
Adverse events of special interest (AESI) are defined as hepatic, small bowel/intestinal, pancreatic and colorectal tumours, hepatic 
abnormalities, gastrointestinal effects and major congenital abnormality AEs. 
If a subject experienced more than one TEAE, the subject is counted once for each system organ class (SOC) and once for each preferred term 
(PT). 
SOCs are ordered in decreasing frequency of the total number of subjects with TEAEs reported in each SOC and PTs are ordered within a SOC in 
decreasing frequency of the total number of subjects with each TEAE. 
Adverse events were coded using the MedDRA Dictionary, version xx.x. 
N = the number of subjects in the analysis set. (%) = Subjects/N*100. 
Source: Listing 16.2.7.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.11 Summary of Gastrointestinal (GI) Adverse Events by MedDRA System Organ Class and Preferred Term 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
System organ class 
   Preferred term 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Events 
Subjects (%) 
Events 
Subjects (%) 
Events 
Subjects (%) 
 
 
 
 
 
 
 
Total number of GI Adverse Events 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
System organ class 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 2 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 3 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 4 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
System organ class 2 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 2 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 3 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 4 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Etc
 
 
 
 
 
 
 
 
If a subject experienced more than one TEAE, the subject is counted once for each system organ class (SOC) and once for each preferred term 
(PT). 
SOCs are ordered in decreasing frequency of the total number of subjects with TEAEs reported in each SOC and PTs are ordered within a SOC in 
decreasing frequency of the total number of subjects with each TEAE. 
Adverse events were coded using the MedDRA Dictionary, version xx.x. 
N = the number of subjects in the analysis set. (%) = Subjects/N*100. 
Source: Listing 16.2.7.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.12 Summary of Most Frequent Treatment-Emergent Adverse Events by MedDRA System Organ Class and Preferred Term 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
System organ class 
   Preferred term 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Events 
Subjects (%) 
Events 
Subjects (%) 
Events 
Subjects (%) 
 
 
 
 
 
 
 
Total number of TEAEs 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
System organ class 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 2 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 3 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 4 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
System organ class 2 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 1 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 2 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 3 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
   Preferred term 4 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
Etc
 
 
 
 
 
 
 
 
Only TEAEs that occurred in at least 2 subjects are presented. 
Treatment emergent adverse events (TEAEs) are defined as an adverse event that started after administration of study drug. 
If a subject experienced more than one TEAE, the subject is counted once for each system organ class (SOC) and once for each preferred term 
(PT). 
SOCs are ordered in decreasing frequency of the total number of subjects with TEAEs reported in each SOC and PTs are ordered within a SOC in 
decreasing frequency of the total number of subjects with each TEAE. 
Adverse events were coded using the MedDRA Dictionary, version xx.x. 
N = the number of subjects in the analysis set. (%) = Subjects/N*100. 
Source: Listing 16.2.7.1 and Listing 16.2.7.2 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Present only TEAEs that occured in at least 2 subjects. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.13 Time to First Gastrointestinal Treatment-Emergent Adverse Events 
(Safety Analysis Set) 
 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
Number of subjects with a gastrointestinal TEAE, 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Number of subjects censored, n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Kaplan-Meier estimates of time to first 
gastrointestinal TEAE (days) [1] 
 
 
 
  25th percentile 
XX.X 
XX.X 
XX.X 
  95% CI [3] 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
  Median 
XX.X 
XX.X 
XX.X 
  95% CI [3] 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
  75th percentile 
XX.X 
XX.X 
XX.X 
  95% CI [3] 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
 
 
 
 
Kaplan-Meier estimates of duration of 
gastrointestinal TEAE (days) [2] 
 
 
 
  25th percentile 
XX.X 
XX.X 
XX.X 
  95% CI [3] 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
  Median 
XX.X 
XX.X 
XX.X 
  95% CI [3] 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
  75th percentile 
XX.X 
XX.X 
XX.X 
  95% CI [3] 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
(XX.XX, XX.XX) 
 
 
 
 
 
 
 
 
 
[1] Time to first gastrointestinal TEAE is defined as the time (days) from the first dose to the time of first gastrointestinal TEAE, if any. 
[2] Duration is derived as: Date of resolution of the TEAE - Date of start of TEAE. Subjects with an ongoing TEAE will be censored at their 
last assessment date. 
[3] 95% Confidence Interval for Kaplan-Meier estimate. 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. 
(%) = n/N*100. 
Source: Listing 16.2.7.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.14 Time to First Hepatic Treatment-Emergent Adverse Events 
(Safety Analysis Set) 
 
 
 
 
 
Repeat of Table 14.3.1.13 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.3.1.13 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.15 Summary of Treatment-Emergent Adverse Events, by Sex 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
Repeat of Table 14.3.1.1 by sex 
 
 
Treatment emergent adverse events (TEAEs) are defined as an adverse event that started after administration of study drug. 
[1] If a subject experienced more than one TEAE, the subject is counted once at the most severe or most related event. 
[2] Unrelated adverse events are those classified as having a non-reasonable causal relationship to the study treatment. 
[3] Related adverse events are those classified as having a reasonable causal relationship to the study treatment. 
N = the number of subjects in the analysis set. (%) = Subjects/N*100. 
*Major Adverse Cardiac Events are defined by the clinical team 
Source: Listing 16.2.7.1 and Listing 16.2.7.2 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat of Table 14.3.1.1 by sex (Male, Female) instead of age group 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.16 Summary of Adverse Events of Special Interest (AESI) by AESI Category, MedDRA System Organ Class and Preferred Term, by Sex 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
Repeat of Table 14.3.1.10 by sex 
 
 
Adverse events of special interest (AESI) are defined as hepatic, small bowel/intestinal, pancreatic and colorectal tumours, hepatic 
abnormalities, gastrointestinal effects and major congenital abnormality AEs. 
If a subject experienced more than one TEAE, the subject is counted once for each system organ class (SOC) and once for each preferred term 
(PT). 
SOCs are ordered in decreasing frequency of the total number of subjects with TEAEs reported in each SOC and PTs are ordered within a SOC in 
decreasing frequency of the total number of subjects with each TEAE. 
Adverse events were coded using the MedDRA Dictionary, version xx.x. 
N = the number of subjects in the analysis set. (%) = Subjects/N*100. 
Source: Listing 16.2.7.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat of Table 14.3.1.10 by sex (Male, Female) instead of age group 
 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.1.17 Summary of Elevation in Serum Transaminases Related Treatment-Emergent Adverse Events by MedDRA System Organ Class and 
Preferred Term, by Country 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
System organ class 
   Preferred term 
Country 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
Events 
Subjects (%) 
Events 
Subjects (%) 
Events 
Subjects (%) 
 
 
 
 
 
 
 
 
Total number of TEAEs 
Overall 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Germany 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Spain 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
 
System organ class 1 
Overall 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Germany 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Spain 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
 
   Preferred term 1 
Overall 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
    
Germany 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
    
Spain 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
 
   Preferred term 2 
Overall 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Germany 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
Spain 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
XX 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
Only elevated serum transaminases related TEAEs are presented.   
Treatment emergent adverse events (TEAEs) are defined as an adverse event that started after administration of study drug. 
If a subject experienced more than one TEAE, the subject is counted once for each system organ class (SOC) and once for each preferred term 
(PT). 
SOCs are ordered in decreasing frequency of the total number of subjects with TEAEs reported in each SOC and PTs are ordered within a SOC in 
decreasing frequency of the total number of subjects with each TEAE. 
Adverse events were coded using the MedDRA Dictionary, version xx.x. 
N = the number of subjects in the analysis set. (%) = Subjects/N*100. 
Source: Listing 16.2.7.1 and Listing 16.2.7.2 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
NOTES: Repeat for overall and all study phases.  
Include all countries as applicable  
Include related events only 
Elevated serum transaminases defined as: aedecod in ("Alanine aminotransferase increased", "Aspartate aminotransferase increased",
"Hypertransaminasaemia", "Transaminases increased")


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.2.1 Haematology Values and Change from Baseline over Time 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Visit 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
Observed 
value 
Change 
from 
baseline 
Observed 
value 
Change 
from 
baseline 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
 
XX 
 
XX 
 
 
Mean 
XX.X 
 
XX.X 
 
XX.X 
 
 
SD 
XX.XX 
 
XX.XX 
 
XX.XX 
 
 
Minimum 
XX 
 
XX 
 
XX 
 
 
Median 
XX.X 
 
XX.X 
 
XX.X 
 
 
Maximum 
XX 
 
XX 
 
XX 
 
 
25th percentile 
XX.X 
 
XX.X 
 
XX.X 
 
 
75th percentile 
XX.X 
 
XX.X 
 
XX.X 
 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
XX 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
At each time point, only subjects with a value at both baseline and that time point are included in the change from baseline column. 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.8.9 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits and parameters. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.2.2 Clinical Significance of Haematology Values over Time 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Visit 
Result 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
XXX 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
NCS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
CS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
XXX 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
NCS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
CS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
XXX 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
NCS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
CS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
... 
 
 
 
 
 
CS = clinically significant, NCS = not clinically significant. 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number with a value at that 
visit)*100]. 
Source: Listing 16.2.8.9 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits and parameters. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.2.3 Shift in Haematology Values over Time 
(Safety Analysis Set) 
 
Age Group = XXX 
Parameter: <Parameter (Unit)> 
 
 
Visit 
Result 
Baseline 
Normal 
n (%) 
CS & Low 
n (%) 
CS & High 
n (%) 
NCS & Low 
n (%) 
NCS & High 
n (%) 
Total 
n (%) 
 
 
 
 
 
 
 
 
XXX 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
CS & Low 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
CS & High 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
NCS & Low 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
NCS & High 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
XXX 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
CS & Low 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
CS & High 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
NCS & Low 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
NCS & High 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
... 
 
 
 
 
 
 
 
 
CS = clinically significant, NCS = not clinically significant. 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number with a value at that 
visit)*100]. 
Source: Listing 16.2.8.9 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all treatment groups, post-baseline visits and parameters. 
 
Age group = 5 to 10 years; 11 to 17 years; Overall 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.3.1 Serum Clinical Chemistry Values and Change from Baseline over Time 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
 
Visit 
Statistics 
5 to 10 years 
(N=XX) 
 
11 to 17 years 
(N=XX) 
 
Overall 
(N=XX) 
 
Observed 
value 
Change 
from 
baseline 
% Change 
from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change 
from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
 
 
XX 
 
 
XX 
 
 
 
Mean 
XX.X 
 
 
XX.X 
 
 
XX.X 
 
 
 
SD 
XX.XX 
 
 
XX.XX 
 
 
XX.XX 
 
 
 
Minimum 
XX 
 
 
XX 
 
 
XX 
 
 
 
Median 
XX.X 
 
 
XX.X 
 
 
XX.X 
 
 
 
Maximum 
XX 
 
 
XX 
 
 
XX 
 
 
 
25th 
percentile 
XX.X 
 
 
XX.X 
 
 
XX.X 
 
 
 
75th 
percentile 
XX.X 
 
 
XX.X 
 
 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
25th 
percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
75th 
percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
At each time point, only subjects with a value at both baseline and that time point are included in the change from baseline column. 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Source: Listings 16.2.8.1, 16.2.8.2, 16.2.8.3, 16.2.8.4, 16.2.8.5, 16.2.8.6, 16.2.8.7, 16.2.8.8 
Repeat for all visits and parameters (metabolic panel, LFTS, Fasting Lipid panel (local and central), EFAs, Fat-soluble vitamin 
levels, hormones, sex hormones, serum lipase).
Footnotes as per Table 14.3.2.1 (as applicable)


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.3.2 Clinical Significance of Serum Clinical Chemistry Values over Time 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Repeat of Table 14.3.2.2 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Source: Listings 16.2.8.1, 16.2.8.2, 16.2.8.3, 16.2.8.4, 16.2.8.5, 16.2.8.6, 16.2.8.7, 16.2.8.8 
 
Repeat for all visits and parameters (metabolic panel, LFTS, Fasting Lipid panel (local and central), EFAs, Fat-soluble vitamin 
levels, hormones, sex hormones, serum lipase). 
 
Footnotes as per Table 14.3.2.1 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.3.3 Shift in Clinical Chemistry Values over Time 
(Safety Analysis Set) 
 
Age Group = XXX 
Parameter: <Parameter (Unit)> 
 
 
Repeat of Table 14.3.2.3 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Source: Listings 16.2.8.1, 16.2.8.2, 16.2.8.3, 16.2.8.4, 16.2.8.5, 16.2.8.6, 16.2.8.7, 16.2.8.8 
 
Repeat for all visits and parameters (metabolic panel, LFTS, Fasting Lipid panel (local and central), EFAs, Fat-soluble vitamin 
levels, hormones, sex hormones, serum lipase). 
 
Footnotes as per Table 14.3.2.1 (as applicable) 
 
Age group = 5 to 10 years; 11 to 17 years; Overall 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.3.4 Summary of Maximum Clinical Chemistry Values 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
Parameter 
Statistics 
5 to 10 years 
(N=XX) 
 
11 to 17 years 
(N=XX) 
 
 
 
 
 
Alanine Transaminase 
n 
XX 
 
XX 
 
Mean 
XX.X 
 
XX.X 
 
SD 
XX.XX 
 
XX.XX 
 
Minimum 
XX 
 
XX 
 
Median 
XX.X 
 
XX.X 
 
Maximum 
XX 
 
XX 
 
25th percentile 
XX.X 
 
XX.X 
 
75th percentile 
XX.X 
 
XX.X 
 
 
 
 
 
Aspartate Aminotransferase 
n 
XX 
 
XX 
 
Mean 
XX.X 
 
XX.X 
 
SD 
XX.XX 
 
XX.XX 
 
Minimum 
XX 
 
XX 
 
Median 
XX.X 
 
XX.X 
 
Maximum 
XX 
 
XX 
 
25th percentile 
XX.X 
 
XX.X 
 
75th percentile 
XX.X 
 
XX.X 
 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.8.3 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Maximum post-baseline values for ALT, AST, ALP and TBL 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.3.4 Summary of Maximum Clinical Chemistry Values 
(Safety Analysis Set) 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
 
 
 
Parameter 
Statistics 
5 to 10 years 
(N=XX) 
 
11 to 17 years 
(N=XX) 
 
 
 
 
 
Alkaline Phosphatase 
n 
XX 
 
XX 
 
Mean 
XX.X 
 
XX.X 
 
SD 
XX.XX 
 
XX.XX 
 
Minimum 
XX 
 
XX 
 
Median 
XX.X 
 
XX.X 
 
Maximum 
XX 
 
XX 
 
25th percentile 
XX.X 
 
XX.X 
 
75th percentile 
XX.X 
 
XX.X 
 
 
 
 
 
Total Bilirubin 
n 
XX 
 
XX 
 
Mean 
XX.X 
 
XX.X 
 
SD 
XX.XX 
 
XX.XX 
 
Minimum 
XX 
 
XX 
 
Median 
XX.X 
 
XX.X 
 
Maximum 
XX 
 
XX 
 
25th percentile 
XX.X 
 
XX.X 
 
75th percentile 
XX.X 
 
XX.X 
 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.8.3 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Maximum post-baseline values for ALT, AST, ALP and TBL 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.3.5 Summary of Subjects Exceeding Hepatotoxicity Thresholds over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
Parameter 
Statistics 
5 to 10 years 
11 to 17 years 
Overall 
 
 
 
 
 
 
XXX 
AST 
> 3 x ULN 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
> 5 x ULN 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
> 10 x ULN 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
> 20 x ULN 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
ALT 
> 3 x ULN 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
> 5 x ULN 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
> 10 x ULN 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
> 20 x ULN 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
ALP 
> 1.5 x ULN 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
TBL 
> 1.5 x ULN 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
> 2 x ULN 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
ALP = Alkaline Phosphatase. ALT = Alanine Transaminase. AST = Aspartate Aminotransferase. TBL = Total Bilirrubin. 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.8.3 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for each post-baseline visit. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.3.6 Time to Onset of Liver Function Test Abnormality 
(Safety Analysis Set) 
Parameter: <Parameter (Unit)> 
 
 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
 
 
 
Number of subjects with LFT > x 3 ULN, n (%) 
XX (XX.X) 
XX (XX.X) 
 
 
 
Time to onset (days) [1] 
 
 
   n 
XX 
XX 
   Mean 
XX.X 
XX.X 
   SD 
XX.XX 
XX.XX 
   Minimum 
XX 
XX 
   Median 
XX.X 
XX.X 
   Maximum 
XX 
XX 
   25th percentile 
XX.X 
XX.X 
   75th percentile 
XX.X 
XX.X 
 
 
 
Number of subjects with ongoing elevation, n (%) 
XX (XX.X) 
XX (XX.X) 
 
 
 
Duration of abnormality (days) [2] 
 
 
   n 
XX 
XX 
   Mean 
XX.X 
XX.X 
   SD 
XX.XX 
XX.XX 
   Minimum 
XX 
XX 
   Median 
XX.X 
XX.X 
   Maximum 
XX 
XX 
   25th percentile 
XX.X 
XX.X 
   75th percentile 
XX.X 
XX.X 
 
CI = Confidence Interval. LFT = Liver Function Test. ULN = Upper Limit of Normal. 
[1] Time to first LFT abnormality is derived as: Date of the first LFT assessment that is >= 3 x ULN or greater - Date of first dose + 1.  
[2] Duration is derived as: Date of resolution of the first LFT abnormality (resolution defined as <3 x ULN) - Date of the first LFT 
assessment that is 3 x ULN. Subjects with an ongoing elevation will be censored at their last laboratory assessment date containing both AST 
and ALT results. 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. 
(%) = n/N*100. 
Source: Listing 16.2.8.3 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES:
Present for ALT and AST abnormalities.


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.4.1 Urinalysis Values and Change from Baseline over Time 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Repeat of Table 14.3.2.1 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.3.2.1 (as applicable) 
 
Repeat for all visits and parameters. 
 
Source: Listing 16.2.8.10 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.4.2 Clinical Significance of Urinalysis Values over Time 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Repeat of Table 14.3.2.2 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.3.2.2 (as applicable) 
 
Repeat for all visits and parameters. 
 
Source: Listing 16.2.8.10 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.4.3 Shift in Urinalysis Values over Time 
(Safety Analysis Set) 
 
Age Group = XXX 
Parameter: <Parameter (Unit)> 
 
 
Repeat of Table 14.3.2.3 
 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Table 14.3.2.3 (as applicable) 
 
Repeat for all visits and parameters. 
 
Source: Listing 16.2.8.10 
 
Age group = 5 to 10 years; 11 to 17 years; Overall 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.5.1 Vital Signs and Change from Baseline over Time 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Visit 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change 
from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change 
from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change 
from 
baseline 
 
 
 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
 
 
XX 
 
 
XX 
 
 
 
Mean 
XX.X 
 
 
XX.X 
 
 
XX.X 
 
 
 
SD 
XX.XX 
 
 
XX.XX 
 
 
XX.XX 
 
 
 
Minimum 
XX 
 
 
XX 
 
 
XX 
 
 
 
Median 
XX.X 
 
 
XX.X 
 
 
XX.X 
 
 
 
Maximum 
XX 
 
 
XX 
 
 
XX 
 
 
 
25th percentile 
XX.X 
 
 
XX.X 
 
 
XX.X 
 
 
 
75th percentile 
XX.X 
 
 
XX.X 
 
 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
At each time point, only subjects with a value at both baseline and that time point are included in the change from baseline column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. 
Source: Listing 16.2.9.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits and parameters. 
 
* Present change from baseline for Maximum, Minimum and Last post baseline value for height/BMI percentiles and z-scores only. 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.5.1 Vital Signs and Change from Baseline over Time 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Visit 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change 
from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change 
from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change 
from 
baseline 
 
 
 
 
 
 
 
 
 
 
 
Maximum Post-baseline 
Value * 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
Minimum Post-baseline 
Value * 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
Last Post-baseline Value * 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4).
At each time point, only subjects with a value at both baseline and that time point are included in the change from baseline column.
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement.


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Source: Listing 16.2.9.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits and parameters. 
 
* Present change from baseline for Maximum, Minimum and Last post baseline value for height/BMI percentiles and z-scores only. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.6.1 Summary of Overall ECG Interpretation over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
Result 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
XXX 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Abnormal, NCS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Abnormal, CS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
XXX 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Abnormal, NCS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Abnormal, CS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
... 
 
 
 
 
 
NCS = not clinically significant, CS = clinically significant. 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number who have a value at that 
visit)*100]. 
Source: Listing 16.2.10.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.6.2 Shift in Overall ECG Interpretation over Time 
(Safety Analysis Set) 
 
Age Group = XXX 
 
 
 
Visit 
Result 
Baseline 
Normal 
n (%) 
Abnormal, NCS 
n (%) 
Abnormal, CS 
n (%) 
Total 
n (%) 
 
 
 
 
 
 
XXX 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Abnormal, NCS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Abnormal, CS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
XXX 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Abnormal, NCS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Abnormal, CS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
... 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4).. 
NCS = not clinically significant, CS = clinically significant. 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number who have a value at that 
visit)*100]. 
Source: Listing 16.2.10.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all post-baseline visits. 
 
Age group = 5 to 10 years; 11 to 17 years;  Overall. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.7.1 Summary of Echocardiography (Standard of Care) over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
 
Result 
5 to 10 years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
XXX 
Echocardiography performed? 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
N/A 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Atherosclerosis and/or aortic valve disease? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
N/A 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Thickening of aortic valve leaflets 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
N/A 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this new? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this progression of the condition 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number who have a value at that 
visit)*100]. 
Source: Listing 16.2.11.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits (Baseline, week 24, week 56, week 104). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.7.1 Summary of Echocardiography (Standard of Care) over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
 
Result 
5 to 10 years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
 
Fusion of the aortic valve leaflets 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
N/A 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this new? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this progression of the condition 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Thickening of the aortic root 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
N/A 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this new? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this progression of the condition 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number who have a value at that 
visit)*100]. 
Source: Listing 16.2.11.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits (Baseline, week 24, week 56, week 104). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.7.1 Summary of Echocardiography (Standard of Care) over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
 
Result 
5 to 10 
years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
 
Flow acceleration or turbulence over the aortic valve 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
N/A 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this new? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this progression of the condition 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Regions present? 
Supravalvular region 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
In the ascending aorta 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Aortic valve regurgitation? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
N/A 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this new? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this progression of the condition 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number who have a value at that 
visit)*100]. 
Source: Listing 16.2.11.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits (Baseline, week 24, week 56, week 104). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.7.1 Summary of Echocardiography (Standard of Care) over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
 
Result 
5 to 10 years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
 
Coronary ostial narrowing or flow disturbances? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
N/A 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this new? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this progression of the condition 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Ventricular findings? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
N/A 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Left ventricular hypertrophy? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
N/A 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this new? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this progression of the condition 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number who have a value at that 
visit)*100]. 
Source: Listing 16.2.11.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits (Baseline, week 24, week 56, week 104). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.7.1 Summary of Echocardiography (Standard of Care) over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
 
Result 
5 to 10 years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
 
Impairment of left ventricular function? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
N/A 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this new? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
    Is this progression of the condition 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
... 
 
 
 
 
 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number who have a value at that 
visit)*100]. 
Source: Listing 16.2.11.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits (Baseline, week 24, week 56, week 104). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.7.2 Summary of Subjects with Worsening in Echocardiography over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
Number of subjects with a worsening from 
baseline by: 
 
 
 
Week 24 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Week 56 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
EOT / Week 104 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/N)*100]. 
Source: Listing 16.2.11.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.8.1.1 Summary of Lipid Accumulation in the Liver over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
Result 
 NMR Scan 
(N=XX) 
 Ultrasound Scan 
(N=XX) 
Overall 
(N=XX) 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
 
 
 
 
 
 
 
XXX 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 10% liver fat 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
> 10% and  20% liver fat 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
> 20% liver fat 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
XXX 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 10% liver fat 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
> 10% and  20% liver fat 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
> 20% liver fat 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
... 
 
 
 
 
 
 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number who have a value at that 
visit)*100]. 
Source: Listing 16.2.12.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits. 
 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.8.1.2 Summary of Lipid Accumulation in the Liver over Time (Sensitivity Analysis - Excluding Site 12) 
(Safety Analysis Set) 
Excluding Site 12 
 
 
 
 
Repeat of Table 14.3.8.1.1 
 
 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number who have a value at that 
visit)*100]. 
Source: Listing 16.2.12.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits. 
 
Exclude Site 12 data 
 
Repeat for Site 12 only 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.8.2.1 Shift in Lipid Accumulation in the Liver over Time 
(Safety Analysis Set) 
 
Age Group = XXX 
 
 
 
Visit 
Result 
Baseline 
 10% liver fat 
n (%) 
>10% and  20% 
liver fat 
n (%) 
>20% liver fat 
n (%) 
Total 
n (%) 
 
 
 
 
 
 
XXX 
 10% liver fat 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
> 10% and  20% liver fat 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
> 20% liver fat 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
XXX 
 10% liver fat 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
> 10% and  20% liver fat 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
> 20% liver fat 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
... 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number who have a value at that 
visit)*100]. 
Source: Listing 16.2.12.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all post-baseline visits. 
 
Age group = 5 to 10 years; 11 to 17 years; Overall. 
 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.8.2.2 Shift in Lipid Accumulation in the Liver over Time (Sensitivity Analysis - Excluding Site 12) 
(Safety Analysis Set) 
Excluding Site 12 
Age Group = XXX 
 
 
 
Repeat of Table 14.3.8.2.1 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number who have a value at that 
visit)*100]. 
Source: Listing 16.2.12.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all post-baseline visits. 
 
Age group = 5 to 10 years; 11 to 17 years; Overall. 
 
Exclude Site 12 data 
 
Repeat for Site 12 only 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.8.3.1 Summary of Lipid Accumulation in the Liver over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Observed 
value 
Change 
from 
baseline 
% Change 
from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change 
from 
baseline 
Observed 
value 
Change 
from 
baseline 
% Change 
from 
baseline 
 
 
 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
 
 
XX 
 
 
XX 
 
 
 
Mean 
XX.X 
 
 
XX.X 
 
 
XX.X 
 
 
 
SD 
XX.XX 
 
 
XX.XX 
 
 
XX.XX 
 
 
 
Minimum 
XX 
 
 
XX 
 
 
XX 
 
 
 
Median 
XX.X 
 
 
XX.X 
 
 
XX.X 
 
 
 
Maximum 
XX 
 
 
XX 
 
 
XX 
 
 
 
25th percentile 
XX.X 
 
 
XX.X 
 
 
XX.X 
 
 
 
75th percentile 
XX.X 
 
 
XX.X 
 
 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
Only NMR scan assessments are included. 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
At each time point, only subjects with a value at both baseline and that time point are included in the change from baseline column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. 
Source: Listing 16.2.12.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits and parameters. 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.8.3.2 Summary of Lipid Accumulation in the Liver over Time 
(Safety Analysis Set) 
Excluding Site 12 
 
 
 
 
Repeat of Table 14.3.8.3.1 
 
 
 
Only NMR scan assessments are included. 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
At each time point, only subjects with a value at both baseline and that time point are included in the change from baseline column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. 
Source: Listing 16.2.12.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits and parameters. 
 
Exclude Site 12 data 
 
Repeat for Site 12 only 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.8.4.1 Summary of Lipid Accumulation Increase over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
XXX 
>5% 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
>10% 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
>15% 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
>20% 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
XXX 
>5% 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
>10% 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
>15% 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
>20% 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
Only NMR scan assessments are included. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. 
Source: Listing 16.2.12.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for each visit 
 
The increases will be presented cumulatively. 
 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.8.4.2 Summary of Lipid Accumulation Increase over Time 
(Safety Analysis Set) 
Excluding Site 12 
 
 
 
 
Repeat of Table 14.3.8.4.1 
 
 
 
Only NMR scan assessments are included. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. 
Source: Listing 16.2.12.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: FOOTNOTE 
 
Repeat for each visit 
 
The increases will be presented cumulatively. 
 
Present the maximum post-baseline change at the end. 
 
Exclude Site 12 data 
 
Repeat for Site 12 only 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.9.1 Summary of Tanner Staging over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
Result 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
XXX 
Stage 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Stage 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Stage 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Stage 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Stage 5 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
XXX 
Stage 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Stage 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Stage 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Stage 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Stage 5 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
... 
 
 
 
 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number who have a value at that 
visit)*100]. 
Source: Listing 16.2.12.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Visit 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Observed 
value 
Change from 
baseline 
Observed 
value 
Change from 
baseline 
Observed 
value 
Change from 
baseline 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
 
XX 
 
XX 
 
 
Mean 
XX.X 
 
XX.X 
 
XX.X 
 
 
SD 
XX.XX 
 
XX.XX 
 
XX.XX 
 
 
Minimum 
XX 
 
XX 
 
XX 
 
 
Median 
XX.X 
 
XX.X 
 
XX.X 
 
 
Maximum 
XX 
 
XX 
 
XX 
 
 
25th percentile 
XX.X 
 
XX.X 
 
XX.X 
 
 
75th percentile 
XX.X 
 
XX.X 
 
XX.X 
 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
XX 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
At each time point, only subjects with a value at both baseline and that time point are included in the change from baseline column. 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement. 
Source: Listing 16.2.13.2 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits and parameters (serum testosterone, serum oestradiol). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.9.3 Shift in Tanner Staging Over Time 
(Safety Analysis Set) 
 
Age Group = XXX 
 
 
 
Visit 
Tanner Staging 
Baseline Tanner Staging 
1 
2 
3 
3 
5 
Total 
 
 
 
 
 
 
 
 
XXX 
1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
5 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
XXX 
1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
5 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
. Etc 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set. n = the number of subjects with a measurement.  (%) = [(n/number who have a value at that 
visit)*100]. 
[-] denotes a zero count in the table. 
Source: Listing 16.2.13.2 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits 
 
Age group = 5 to 10 years; 11 to 17 years; Overall. 
 
Please display '-' instead of '0' for zero counts and foornote to say that '-' represents a zero count in the table? 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.10.1 Summary of Pulmonary Function Test (PFT) Parameters and Change from Baseline over Time 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Visit 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Observed 
value 
Change from 
baseline 
Observed 
value 
Change from 
baseline 
Observed 
value 
Change from 
baseline 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
 
XX 
 
XX 
 
 
Mean 
XX.X 
 
XX.X 
 
XX.X 
 
 
SD 
XX.XX 
 
XX.XX 
 
XX.XX 
 
 
Minimum 
XX 
 
XX 
 
XX 
 
 
Median 
XX.X 
 
XX.X 
 
XX.X 
 
 
Maximum 
XX 
 
XX 
 
XX 
 
 
25th percentile 
XX.X 
 
XX.X 
 
XX.X 
 
 
75th percentile 
XX.X 
 
XX.X 
 
XX.X 
 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
XX 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
... 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
At each visit time point, only subjects with a value at both baseline and that time point are included in the change from baseline column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. 
Source: Listing 16.2.13.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits and parameters. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.1 Summary of Xanthoma Assessment over Time 
(Safety Analysis Set) 
 
 
 
Visit 
 
Result 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
XXX 
Pre-existing xanthomas 
present 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Pre-existing tendon 
xanthomas present 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Anatomical locations 
(tendon) 
Achilles tendon 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Dorsum of the hands 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Pre-existing cutaneous 
xanthomas present 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Anatomical locations 
(cutaneous) 
Tuberous, elbow 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Tuberous, knee 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Planar, palm of the hands 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Planar, soles of the feet 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Intertriginous, fingers 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Xanthelasmas, eyelids 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
XXX 
etc
 
 
 
 
 
 
 
 
 
 
 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = [(n/number who have a value at that 
visit)*100]. 
Source: Listing 16.2.17.1
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX
NOTES:
Repeat for all visits (baseline, week 56, week 104).


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.2 Changes to pre-existing Xanthoma over Time 
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
Result 
5 to 10 years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
Pre-existing xanthomas present 
 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
Pre-existing xanthomas changed since previous visit 
Week 4 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 20 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 24 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 28 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 32 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 36 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 40 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 44 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 48 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 52 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 56 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 68 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 80 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 92 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
EOT / Week 104 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. (%) 
= [(n/number who have pre-existing xanthoma)*100], unless otherwise stated. 
[*] (%) = [n / N] 
Source: Listing 16.2.17.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.2 Changes to pre-existing Xanthoma over Time 
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
Result 
5 to 10 years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
Xanthomas reduced in size 
Week 4 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 20 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 24 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 28 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 32 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 36 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 40 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 44 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 48 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 52 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 56 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 68 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 80 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 92 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
EOT / Week 104 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. (%) 
= [(n/number who have pre-existing xanthoma)*100], unless otherwise stated. 
[*] (%) = [n / N] 
Source: Listing 16.2.17.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.2 Changes to pre-existing Xanthoma over Time 
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
Result 
5 to 10 years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
Xanthomas resolved 
Week 4 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 20 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 24 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 28 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 32 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 36 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 40 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 44 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 48 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 52 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 56 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 68 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 80 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 92 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
EOT / Week 104 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. (%) 
= [(n/number who have pre-existing xanthoma)*100], unless otherwise stated. 
[*] (%) = [n / N] 
Source: Listing 16.2.17.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.2 Changes to pre-existing Xanthoma over Time 
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
Result 
5 to 10 years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
Xanthomas increased in size 
Week 4 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 20 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 24 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 28 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 32 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 36 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 40 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 44 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 48 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 52 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 56 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 68 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 80 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 92 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
EOT / Week 104 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. (%) 
= [(n/number who have pre-existing xanthoma)*100], unless otherwise stated. 
[*] (%) = [n / N] 
Source: Listing 16.2.17.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.2 Changes to pre-existing Xanthoma over Time 
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
Result 
5 to 10 years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
New xanthomas present* 
Week 4 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 20 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 24 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 28 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 32 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 36 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 40 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 44 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 48 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 52 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 56 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 68 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 80 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 92 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
EOT / Week 104 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. (%) 
= [(n/number who have pre-existing xanthoma)*100], unless otherwise stated. 
[*] (%) = [n / N] 
Source: Listing 16.2.17.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.3 Summary of new xanthomas over Time 
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
Result 
5 to 10 
years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
Pre-existing xanthomas present 
 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
New tendon xanthomas present* 
Week 4 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 20 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 24 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 28 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 32 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 36 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 40 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 44 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 48 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 52 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 56 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 68 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 80 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 92 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
EOT / Week 104 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. (%) 
= [(n/number who have pre-existing xanthoma)*100], unless otherwise stated. 
[*] (%) = [n / N] 
Source: Listing 16.2.17.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.3 Summary of new xanthomas over Time 
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
Result 
5 to 10 
years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
Anatomical locations (tendon)* 
Week 4 
Achilles tendon 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Dorsum of the hands 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
Achilles tendon 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Dorsum of the hands 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
Achilles tendon 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Dorsum of the hands 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
Achilles tendon 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Dorsum of the hands 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Etc
... 
 
 
 
 
 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. (%) 
= [(n/number who have pre-existing xanthoma)*100], unless otherwise stated. 
[*] (%) = [n / N] 
Source: Listing 16.2.17.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.3 Summary of new xanthomas over Time 
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
Result 
5 to 10 
years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
New cutaneous xanthomas present* 
Week 4 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 20 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 24 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 28 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 32 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 36 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 40 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 44 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 48 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 52 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 56 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 68 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 80 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 92 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
EOT / Week 104 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. (%) 
= [(n/number who have pre-existing xanthoma)*100], unless otherwise stated. 
[*] (%) = [n / N] 
Source: Listing 16.2.17.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.3 Summary of new xanthomas over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
Result 
5 to 10 
years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
Anatomical locations (cutaneous)* 
Week 4 
Tuberous, elbow 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Tuberous, knee 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Planar, palm of the hands 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Planar, soles of the feet 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Intertriginous, fingers 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Xanthelasmas, eyelids 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
Tuberous, elbow 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Tuberous, knee 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Planar, palm of the hands 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Planar, soles of the feet 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Intertriginous, fingers 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Xanthelasmas, eyelids 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
Tuberous, elbow 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Tuberous, knee 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Planar, palm of the hands 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Planar, soles of the feet 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Intertriginous, fingers 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Xanthelasmas, eyelids 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
Tuberous, elbow 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Tuberous, knee 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Planar, palm of the hands 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Planar, soles of the feet 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Intertriginous, fingers 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Xanthelasmas, eyelids 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Etc
... 
 
 
 
 
 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. (%) 
= [(n/number who have pre-existing xanthoma)*100], unless otherwise stated.
[*] (%) = [n / N]
Source: Listing 16.2.17.1
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.4 Cumulative changes to pre-existing Xanthoma over Time 
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Pre-existing xanthomas present 
 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
Xanthomas reduced in size by: 
Week 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 20 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 24 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 28 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 32 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 36 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 40 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 44 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 48 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 52 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 56 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 68 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 80 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 92 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
EOT / Week 104 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. [*] 
(%) = [n / N] 
Source: Listing 16.2.17.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.4 Cumulative changes to pre-existing Xanthoma over Time 
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Xanthomas resolved by: 
Week 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 20 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 24 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 28 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 32 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 36 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 40 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 44 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 48 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 52 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 56 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 68 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 80 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 92 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
EOT / Week 104 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. [*] 
(%) = [n / N] 
Source: Listing 16.2.17.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.4 Cumulative changes to pre-existing Xanthoma over Time 
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Xanthomas increased in size by: 
Week 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 20 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 24 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 28 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 32 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 36 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 40 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 44 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 48 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 52 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 56 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 68 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 80 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 92 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
EOT / Week 104 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. [*] 
(%) = [n / N] 
Source: Listing 16.2.17.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.11.4 Cumulative changes to pre-existing Xanthoma over Time 
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
New xanthomas present by: 
Week 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 20 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 24 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 28 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 32 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 36 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 40 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 44 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 48 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 52 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 56 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 68 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 80 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 92 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
EOT / Week 104 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
At each time point, only subjects with a value at both baseline and that time point are included in the column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. [*] 
(%) = [n / N] 
Source: Listing 16.2.17.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.12.1 Carotid Intima-Media Thickness and Flow-mediated Dilation Summary and Percentage Change from Baseline over Time 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Visit 
Statistics 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
Observed 
value 
% Change 
from 
baseline 
Observed 
value 
% Change 
from 
baseline 
Observed 
value 
% Change 
from 
baseline 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
 
XX 
 
XX 
 
 
Mean 
XX.X 
 
XX.X 
 
XX.X 
 
 
SD 
XX.XX 
 
XX.XX 
 
XX.XX 
 
 
Minimum 
XX 
 
XX 
 
XX 
 
 
Median 
XX.X 
 
XX.X 
 
XX.X 
 
 
Maximum 
XX 
 
XX 
 
XX 
 
 
25th percentile 
XX.X 
 
XX.X 
 
XX.X 
 
 
75th percentile 
XX.X 
 
XX.X 
 
XX.X 
 
 
 
 
 
 
 
 
 
XXX 
n 
XX 
XX 
XX 
XX 
XX 
XX 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
 
25th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
75th percentile 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject receiving study 
treatment in the Efficacy Phase (Visit 4). 
At each time point, only subjects with a value at both baseline and that time point are included in the change from baseline column. 
N = the number of subjects in the analysis set who receive the respective treatment/dose. n = the number of subjects with a measurement. 
Source: Listing 16.2.17.2  and 16.2.17.3 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits and parameters (right CIMT, left CIMT, FMD baseline diameter, FMD maximum diameter, %FMD). 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.13.1 Summary of Palatability over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
 
Result 
5 to 10 
years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
XXX 
Able to swallow capsule? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
If no, food media used? 
Mashed banana 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Apple Sauce 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
First occasion subject used this food media? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
If yes, palatability rate? 
Super bad 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Bad 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Maybe Good or Maybe 
Bad 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Good 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Super Good 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
Source: Listing 16.2.17.4 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.13.1 Summary of Palatability over Time 
(Safety Analysis Set) 
 
 
 
 
 
Visit 
 
Result 
5 to 10 
years 
(N=XX) 
11 to 17 
years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
 
 
Parent/Guardian interpretation of child's reaction / 
facial expression 
Pleasant 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Unpleasant 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Not sure 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Parent/Guardian Question: Do you sometimes have problems 
giving the medication to your child because he/she 
refuses to take it or throws up immediately after taking 
it? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Parent/Guardian Question: Do you sometimes have problems 
in giving the dietary supplement to your child because 
he/she refuses to take it or throws up immediately after 
taking it? 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
XXX 
etc
 
 
 
 
 
 
 
 
 
 
 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
Source: Listing 16.2.17.4 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.14.1 Summary of Diet Compliance over Time 
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Subjects compliant with low-fat diet, n(%) 
Baseline 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 20 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 24 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 28 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 32 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 36 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 40 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 44 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 48 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 52 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 56 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 68 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 80 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 92 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
EOT / Week 104 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
Subjects compliant with their low-fat diet [1] 
Efficacy phase 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Safety phase (up to 
Week 56): 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Safety phase (up to 
Week 104): 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
[1] Compliance is defined as at least 80% of compliance with the low-fat diet during the respective study phase. 
Source: Listing 16.2.19.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Table 14.3.14.1 Summary of Diet Compliance over Time
(Safety Analysis Set) 
 
 
 
 
 
 
Visit 
5 to 10 years 
(N=XX) 
11 to 17 years 
(N=XX) 
Overall 
(N=XX) 
 
 
 
 
 
Subjects compliant with dietary supplement regimen, n(%) 
Baseline 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 8 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 12 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 16 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 20 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 24 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 28 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 32 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 36 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 40 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 44 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 48 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 52 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 56 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 68 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 80 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Week 92 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
EOT / Week 104 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
Subjects compliant with their dietary supplement regimen 
[1] 
Efficacy phase 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Safety phase (up to 
Week 56): 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Safety phase (up to 
Week 104): 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
N = the number of subjects in the analysis set. n = the number of subjects meeting the criterion. (%) = n/N*100. 
[1] Compliance is defined as at least 80% of compliance with the low-fat diet during the respective study phase. 
Source: Listing 16.2.19.1 
 
PROGRAM NAME:T_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.1.1 Subject Completions and Withdrawals 
(Enrolled Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Did the 
subject 
complete 
the 
study? 
Completion/ 
Withdrawal 
date  
(Study day 
[1]) 
Primary 
reason 
for 
withdrawal 
Relevant 
Details 
Date of 
last IMP 
Dose 
(Study day 
[1]) 
Study 
duration 
(days) 
[2] 
Treatment 
duration 
(days) [3] 
Date of 
Death 
(Study day 
[1]) 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 years 
Yes/No 
DDMONYYYY 
(XX) 
XXXXXXXXXX 
XXXXXXXXXX 
DDMONYYYY 
(XX) 
XX 
XX 
DDMONYYYY 
(XX) 
XXX/XXX 
11 to 17 years 
Yes/No 
DDMONYYYY 
(XX) 
Other: 
XXXXX 
XXXXXXXXXX 
DDMONYYYY 
(XX) 
XX 
XX 
DDMONYYYY 
(XX) 
XXX/XXX 
5 to 10 years 
Yes/No 
DDMONYYYY 
(XX) 
Adverse 
event: <AE 
number> 
XXXXXXXXXX 
DDMONYYYY 
(XX) 
XX 
XX 
DDMONYYYY 
(XX) 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
[2] Study duration is the number of days between first visit and the date of completion/withdrawal, derived as: (date of 
completion/withdrawal - date of first visit + 1). 
[3] Treatment duration is the number of days between first administration of study treatment in period 1 and the date of 
completion/withdrawal, derived as: (date of completion/withdrawal - date of first administration of study treatment in period 1 + 1). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.2.1 Eligibility 
(Enrolled Set) 
 
 
 
 
 
Site/Subject 
number 
Age group 
Were all 
inclusion/exclusion 
criteria met? 
Inclusion/Exclusion 
criteria not met 
Informed 
consent 
given? 
Assent 
given? 
Protocol 
Version 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 years 
Yes 
 
Yes/No 
Yes/No 
XXX 
XXX/XXX 
11 to 17 years 
No 
IXXX, EXXX 
Yes/No 
Yes/No 
XXX 
XXX/XXX 
5 to 10 years 
Yes 
 
Yes/No 
Yes/No 
XXX 
 
Criterion numbers prefixed by I are inclusion criteria, those prefixed by E are exclusion criteria. 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.2.2 Protocol Deviations 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Major/Minor 
[2] 
Start date 
(Study day 
[1]) 
End date 
(Study day 
[1]) 
Deviation category 
(I/II/III) 
Deviation details 
Action 
Taken 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 years 
Major / 
Minor 
DDMONYYYY (XX) 
DDMONYYYY (XX) 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
XXX/XXX 
11 to 17 years 
Major / 
Minor 
DDMONYYYY (XX) 
DDMONYYYY (XX) 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
XXX/XXX 
11 to 17 years 
Major / 
Minor 
DDMONYYYY (XX) 
DDMONYYYY (XX) 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
XXXXXXXXXX 
XXXXXXXXXX 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
[2] Major protocol deviations are a subset of protocol deviations that may significantly impact the completeness, accuracy and/or reliability 
of the study data or that may significantly affect a subject's rights, safety or well-being. 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat protocol deviation listing for all protocol deviations regarding visits and assessments due to the COVID-19 pandemic. Add 
subheader accordingly to identify the PDs regarding the COVID-19 pandemic. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.2.3 COVID-19 Protocol Deviations 
(Safety Analysis Set) 
 
 
 
 
 
Repeat of Listing 16.2.2.2 
 
 
 
 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Listing 16.2.2.2 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.3.1 Analysis Sets 
(Enrolled Set) 
 
 
 
 
 
Site/Subject 
number 
Age group 
Age/Sex/Race 
Eligible for analysis set? 
Reason for 
exclusion 
Safety [1] 
FAS [2] 
CAS [3] 
PPS [4] 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 years 
XX/Female/White 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
XXXXXXXXXX 
XXX/XXX 
11 to 17 years 
XX/Female/White 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
XXXXXXXXXX 
XXX/XXX 
11 to 17 years 
XX/Female/White 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
XXXXXXXXXX 
 
[1] The Safety Analysis Set includes all subjects who are treated with at least one dose of the IMP. 
[2] The Full Analysis Set includes all subjects who receive at least one dose of the IMP and who have a baseline and at least one post-
baseline measurement of LDL-C. 
[3] The Completers Analysis Set includes all subjects from the FAS who have not discontinued the Efficacy Phase (up to Week 24) of the study 
early irrespective of the reason for discontinuation. 
[4] The Per Protocol Set includes all patients from the FAS who reasonably adhere to all protocol conditions (i.e. who have met the 
eligibility criteria and receive planned study medication without important protocol deviations considered to have a serious impact on the 
efficacy results within the Efficacy Phase of the trial). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.4.1 Demography 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age group 
Age 
(years) 
Age 
(months) 
Sex 
Race 
Ethnicity 
Height 
(cm) 
Weight 
(kg) 
Body mass  
index 
(kg/m^2) 
[1] 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 years 
XXX 
XXX 
Male 
XXXXXXXXXX 
XXXXXXXXXX 
XXX 
XX.X 
XX.X 
XXX/XXX 
11 to 17 
years 
XXX 
XXX 
Female 
XXXXXXXXXX 
XXXXXXXXXX 
XXX 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
Height and weight recorded at Screening. 
[1] Body mass index (BMI) is calculated as (weight (kg)/height (m)^2). 
[2] BSA  (m^2) = [{height(cm) x weight(kg)} / 3600]   [Mosteller formula] 
[3] z scores and percentiles calculated using the WHO growth reference indicators for children aged 5 to 19 years. 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.4.1 Demography 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Body surface area 
[2] 
Height z score 
[3] 
Height percentile [3] 
BMI z score 
[3] 
BMI percentile [3] 
 
 
 
 
 
 
XXX/XXX 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XXX/XXX 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
Height and weight recorded at Screening. 
[1] Body mass index (BMI) is calculated as (weight (kg)/height (m)^2). 
[2] BSA  (m^2) = [{height(cm) x weight(kg)} / 3600]   [Mosteller formula] 
[3] z scores and percentiles calculated using the WHO growth reference indicators for children aged 5 to 19 years. 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.4.2 Diagnosis of HoFH 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age/Sex/Race 
Age group 
Duration 
of 
diagnosis 
(months) 
Genetic 
confirmation 
of 2 mutant 
alleles? 
Type of 
mutant 
allele 
LDL-C 
receptor 
function 
Untreated 
LDL-
C>500mg/dL 
or treated 
LDL-
C 300mg/dL? 
Cutaneous 
or tendon 
xanthoma 
before age 
10 years? 
Untreated 
LDL-C level 
consistent 
with HoFH 
on both 
parents? 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
XX/Female/White 
5 to 10 
years 
XX.X 
Yes/No 
XXXXXXXXXX 
XXXXX 
Yes/No 
Yes/No 
Yes/No 
XXX/XXX 
XX/Female/White 
11 to 17 
years 
XX.X 
Yes/No 
XXXXXXXXXX 
XXXXX 
Yes/No 
Yes/No 
Yes/No 
 
 
 
 
 
 
 
 
 
 
 
Duration of diagnosis (months) = 12*[(date of baseline - date of HoFH diagnosis)+1]/365.25 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.4.3 Medical History 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age/Sex/Race 
Age Group 
Reported term 
   System organ class 
      Preferred term 
Start date 
Stop date 
 
 
 
 
 
 
XXX/XXX 
XX/Female/White 
5 to 10 years 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
DDMONYYYY 
DDMONYYYY 
XXX/XXX 
XX/Female/White 
11 to 17 years 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
DDMONYYYY 
Ongoing 
 
Only subjects with medical history are listed. 
Medical history events were coded using the MedDRA Dictionary, version xx.x. 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.4.4 Cardiovascular Medical History 
(Safety Analysis Set) 
 
 
 
 
 
Repeat of Listing 16.2.4.3 
 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Listing 16.2.4.3 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.4.5 Prior/Run-in/Concomitant Medications 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Age/Sex/Race 
Timing 
Reported name 
  Medication class 
     Standardised 
medication name 
Dose 
Dose 
unit 
Frequency 
Route 
 
 
 
 
 
 
 
 
 
XXX/XXX 
11 to 17 
years 
XX/Female/White 
P / R / C 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
XXX 
XXX 
XXX 
XXX 
XXX/XXX 
5 to 10 
years 
XX/Female/White 
 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
XXX 
XXX 
XXX 
XXX 
 
Only subjects who have recorded any medications during the study are listed. 
Medications were coded using WHO Drug Dictionary, version xxx. 
[1] Timing of Medication: P = Prior; R = 'Run-in'; C = Concomitant 
[2] Study day is relative to the date of first administration of study drug (Day 0). 
Prior medications / procedures are defined as those that started and ended prior to the enrolment date visit (visit 2) (i.e. start of the 
'run-in period'). 
Run-in period' medications / procedures are defined as those that are ongoing at the time of starting the run-in  period (i.e. Visit 2) or 
started after the start of the run-in  period, but before the time of first administration of study treatment. 
Concomitant medications / procedures are defined as those that are ongoing at the time of first administration of study treatment or started 
on or after the time of first administration of study treatment or started prior to the end / last dose of study treatment. If medication / 
procedure dates are incomplete and it is not clear whether the medication / procedure was concomitant, it will be assumed to be concomitant. 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: If a medication is defined as prior medication only then timing = P. 
 
If a medication is defined as run-in medication then timing = R. 
 
If a medication is defined as concomitant medication then timing = C. 
 
If a medication is taken during run-in and concomitantly then timing = C. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.4.5 Prior/Run-in/Concomitant Medications 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Age/Sex/Race 
Timing 
Reported name 
  Medication class 
     Standardised medication 
name 
Date (Study day [2]) 
Indication 
Start of 
medication 
End of 
medication 
 
 
 
 
 
 
 
 
XXX/XXX 
11 to 17 
years 
XX/Female/White 
P / R / C 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
XXXXXXXXXX 
XXX/XXX 
5 to 10 years XX/Female/White 
 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
DDMONYYYY 
(XX) 
Ongoing 
XXXXXXXXXX 
 
Only subjects who have recorded any medications during the study are listed. 
Medications were coded using WHO Drug Dictionary, version xxx. 
[1] Timing of Medication: P = Prior; R = 'Run-in'; C = Concomitant 
[2] Study day is relative to the date of first administration of study drug (Day 0). 
Prior medications / procedures are defined as those that started and ended prior to the enrolment date visit (visit 2) (i.e. start of the 
'run-in period'). 
Run-in period' medications / procedures are defined as those that are ongoing at the time of starting the run-in  period (i.e. Visit 2) or 
started after the start of the run-in  period, but before the time of first administration of study treatment. 
Concomitant medications / procedures are defined as those that are ongoing at the time of first administration of study treatment or started 
on or after the time of first administration of study treatment or started prior to the end / last dose of study treatment. If medication / 
procedure dates are incomplete and it is not clear whether the medication / procedure was concomitant, it will be assumed to be concomitant. 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: If a medication is defined as prior medication only then timing = P. 
 
If a medication is defined as run-in medication then timing = R. 
 
If a medication is defined as concomitant medication then timing = C. 
 
If a medication is taken during run-in and concomitantly then timing = C. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.4.6 Lipid-lowering-therapy (LLT) Medications 
(Safety Analysis Set) 
 
 
 
 
 
Repeat of Listing 16.2.4.5 
 
 
Only subjects who have recorded any medications during the study are listed. 
Medications were coded using WHO Drug Dictionary, version xxx. 
Procedures were coded using the MedDRA Dictionary, version xx.x. 
[1] <LLTMDEF> 
[2] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Listing 16.2.4.5 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.4.7 Prior/Run-in/Concomitant Procedures 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Age/Sex/Race 
Study 
Phase 
Timing 
Reported name 
  Procedure Category 
     Indication 
Frequency 
Date (Study day [2]) 
Start of 
procedure 
End of 
procedure 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 
years 
XX/Female/White 
Efficacy 
/ Safety 
P / R / C 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
XXX 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
XXX/XXX 
11 to 17 
years 
XX/Female/White 
 
 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
XXX 
DDMONYYYY 
(XX) 
Ongoing 
 
Only subjects who have recorded any procedures during the study are listed. 
Procedures were coded using the MedDRA Dictionary, version xx.x. 
[1] Timing of Procedure: P = Prior; R = 'Run-in'; C = Concomitant 
[2] Study day is relative to the date of first administration of study drug (Day 0). 
Prior medications / procedures are defined as those that started and ended prior to the enrolment date visit (visit 2) (i.e. start of the 
'run-in period'). 
Run-in period' medications / procedures are defined as those that are ongoing at the time of starting the run-in  period (i.e. Visit 2) or 
started after the start of the run-in  period, but before the time of first administration of study treatment. 
Concomitant medications / procedures are defined as those that are ongoing at the time of first administration of study treatment or started 
on or after the time of first administration of study treatment or started prior to the end / last dose of study treatment. If medication / 
procedure dates are incomplete and it is not clear whether the medication / procedure was concomitant, it will be assumed to be concomitant. 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.5.1 IMP Administration 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Visit 
Study Drug 
Administration* 
Date of 
Dispensing 
(Study day 
[1]) 
Strength and 
Number of 
Capsules 
Dispensed 
[2] 
Daily Dose 
(Increase 
(I), 
Decrease 
(D), 
Unchanged 
(U)) (mg)** 
Reason Dose 
Increased/Decreased/Unchanged 
 
 
 
 
 
 
 
 
XXX/XXX 
11 to 17 
years 
XXX 
Yes (F) 
DDMONYYYY 
(XX) 
XXXXXXXXXX 
n=xx 
XXX 
XXXXXXXXXX 
XXX/XXX 
5 to 10 
years 
XXX 
Yes 
DDMONYYYY 
(XX) 
XXXXXXXXXX 
n=xx 
XXX 
(I)(MTD) 
(Maint) 
XXXXXXXXXX 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
[2] Capsules are dispensed as 2mg, 5mg, 10mg and 20mg 
[3] Derived total number of weeks exposure to study medication = [(date of last dose - date of first dose)+1]/7 
[4] Derived total exposure (mg/day) to study medication = ([number of doses received*treatment dose(mg)] / number of days exposed 
[5] Derived total number of weeks of exposure to maintenance dose = [(date of last dose - date when maintenance dose is reached)+1]/7. 
*F denotes date of first dose (i.e. date of first study drug administration) 
** MTD denotes maximum tolerated dose. Maint denotes maintenance dose. 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.5.1 IMP Administration 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age 
Group 
Visit 
Were 
Capsules 
Returned? 
Strength 
and number 
of 
capsules 
returned 
[2] 
Has 
subject 
complied 
with IMP 
dosing as 
per 
protocol? Reason missed doses 
Number missed 
Consecutively or intermittently 
 
 
 
 
 
 
 
 
 
XXX/XXX 
11 to 17 
years 
XXX 
No 
 
Yes/No 
 
 
 
XXX/XXX 
5 to 10 
years 
XXX 
Yes 
XXXXXXXXXX 
n=xx 
Yes/No 
XXXXXXXXXX 
XX 
XXXXXXXXXX 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
[2] Capsules are dispensed as 2mg, 5mg, 10mg and 20mg 
[3] Derived total number of weeks exposure to study medication = [(date of last dose - date of first dose)+1]/7 
[4] Derived total exposure (mg/day) to study medication = ([number of doses received*treatment dose(mg)] / number of days exposed 
[5] Derived total number of weeks of exposure to maintenance dose = [(date of last dose - date when maintenance dose is reached)+1]/7. 
*F denotes date of first dose (i.e. date of first study drug administration) 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.5.1 IMP Administration 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subjec
t 
number 
Age 
Grou
p 
Visi
t 
Was the 
treatment 
interrupted
? 
Reason for 
interruptio
n 
Date (Study Day [1]) 
Derived 
total 
number of 
weeks 
exposure 
to study 
medicatio
n [3] 
Derived 
total 
exposure 
(mg/day) 
to study 
medicatio
n [4] 
Derived 
total 
number of 
weeks 
exposure 
to 
maintenanc
e dose [5] 
Time 
(weeks) 
to dose 
reductio
n 
Time 
(weeks) to 
dose 
interruptio
n 
Start of 
interruptio
n 
End of 
interruptio
n 
 
 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
11 
to 
17 
year
s 
XXX 
 
 
 
 
XXX 
XXX 
XXX 
XXX 
XXX 
XXX/XXX 
5 to 
10 
year
s 
XXX 
Yes/No 
XXXXXXXXXX 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
XXX 
XXX 
XXX 
XXX 
XXX 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
[2] Capsules are dispensed as 2mg, 5mg, 10mg and 20mg 
[3] Derived total number of weeks exposure to study medication = [(date of last dose - date of first dose)+1]/7 
[4] Derived total exposure (mg/day) to study medication = ([number of doses received*treatment dose(mg)] / number of days exposed 
[5] Derived total number of weeks of exposure to maintenance dose = [(date of last dose - date when maintenance dose is reached)+1]/7. 
*F denotes date of first dose (i.e. date of first study drug administration) 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.6.1 Lipoprotein Apheresis (LA) History 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age 
Group 
Age/Sex/Race 
Receiving / Received 
(i.e.previous 60 days) LA 
treatment? 
Date LA 
started [1] 
Receive LA during run-in 
period and through Week 
24? 
Planned frequency 
of LA treatments 
 
 
 
 
 
 
 
XXX/XXX 
11 to 17 
years 
XX/Female/White Yes/No 
DDMONYYYY 
(XX) 
Yes/No 
XXXXXXXXXX 
XXX/XXX 
5 to 10 
years 
XX/Female/White Yes/No 
DDMONYYYY 
(XX) 
Yes/No 
Other:  XXXXXXXXXX 
 
 
 
 
... 
 
 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.6.2 Lipoprotein Apheresis (LA) Treatment 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age 
Group 
Age/Sex/Race 
Study 
Phase 
Visit 
Received 
LA 
treatment 
since 
last 
visit? 
Date of 
LA [1] 
Scheduled / 
Unscheduled 
Days 
since 
previous 
LA 
Change 
to 
ConMeds? 
Fasting 
lipid 
panel 
local lab 
sample 
taken 
before 
scheduled 
LA? 
Days to 
next LDL-C 
assessment 
 
 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
11 to 
17 
years 
XX/Female/White Efficacy 
/ Safety 
XXX 
Yes/No 
DDMONYYYY 
(XX) 
Scheduled / 
Unscheduled 
XX 
Yes/No 
Yes/No 
XX 
 
 
 
 
Run-in 
weighted 
average* 
 
 
 
XX 
 
 
 
 
 
 
 
 
 
... 
 
 
 
 
 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
* Weighted averaged regimen during run-in. 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits. 
 
Study Phase: Efficacy - up to (and including) Week 24; Safety - up to (and including) Week 104. 
 
After run-in, add Run-in weighted average. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.7.1 Adverse Events 
(Enrolled Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Age/Sex/Race 
TE? 
[1] 
Reported term 
   System organ 
class 
      Preferred 
term 
Date (Study day [2]) Time [3] 
Time 
to  
onset 
[4] 
[5] 
(days) 
Duration 
[5] 
(d:hh:mm) 
Start 
End 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 
years 
XX/Female/White Yes/No 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX G 
DDMONYYYY (XX) 
HH:MM 
DDMONYYYY (XX) 
HH:MM 
XXX 
d:hh:mm 
XXX/XXX 
11 to 17 
years 
XX/Female/White Yes/No 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
DDMONYYYY (XX) 
HH:MM 
Ongoing 
XXX 
UK 
 
G = Gastrointestinal event, H = Hepatic event. 
Only subjects with any adverse event are listed. 
Adverse events were coded using the MedDRA Dictionary, version xx.x. 
[1] TE = Treatment-emergent adverse event defined as an adverse event that started after administration of study drug. 
[2] Study day is relative to the date of first administration of study drug (Day 0). 
[3] 24-hour clock (HH:MM). 
[4] Time from date of first administration of study drug to onset of adverse event. 
[5] For missing or partial dates and times, not calculated and is reported as unknown (UK). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Listing can go over multiple pages. Data for a given subject will appear on the consecutive page 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.7.1 Adverse Events 
(Enrolled Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group Age/Sex/Race 
TE? 
[1] 
Reported term 
   System 
organ class 
      
Preferred term 
Was adverse 
event serious? 
Serious 
Criteria 
Adverse Event of Special 
Interest? If yes, reason 
Severity 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 
years 
XX/Female/White Yes/No 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
Yes 
XXXXXXXXXX 
Yes, XXXXXXXXXX 
XXX 
XXX/XXX 
11 to 17 
years 
XX/Female/White Yes/No 
XXXXXXXX 
   XXXXXXXX 
      XXXXXXXX 
No 
XXXXXXXXXX 
No 
XXX 
 
Only subjects with any adverse event are listed. 
Adverse events were coded using the MedDRA Dictionary, version xx.x. 
[1] TE = Treatment-emergent adverse event defined as an adverse event that started after administration of study drug. 
[2] Study day is relative to the date of first administration of study drug (Day 0). 
[3] 24-hour clock (HH:MM). 
[4] Time from date of first administration of study drug to onset of adverse event. 
[5] For missing or partial dates and times, not calculated and is reported as unknown (UK). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Listing can go over multiple pages. Data for a given subject will appear on the consecutive page 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.7.1 Adverse Events 
(Enrolled Set) 
 
 
 
 
 
Site/Subject 
number 
Age 
Group 
Age/Sex/Race 
TE? 
[1] 
Reported 
term 
   System 
organ class 
      
Preferred 
term 
Relationship 
to 
study 
treatment 
Action 
taken 
with 
study 
treatment 
Other 
action 
taken 
Was a concomitant 
treatment given for this 
adverse event? 
Outcome  
 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 
years 
XX/Female/White Yes/No 
XXXXXXXX 
   XXXXXXXX 
      
XXXXXXXX 
XXX 
XXX 
XXX 
Yes 
XXX 
 
XXX/XXX 
11 to 
17 
years 
XX/Female/White Yes/No 
XXXXXXXX 
   XXXXXXXX 
      
XXXXXXXX 
XXX 
XXX 
XXX 
No 
XXX 
 
 
Only subjects with any adverse event are listed. 
Adverse events were coded using the MedDRA Dictionary, version xx.x. 
[1] TE = Treatment-emergent adverse event defined as an adverse event that started after administration of study drug. 
[2] Study day is relative to the date of first administration of study drug (Day 0). 
[3] 24-hour clock (HH:MM). 
[4] Time from date of first administration of study drug to onset of adverse event. 
[5] For missing or partial dates and times, not calculated and is reported as unknown (UK). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Listing can go over multiple pages. Data for a given subject will appear on the consecutive page 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.7.2 Serious Adverse Events 
(Enrolled Set) 
 
 
 
 
 
Repeat of Listing 16.2.7.1 but just for Serious AEs 
 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as Listing 16.2.7.1 (as appropriate) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.1 Serum Clinical Chemistry (Fasting Lipid Panel) Values 
(Safety Analysis Set) 
 
 
 
 
 
Parameter 
Local lab 
 
Central lab 
Unit 
Site 
Age range 
Sex 
Normal range 
 
Unit 
Age range 
Sex 
Normal range 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.1 Serum Clinical Chemistry (Fasting Lipid Panel) Values 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Site/Subject 
number 
Age Group 
Age/Sex/Race 
Visit Lomitapide Dose (mg) 
Date of  
collection 
(Study day [1]) 
Time 
[2] 
Local Lab 
Observed 
% Change from 
baseline 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 years 
XX/Female/White XXX 
2 / 5 / 10 / 20 / 30 / 40 / 60 
DDMONYYYY (XX) 
HH:MM XX.X B NCS H 
 
 
 
 
XXX 
2 / 5 / 10 / 20 / 30 / 40 / 60 
DDMONYYYY (XX) 
HH:MM XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
CS = clinically significant, NCS = not clinically significant. 
H = High, L = Low. * = Maximum post-baseline value. 
B = baseline value. Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject 
receiving study treatment in the Efficacy Phase (Visit 4). 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
[2] 24-hour clock (HH:MM). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments will be included in the listing and flagged as such in the visit column. 
 
The listing may go over multiple pages to capture all data. 
 
Repeat for all visits and all parameters (i.e. LDL-C, Non-HDL-C, TC, VLDL-C, apo B, TG, Lp(a) in this order). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.1 Serum Clinical Chemistry (Fasting Lipid Panel) Values 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Site/Subject 
number 
Age Group 
Age/Sex/Race 
Visit Lomitapide Dose (mg) 
Date of  
collection 
(Study day 
[1]) 
Time 
[2] 
Central 
lab 
Central Lab 
Observed 
Change 
from 
baseline 
% Change 
from 
baseline 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 
years 
XX/Female/White XXX 
2 / 5 / 10 / 20 / 40 / 
60 
DDMONYYYY (XX) 
HH:MM XX.X B NCS 
 
 
 
 
 
XXX 
2 / 5 / 10 / 20 / 40 / 
60 
DDMONYYYY (XX) 
HH:MM XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
CS = clinically significant, NCS = not clinically significant. 
B = baseline value. Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject 
receiving study treatment in the Efficacy Phase (Visit 4). 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
[2] 24-hour clock (HH:MM). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments will be included in the listing and flagged as such in the visit column. 
 
The listing may go over multiple pages to capture all data. 
 
Repeat for all visits and all parameters (i.e. LDL-C, Non-HDL-C, TC, VLDL-C, apo B, TG, Lp(a) in this order). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.2 Serum Clinical Chemistry (Metabolic Panel) Values 
(Safety Analysis Set) 
 
 
 
 
 
Parameter 
Local lab 
Unit 
Site 
Age range 
Sex 
Normal range 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.2 Serum Clinical Chemistry (Metabolic Panel) Values 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Site/Subject 
number 
Age Group 
Age/Sex/Race 
Visit Lomitapide Dose (mg) 
Date of  
collection 
(Study day 
[1]) 
Time 
[2] 
Local Lab 
Observed 
Change 
from 
baseline 
% Change 
from 
baseline 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
11 to 17 
years 
XX/Female/White XXX 
2 / 5 / 10 / 20 / 40 
/ 60 
DDMONYYYY 
(XX) 
HH:MM XX.X B NCS 
H 
 
 
 
 
 
 
 
 
HH:MM XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
CS = clinically significant, NCS = not clinically significant. 
H = High, L = Low. 
B = baseline value. Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject 
receiving study treatment in the Efficacy Phase (Visit 4). 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
[2] 24-hour clock (HH:MM). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments will be included in the listing and flagged as such in the visit column. 
 
The listing may go over multiple pages to capture all data. 
 
Repeat for all visits and all parameters. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.3 Serum Clinical Chemistry (Liver Function Tests) Values 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Repeat of Listing 16.2.8.2 
 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Listing 16.2.8.2 (as applicable) 
Add *, ^, +, ! flags with footnote: 
[*] = > 3 x ULN (ALP and AST) or > 1.5 x ULN (ALP and TBL). [^] = > 5 x ULN (ALT and AST) or > 2 x ULN (TBL).  
[+] = > 10 x ULN (ALT and AST). [!] = > 20 x ULN (ALT and AST). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.4 Serum Clinical Chemistry (Essential Fatty Acids) Values 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Parameter 
Central lab 
Unit 
Age range 
Sex 
Normal range 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Columns for site, age range and sex will be included in the final listing output if required. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.4 Serum Clinical Chemistry (Essential Fatty Acids) Values 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Site/Subject 
number 
Age Group 
Age/Sex/Race 
Visit Lomitapide Dose (mg) 
Date of  
collection 
(Study day 
[1]) 
Time 
[2] 
Central Lab 
Observed 
Change 
from 
baseline 
% Change 
from 
baseline 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
11 to 17 
years 
XX/Female/White XXX 
2 / 5 / 10 / 20 / 40 
/ 60 
DDMONYYYY 
(XX) 
HH:MM XX.X B NCS 
H 
 
 
 
 
 
 
 
 
HH:MM XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
CS = clinically significant, NCS = not clinically significant. 
H = High, L = Low. 
B = baseline value. Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject 
receiving study treatment in the Efficacy Phase (Visit 4). 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
[2] 24-hour clock (HH:MM). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments will be included in the listing and flagged as such in the visit column. 
 
The listing may go over multiple pages to capture all data. 
 
Repeat for all visits and all parameters. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.5 Serum Clinical Chemistry (Fat Soluble Vitamin Levels) Values 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Repeat of Listing 16.2.8.4 
 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Listing 16.2.8.4 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.6 Serum Clinical Chemistry (Hormones) Values 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Repeat of Listing 16.2.8.2 
 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Listing 16.2.8.2 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.7 Serum Clinical Chemistry (Sex Hormones) Values 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Repeat of Listing 16.2.8.2 
 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Listing 16.2.8.2 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.8 Serum Clinical Chemistry (Serum Lipase) Values 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Repeat of Listing 16.2.8.2 
 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Listing 16.2.8.2 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.9 Serum Haematology Values 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Repeat of Listing 16.2.8.2 
 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Listing 16.2.8.2 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.8.10 Urinalysis Values 
(Safety Analysis Set) 
 
 
Parameter: <Parameter (Unit)> 
 
 
Repeat of Listing 16.2.8.2 
 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Footnotes as per Listing 16.2.8.2 (as applicable) 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.9.1 Vital Signs 
(Safety Analysis Set) 
 
Parameter: <Parameter (Unit)> 
 
 
 
Site/Subject 
number 
Age Group 
Age/Sex/Race 
Visit 
Date of  
collection 
(Study day [1]) 
Observed 
Change from 
baseline 
% Change from 
baseline 
 
 
 
 
 
 
 
 
XXX/XXX* 
11 to 17 years 
XX/Female/White 
XXX 
DDMONYYYY (XX) 
XX.X B 
 
 
 
 
 
XXX 
DDMONYYYY (XX) 
XX.X    Min 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
* = Subject just met inclusion criterion #3 of having a body weight 15 kg. 
B = baseline value. Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject 
receiving study treatment in the Efficacy Phase (Visit 4). 
Min = Minimum Post Baseline Value, Max=Maximum Post Baseline Value, Last=Last Post Baseline Value (for height and weight parameters only). 
[1] Study day is relative to the date of first administration of study drug (Day 0) 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments should be included in the listing and flagged as such in the visit column. 
 
The listing may go over multiple pages to capture all data. 
 
Repeat for all visits. Parameters (i.e. weight, height, BMI, BSA, heart rate, respiration rate, SBP, DBP, body temp, BMI, height & 
weight percentile, BMI, height & weight Z score). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.10.1 ECG Results 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Visit 
Date of assessment 
(Study day [1]) 
Overall interpretation 
 
 
 
 
 
XXX/XXX 
11 to 17 years 
XXX 
DDMONYYYY (XX) 
Normal 
XXX/XXX 
5 to 10 years 
XXX 
DDMONYYYY (XX) 
Abnormal, NCS 
XXX/XXX 
11 to 17 years 
XXX 
DDMONYYYY (XX) 
Abnormal, CS 
 
CS = clinically significant, NCS = not clinically significant. 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments will be included in the listing and flagged as such in the visit column. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.11.1 Echocardiography Results 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age 
Group 
Visit 
Scan 
performed? 
Date of 
assessment 
(Study day 
[1]) 
Atherosclerosis and/or 
aortic valve disease? 
Thickening aortic 
valve leaflets 
New (N): 
Progression (P): 
Fusion of aortic 
valve leaflets 
New (N): 
Progression (P): 
Thickening of 
aortic root 
New (N): 
Progression 
(P): 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 
years 
XXX 
Yes/No 
DDMONYYYY 
(XX) 
Yes / No / N/A 
Yes / No / N/A 
N: Yes/No 
P: Yes/No 
Yes / No / N/A 
N: Yes/No 
P: Yes/No 
Yes / No / N/A 
N: Yes/No 
P: Yes/No 
 
 
 
 
 
 
 
 
 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments will be included in the listing and flagged as such in the visit column. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.11.1 Echocardiography Results 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Visit 
Scan 
performed? 
Flow acceleration / turbulence 
over aortic valve 
New (N): 
Progression (P): 
Region (Re): 
Aortic valve 
regurgitation 
New (N): 
Progression (P): 
Coronary ostial narrowing / 
flow disturbances 
New (N): 
Progression (P): 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 
years 
XXX 
Yes/No 
Yes / No / N/A 
N: Yes/No 
P: Yes/No 
Re: Supravalvular / ascending 
aorta 
Yes / No / N/A 
N: Yes/No 
P: Yes/No 
Yes / No / N/A 
N: Yes/No 
P: Yes/No 
 
 
 
 
 
 
 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments will be included in the listing and flagged as such in the visit column. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.11.1 Echocardiography Results 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Visit 
Scan 
performed? 
Ventricular 
findings 
 
Left ventricular 
hypertrophy 
New (N): 
Progression (P): 
Impairment of left 
ventricular function 
New (N): 
Progression (P): 
Other relevant 
findings 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 
years 
XXX 
Yes/No 
Yes / No / N/A 
 
Yes / No / N/A 
N: Yes/No 
P: Yes/No 
Yes / No / N/A 
N: Yes/No 
P: Yes/No 
Yes/No 
Yes: XXXXXXXXXX 
 
 
 
 
 
 
 
 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments will be included in the listing and flagged as such in the visit column. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.12.1 Lipid Accumulation in the Liver Results 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age 
Group 
Visit 
NMR Scan 
performed? 
Reason not 
performed? 
Date of 
scan 
(Study 
day [1]) 
Ultrasound 
Scan 
performed? 
Reason not 
performed? 
Date of 
scan 
(Study 
day [1]) 
Result 
Change 
from 
baseline 
% Change 
from 
baseline 
 
 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
11 to 
17 
years 
XXX 
Yes/No 
 
DDMONYYYY 
(XX) 
Yes/No 
 
DDMONYYYY 
(XX) 
XXX 
XXX 
XXX 
XXX/XXX 
5 to 
10 
years 
XXX 
Yes/No 
XXXXXXXXXX 
DDMONYYYY 
(XX) 
Yes/No 
XXXXXXXXXX 
 
 
 
 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments will be included in the listing and flagged as such in the visit column. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.13.1 Physical Examination 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Visit 
Assessment 
performed? 
Reason not 
performed? 
Date of  
examination 
(Study day 
[1]) 
Body 
System 
Physical Examination 
Findings 
Comments 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 
years 
XXX 
Yes/No 
 
DDMONYYYY 
(XX) 
XXXXXXXXXX 
Normal / Abnormal / Not 
Done 
XXXXXXXXXX 
XXX/XXX 
11 to 17 
years 
XXX 
Yes/No 
XXXXXXXXXX 
DDMONYYYY 
(XX) 
XXXXXXXXXX 
Normal / Abnormal / Not 
Done 
XXXXXXXXXX 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits recorded 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.13.2 Tanner Staging 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Age/Sex/Race 
Visit 
Date ( Study Day 
[1]) 
Was assessment 
performed? 
Reason not 
performed? 
Tanner 
Stage 
 
 
 
 
 
 
 
 
XXX/XXX 
11 to 17 
years 
XX/Female/White XXX 
DDMMMYYYY (XX) 
Y 
 
XXX 
XXX/XXX 
5 to 10 years 
XX/Female/White XXX 
DDMMMYYYY (XX) 
N 
XXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
B = baseline value. Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject 
receiving study treatment in the Efficacy Phase (Visit 4). 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments should be included in the listing and flagged as such in the visit column. 
 
The listing may go over multiple pages to capture all data. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.14.1 Pulmonary Function Test 
(Safety Analysis Set) 
 
Parameter: <Parameter (Unit)> 
 
 
 
Site/Subject 
number 
Age Group 
Age/Sex/Race 
Visit 
Was assessment 
performed? 
Reason not 
performed? 
Date of  
assessment 
(Study day 
[1]) 
Observed 
Change 
from 
baseline 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 
years 
XX/Female/White XXX 
Yes 
 
DDMONYYYY (XX) 
XX.X B 
 
 
 
 
XXX 
Yes 
 
DDMONYYYY (XX) 
XX.X 
XX.X 
 
 
 
XXX 
No 
XXXXXXXXXX 
 
 
 
 
B = baseline value. Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject 
receiving study treatment in the Efficacy Phase (Visit 4). 
[1] Study day is relative to the date of first administration of study drug (Day 0) 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments should be included in the listing and flagged as such in the visit column. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.15.1 Pregnancy Test 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Visit 
Was a pregnancy 
test performed? 
If No, reason pregnancy 
test not performed 
If Yes, date of 
pregnancy test 
(Study day [1]) 
Result 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 years 
XXX 
Yes/No 
 
DDMONYYYY (XX) 
Negative/Positive 
XXX/XXX 
11 to 17 years 
XXX 
Yes/No 
Subject is premenarchal 
 
 
XXX/XXX 
11 to 17 years 
XXX 
Yes/No 
Subject is male 
 
 
 
Pregnancy test data was collected at Screening. 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.16.1 Visit Dates 
(Enrolled Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Screening 
Baseline 
(Study Day 
1) 
Week 4 
(Study Day 
28) 
Week 8 
(Study Day 
56) 
Week 12 
(Study Day 
84) 
Week 16 
(Study Day 
112) 
Week 20 
(Stusy Day 
140) 
Week 24 
(Study Day 
168) 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 
years 
DDMONYYYY DDMONYYYY 
(1) 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
 
Study Day in relation to Baseline visit date (Study Day 1) presented in brackets. 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.16.1 Visit Dates 
(Enrolled Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Week 28 
(Study Day 
196) 
Week 32 
(Study Day 
224) 
Week 36 
(Study Day 
252) 
Week 40 
(Study Day 
280) 
Week 44 
(Study Day 
308) 
Week 48 
(Study Day 
336) 
Week 52 
(Study Day 
364) 
Week 56 
(Study Day 
392) 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 
years 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
DDMONYYYY 
(XX) 
 
Study Day in relation to Baseline visit date (Study Day 1) presented in brackets. 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.16.1 Visit Dates 
(Enrolled Set) 
 
 
 
 
 
Site/Subject 
number 
Age Group 
Week 68 
(Study Day 476) 
Week 80 
(Study Day 560) 
Week 92 
(Study Day 644) 
Week 104 
(Study Day 728) 
Week 108 
(Study Day 756) 
 
 
 
 
 
 
 
XXX/XXX 
5 to 10 years 
DDMONYYYY (XX) 
DDMONYYYY (XX) 
DDMONYYYY (XX) 
DDMONYYYY (XX) 
DDMONYYYY (XX) 
 
Study Day in relation to Baseline visit date (Study Day 1) presented in brackets. 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.17.1 Xanthoma Examination 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age 
Group 
Visit 
Was 
assessment 
performed? 
Reason not 
performed? 
Date of  
assessment 
(Study day 
[1]) 
Were there 
pre-existing 
xanthomas 
present? 
Were there 
pre-existing 
tendon 
xanthomas 
present? 
Anatomical 
location 
Pre-existing 
cutaneous 
xanthomas 
present 
Anatomical 
location 
 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 
10 
years 
XXX 
Y 
 
DDMONYYYY 
(XX) 
Yes/No 
Yes/No 
XXXXXXXXXX 
Yes/No 
XXXXXXXXXX 
XXX/XXX 
11 to 
17 
years 
XXX 
N 
XXXXXXXXXX 
DDMONYYYY 
(XX) 
Yes/No 
Yes/No 
Other: 
XXXXXXXXXX 
Yes/No 
Other: 
XXXXXXXXXX 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits recorded 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.17.1 Xanthoma Examination 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age 
Group 
Visit 
Pre-
existing 
xanthomas 
changed 
since last 
visit? 
If yes, 
have 
they 
reduced 
in size? 
Have they 
resolved? 
(Date of 
resolution) 
Have they 
increased 
in size? 
Were new 
xanthomas 
present? 
Were new 
tendon 
xanthomas 
present? 
Anatomical 
location 
Were new 
cutaneous 
xanthomas 
present? 
Anatomical 
location 
 
 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 
10 
years 
XXX 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
XXXXXXXXXX 
Yes/No 
XXXXXXXXXX 
XXX/XXX 
11 to 
17 
years 
XXX 
Yes/No 
Yes/No 
Yes/No 
(DDMONYYYY) 
Yes/No 
Yes/No 
Yes/No 
Other: 
XXXXXXXXXX 
Yes/No 
Other: 
XXXXXXXXXX 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits recorded 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.17.2 Carotid Intima-Media Thickness (CIMT) 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age 
Group 
Age/Sex/Race 
Visit 
Was CIMT 
assessment 
performed? 
Reason not 
performed? 
Date of  
collection 
(Study day 
[1]) 
Parameter Unit Observed 
Change 
from 
baseline 
% Change 
from 
baseline 
 
 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
11 to 
17 
years 
XX/Female/White XXX 
Y 
 
DDMONYYYY 
(XX) 
XXX 
XXX 
XX.X B 
 
 
 
 
 
XXX 
N 
XXXXXXXXXX 
DDMONYYYY 
(XX) 
XXX 
XXX 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
B = baseline value. Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject 
receiving study treatment in the Efficacy Phase (Visit 4). 
[1] Study day is relative to the date of first administration of study drug (Day 0) 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments should be included in the listing and flagged as such in the visit column. 
 
The listing may go over multiple pages to capture all data. 
 
Repeat for all visits. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.17.3 Flow-mediated Dilation (FMD) 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age 
Group 
Age/Sex/Race 
Visit 
Was FMD 
assessment 
performed? 
Reason not 
performed? 
Date of  
collection 
(Study day 
[1]) 
Parameter Unit Observed 
Change 
from 
baseline 
% Change 
from 
baseline 
 
 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
5 to 
10 
years 
XX/Female/White XXX 
Y 
 
DDMONYYYY 
(XX) 
XXX 
XXX 
XX.X B 
 
 
 
 
 
XXX 
N 
XXXXXXXXXX 
DDMONYYYY 
(XX) 
XXX 
XXX 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
B = baseline value. Baseline is defined as the last non-missing value (including scheduled and unscheduled assessments) prior to the subject 
receiving study treatment in the Efficacy Phase (Visit 4). 
[1] Study day is relative to the date of first administration of study drug (Day 0) 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Unscheduled assessments should be included in the listing and flagged as such in the visit column. 
 
The listing may go over multiple pages to capture all data. 
 
Repeat for all visits. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.17.4 Palatability 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age 
Group 
Visit 
Was 
assessment 
performed? 
Reason not 
performed? 
Date of  
assessment 
(Study day 
[1]) 
Able to 
swallow 
capsule? 
If no, food 
media used? 
First occasion 
used this food 
media 
If yes, rate 
palatability 
 
 
 
 
 
 
 
 
 
 
XXX/XXX 
11 to 
17 
years 
XXX 
Y 
 
DDMONYYYY 
(XX) 
Yes/No 
 
 
 
XXX/XXX 
5 to 10 
years 
XXX 
N 
XXXXXXXXXX 
DDMONYYYY 
(XX) 
Yes/No 
XXXXXXXXXX 
Yes/No 
XXXXXXXXXX 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits recorded 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.17.4 Palatability 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age 
Group 
Visit 
Was 
assessment 
performed? 
Parent / guardian 
interpretation of child's 
reaction / facial 
expression 
Problems giving medication 
to child as refuses to take 
or throws up immediately 
after? 
Problems giving dietary 
supplements to child as 
refuses to take or throws up 
immediately after? 
 
 
 
 
 
 
 
XXX/XXX 
11 to 
17 
years 
XXX 
Y 
XXXXXXXXXX 
Yes/No 
Yes/No 
XXX/XXX 
5 to 10 
years 
XXX 
N 
XXXXXXXXXX 
Yes/No 
Yes/No 
 
[1] Study day is relative to the date of first administration of study drug (Day 0). 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all visits recorded 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Listing 16.2.19.1 Diet and Dietary Supplement Compliance 
(Safety Analysis Set) 
 
 
 
 
 
Site/Subject 
number 
Age 
Group 
Visit 
Were 2-day diet 
records 
completed? 
Were 2-day 
diet records 
checked? 
Dietary 
discussion took 
place? 
Subject 
compliant with 
low fat diet? 
Dietary 
supplements 
dispensed? 
Subject compliant 
with dietary 
supplement regimen? 
 
 
 
 
 
 
 
 
 
XXX/XXX 
11 to 
17 
years 
XXX 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
XXX/XXX 
5 to 10 
years 
XXX 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
 
PROGRAM NAME:L_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all study visits 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.1.5.1 Kaplan-Meier Plot of Time to Dose Reduction 
(Safety Analysis Set) 
 
 
 
 Kaplan-Meier plot of time to dose reduction 
 
 
Time to dose reduction is defined as the time (weeks) from the date of the start of the safety phase to the time of first dose reduction, if 
any. Subjects who do not enter the safety phase will be censored at time 0. If a patient discontinues study drug they will be counted as an 
event at the time of study discontinuation. If a patient has not had a dose reduction and is still on study drug, they will be censored at 
their last visit assessment date. 
N = the number of subjects in the analysis set. 
Source: Listing 16.2.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Treatment group N counts should be presented in the legend. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.1.5.2 Kaplan-Meier Plot of Time to Dose Interruption 
(Safety Analysis Set) 
 
 
 
 Kaplan-Meier plot of time to dose interruption 
 
 
Time to dose interruption is defined as the time (weeks) from the date of the start of the safety phase to the time of first dose 
interruption, if any. Subjects who do not enter the safety phase will be censored at time 0. If a patient discontinues study drug they will 
be counted as an event at the time of study discontinuation. If a patient has not had a dose interruption and is still on study drug, they 
will be censored at their last visit assessment date. 
N = the number of subjects in the analysis set. 
Source: Listing 16.2.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Treatment group N counts should be presented in the legend. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.2.1.1 Waterfall Plot of Percentage Change (%) from Baseline in Fasting Lipid Panel at Week 24 by age group 
(Full Analysis Set) 
 
Parameter: <Parameter (Unit)> 
 
y-axis: percentage change from baseline at Week 24.  
x-axis: subject.  
Use 3 colours for the blocks representing the respective age group for the subject and overall. 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.1.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all parameters. 
 
Include reference line at 0. 
 
Please present LDL-C first and then same order as specified in SAP rather than alphabetically. 
 
Update table source according to parameter Table 14.2.1.1 (LDL-C), Table 14.2.2.1 (Non-HDL-C), Table 14.2.3.1 (TC), Table 14.2.4.1 
(VLDL-C), Table 14.2.5.1 (Apo B), Table 14.2.6.1 (TG), Table 14.2.7.1 (Lp(a) 
 
Use analysis study visit data. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.2.1.2 Forest Plot of Sub-group analysis for primary end point (percentage change at week 24) 
(Full Analysis Set) 
 
Analysis Study Visit 
 
 
 
x-axis: Mean difference in percentage change at week 24. 
y-axis: Overall estimate and Sub-group analysis references (i.e. SG1 to SG7). 
Point estimate and 95% confidence interval. Point estimate will be estimated as the mean percentage change and corresponding 95% CI 
calculated from the ANCOVA model. 
 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.1.4 (SG1), Table 14.2.1.5 (SG2), Table 14.2.1.6 (SG3), Table 14.2.1.7 (SG4), Table 14.2.1.8 (SG5), Table 
14.2.1.9 (SG6), Table 14.2.1.10 (SG7) 
SG1: Age cohorts i.e. 2 age groups). 
SG2: Documented CVD vs no documented CVD history at screening (pooled across age groups). 
SG3: Established CVD history (defined as aortic valve disease and/or coronary atherosclerosis) vs no established CVD history (as defined 
previously) at screening (pooled across age groups). 
SG4: Taken concomitant LLT medications vs not taken concomitant LLT medications (pooled across age groups). 
SG5: No dose reductions vs at least one dose reduction (pooled across age groups). 
SG6: Reached MTD for age group vs did not reach MTD for age group. 
SG7: Male vs Female (pooled across age groups). 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for Nominal Study Visit. 
 
Include reference line at 0. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.2.1.3 Profile Plot of LSMeans percentage change from baseline over time in Fasting Lipid Panel 
(Full Analysis Set) 
 
Parameter: <Parameter (Unit)> 
 
x-axis: time (weeks) relative to baseline. 
y-axis: dynamic based on the parameter <Parameter (Unit)>. 
Point estimate and corresponding error bar. LS mean percentage change at time point with corresponding standard error. The mean and median 
dose at each timepoint will be added. 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.9.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all parameters. 
 
Include reference line at 0. 
 
Please present Week 104 as EOT / Week 104 (as we do in the tables) 
 
Update table source according to parameter Table 14.2.9.1 (LDL-C), Table 14.2.9.2 (Non-HDL-C), Table 14.2.9.3 (TC), Table 14.2.9.4 
(VLDL-C), Table 14.2.9.5 (Apo B), Table 14.2.9.6 (TG), Table 14.2.9.7 (Lp(a)), Table 14.2.9.8 (TC/HDL-C) and Table 14.2.12.2 (HDL-
C) 
 
Use analysis study visit data. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.2.1.4 Forest Plot of Sub-group analysis for key secondary endpoint: Non-HDL-C (percentage change at week 24) 
(Full Analysis Set) 
 
Analysis Study Visit 
 
 
 
Repeat of Figure 14.2.1.2 for NON-HDL-C 
 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.2.4 (SG1), Table 14.2.2.5 (SG2), Table 14.2.2.6 (SG3), Table 14.2.2.7 (SG4), Table 14.2.2.8 (SG5), Table 
14.2.2.9 (SG6), Table 14.2.2.10 (SG7) 
SG1: Age cohorts i.e. 2 age groups). 
SG2: Documented CVD vs no documented CVD history at screening (pooled across age groups). 
SG3: Established CVD history (defined as aortic valve disease and/or coronary atherosclerosis) vs no established CVD history (as defined 
previously) at screening (pooled across age groups). 
SG4: Taken concomitant LLT medications vs not taken concomitant LLT medications (pooled across age groups). 
SG5: No dose reductions vs at least one dose reduction (pooled across age groups). 
SG6: Reached MTD for age group vs did not reach MTD for age group 
SG7: Male vs Female (pooled across age groups). 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for Nominal Study Visit. 
 
Include reference line at 0. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.2.1.5 Forest Plot of Sub-group analysis for key secondary endpoint: TC (percentage change at week 24) 
(Full Analysis Set) 
 
Analysis Study Visit 
 
 
 
Repeat of Figure 14.2.1.2 for TC 
 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.3.4 (SG1), Table 14.2.3.5 (SG2), Table 14.2.3.6 (SG3), Table 14.2.3.7 (SG4), Table 14.2.3.8 (SG5), Table 
14.2.3.9 (SG6), Table 14.2.3.10 (SG7) 
SG1: Age cohorts i.e. 2 age groups). 
SG2: Documented CVD vs no documented CVD history at screening (pooled across age groups). 
SG3: Established CVD history (defined as aortic valve disease and/or coronary atherosclerosis) vs no established CVD history (as defined 
previously) at screening (pooled across age groups). 
SG4: Taken concomitant LLT medications vs not taken concomitant LLT medications (pooled across age groups). 
SG5: No dose reductions vs at least one dose reduction (pooled across age groups). 
SG6: Reached MTD for age group vs did not reach MTD for age group 
SG7: Male vs Female (pooled across age groups). 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for Nominal Study Visit. 
 
Include reference line at 0. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.2.1.6 Forest Plot of Sub-group analysis for key secondary endpoint: VLDL-C (percentage change at week 24) 
(Full Analysis Set) 
 
Analysis Study Visit 
 
 
 
Repeat of Figure 14.2.1.2 for VLDL-C 
 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.4.4 (SG1), Table 14.2.4.5 (SG2), Table 14.2.4.6 (SG3), Table 14.2.4.7 (SG4), Table 14.2.4.8 (SG5), Table 
14.2.4.9 (SG6), Table 14.2.4.10 (SG7) 
SG1: Age cohorts i.e. 2 age groups). 
SG2: Documented CVD vs no documented CVD history at screening (pooled across age groups). 
SG3: Established CVD history (defined as aortic valve disease and/or coronary atherosclerosis) vs no established CVD history (as defined 
previously) at screening (pooled across age groups). 
SG4: Taken concomitant LLT medications vs not taken concomitant LLT medications (pooled across age groups). 
SG5: No dose reductions vs at least one dose reduction (pooled across age groups). 
SG6: Reached MTD for age group vs did not reach MTD for age group 
SG7: Male vs Female (pooled across age groups). 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for Nominal Study Visit. 
 
Include reference line at 0. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.2.1.7 Forest Plot of Sub-group analysis for key secondary endpoint: Apo B (percentage change at week 24) 
(Full Analysis Set) 
 
Analysis Study Visit 
 
 
 
Repeat of Figure 14.2.1.2 for Apo B 
 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.5.4 (SG1), Table 14.2.5.5 (SG2), Table 14.2.5.6 (SG3), Table 14.2.5.7 (SG4), Table 14.2.5.8 (SG5), Table 
14.2.5.9 (SG6), Table 14.2.5.10 (SG7) 
SG1: Age cohorts i.e. 2 age groups). 
SG2: Documented CVD vs no documented CVD history at screening (pooled across age groups). 
SG3: Established CVD history (defined as aortic valve disease and/or coronary atherosclerosis) vs no established CVD history (as defined 
previously) at screening (pooled across age groups). 
SG4: Taken concomitant LLT medications vs not taken concomitant LLT medications (pooled across age groups). 
SG5: No dose reductions vs at least one dose reduction (pooled across age groups). 
SG6: Reached MTD for age group vs did not reach MTD for age group 
SG7: Male vs Female (pooled across age groups). 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for Nominal Study Visit. 
 
Include reference line at 0. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.2.1.8 Forest Plot of Sub-group analysis for key secondary endpoint: TG (percentage change at week 24) 
(Full Analysis Set) 
 
Analysis Study Visit 
 
 
 
Repeat of Figure 14.2.1.2 for TG 
 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.6.4 (SG1), Table 14.2.6.5 (SG2), Table 14.2.6.6 (SG3), Table 14.2.6.7 (SG4), Table 14.2.6.8 (SG5), Table 
14.2.6.9 (SG6), Table 14.2.6.10 (SG7) 
SG1: Age cohorts i.e. 2 age groups). 
SG2: Documented CVD vs no documented CVD history at screening (pooled across age groups). 
SG3: Established CVD history (defined as aortic valve disease and/or coronary atherosclerosis) vs no established CVD history (as defined 
previously) at screening (pooled across age groups). 
SG4: Taken concomitant LLT medications vs not taken concomitant LLT medications (pooled across age groups). 
SG5: No dose reductions vs at least one dose reduction (pooled across age groups). 
SG6: Reached MTD for age group vs did not reach MTD for age group 
SG7: Male vs Female (pooled across age groups). 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for Nominal Study Visit. 
 
Include reference line at 0. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.2.1.9 Forest Plot of Sub-group analysis for key secondary endpoint: Lp(a) (percentage change at week 24) 
(Full Analysis Set) 
 
Analysis Study Visit 
<Unit> 
 
 
Repeat of Figure 14.2.1.2 for Lp(a) 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.7.4 (SG1), Table 14.2.7.5 (SG2), Table 14.2.7.6 (SG3), Table 14.2.7.7 (SG4), Table 14.2.7.8 (SG5), Table 
14.2.7.9 (SG6), Table 14.2.7.10 (SG7) 
SG1: Age cohorts i.e. 2 age groups). 
SG2: Documented CVD vs no documented CVD history at screening (pooled across age groups). 
SG3: Established CVD history (defined as aortic valve disease and/or coronary atherosclerosis) vs no established CVD history (as defined 
previously) at screening (pooled across age groups). 
SG4: Taken concomitant LLT medications vs not taken concomitant LLT medications (pooled across age groups). 
SG5: No dose reductions vs at least one dose reduction (pooled across age groups). 
SG6: Reached MTD for age group vs did not reach MTD for age group 
SG7: Male vs Female (pooled across age groups). 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for Nominal Study Visit. 
 
Include reference line at 0. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.2.1.10 Profile Plot of percentage change from baseline over time in Fasting Lipid Panel 
(Full Analysis Set) 
 
Parameter: <Parameter (Unit)> 
 
x-axis: time (weeks) relative to baseline. 
y-axis: dynamic based on the parameter <Parameter (Unit)>. 
Percentage change at time point. The mean and median dose at each timepoint will be added. 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.8.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for all parameters. 
 
Include reference line at 0. 
 
Please present Week 104 as EOT / Week 104 (as we do in the tables) 
 
Update table source according to parameter Table 14.2.8.1 (LDL-C), Table 14.2.8.2 (Non-HDL-C), Table 14.2.8.3 (TC), Table 14.2.8.4 
(VLDL-C), Table 14.2.8.5 (Apo B), Table 14.2.8.6 (TG), Table 14.2.8.7 (Lp(a)), Table 14.2.8.8 (TC/HDL-C) and Table 14.2.12.1 (HDL-
C) 
 
Use analysis study visit data. 
 
Include reference line at 0. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.2.1 Cumulative distribution function (CDF) plot of LDL-C at Week 24 
(Full Analysis Set) 
 
 
 
 
 
x-axis: LDL-C (mg/dL) at Week 24. 
y-axis: cumulative percentage. 
The cumulative distribution function for LDL-C at week 24 will be plotted with a reference line at 135 mg/dL. 
Use 3 different coloured lines to represent each of the 2 age groups and overall. 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.8.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Include reference line at 135. 
 
Use analysis study visit Week 24. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.2.2 Cumulative distribution function (CDF) plot of LDL-C over time 
(Full Analysis Set) 
 
 
 
 
 
x-axis: LDL-C (mg/dL) at Week X. 
Y-axis: cumulative percentage. 
The cumulative distribution function for LDL-C at Week X will be plotted with a reference line at 135 mg/dL. 
Use 3 different coloured lines to represent each of the 2 age groups and overall. 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.11.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for each analysis study visit within the efficacy and safety phase (except week 24). Replace Week X with corresponding 
analysis study visit for each run, 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.2.3 Cumulative distribution function (CDF) plot of percentage change in LDL-C at Week 24 
(Full Analysis Set) 
 
 
 
 
 
x-axis: percentage change in LDL-C (%) at Week 24. 
y-axis: cumulative percentage. 
The cumulative distribution function for percentage change in LDL-C at week 24 will be plotted with a reference line at -15, -25 and -50%. 
Use 3 different coloured lines to represent each of the 2 age groups and overall. 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.8.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Include reference line at -15, -25 and -50. 
 
Use analysis study visit Week 24. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.2.4 Cumulative distribution function (CDF) plot of lowest percentage change in LDL-C from Week 8 
(Full Analysis Set) 
 
 
 
 
 
x-axis: lowest percentage change in LDL-C (%) from Week 8. 
y-axis: cumulative percentage. 
The cumulative distribution function for percentage change in LDL-C from Week 8 will be plotted with a reference line at -15, -25 and -
50%. 
Use 3 different coloured lines to represent each of the 2 age groups and overall. 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.8.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Include reference line at -15, -25 and -50. 
 
 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.1.1 Subject profile for distribution of Treatment-Emergent adverse events and dose at time of event 
(Safety Analysis Set) 
 
All subjects 
 
 
 
Each subject would have a horizontal bar. The length of the bar would represent the time on the study. 
For each subject bar, the colour of the bar would change over time, with each colour representing the dose of the drug the subject was on 
at that time. 
Any periods the subject was unable to take any dose should be clearly marked in a grey or white colour (for example). 
Overlayed on each subject bar will be a symbol to represent the TEAE PT (e.g. vomiting, abdominal pain, diarrhoea, etc). 
The symbol will be placed at the relevant timepoint the TEAE began and an arrow added to represent the duration of the TEAE. 
Each TEAE experienced by the subject will be represented in a similar manner. 
The colour of the arrow for each TEAE will correspond to the TEAE being related / unrelated to lomitapide. 
The line style of the arrow for each TEAE will correspond to the TEAE severity. 
Y-axis = subject number. 
X-axis = Time (weeks). 
Note: Time (weeks) should correspond with visits and days used for TEAE onset and recovery. 
 
 
 
Source: Listing 16.2.7.1, Table 14.3.1.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 
Repeat for: Compliant with diet - All subjects; Compliant with diet - All subjects aged 5 to 10 years; Compliant with diet - All 
subjects aged 11 to 17 years. 
 
Repeat for: Non-compliant with diet - All subjects; Non- compliant with diet - All subjects aged 5 to 10 years; Non-compliant with 
diet - All subjects aged 11 to 17 years. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.1.2 Age profile for distribution of Treatment-Emergent adverse events and MTD 
(Safety Analysis Set) 
 
Overall - All subjects 
 
 
 
Each subject would have a vertical bar.  
The length of the bar would represent the time on study.  
Under the x-axis, rather than the subject number being displayed the subject s age will be displayed on the graphic.  
The patients will be ordered by age starting with the youngest age closest to the y-axis and moving in an ascending order of age.  
For each patient bar, the colour of bar would represent the MTD the subject achieved, with each colour representing the MTD the subject 
achieved.  
Y-axis = Time (weeks). 
X-axis = Subject. 
Note: Time (weeks) should correspond with visits. 
Overlayed on each patient bar will be a symbol to represent the TEAE PT (e.g. vomiting, abdominal pain, diarrhoea, etc). The symbol will 
be placed at the relevant timepoint the TEAE began. Each TEAE experienced by the subject will be represented in a similar manner. 
 
 
 
Source: Listing 16.2.7.1, Table 14.3.1.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 
Repeat for: Related TEAEs - All subjects; Related TEAEs - All subjects aged 5 to 10 years; Related TEAEs - All subjects aged 11 to 
17 years. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.1.3 Histogram of Time to First Gastrointestinal Treatment-Emergent Adverse Event 
(Safety Analysis Set) 
 
Overall 
 
 
 
Histogram showing the time (days) of onset from the first dose to the first gastrointestinal TEAE 
 
 
 
Source: Listing 16.2.7.1, Table 14.3.1.13 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Subjects aged 5 to 10 years; Subjects aged 11 to 17 years. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.1.4 Histogram of Time to First Hepatic Treatment-Emergent Adverse Event 
(Safety Analysis Set) 
 
Overall 
 
 
 
Histogram showing the time of onset from the first dose to the first hepatic TEAE 
 
 
 
Source: Listing 16.2.7.1, Table 14.3.1.14 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Subjects aged 5 to 10 years; Subjects aged 11 to 17 years. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.3.1 Individual subject profiles of liver function data 
(Safety Analysis Set) 
 
Subject XXXX 
 
 
 
For each patient, at each time point the corresponding liver function tests value will be plotted.  
Heptic fat will also be added with a second y-axis with the hepatic fat scale. 
A line joining all plotted values will be added to show the patient profile of the liver function test over time. 
A separate line will be generated for each liver function test profile over time. 
Each line will be colour coordinated by the liver function test (e.g. AST, ALT, GGT, Alk Phos, Total bilirubin, serum albumin). 
Each patient would have their own plot to show all liver function tests on one page. 
Patient's dose of drug included under the x-axis at each of the analysis study weeks. 
Y-axis = liver function scale. 
Y-axis2 = hepatic fat scale. 
X-axis = Analysis Study Week. 
 
 
 
Source: Listing 16.2.8.3, Table 14.3.3.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Screening will be defined at week -12. 
 
Time (week) on x-axis will use the analysis study week window for statistical analyses as defined in the SAP to determine study 
week for the time axis. 
 
Include unscheduled visits in figure (as approporiate). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.3.2 AST profiles over time, by subject age 
(Safety Analysis Set) 
 
Overall - All subjects 
 
 
 
For each patient, at each time point the corresponding AST liver function tests value will be plotted.  
A line joining all plotted values will be added to show the patient profile of the liver function test over time. 
Each line will be colour coordinated by patient's age. 
Y-axis = AST liver function scale. 
X-axis = time (weeks). 
 
 
 
Source: Listing 16.2.8.3, Table 14.3.3.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 
Screening will be defined at week -12. 
 
Time (week) on x-axis will use the study say window for statistical analyses as defined in the SAP to determine study week for the 
time axis. 
 
Include unscheduled visits in figure (as approporiate). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.3.3 ALT profiles over time, by subject age 
(Safety Analysis Set) 
 
Subject XXXX 
 
 
 
For each patient, at each time point the corresponding ALT liver function tests value will be plotted.  
A line joining all plotted values will be added to show the patient profile of the liver function test over time. 
Each line will be colour coordinated by patient's age. 
Y-axis = ALT liver function scale. 
X-axis = time (weeks). 
 
 
 
Source: Listing 16.2.8.3, Table 14.3.3.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 
Screening will be defined at week -12. 
 
Time (week) on x-axis will use the study say window for statistical analyses as defined in the SAP to determine study week for the 
time axis. 
 
Include unscheduled visits in figure (as approporiate). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.3.4 AST profiles over time, by subject MTD 
(Safety Analysis Set) 
 
Overall - All subjects 
 
 
 
For each patient, at each time point the corresponding AST liver function tests value will be plotted.  
A line joining all plotted values will be added to show the patient profile of the liver function test over time. 
Each line will be colour coordinated by patient's MTD. 
Y-axis = AST liver function scale. 
X-axis = time (weeks). 
 
 
 
Source: Listing 16.2.8.3, Table 14.3.3.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 
Screening will be defined at week -12. 
 
Time (week) on x-axis will use the study say window for statistical analyses as defined in the SAP to determine study week for the 
time axis. 
 
Include unscheduled visits in figure (as approporiate). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.3.5 ALT profiles over time, by subject MTD 
(Safety Analysis Set) 
 
Overall - All subjects 
 
 
 
For each patient, at each time point the corresponding ALT liver function tests value will be plotted.  
A line joining all plotted values will be added to show the patient profile of the liver function test over time. 
Each line will be colour coordinated by patient's MTD. 
Y-axis = ALT liver function scale. 
X-axis = time (weeks). 
 
 
 
Source: Listing 16.2.8.3, Table 14.3.3.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 
Screening will be defined at week -12. 
 
Time (week) on x-axis will use the study say window for statistical analyses as defined in the SAP to determine study week for the 
time axis. 
 
Include unscheduled visits in figure (as approporiate). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.3.6 Individual subject profiles of LDL-C data 
(Safety Analysis Set) 
 
Subject XXXX 
 
 
 
For each patient, at each time point the corresponding LDL-C value will be plotted.  
A line joining all plotted values will be added to show the patient profile of the LDL-C over time. 
Markers will be added to each LDL-C profile line to denote the treatment dose the patient was on at that time point.  
Any periods the subject was unable to take any dose should also be clearly marked using a different marker. 
Dose adjustments will be identified with a different marker and lipoprotein apheresis with a vertical line. 
Each patient would have their own plot to show their LDL-C profile. 
A horizontal line denoting an LDL-C of 110 mg/dL will be added. 
Y-axis = LDL-C scale. 
X-axis = time (weeks). 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.8.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 
Screening will be defined at week -12. 
 
Time (week) on x-axis will use the study say window for statistical analyses as defined in the SAP to determine study week for the 
time axis. 
Add a reference line at y=110 mg/dL. 
 
Include unscheduled visits in figure (as approporiate). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.3.7 LDL-C profiles over time, by subject age 
(Safety Analysis Set) 
 
Overall - All subjects 
 
 
 
For each patient, at each time point the corresponding LDL-C value will be plotted.  
A line joining all plotted values will be added to show the patient profile of the LDL-C over time. 
Each line will be colour coordinated by patient's age. 
Y-axis = LDL-C scale. 
X-axis = time (weeks). 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.8.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 
Screening will be defined at week -12. 
 
Time (week) on x-axis will use the analysis study week window for statistical analyses as defined in the SAP to determine study 
week for the time axis. 
 
Patients who discontinue early and use EOT/Week 104, please use the calculated study day the EOT was completed to assign the 
subject to the relevant analysis study week window (e.g. patients 01-02 and 01-03). 
 
Include unscheduled visits in figure (as approporiate). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.3.8 LDL-C profiles over time, by subject MTD 
(Safety Analysis Set) 
 
Overall - All subjects 
 
 
 
For each patient, at each time point the corresponding LDL-C value will be plotted.  
A line joining all plotted values will be added to show the patient profile of the LDL-C over time. 
Each line will be colour coordinated by patient's MTD. 
Y-axis = LDL-C scale. 
X-axis = time (weeks). 
 
 
 
Source: Listing 16.2.8.1, Table 14.2.8.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 
Screening will be defined at week -12. 
 
Time (week) on x-axis will use the study say window for statistical analyses as defined in the SAP to determine study week for the 
time axis. 
 
Include unscheduled visits in figure (as approporiate). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.3.9 Spaghetti plot of lipid profiles over time 
(Safety Analysis Set) 
Parameter: <Parameter (Unit)> 
Overall - All subjects 
 
 
 
For each patient, at each time point the corresponding lipid value will be plotted.  
A separate line will be generated for each patient to show their individual parameter value over time. 
Y-axis = Lipid value. 
X-axis = time (weeks). 
 
 
 
Source: Listing 16.2.8.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 
Inlcude assessments from Run-in up to Week 104/EoT. 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.3.10 eDISH plot of Maximum Post-Baseline ALT by Maximum Post-Baseline Total Bilirubin 
(Safety Analysis Set) 
 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
x-axis: Maximum post-baseline ALT (x ULN) 
y-axis: Maximum post-baseline TBL (x ULN) 
Plot maximum post baseline ALT by maximum post baseline TBL for each patient. Use log scale for both sets of axes.  
 
Include the following reference lines: x-axis (vertical line) = 3, y-axis (horizontal line) = 2. 
Include reference lines also where x = y = 1 (will create a 'box' in the lower left of the plot). 
Label the 4 quadrants created by the reference lines: Top left = Hyperbilirubinemia; Top right = Hy's Law range; Bottom right = Temple's 
Corollary range; Bottom left: Normal Range (inside 'box' created by x = y = 1 reference lines). 
 
 
ALT = Alanine Aminotransaminase, TBL = Total Bilirubin, ULN = Upper Limit of Normal. 
Source: Listing 16.2.8.3 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Different coulour/symbol for each age group 
 
Include any abnormal observation (scheduled or unscheduled) 
 
Repeat for each study phase 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.3.11 eDISH plot of Maximum Post-Baseline AST by Maximum Post-Baseline Total Bilirubin 
(Safety Analysis Set) 
 
Overall / Efficacy Phase / Safety Phase / Follow-up 
 
Repeat Figure 14.3.3.9 for AST 
 
 
AST = Aspartate Aminotransferase, TBL = Total Bilirubin, ULN = Upper Limit of Normal. 
Source: Listing 16.2.8.3 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Different coulour/symbol for each age group 
 
Include any abnormal observation (scheduled or unscheduled) 
 
Repeat for each study phase 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.3.12 Subject profile for distribution of Liver Function Test Abnormalities and dose at time of event 
(Safety Analysis Set) 
 
All subjects 
 
 
 
Each subject would have a horizontal bar. 
Each subject experiencing an LFT abnormality will be identified with a bar starting at LFT elevation start and ending at the date when the 
LFT abnormality ends. 
Dose taken will be marked in the plot. Any periods the subject was unable to take any dose should be clearly marked. 
Overlayed on each subject bar will be a symbol to represent the Hepatic TEAE PT (e.g. vomiting, abdominal pain, diarrhoea, etc). 
The symbol will be placed at the relevant timepoint the TEAE began and an arrow added to represent the duration of the TEAE. 
Each Hepatic TEAE experienced by the subject will be represented in a similar manner. 
 
Y-axis = subject number. 
X-axis = Time (weeks). 
 
 
 
Source: Listing 16.2.5.1, Listing 16.2.7.1, Listing 16.2.8.3 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.5.1 Boxplot of Observed Vital Signs over Time 
(Safety Analysis Set) 
 
|L|Parameter: <Parameter (Unit)> 
 
x-axis: Time (weeks) 
y-axis: Observed value 
 
Boxplot of the observed value for the respective parameter over time. A boxplot will be displayed for each age group at each side of the 
tick mark, Use a different colour for each age group. 
 
 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Different coulour/symbol for each age group 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.5.2 Boxplot of Change from Baseline Vital Signs over Time 
(Safety Analysis Set) 
 
|L|Parameter: <Parameter (Unit)> 
 
Repeat Figure 14.3.5.1 for change from baseline 
 
 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Different coulour/symbol for each age group 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.5.3 Waterfall plot of change in BMI at Week 24, 56 and 104, by patient sex 
(Safety Analysis Set) 
Week 24 
Overall - All subjects 
 
 
 
Each patient will be represented by a vertical bar, where the length of the bar represents the change in BMI (baseline to the respective 
week, as applicable). 
Order the vertical bars in decreasing order of size of change in BMI. 
For each patient bar, the colour of the bar will represent the sex of the patient. 
Y-axis = change in BMI. 
X-axis = subject. 
 
 
 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.8.1 Scatter plot of change in hepatic fat up with change in BMI Z score up to week 56 and 104, by subject age 
(Safety Analysis Set) 
Week 56 
Overall - All subjects 
 
 
 
Each patient will be represented with a mark on the graphic displaying their change in BMI Z score and corresponding change in hepatic 
fat.  
Each symbol will be colour coded to represent the patient s age in years. 
Y-axis = change in hepatic fat. 
X-axis = change in BMI Z score. 
 
 
 
Only NMR scan assessments are included. 
Source: Listing 16.2.12.1, Table 14.3.8.1.1, Table 14.1.2.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
Repeat for Week 104 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.8.2 Scatter plot of change in hepatic fat with change in BMI Z score up to week 56 and 104, by subject MTD 
(Safety Analysis Set) 
Week 56 
Overall  All subjects 
 
 
 
Each patient will be represented with a mark on the graphic displaying their change in BMI Z score and corresponding change in hepatic 
fat.  
Each symbol will be colour coded to represent the patient s MTD they achieved. 
Y-axis = change in hepatic fat. 
X-axis = change in BMI Z score. 
 
 
 
Only NMR scan assessments are included. 
Source: Listing 16.2.12.1, Table 14.3.8.1.1, Table 14.1.2.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall  All subjects aged 5 to 10 years; Overall  All subjects aged 11 to 17 years. 
Repeat for week 104 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.8.3 Scatter plot of change in hepatic fat up to week 56 and 104 and time fom Lomitapide administration, by subject age 
(Safety Analysis Set) 
Week 56 
Overall - All subjects 
 
 
 
Each patient will be represented with a mark on the graphic displaying their time from lomitapide administration and corresponding change 
in hepatic fat up to week 56.  
Each symbol will be colour coded to represent the patient s age in years. 
Y-axis = change in hepatic fat. 
X-axis = time from lomitapide administration. 
 
 
 
Only NMR scan assessments are included. 
Source: Listing 16.2.12.1, Table 14.3.8.1.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
Repeat for week 104 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.8.4 Scatter plot of change in hepatic fat up to week 56 and 104 and time from Lomitapide administration, by subject MTD 
(Safety Analysis Set) 
Week 56 
Overall - All subjects 
 
 
 
Each patient will be represented with a mark on the graphic displaying their time from lomitapide administration and corresponding change 
in hepatic fat up to week 56.  
Each symbol will be colour coded to represent the patient s MTD they achieved. 
Y-axis = change in hepatic fat. 
X-axis = time from lomitapide administration. 
 
 
Only NMR scan assessments are included. 
Source: Listing 16.2.12.1, Table 14.3.8.1.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
Repeat for Week 104 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.8.5 Cumulative distribution function (CDF) plot of percentage change in hepatic fat over time 
(Safety Analysis Set) 
 
Analysis Study Week XX 
 
 
 
x-axis: Percentage change from baseline in hepatic fat. 
y-axis: cumulative percentage. 
The cumulative distribution function for percentage change in hepatic fat will be plotted with a reference line at 5, 10, 15 and 20%. 
Use 3 different coloured lines to represent each of the 2 age groups and overall. 
 
 
Only NMR scan assessments are included. 
Source: Listing 16.2.12.1, Table 14.3.8.3.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Include reference line at  5, 10, 15 and 20%. 
 
Repeat for each analysis study week. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.8.6 Scatter plot of ALT vs hepatic fat over time 
(Safety Analysis Set) 
 
Imaging technology: NMR 
All subjects 
 
 
x-axis: Hepatic fat 
y-axis: Observed ALT (in x ULN) 
Scatter plot of ALT vs hepatic fat will be plotted at baseline, Week 24, Week 56 and Week 104/EOT. 
Use different colour to represent each age group. Use different symbols for each time point. 
Add Pearson s correlation coefficient (NMR) or Spearman s Rank correlation coefficient (Ultrasound) 
 
 
 
Source: Listing 16.2.8.3, Listing 16.2.12.1, Table 14.3.8.3.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for each age group and for ultrasound scan 
 
Present ALT as x times ULN. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.8.7 Scatter plot of AST vs hepatic fat over time 
(Safety Analysis Set) 
 
Imaging technology: NMR 
All subjects 
 
 
Repeat of Figure 14.3.8.6 
 
 
 
Source: Listing 16.2.8.3, Listing 16.2.12.1, Table 14.3.8.3.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for each age group and for ultrasound scan 
 
Present AST as x times ULN. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.9.1 Waterfall plot of change in BMI Z score at Week 24, 56 and 104, by patient age 
(Safety Analysis Set) 
Week XX 
Overall - All subjects 
 
 
 
Each patient will be represented by a vertical bar, where the length of the bar represents the change in BMI Z score (baseline to week 24, 
56 or 104). 
Order the vertical bars in decreasing order of size of change in BMI Z score. 
For each patient bar, the colour of the bar will represent the age (years) of the patient. 
Y-axis = change in BMI Z score. 
X-axis = subject. 
 
 
 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
Present for Weeks 24, 56 and 104. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.9.2 Waterfall plot of change in BMI Z score at Week 24, 56 and 104, by patient sex 
(Safety Analysis Set) 
Week XX 
Overall - All subjects 
 
 
 
Each patient will be represented by a vertical bar, where the length of the bar represents the change in BMI Z score (baseline to week 24, 
56 or 104). 
Order the vertical bars in decreasing order of size of change in BMI Z score. 
For each patient bar, the colour of the bar will represent the age (years) of the patient. 
Y-axis = change in BMI Z score. 
X-axis = subject. 
 
 
 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
Present for Week 24, 56 and 104. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.9.3 Spaghetti plot of BMI Z score over time, by patient age and sex 
(Safety Analysis Set) 
 
Overall - All subjects 
 
 
 
For each patient, at each time point the corresponding BMI Z score will be plotted.  
A separate line will be generated for each patient to show their individual BMI Z score profile over time. 
Each line will be colour co-ordinated by the patient s age. 
The symbol used for the patient to generate their profile spaghetti line will represent the patient s sex. 
Y-axis = BMI Z score value. 
X-axis = time (weeks). 
 
 
 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.9.4 Spaghetti plot of BMI absolute value over time, by patient age and sex 
(Safety Analysis Set) 
 
Overall - All subjects 
 
 
 
For each patient, at each time point the corresponding BMI absolute value will be plotted.  
A separate line will be generated for each patient to show their individual BMI absolute value profile over time. 
Each line will be colour co-ordinated by the patient s age. 
The symbol used for the patient to generate their profile spaghetti line will represent the patient s sex. 
Y-axis = BMI absolute value. 
X-axis = time (weeks). 
 
 
 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.9.5 Spaghetti plot of weight absolute value over time, by patient age and sex 
(Safety Analysis Set) 
 
Overall - All subjects 
 
 
 
For each patient, at each time point the corresponding weight absolute value will be plotted.  
A separate line will be generated for each patient to show their individual weight absolute value profile over time. 
Each line will be colour co-ordinated by the patient s age. 
The symbol used for the patient to generate their profile spaghetti line will represent the patient s sex. 
Y-axis = weight absolute value. 
X-axis = time (weeks). 
 
 
 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.9.6 Spaghetti plot of sexual maturation development over time 
(Full Analysis Set) 
 
Age Group = 5 to 10 years; Sex = Male/Female 
 
 
 
x-axis: time (weeks) relative to baseline. 
y-axis: tanner staging category (1 to 5). 
Separate line for each subject plotting tanner stage category over time. 
Generate 4 different plots for each age group and sex. 
 
 
 
Source: Listing 16.2.13.2, Table 14.3.9.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.9.7 Spaghetti plot of growth development over time 
(Full Analysis Set) 
 
Age Group = 5 to 10 years; Sex = Male/Female 
 
 
 
x-axis: time (weeks) relative to baseline. 
y-axis: BMI percentile (scale 1 to 100). 
Separate line for each subject plotting BMI percentile over time. 
Generate 4 different plots for each age group and sex. 
 
 
 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.9.8 Waterfall plot of change in BMI Z-score at Week 24, 56 and 104, by baseline BMI for Age Z-score 
(Safety Analysis Set) 
 
Overall - All subjects 
 
 
 
Each patient will be represented by a vertical bar, where the length of the bar represents the change in BMI Z score (baseline to week 24, 
56 or 104). 
Order the vertical bars in decreasing order of size of change in BMI Z-score. 
For each patient bar, the colour of the bar will represent the baseline BMI for Age Z-score of the patient. 
Y-axis = change in BMI Z-score. 
X-axis = subject. 
 
 
 
BMI for Age Z-score cut-points are lower than -2.0 (wasted), between -2.0 and 1.0 (normal), between 1.0 and 2.0 (risk of overweight), between 
2.0 and 3.0 (overweight) and more than 3.0 (obese). 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 
Group baseline BMI for Age Z score in the following categories: <-2.0 (wasted); >= -2.0 and <= 1.0 (normal); > 1.0 and <= 2.0 
(risk of overweight); > 2.0 and <= 3.0 (overweight); > 3.0 (obese). 
Present for weeks 24, 56 and 104. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.9.9 Spaghetti plot of BMI Z-score over time, by baseline BMI for Age Z-score 
(Safety Analysis Set) 
 
Overall - All subjects 
 
 
 
For each patient, at each time point the corresponding BMI Z-score will be plotted.  
A separate line will be generated for each patient to show their individual BMI Z-score profile over time. 
Each line will be colour co-ordinated by the patient s baseline BMI for Age Z-score (<-2, -2 <= x <= 1, 1 < x <= 2, 2 < x <= 3 and > 3). 
The symbol used for the patient to generate their profile spaghetti line will represent the patient s sex. 
Y-axis = BMI Z-score value. 
X-axis = time (weeks). 
 
 
 
BMI for Age Z-score cut-points are lower than -2.0 (wasted), between -2.0 and 1.0 (normal), between 1.0 and 2.0 (risk of overweight), between 
2.0 and 3.0 (overweight) and more than 3.0 (obese). 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 
Group baseline BMI for Age Z-score in the following categories: <-2.0 (wasted); >= -2.0 and <= 1.0 (normal); > 1.0 and <= 2.0 
(risk of overweight); > 2.0 and <= 3.0 (overweight); > 3.0 (obese). 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.9.10 Individual spaghetti plot of weight and Z scores over time 
(Safety Analysis Set) 
 
Subject XXX 
 
 
 
For each patient, at each time point the corresponding Weight and Z scores will be plotted.  
There will be one Y axis for Z-scores and a second Y-axis for absolute weight. 
A separate line will be generated for each parameter over time. 
 
Y-axis = Height, Weight and BMI Z scores values. 
Y2-axis = absolute weight. 
X-axis = time (weeks). 
 
 
 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.9.11 Waterfall plot of change from baseline to maximum weight loss 
(Safety Analysis Set) 
 
Overall - All subjects 
 
 
 
Each patient will be represented by a vertical bar, where the length of the bar represents the change form basleline to the minimum post-
baseline weight (baseline to the respective week, as applicable). 
Order the vertical bars in decreasing order of size of change in weight. 
For each patient bar, the colour of the bar will represent the sex of the patient. 
Y-axis = change in BMI. 
X-axis = subject. 
 
 
 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 


SQN Clinical study no: OCH19003 
 
 
 
 
Amryt Pharma study no: APH-19 
Figure 14.3.9.12 Waterfall plot of change from baseline to minimum BMI z-score change 
(Safety Analysis Set) 
Overall - All subjects 
 
 
 
Each patient will be represented by a vertical bar, where the length of the bar represents the change form baseline to the minimum BMI z-
score change (baseline to the respective week, as applicable). 
Order the vertical bars in decreasing order of size of change in z-score. 
For each patient bar, the colour of the bar will represent the sex of the patient. 
Y-axis = Change from baseline to minimum BMI Z-score. 
X-axis = subject. 
 
 
 
Source: Listing 16.2.9.1, Table 14.3.5.1 
 
PROGRAM NAME:F_XXX_01.SAS      DATE OF RUN:XXXXXXXXX    TIME OF RUN: XX:XX:XX   DATE OF EXTRACTION:XXXXXXXXX 
 
NOTES: Repeat for: Overall - All subjects aged 5 to 10 years; Overall - All subjects aged 11 to 17 years. 
 
 

Prot_000.pdf: 
 
 
C O N F I D E N T I A L  
Confidentiality Statement 
The information contained in this document, especially unpublished data, is the property of Amryt 
Pharmaceuticals DAC, and is therefore provided to you in confidence as an investigator, potential 
investigator, member of regulatory authorities or consultant, for review by you, your staff and an 
applicable Independent Ethics Committee. It is understood that this information will not be disclosed 
to others without written authorisation from Amryt Pharmaceuticals DAC, except to the extent 
necessary to obtain written informed consent from those persons to whom the drug may be 
administered. 
Study Protocol 
 
Phase III, Single-arm, Open-label, International, Multi-centre Study 
to Evaluate the Efficacy and Safety of Lomitapide in Paediatric 
Patients with Homozygous Familial Hypercholesterolaemia (HoFH) 
on Stable Lipid-lowering Therapy 
 
Investigational product 
Lomitapide 
Indication 
Homozygous Familial Hypercholesterolaemia (HoFH) 
Identifier 
EudraCT No. 2019-002278-30 
Study number 
APH-19 
Development phase 
Phase III 
Document 
Study Protocol APH-19 
Version number 
7.0 
Status 
Final 
Release date 
09 February 2023 
Revision chronology 
Version 1.0 
19 July 2019 
 
Version 2.0 
18 August 2019 
 
Version 3.0 
04 December 2019 
 
Version 4.0 
14 February 2020 
 
Version 5.0 
04 September 2020 
 
Version 5.1 
Version 5.2 (Germany) 
21 September 2020 
17 November 2020 
 
Version 6.0 
05 May 2022 
Author(s) 
Dr Tracy Cunningham, LRCPI & SI, MB, BCh, BAO, FRCPI, AFPM 
Compliance 
The study will be conducted in accordance with standards of Good 
Clinical Practice, as defined by the International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) and all applicable federal and local regulations. 
Sponsor 
Amryt Pharmaceuticals DAC 
45 Mespil Road, Dublin 4, Ireland 
Phone: +35-3-1-518-0200 
 
 






Amryt Pharmaceuticals DAC 
Study Protocol APH-19 
Version: 7.0 / Final / 09 February 2023 
Page 4 of 111 
C O N F I D E N T I A L  
TABLE OF CONTENTS 
LIST OF TERMS AND ABBREVIATIONS ............................................................................. 9 
1 
SUMMARY OF CLINICAL STUDY ................................................................................ 12 
1.1 
Study Synopsis .................................................................................................. 12 
1.2 
Flow Chart of Study and Follow-up ..................................................................... 23 
2 
INTRODUCTION ............................................................................................................ 27 
2.1 
Background ........................................................................................................ 27 
2.1.1 
Homozygous Familial Hypercholesterolaemia ..................................... 27 
2.1.2 
Treatment Options and Medical Need ................................................. 27 
2.2 
Investigational Product ....................................................................................... 29 
2.3 
Summary of Non-clinical Studies with Lomitapide .............................................. 29 
2.4 
Summary of Clinical Studies with Lomitapide ..................................................... 29 
2.4.1 
Clinical Pharmacology and Pharmacokinetics ..................................... 29 
2.4.2 
Clinical Efficacy and Safety ................................................................. 29 
2.5 
Rationale for Dose Selection .............................................................................. 33 
2.6 
Known and Potential Benefits and Risks ............................................................ 34 
2.6.1 
Unmet Medical Need ........................................................................... 34 
2.6.2 
Known and Potential Benefits .............................................................. 35 
2.6.3 
Known and Potential Risks .................................................................. 36 
2.6.4 
Benefits and Risks Conclusions .......................................................... 38 
2.7 
Rationale of the Study and of the Study Design ................................................. 38 
3 
STUDY OBJECTIVES .................................................................................................... 39 
3.1 
Primary Objective ............................................................................................... 39 
3.2 
Secondary Objectives ........................................................................................ 39 
3.3 
Safety Objectives ............................................................................................... 39 
3.4 
Exploratory Objectives ....................................................................................... 40 
3.5 
Palatability Objective .......................................................................................... 40 
3.6 
Pharmacokinetic Objective ................................................................................. 40 
4 
INVESTIGATIONAL PLAN ............................................................................................ 41 
4.1 
Study Endpoints ................................................................................................. 41 
4.1.1 
Primary Endpoint ................................................................................. 41 
4.1.2 
Secondary Endpoints .......................................................................... 41 
4.1.3 
Safety Endpoints ................................................................................. 41 
4.1.4 
Exploratory Endpoints ......................................................................... 42 
4.1.5 
Palatability Endpoints .......................................................................... 42 
4.1.6 
Pharmacokinetic Endpoint ................................................................... 42 
4.2 
Overall Study Design .......................................................................................... 42 
4.2.1 
Study ................................................................................................... 43 
4.2.2 
End of Study ....................................................................................... 46 
4.3 
Data Safety Monitoring Board ............................................................................ 46 
5 
STUDY POPULATION ................................................................................................... 46 
5.1 
Inclusion Criteria ................................................................................................ 46 
5.2 
Exclusion Criteria ............................................................................................... 47 
6 
STUDY MEDICATION .................................................................................................... 48 
6.1 
Description of the Investigational Product ........................................................... 48 


Amryt Pharmaceuticals DAC 
Study Protocol APH-19 
Version: 7.0 / Final / 09 February 2023 
Page 5 of 111 
C O N F I D E N T I A L  
6.1.1 
Formulation, Packaging and Labelling ................................................. 48 
6.1.2 
Storage and Stability ........................................................................... 48 
6.1.3 
Drug and Dietary Supplements Accountability ..................................... 48 
6.2 
Investigational Product Compliance ................................................................... 49 
6.3 
Dietary Supplements .......................................................................................... 49 
7 
STUDY TREATMENT .................................................................................................... 49 
7.1 
Treatment Assignment, Blinding Procedure ....................................................... 49 
7.2 
Treatment Schedule ........................................................................................... 49 
7.3 
Dose Modifications and Interruptions ................................................................. 50 
7.3.1 
Dose Escalation, Dose Reduction and Re-challenge .......................... 50 
7.3.2 
Dose Modification, Interruption or Discontinuation for Adverse 
Events ................................................................................................. 51 
7.3.3 
Dose Modification for Concomitant Medication .................................... 54 
7.4 
Patient Discontinuation Criteria .......................................................................... 55 
7.5 
Overdose ........................................................................................................... 56 
7.6 
Concomitant Medication ..................................................................................... 57 
7.6.1 
Concomitant Lipid-lowering Treatment ................................................ 57 
7.6.2 
Permitted Concomitant Medication ...................................................... 57 
7.6.3 
Non-permitted Concomitant Medication, Food or Substances ............. 58 
8 
ASSESSMENTS ............................................................................................................ 59 
8.1 
Eligibility and Safety Assessments ..................................................................... 59 
8.1.1 
Eligibility Assessments ........................................................................ 59 
8.1.2 
Safety Assessments ............................................................................ 60 
8.2 
Pharmacokinetics ............................................................................................... 63 
8.3 
Assessment of Efficacy ...................................................................................... 63 
8.3.1 
Fasting Lipid Panel .............................................................................. 63 
8.3.2 
LDL-C Treatment Criteria .................................................................... 64 
8.4 
Exploratory Assessments ................................................................................... 64 
8.4.1 
Regression or Resolution of Xanthomas ............................................. 64 
8.4.2 
Assessment of Carotid Intima-Media Thickness and Flow-mediated 
Dilation ................................................................................................ 64 
8.4.3 
Liposcale® Test ................................................................................... 64 
8.5 
Palatability .......................................................................................................... 65 
8.6 
Other Assessments ............................................................................................ 65 
8.6.1 
Diet Instructions and Diet Records ...................................................... 65 
9 
VISIT SCHEDULE .......................................................................................................... 66 
9.1 
Screening Period (Starting at Week -12, i.e., ≤12 Weeks Prior to Baseline for a 
Minimum of 6 Weeks), Visit 1 ............................................................................. 66 
9.1.1 
Visit 1 (Up to Week -12) ...................................................................... 67 
9.2 
Re-screening ...................................................................................................... 67 
9.3 
Stratified Enrolment and Start of Run-in Period (Starting at Minimum at 
Week -6, i.e., 6 Weeks Prior to Baseline for a Minimum of 6 Weeks, Visits 2 to 
3 ......................................................................................................................... 68 
9.3.1 
Visit 2 (Stratified Enrolment and Start of Run-in Period, at Minimum 
Week -6) ............................................................................................. 68 
9.3.2 
Visit 3 (Compliance, Week -3 to Week -2) ........................................... 68 
9.4 
Efficacy Phase (Baseline, D0 to Week 24±3 days), Visits 4 to 10 ....................... 68 
9.4.1 
Visit 4 (Baseline, D0) ........................................................................... 68 


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C O N F I D E N T I A L  
9.4.2 
Visits 5, 6, 8, and 9 (Week 4±3 days, Week 8±3 days, 
Week 16±3 days, and Week 20±3 days) ............................................. 70 
9.4.3 
Visit 7 (Week 12±3 days) .................................................................... 71 
9.4.4 
Visit 10 (Week 24±3 days)................................................................... 72 
9.5 
Safety Phase (Week 28±3 Days to Week 92±1 Week), Visits 11 to 21 ............... 73 
9.5.1 
Visits 11 to 17 (Week 28±3 days, Week 32±3 days, 
Week 36±3 days, Week 40±3 days, Week 44±3 days, 
Week 48±3 days, and Week 52±3 days) ............................................. 73 
9.5.2 
Visit 18 (Week 56±3 days)................................................................... 73 
9.5.3 
Visits 19 to 21 (Week 68±1 week, Week 80±1 week, and 
Week 92±1 week) ............................................................................... 75 
9.6 
Unscheduled Visits ............................................................................................. 75 
9.7 
End of Treatment (Week 104±1 week), Visit 22 .................................................. 76 
9.8 
Follow-up (Week 108), Visit 23 ........................................................................... 77 
9.8.1 
Visit 23 (Week 108) ............................................................................. 77 
10 COLLECTION, STORAGE AND SHIPMENT OF LABORATORY SAMPLES ............... 78 
11 DRUG SAFETY .............................................................................................................. 79 
11.1 
Definitions .......................................................................................................... 79 
11.1.1 
Adverse Event ..................................................................................... 79 
11.1.2 
Adverse Drug Reaction ....................................................................... 79 
11.1.3 
Unexpected Adverse Drug Reaction ................................................... 79 
11.1.4 
Serious Adverse Event or Adverse Drug Reaction .............................. 79 
11.1.5 
Suspected Unexpected Serious Adverse Reaction ............................. 80 
11.1.6 
Adverse Events of Special Interest ...................................................... 80 
11.2 
Recording of Adverse Events and Serious Adverse Events................................ 81 
11.2.1 
Assessment of Seriousness ................................................................ 81 
11.2.2 
Assessment of Severity ....................................................................... 81 
11.2.3 
Assessment of Causality ..................................................................... 81 
11.3 
Monitoring Laboratory Assessments .................................................................. 82 
11.4 
Documenting of Adverse Events and Serious Adverse Events ........................... 82 
11.5 
Immediately Reportable Information ................................................................... 83 
11.5.1 
Reporting of Serious Adverse Events .................................................. 83 
11.5.2 
Reporting of Adverse Events of Special Interest.................................. 83 
11.5.3 
Reporting Safety Observations by the Investigator to the IEC/IRB ...... 84 
11.5.4 
Other Reportable Information: Pregnancy ........................................... 84 
12 STATISTICAL ANALYSIS ............................................................................................. 84 
12.1 
Statistical Methods ............................................................................................. 84 
12.1.1 
Tests of Hypotheses and Significance Levels ..................................... 84 
12.1.2 
Determination of Sample Size ............................................................. 85 
12.2 
Definition of Study Populations ........................................................................... 85 
12.3 
Planned Analysis ................................................................................................ 86 
12.3.1 
Disposition and Exposure .................................................................... 86 
12.3.2 
Demographic Data and other Baseline Characteristics ........................ 86 
12.3.3 
Interim Analysis ................................................................................... 86 
12.3.4 
Planned Analysis for Primary Endpoint ............................................... 86 
12.3.5 
Planned Analysis for Secondary Endpoints ......................................... 87 
12.3.6 
Planned Analysis for Safety Endpoints ................................................ 87 


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C O N F I D E N T I A L  
12.3.7 
Planned Analysis for Exploratory Endpoints ........................................ 88 
12.3.8 
Planned Analysis for Palatability Endpoints ......................................... 88 
12.3.9 
Planned Analysis for Pharmacokinetic Endpoint .................................. 88 
12.4 
Statistical Criteria for Study Termination ............................................................. 88 
12.5 
Handling of Missing Data ................................................................................... 88 
12.6 
Time Windows .................................................................................................... 88 
13 QUALITY CONTROL AND QUALITY ASSURANCE ..................................................... 89 
13.1 
Pre-study Documentation ................................................................................... 89 
13.2 
Monitoring .......................................................................................................... 89 
13.3 
Data Management and Processing .................................................................... 89 
13.3.1 
Data Collection .................................................................................... 90 
13.3.2 
Data Management Procedures ............................................................ 90 
13.3.3 
Data Verification Procedures ............................................................... 90 
13.3.4 
Coding ................................................................................................ 90 
13.3.5 
Procedures for Analysis of Consistency and Medical Plausibility ......... 90 
13.3.6 
Data to be Recorded Directly into the Electronic Case Report Form ... 90 
13.4 
Study and Site Closure ....................................................................................... 90 
13.5 
Audits and Inspections ....................................................................................... 91 
14 LEGAL AND ETHICAL REQUIREMENTS ..................................................................... 91 
14.1 
Regulatory Authority Approval ............................................................................ 91 
14.2 
Independent Ethics Committee/Institutional Review Board ................................. 91 
14.3 
Patient and Parent/Legal Guardian Information and Informed Consent .............. 91 
14.4 
Data Protection .................................................................................................. 92 
14.5 
Notification of Primary Care Physician................................................................ 92 
14.6 
Investigator Reporting Requirements ................................................................. 92 
14.7 
Record Retention ............................................................................................... 92 
15 PROTOCOL AMENDMENTS ......................................................................................... 93 
16 DISCLOSURE OF INFORMATION ................................................................................ 93 
16.1 
Publication of Study Findings ............................................................................. 93 
17 COMPENSATION FOR INJURIES ................................................................................ 93 
18 REFERENCES ............................................................................................................... 94 
18.1 
Source Documents ............................................................................................. 94 
18.2 
Literature ............................................................................................................ 94 
19 APPENDICES ................................................................................................................ 98 
 
 
 


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C O N F I D E N T I A L  
LIST OF TABLES 
Table 1 
Suggested 
Lomitapide 
Starting 
Doses 
by 
Age 
Group 
Based 
on 
Physiologically-based Pharmacokinetic Modelling and Allometric Scaling .......... 34 
Table 2 
Lomitapide Starting Dose and Dose Escalation by Age Group ........................... 49 
 
LIST OF FIGURES 
Figure 1 
Percentage of Patients Achieving EAS Treatment Goals with Lomitapide across 
Pivotal Studies and in Real-world Evidence ....................................................... 33 
Figure 2 
Proposed 
Mean 
Lomitapide 
Paediatric 
Starting 
Dose 
Based 
on 
Physiologically-based Pharmacokinetic Modelling and Allometric Scaling .......... 34 
Figure 3 
Design of Study .................................................................................................. 45 
Figure 4 
Example of a 5-Point Facial Hedonic Scale Used for Hedonic Ratings by 
Children (Guinard 2000) ..................................................................................... 65 
 
LIST OF APPENDICES 
Appendix 1 Child-Pugh Score ............................................................................................... 98 
Appendix 2 Schwartz Formula .............................................................................................. 99 
Appendix 3 Common Terminology Criteria for Adverse Events (CTCAE), Hepatobiliary 
Disorders .......................................................................................................... 100 
Appendix 4 WHO Growth Charts for Boys and Girls 5 to 19 Years of Age .......................... 102 
Appendix 5 Tanner Staging ................................................................................................. 104 
Appendix 6 Laboratory Tests .............................................................................................. 105 
Appendix 7 Declaration of Helsinki ...................................................................................... 107 
 
 
 


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C O N F I D E N T I A L  
LIST OF TERMS AND ABBREVIATIONS 
Term or Abbreviation 
Description 
AA 
Arachidonic acid 
ACTH 
Adrenocorticotrophic hormone 
ADR 
Adverse drug reaction 
AE 
Adverse event 
AESI 
Adverse Event of Special Interest 
ALA 
Alpha-linolenic acid 
ALT 
Alanine transaminase 
ANCOVA 
Analysis of covariance 
AP 
Alkaline phosphatase 
apo A-I 
Apolipoprotein A-I 
apo B 
Apolipoprotein B 
ASCVD 
Atherosclerotic cardiovascular disease 
AST 
Aspartate transaminase 
ATC 
Anatomical Therapeutic Chemical 
BG 
Blood glucose 
BMI 
Body mass index 
BSA 
Body surface area 
BUN 
Blood urea nitrogen 
Ca 
Calcium 
CAS 
Completer analysis set 
CBC 
Complete blood count 
c-het 
compound heterozygous 
CIMT 
Carotid intima-media thickness 
CK 
Creatinine kinase 
Cl 
Chloride 
Cmax 
Maximum concentration 
C-R 
Concentration-Response 
CRP 
C-reactive protein 
CTCAE 
Common Terminology Criteria for Adverse Events 
CVD 
Cardiovascular disease 
CYP 
Cytochrome P 450 
D 
Day(s) 
DHA 
Docosahexaenoic acid 
DSMB 
Data Safety Monitoring Board 
EAP 
Expanded Access Programme 
EAS 
European Atherosclerosis Society 
EASL 
European Association for the Study of the Liver 
EC 
European Commission 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EEA 
European Economic Area 
EFA 
Essential fatty acids 


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C O N F I D E N T I A L  
Term or Abbreviation 
Description 
EMA 
European Medicines Agency 
EoT 
End of Treatment 
EPA 
Eicosapentaenoic acid 
EPAR 
European Public Assessment Report 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
FH 
Familial Hypercholesterolaemia 
FMD 
Flow-mediated dilatation 
FSH 
Follicle stimulating hormone 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GGT 
Gamma-glutamyl transferase 
GI 
Gastrointestinal 
HDL-C 
High-density lipoprotein cholesterol 
HMG-CoA 
3-hydroxy-3-methylglutaryl coenzyme A 
HoFH 
Homozygous familial hypercholesterolaemia 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
IDL 
Intermediate density lipoprotein 
IEC 
Independent Ethics Committee 
INR 
International normalised ratio 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat (analysis set) 
IU 
International units 
IV 
Intravenous 
K 
Potassium 
LA 
Lipoprotein apheresis 
LDL 
Low-density lipoprotein 
LDL-C 
Low-density lipoprotein cholesterol (conventional mg/dL units 
can be converted to SI [mmol/L] units using the factor 0.0259) 
LDLR 
LDL receptor 
LDLRAP1 
LDL-receptor adapter protein 1 
LFT 
Liver function test 
LH 
Luteinising hormone 
LLT 
Lipid-lowering therapy (including LA, where applicable) 
LOCF 
Last observation carried forward 
LOWER 
Lomitapide Observational Worldwide Evaluation Registry 
Lp(a) 
Lipoprotein a 
MACE 
Major adverse cardiac event(s) 
MCH 
Mean corpuscular haemoglobin 
MCHC 
Mean corpuscular haemoglobin concentration 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 


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C O N F I D E N T I A L  
Term or Abbreviation 
Description 
MTD 
Maximum tolerated dose 
MTP 
Microsomal triglyceride transfer protein 
Na 
Sodium 
NASH 
Non-alcoholic steatohepatitis 
NMR 
Nuclear magnetic resonance 
Non-HDL-C 
Non-high-density lipoprotein cholesterol 
NYHA 
New York Heart Association 
PBPK 
Physiologically based pharmacokinetic modelling 
PCSK9 
Proprotein convertase subtilisin/kexin type 9 
PFT 
Pulmonary function test 
PK 
Pharmacokinetics 
PP 
Per-protocol (analysis set) 
RMP 
Risk Management Plan 
SADR 
Serious adverse drug reaction 
SAE 
Serious adverse event 
SAF 
Safety analysis set 
SD 
Standard deviation 
SOC 
Standard of care 
SPC 
Summary of Product Characteristics 
SUSAR 
Suspected unexpected serious adverse reaction 
TC 
Total cholesterol 
TG 
Triglycerides 
TSH 
Thyroid stimulating hormone 
ULN 
Upper limit of normal 
V 
Visit 
VLDL-C 
Very low-density lipoprotein cholesterol 
W 
Week(s) 
WHO 
World Health Organization 
 
 


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C O N F I D E N T I A L  
1 
SUMMARY OF CLINICAL STUDY 
1.1 
Study Synopsis 
 
Title of study 
Phase III, single-arm, open-label, international, multi-centre study to evaluate the efficacy and safety of 
lomitapide in paediatric patients with Homozygous Familial Hypercholesterolaemia (HoFH) on stable 
lipid-lowering therapy 
Sponsor 
Amryt Pharmaceuticals DAC, 45 Mespil Road, Dublin 4, Ireland 
Coordinating investigator 
Prof. Luis Masana, Director of Vascular Medicine and Metabolism Unit, Research Unit on Lipids and 
Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira I Virgili, IISPV, 43201 Reus, Spain.  
Study centres 
International multi-centre study with approximately 15 study sites 
Countries 
Germany, Israel, Italy, Saudi Arabia, Spain, and Tunisia with potential for others as needed 
Phase of development 
Phase III 
Number of patients 
Approximately 45 patients to achieve 30 evaluable patients at Week 24±3 days 
Study objectives 
Primary objective 
To evaluate the efficacy of lomitapide, as defined by the percent change in low-density lipoprotein 
cholesterol (LDL-C) at the maximum tolerated dose (MTD) at Week 24±3 days compared to Baseline, 
when added to stable lipid-lowering therapy (LLT, including lipoprotein apheresis [LA] where applicable) 
in paediatric patients (5 to ≤17 years of age) with HoFH. 
Secondary objectives 
To evaluate the efficacy of lomitapide in paediatric HoFH patients as assessed by: 
• Percent change from Baseline at Week 24±3 days in lipid parameters, including total cholesterol 
(TC), non high-density lipoprotein cholesterol (Non-HDL-C), very low-density lipoprotein cholesterol 
(VLDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], and apolipoprotein B (apo B). 
• Percent change from Baseline in TC, non-HDL-C, LDL-C, TG, VLDL-C, Lp(a), and apo B at all other 
time-points through Week 104±1 week. 
• Change in LLT and LA from Week 24±3 days through Week 104±1 week. 
• Number (percent) of paediatric HoFH patients achieving the European Atherosclerosis Society 
(EAS) recommended target LDL-C of <135 mg/dL (3.5 mmol/L) at Week 24±3 days and at any time 
on study. 
Safety objectives 
To evaluate the long-term safety and tolerability of lomitapide in paediatric HoFH patients as assessed 
by: 
• Incidence in reported adverse events (AEs) and in clinically significant abnormal findings of physical 
examinations including weight and body mass index (BMI), electrocardiogram (ECG), standard of 
care echocardiography (if available), vital signs, pulmonary function tests (PFT), and laboratory 
parameters including hepatic and renal function tests. 
 
 
 


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C O N F I D E N T I A L  
Safety objectives (continued) 
• Effects on growth, bone health and bone age will be assessed using both measurements of 
children’s height and growth charts to track age-appropriate progress at Screening and from 
Baseline at every visit through Week 104±1 week and/or at EoT, together with analysis of Vitamin D 
and K levels at Screening, Baseline, Week 24±3 days, Week 56±3 days, Week 80±1 week, 
Week 104±1 week and/or at EoT (and at Week 108 for patients who opt not to participate in or are 
unsuitable for the Expanded Access Programme [EAP; <18 years of age]/opt not to transition to 
commercial product [≥18 years of age]). 
• Potential effects on maturation, reproductive development, gonadotropins, and variables of the 
pituitary-adrenal axis at Screening, Baseline, Week 56±3 days, Week 104±1 week and/or at EoT will 
be analysed; potential effects on the levels of sex steroids will be analysed for patients assessed as 
Tanner Stage ≥2. 
• Lipid accumulation in the liver as measured by nuclear magnetic resonance (NMR) imaging or 
echography (i.e., ultrasound scan) at Baseline and at Week 24±3 days, Week 56±3 days, and at 
Week 104±1 week (for patients who opt not to participate in or are unsuitable for the EAP [<18 years 
of age]/opt not to transition to commercial product [≥18 years of age], lipid accumulation in the liver 
will be measured at Baseline, at Week 24±3 days, Week 56±3 days, and at Week 108). All patients 
will undergo NMR imaging unless it is contraindicated or not feasible (e.g., due to the need for 
sedation or general anaesthesia in very young or anxious patients). In this case, ultrasound scans 
will be used at the discretion of the investigator. 
Exploratory objectives 
To evaluate the exploratory assessments of: 
• Change from Baseline at Week 56±3 days and Week 104±1 week in mean carotid intima-media 
thickness (CIMT, mandatory) and flow-mediated dilatation (FMD, whenever possible). 
• Resolution 
and/or 
regression 
of 
pre-existing 
xanthomas 
at 
Week 56±3 days 
and 
at 
Week 104±1 week. 
• Changes from Baseline through Week 24±3 days in cholesterol and triglyceride content of VLDL, 
intermediate density lipoprotein (IDL), LDL and HDL, particle number and size of VLDL, LDL, and 
HDL as well as particle number of their respective lipoprotein subclasses (large, medium, and small) 
as assessed based on 2D NMR (Liposcale® Test) of pharmacokinetics (PK) samples. 
Palatability objective 
• Assess the palatability of the study medication using a 5-point facial hedonic scale, anchored with 
descriptors, to record the children’s assessment of palatability in terms of overall liking.  
• The parent(s)/legal guardian(s) interpretation of the child’s reaction/facial expression will be used to 
determine whether they find lomitapide “pleasant”, “unpleasant” or are “not sure”.  
• Ease of administration of the study medication and dietary supplements by the parent(s)/legal 
guardian(s) will be assessed using the following question at each visit during the treatment phase: 
“Do you sometimes have problems in giving the medication to your child because he/she refuses to 
take it or throws it up immediately after taking it? (Yes/No).” 
Pharmacokinetics objective 
• To evaluate the pharmacokinetics (PK) of lomitapide in paediatric HoFH patients through sparse 
blood sampling. 
Study endpoints 
Primary endpoint 
Percent change from Baseline in LDL-C at Week 24±3 days. 
Secondary endpoints 
• Percent change from Baseline at Week 24±3 days for the following lipid parameters: TC, 
Non-HDL-C, VLDL-C, TG, Lp(a), and apo B. 
• Percent change from Baseline at all other time points through Week 104±1 week for the following 
lipid parameters: LDL-C, TC, Non-HDL-C, VLDL-C, TG, Lp(a), and apo B. 
• Total number and percent of patients with a change from Baseline in LLT and LA from 
Week 24±3 days through Week 104±1 week. 
• Total number and percent of patients achieving the EAS recommended target LDL-C of <135 mg/dL 
(3.5 mmol/L) in paediatric HoFH patients at Week 24±3 days and at any time on study. 


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C O N F I D E N T I A L  
Safety endpoints 
Safety evaluations and endpoints from Baseline through Week 104±1 week include: 
• Incidence of AEs overall and by severity and relatedness. 
• Physical examinations including regular measurements of height, weight, and BMI. 
• Sexual maturation (Tanner staging):  
− In patients with Tanner Stage ≥2: Changes from Baseline in sex hormones (serum testosterone 
and serum oestradiol). 
• 12-Lead safety ECG (read locally), standard of care echocardiography (if available), vital signs and 
blood pressure. 
• PFT. 
• Laboratory tests:  
− Standard haematology (complete blood count [CBC]) and clinical chemistry panels. 
− Liver 
function 
tests: 
Alanine 
transaminase 
(ALT), 
aspartate 
transaminase 
(AST), 
gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), total bilirubin, and serum 
albumin. 
− High-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apo A-I). 
− Creatinine kinase (CK). 
− Serum lipase. 
− Serum levels of essential fatty acids (EFA): Linoleic acid, alpha linoleic acid (ALA), 
eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and 
eicosatrienoic acid. 
− Serum concentrations of fat-soluble vitamins: Vitamin A (retinol), vitamin E (alpha tocopherol), 
ratio of vitamin E to total lipids (total cholesterol plus fasting triglycerides), and vitamin D 
(25-hydroxy-D). Levels of vitamin K will be assessed indirectly by measuring total and 
uncarboxylated levels of serum osteocalcin. (Bone health will be assessed indirectly using growth 
to track age-appropriate progress, and measurement of 25-hydroxy-D as well as total and 
uncarboxylated osteocalcin levels.). 
− Pituitary-adrenal hormone levels (thyroid stimulating hormone [TSH], follicle stimulating hormone 
[FSH], luteinising hormone [LH], adrenocorticotrophic hormone [ACTH], and morning serum 
cortisol). 
− Urinalysis. 
• Lipid accumulation in the liver as measured by NMR imaging or echography (i.e., ultrasound scan) 
at Baseline and at Week 24±3 days, Week 56±3 days, and at Week 104±1 week (Week 108 for 
patients who opt not to participate in or are unsuitable for the EAP [<18 years of age]/opt not to 
transition to commercial product [≥18 years of age]). All patients will undergo NMR imaging unless 
it is contraindicated or not feasible (e.g., due to the need for sedation or general anaesthesia in very 
young or anxious patients). In this case, ultrasound scans will be used at the discretion of the 
investigator. 
Exploratory endpoints 
• Percent change from Baseline at Week 56±3 days and Week 104±1 week in CIMT and FMD. 
• Total number and percent of patients with resolution and/or regression of pre-existing xanthomas at 
Week 56±3 days and at Week 104±1 week. 
• Changes from Baseline through Week 24±3 days in cholesterol and triglyceride content of VLDL, 
IDL, LDL and HDL, particle number and size of VLDL, LDL, and HDL as well as particle number of 
their respective lipoprotein subclasses (large, medium, and small) as assessed based on 2D NMR 
(Liposcale® Test) of PK samples at Week 4±3 days, Week 8±3 days, Week 12±3 days, 
Week 16±3 days, Week 20±3 days and at Week 24±3 days. 


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C O N F I D E N T I A L  
Palatability endpoints 
• 
Total number and percent of patients for each response of palatability: 
− Able to swallow capsule (including food media responses if used). 
− Palatability rating (using a 5-point facial hedonic scale). 
− Parent/guardian interpretation of child’s reaction/facial expression (using a 3-point scale). 
− Parent/guardian experience problems in giving medication to child because they refuse to take 
or throw up immediately after taking. 
− Parent/guardian experience problems in giving dietary supplement to child because they refuse 
to take or throw up immediately after taking. 
Pharmacokinetic endpoints 
• 
The PK data from this study will be incorporated into an existing population PK model in adult 
HoFH patients. 
Study design 
This is a single-arm, open-label, multi-centre phase III study to evaluate the efficacy and long-term 
safety of lomitapide in paediatric patients with HoFH receiving stable LLT (including LA, when 
applicable) comprising the following phases: 
• Screening Period (starting at Week -12, i.e., ≤12 weeks prior to Baseline for up to 6 weeks). 
• Stratified Enrolment and Start of Run-in Period (starting at minimum at Week -6, i.e., 6 weeks prior 
to Baseline for a minimum of 6 weeks): 
− Enrolment will be stratified to ensure approximately equal numbers of patients in the following 
age groups: 5 to 10 years, 11 to 15 years, and 16 to ≤17 years (with ≥8 patients in any individual 
age group). 
− Patients must be stabilised on current LLT (including LA, when applicable) and established on a 
diet supplying <20% of energy (calories) from fat or <30 g fat, whichever is the lesser amount. 
− Daily supplementation with vitamin E (200 international units [IU] for patients 5 to 8 years of age, 
400 IU for patients 9 to ≤17 years of age) and an EFA supplement containing approximately 
200 mg linoleic acid, 210 mg ALA, 110 mg EPA, and 80 mg DHA starting at Week -2. 
• Efficacy Phase (starting at Baseline, i.e., Day [D] 0 for 24 weeks±3 days): 
− Approximately 45 paediatric patients with HoFH will be treated with lomitapide given orally, added 
to their current, stable LLT (including LA, when applicable) established during the Run-in Period. 
− Assuming a withdrawal rate of approximately 33% by Week 24±3 days, this would result in 
30 evaluable patients at Week 24±3 days (with ≥8 patients in any individual age group). 
− After stabilisation of the patient on his/her current MTD of LLT (including LA, when applicable) 
during the 6-week Run-in Period, treatment with lomitapide will be started as an add-on therapy 
on D0 of the Efficacy Phase. 
− Dosing will be initiated at the recommended starting dose and escalated to the maximum dose 
as applicable to the age groups based upon safety and tolerability in addition to LDL-C values. 
− The first dose of study medication will be administered at the study site on D0. 
− During the 24-week Efficacy Phase, patients will be required to remain on the stable LLT regimen 
(including LA, when applicable) established during the 6-week Run-in Period. 
• Safety Phase (starting at Week 24±3 days for 80±1 weeks): 
− Patients will enter the 80-week Safety Phase after the Week 24±3 days assessments have been 
completed. Each patient will continue receiving the MTD of lomitapide he/she achieved during 
the Efficacy Phase (unless criteria is met for reducing or increasing the dose) for an additional 
80±1 weeks in the Safety Phase. 
− If after Week 24±3 days both the investigator and the sponsor consider a patient 5 to 15 years of 
age to be eligible for further escalation of the lomitapide dose beyond the maximum 
recommended dose by the respective age group, the lomitapide dose can be increased to an 
extent defined by the investigator after consultation with the sponsor based on individual safety, 
efficacy, and concomitant LLT criteria. If the patient tolerates this new dose for ≥4 weeks, then 
this will be considered the new MTD. 


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C O N F I D E N T I A L  
Study design (continued) 
− If after Week 24±3 days, a patient has crossed over into the next age category, the study drug 
can be escalated to the maximum dose applicable for the new age category. If the patient 
tolerates this new dose for ≥4 weeks, then this will be considered the new MTD. 
− During the 80-week Safety Phase, the lomitapide dose can be reduced from the MTD due to 
tolerability or safety issues, and the patient can be re-challenged after a minimum period of 
4 weeks following dose reduction with a higher dose of lomitapide once these issues resolve, but 
the dose during the Safety Phase cannot exceed the MTD established during the Efficacy Phase 
unless eligibility for exceptional dose escalation described above is met. 
− Adjustments to background LLT (including LA, when applicable) will be allowed at the discretion 
of the investigator. 
• Follow-up (starting at Week 104±1 week for 4 weeks): 
− At Week 104±1 week, eligible patients who complete the study per protocol and are <18 years 
of age may choose to enter the EAP. Patients ≥18 years of age may opt to transition to 
commercial product under the approved product label for adults. For both these patient groups, 
a follow-up phone call will be conducted at Week 108±1 week to monitor safety including AE and 
concomitant medication reporting. 
− Patients who opt not to participate in or are unsuitable for the EAP (<18 years of age), or patients 
≥18 years of age who opt not to transition to commercial product will discontinue lomitapide 
treatment at Week 104±1 week and enter a 4-week Follow-up period during which they will 
remain on concomitant LLT (including LA, when applicable). These patients will then attend in 
person for a Week 108±1 week visit. 
Study population 
Paediatric population of male and female patients aged 5 to ≤17 years with HoFH who are receiving 
optimal, stable LLT (including LA, when applicable), and who meet the definition of functional HoFH as 
defined in the Inclusion Criteria below. 
Inclusion criteria 
A patient will be eligible for study participation only, if all of the following criteria apply: 
1. Male and female patients aged 5 to ≤17 years with HoFH as defined by any of the following criteria 
recommended by the Consensus Panel on Familial Hypercholesterolaemia of the EAS (Cuchel, 
Bruckert et al. 2014): 
a. Genetic confirmation of 2 mutant alleles at the LDL receptor (LDLR), apo B, Proprotein 
convertase subtilisin/kexin type 9 (PCSK9), or LDL-receptor adapter protein 1 (LDLRAP1) gene 
locus OR 
b. An untreated LDL-C >500 mg/dL (13 mmol/L) or treated LDL-C ≥300 mg/dL (8 mmol/L) 
together with either 
− Cutaneous or tendon xanthoma before age 10 years or  
− Untreated LDL-C levels consistent with heterozygous FH in both parents. 
2. Baseline LDL-C on LLT (maximum concentration [Cmax] immediately prior to LA, if applicable) of 
either: 
a. >160 mg/dL (4.1 mmol/L, no documented cardiovascular disease [CVD]) or 
b. >130 mg/dL (3.4 mmol/L, established CVD defined as aortic valve disease and/or coronary 
atherosclerosis). 
3. Body weight ≥15 kg or BMI and height both >10th percentile according to World Health Organization 
(WHO) Growth Charts for Boys and Girls 5 to 19 Years of Age. 
4. Patient and/or his/her legal representative has/have been informed, has/have read and understood 
the patient information/informed consent form, and has/have given written informed 
assent/consent. 


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C O N F I D E N T I A L  
Inclusion criteria (continued) 
5. Patient and/or his/her legal representative must be able and willing to follow study procedures and 
instructions, particularly that: 
a. LLT (including LA, when applicable) must be stable for at least 6 weeks prior to Baseline (Run in 
Period) and remain stable through Week 24±3 days (end of Efficacy Phase). 
b. The patient must be compliant with both the low fat diet supplying <20% of energy (calories) from 
fat or <30 g fat, whichever is the lesser amount starting at the beginning of the Run in Period and 
the dietary supplement regimen starting at Week -2 of the Run in Period, both continuing until 
completion of the study (and during the EAP/administration of commercial product, when 
applicable). 
6. Postmenarchal female adolescents must be willing to use an effective form of birth control with 
failure rates <1% per year (e.g., implant, injectable, combined oral contraceptive, intrauterine 
contraceptive device, sexual abstinence, vasectomy or vasectomised partner) during participation 
in the study (and at least 4 weeks thereafter). Patients taking oestrogen-based oral contraceptives 
should be advised about possible loss of effectiveness due to diarrhoea and/or vomiting. Additional 
contraceptive measures should be used for 7 days after resolution of symptoms. 
7. Patient must be in stable physical and mental health at Screening. 
Exclusion criteria 
A patient will not be eligible to participate in this study, if any of the following criteria apply: 
1. Other forms of primary hyperlipoproteinaemia and secondary causes of hypercholesterolaemia 
(e.g., nephrotic syndrome, hypothyroidism). 
2. Contraindications for the use of lomitapide according to section 4.3 of the Summary of Product 
Characteristics (SPC; included in the Lojuxta® SPC in lieu of an Investigator’s Brochure [IB]), such 
as hypersensitivity to the active substance or to any of the excipients listed in Section 6.1 of the 
SPC, known significant or chronic inflammatory bowel disease or malabsorption. 
3. Moderate (Child-Pugh B) or severe hepatic impairment (Child-Pugh C), active liver disease and/or 
abnormal liver function tests at Screening (AST or ALT >1.5 x upper limit of normal (ULN) and/or 
total bilirubin >1.5 x ULN in the absence of Gilbert’s syndrome or AP >1.5 x ULN [based on 
appropriate age and gender normal values]).  
4. Serum CK >2 x ULN. 
5. Chronic renal insufficiency with glomerular filtration rate (GFR) <70 mL/min/1.73 m2 calculated using 
the Schwartz formula. 
6. Uncontrolled hypertension (defined as mean systolic and/or diastolic blood pressure ≥95% of normal 
for age and sex) despite medical therapy. 
7. New York Heart Association (NYHA) Class III or IV congestive heart failure. 
8. Precocious/delayed puberty or endocrine disorder affecting growth (e.g., hypothyroidism, premature 
adrenarche). 
9. History of drug abuse within the last 3 years or habitual alcohol consumption (defined as >1 ounce 
[28 g] of liquor or 4-ounce glass [113 g] of wine, or the equivalent, ≥3 times per week). 
10. Life expectancy predicted to be <5 years. 
11. History of a non-skin malignancy (with the exception of cervical cancer in situ) within 3 years prior 
to enrolment. 
12. Treatment with any Investigational Medicinal Product (IMP) within 6 months or 5 times the terminal 
half-life of the corresponding IMP, whichever is longer, before Screening (Visit 1). 
13. Patient is a dependent of the sponsor, of the investigational team or his/her immediate family. 
14. Pregnant or nursing women. 
 
 


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C O N F I D E N T I A L  
Treatment plan 
Investigational product 
Lomitapide is a first in class oral, selective inhibitor of microsomal transfer protein (MTP), an intracellular 
lipid-transfer protein that is found in the lumen of the endoplasmic reticulum and is responsible for 
binding and shuttling individual lipid molecules between membranes. MTP plays a key role in the 
assembly of apo B containing lipoproteins in the liver and intestines. Inhibition of MTP reduces 
lipoprotein secretion and circulating concentrations of lipoprotein-borne lipids including cholesterol, 
LDL-C and triglycerides. 
The European Commission (EC) granted authorisation for lomitapide under the trade name ‘Lojuxta®’ 
in July 2013. Lomitapide is indicated as an adjunct to a low-fat diet and other lipid-lowering medicinal 
products with or without LA in adult patients with HoFH. Genetic confirmation of HoFH should be 
obtained whenever possible. Other forms of primary hyperlipoproteinaemia and secondary causes of 
hypercholesterolaemia (e.g., nephrotic syndrome, hypothyroidism) must be excluded. 
Dosage and mode of administration 
• Run-in Period (starting at minimum at Week -6, i.e., 6 weeks prior to Baseline for a minimum of 
6 weeks):  
− Patients must be stabilised on current LLT (including LA, when applicable) and established on a 
diet supplying <20% of energy (calories) from fat or <30 g fat, whichever is the lesser amount. 
− Week -2: Start of daily supplementation with vitamin E (200 IU for patients 5 to 8 years of age, 
400 IU for patients 9 to ≤17 years of age) and an EFA supplement containing approximately 
200 mg linoleic acid, 210 mg ALA, 110 mg EPA, and 80 mg DHA. 
• Efficacy Phase (Baseline, D0 for 24 weeks±3 days): 
− During the 24-week Efficacy Phase, patients will be required to remain on the stable LLT 
(including LA, when applicable) regimen established during the 6-week Run-in Period. 
− Lomitapide capsules will be provided in 4 dose strengths: 2, 5, 10 and 20 mg. Each patient will 
take 1 to 3 capsule(s) once daily with a glass of water, without food, at least 2 hours after their 
evening meal to achieve the doses specified in the titration scheme. 
− Oral administration: Patients who are unable to swallow intact capsules may open the capsule 
and sprinkle the capsule content on 1 tablespoon of apple sauce or mashed banana. 
− Titration from 2 mg lomitapide (in 5 to 15 year old patients) or 5 mg lomitapide (in 16 to ≤17 year 
old patients) at D0 to the maximum recommended dose by age group based upon safety and 
tolerability in addition to LDL-C values according to the table below: 
Dose escalation by age group 
Age Group (years) 
Lomitapide Dose (mg) 
D0 
Week 4 
Week 8 
Week 12 
Week 16 
Maximum 
5 to 10 
2 
2 
5 
10 
20 
20 (10, in Child-Pugh A) 
11 to 15 
2 
5 
10 
20 
40 
40 (20, in Child-Pugh A) 
16 to ≤17 
5 
10 
20 
40 
60 
60 (40, in Child-Pugh A) 
− Lomitapide will not be escalated, if LDL-C is less than the target threshold: 
o 
LDL-C is <100 mg/dL (<2.5 mmol/L, in patients without CVD at Baseline) 
o 
LDL-C is <70 mg/dL (<1.8 mmol/L, in patients with CVD at Baseline) 
− Dose must be tolerated for ≥4 consecutive weeks before escalation to the next higher dose. 
− If a dose reduction is required, dosage will either be reduced to the previous tolerated dose or to 
an intermediate dose. Please note that only down-titrations to intermediate doses are allowed, 
dose escalations need to follow the guidance provided in the table above. After resolution of the 
cause for dose reduction, patients may be re-challenged after a minimum period of 4 weeks 
following dose reduction with prior doses in stepwise increments based on dose escalation 
guidelines, but may not exceed the MTD established during the Efficacy Phase until 
Week 24±3 days, after which further increase is only possible if patients have crossed into the 
next age category or if both the investigator and the sponsor consider a patient 5 to 15 years of 
age to be eligible for further escalation of the lomitapide dose beyond the maximum 
recommended dose by the respective age group based on individual safety, efficacy, and 
concomitant LLT criteria. 


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C O N F I D E N T I A L  
Dosage and mode of administration (continued) 
− If the investigator determines that a patient is not tolerating any particular dose (per specified 
criterion), the investigator may request a dose reduction or a hold on the current dose until the 
next scheduled visit. Once the patient has stabilised on the reduced dose, the dose can be 
increased back to the next step again, and the patient may progress through subsequent dose 
increases. If the patient does not tolerate the re-challenge dose, then the MTD is considered the 
reduced dose and will be the highest dose allowed for the remainder of the study. 
− The MTD is defined as the highest dose of lomitapide that does not result in tolerability or safety 
concerns. 
• Efficacy Phase (Baseline, D0 for 24 weeks±3 days): 
− Week 0 through Week 24±3 days establish the MTD; Week 20±3 days is the last visit that the 
lomitapide dose can be increased, except when there has been a down-titration at/or after 
Week 16±3 days. Re-challenging will depend on the assessment of safety and tolerability criteria 
and the LDL-C value relative to the LDL-C goal of <135 mg/dL (3.5 mmol/L), and is at the 
discretion of the investigator except for Hy’s law cases or comparable signs of liver toxicity, 
irrespective of origin, in which no re-challenge will be allowed. The study drug can be escalated 
as a re-challenge dose during the next scheduled visit after a minimum period of 4 weeks 
following dose reduction. In addition, a re-challenge with lomitapide will not be performed, if the 
LDL-C is below the target threshold while the patient was receiving the reduced dose.  
− The dose of lomitapide will be reduced with the addition of a concomitant Cytochrome P 450 
(CYP) 3A4 inhibitor during the Safety Phase; in patients with hepatic or renal impairment; and in 
patients who experience liver enzyme elevations above prespecified thresholds. 
• Safety Phase (Week 24±3 days for 80±1 weeks): 
− 
Adjustments to background LLT (including LA, when applicable) will be allowed at the discretion 
of the investigator. 
− 
If after Week 24±3 days both the investigator and the sponsor consider a patient 5 to 15 years 
of age to be eligible for further escalation of the lomitapide dose beyond the maximum 
recommended dose by the respective age group, the lomitapide dose can be increased to an 
extent defined by the investigator after consultation with the sponsor based on individual safety, 
efficacy, and concomitant LLT criteria. If the patient tolerates this new dose for ≥4 weeks, then 
this will be considered the new MTD. 
• 
Follow-up (Week 104±1 week for 4 weeks): 
− 
At Week 104±1 week, eligible patients who complete the study per protocol and are <18 years 
of age may choose to enter the EAP. Patients ≥18 years of age may opt to transition to 
commercial product under the approved product label for adults. For both these patient groups, 
a follow-up phone call will be conducted at Week 108±1 week to monitor safety including AE 
and concomitant medication reporting. 
− 
Patients who opt not to participate in or are unsuitable for the EAP (<18 years of age), or 
patients ≥18 years of age who opt not to transition to commercial product will discontinue 
lomitapide at Week 104±1 week and enter a 4-week Follow-up period during which they will 
remain on concomitant LLT (including LA, when applicable). These patients will then attend in 
person for a Week 108±1 week visit. 
Concomitant treatment/medication 
Permitted concomitant treatment/medication 
The following medication will be permitted during study and follow-up: 
• Lipid-lowering medicinal products including statins, fibrates, bile acid sequestrants, and 
PCSK9 inhibitors 
Please note: Patients who receive atorvastatin, should separate the dose of the medicinal products 
by 12 hours, e.g., by taking atorvastatin in the morning and lomitapide in the evening. Patients who 
receive bile acid sequestrants, should separate the dose of the medicinal products by 4 hours. 
Concomitant administration of >40 mg simvastatin is not permitted. 


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C O N F I D E N T I A L  
Concomitant treatment/medication (continued) 
• Oestrogen-based oral contraceptives 
Please note: Postmenarchal female adolescent patients taking oestrogen-based oral contraceptives 
should be advised that diarrhoea and/or vomiting may reduce hormone absorption. In case of 
protracted or severe diarrhoea and/or vomiting lasting more than 2 days, the investigator should 
advise according to national practice, which additional contraceptive measures (such as sexual 
abstinence, barrier methods) should be used for 7 days after resolution of symptoms. 
• Supportive therapy upon the investigators’ discretion 
The following medication will be permitted during the Safety Phase of the study: 
• If a weak CYP 3A4 inhibitor, e.g., aminoglutethimide, nafcillin, non-nucleoside reverse transcriptase 
inhibitors, phenobarbital, rifampicin, carbamazepine, pioglitazone, glucocorticoids, modafinil and 
phenytoin inhibitor is required during the Safety Phase, the dose of lomitapide should be reduced. 
Please note: Patients who receive weak CYP 3A4 inhibitors, should separate the dose of the 
medicinal products by 12 hours. 
If atorvastatin is given concomitantly, it should be administered in the morning to separate it from 
lomitapide dosing by 12 hours. In case it is not possible to administer atorvastatin and lomitapide 
12 hours apart, the lomitapide dose should be reduced by half. 
Non-permitted concomitant treatment/medication 
The following medication will not be permitted during the study: 
• Contraindications for the use of lomitapide according to Section 4.3 of the SPC (included in the 
Lojuxta® SPC in lieu of an IB), such as  
− Concomitant administration of >40 mg simvastatin. 
− Concomitant use of strong or moderate CYP 3A4 inhibitors, e.g., antifungal azoles such as 
itraconazole, fluconazole, ketoconazole, voriconazole, posaconazole; macrolide antibiotics such 
as erythromycin or clarithromycin; ketolide antibiotics such as telithromycin; HIV protease 
inhibitors; the calcium channel blockers diltiazem and verapamil, and the anti-arrhythmic 
dronedarone. 
The following medication will not be permitted during the Efficacy Phase of the study: 
Weak CYP 3A4 inhibitors, e.g., aminoglutethimide, nafcillin, non-nucleoside reverse transcriptase 
inhibitors, phenobarbital, rifampicin, carbamazepine, pioglitazone, glucocorticoids, modafinil and 
phenytoin. If a weak cytochrome CYP 3A4 inhibitor is required during the Safety Phase, the dose of 
lomitapide should be reduced and the doses of medicinal products should be separated by 12 hours. 
The use of the following food or substances should be avoided with lomitapide: 
• Alcohol: Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury. 
• Grapefruit juice: Grapefruit juice is a moderate inhibitor of CYP 3A4 and is expected to substantially 
increase exposure to lomitapide. 
• Peppermint oil or Seville oranges. 
• St. John’s Wort (i.e., Hypericum perforatum). 
Duration of patient participation in the study 
Each patient will participate for up to 120 weeks (about 2.5 years) in the study: 
• Screening Period: starting at Week -12, i.e., ≤12 weeks prior to Baseline for up to 6 weeks. 
• Stratified Enrolment and Start of Run-in Period: ≥6 and ≤12 weeks starting at minimum at Week -6, 
i.e., 6 weeks prior to Baseline for a minimum of 6 and a maximum of 12 weeks. 
• Efficacy Phase: 24 weeks±3 days. 
• Safety Phase: 80 weeks±1 week. 
• Follow-up Period: 4 weeks.  
Timelines of study 
• Estimated Date of First Patient Screened: Quarter 4 2020 
• Estimated Date of Last Patient Screened: Quarter 1 2022 
• Estimated Date of Last Patient Last Visit: Quarter 4 2023 
 
 


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C O N F I D E N T I A L  
Number of visits (study) 
There will be 23 visits from Screening through Follow-up: 
• Screening: n = 1. 
• Run-in Period: n = 2. 
• Efficacy Phase: n = 7, every 4 weeks±3 days. 
• Safety Phase including End of Treatment (EoT): 
− After Week 24±3 days through Week 52±3 days: n = 8, every 4 weeks±3 days. 
− After Week 56±3 days through Week 104±1 week: n = 4, every 12 weeks±1 week. 
• Follow-up: n = 1. 
Patient discontinuation criteria 
Patients and/or their parents/legal guardians will have the right to withdraw from the study at any time 
for any reason without prejudice to their future medical care. A patient may be withdrawn from the study 
at any time at either the investigator’s, sponsor’s, or Data Safety Monitoring Boards discretion.  
A patient must be discontinued from the study for any of the following reasons: 
• The patient matches the criteria referred to as “Hy’s law case” according to the European Association 
for the Study of the Liver (EASL) Clinical Practice Guidelines on Drug-induced Liver Injury (EASL 
2019) and the FDA Guidance for Industry Drug-Induced Liver Injury Premarketing Clinical Evaluation 
(FDA 2009). Any Hy's law case or comparable signs of liver toxicity, irrespective of origin, must lead 
to permanent treatment discontinuation of the individual patient (no re-challenge allowed). 
• The patient and/or his/her parent/legal guardian withdraws assent/consent. 
• Pregnancy as evidenced by a positive pregnancy test. 
• If a patient becomes pregnant during the study, during the follow up, or 30 days within the last 
application of study medication, the sponsor will have to be informed within 24 hours. The 
investigator will be asked to complete a pregnancy report provided by the sponsor. He/she will be 
asked to obtain data on the course of the pregnancy, including perinatal and neonatal outcome. 
• Any AE which, in the opinion of the investigator, places the patient at unacceptable risk, including 
intolerable AE(s) after attempted dose reduction. 
The investigator will be able to withdraw patients from the study for the following reasons: 
• Hepatobiliary criteria for discontinuation 
• Hepatobiliary AE Common Terminology Criteria for Adverse Events (CTCAE) Grade 4, regardless 
of relationship to study drug  
• Biochemical hepatobiliary guideline Level 4 Hepatotoxicity or Level 3 Hepatotoxicity that persists 
despite interruption of study drug 
• Histopathological diagnosis of Type 3 or Type 4 non-alcoholic steatohepatitis (NASH) 
• Patient is noncompliant with the study procedures or medications in the opinion of the investigator 
• Progression of a medical condition, which in the opinion of the investigator should preclude further 
participation of the patient in the study (e.g., excessive weight loss) 
• Administration of non-permitted concomitant medication(s), substances, foods, or supplements 
• Investigators’ decision that a change of therapy is in the patients’ best interest 
• Occurrence of an AE (including abnormal laboratory findings), which makes discontinuation 
desirable or necessary in the investigators’ and/or the patients’ and/or parents/legal guardians 
opinion 
If a patient discontinues the study or the follow-up prematurely due to an AE/serious adverse event 
(SAE), he/she will be followed up until the resolution or stabilisation of the AE/SAE. 
If a patient discontinues the study prematurely, the assessment of the EoT visit should be made.  
All data collected before premature discontinuation of the study will be used for analysis. Patients who 
drop out will not be replaced unless the assumptions for drop-out have been exceeded 


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C O N F I D E N T I A L  
Data Safety Monitoring Board 
Periodic safety analyses will be performed by an independent Data Safety Monitoring Board (DSMB). 
The DSMB will have an initial organizational meeting at which time the composition, activities, and 
responsibilities of the DSMB will be detailed in a Charter as agreed upon by the sponsor and the DSMB 
members. The DSMB will be comprised of at least 3 members who are not otherwise involved in the 
conduct of the study; at least 1 of whom will be a statistician. The DSMB will meet at least 3 times during 
the conduct of the study. The DSMB in consultation with the sponsor will have the authority to stop the 
study for any reason including, but not limited to, unacceptable safety risks. Interim safety analyses 
may be performed by the DSMB at their discretion, at any time, on an ‘as needed’ basis according to 
ongoing study results. If a patient discontinues treatment permanently due to a Hy’s law case or 
comparable signs of liver toxicity irrespective of origin, the DSMB will initiate an immediate recruitment 
stop as an urgent safety measure and will assess individual benefits and risks for the patients being 
treated with study medication regarding further therapy. 
Statistical methods 
The primary efficacy analysis will be conducted once all patients have completed (or withdrawn prior 
to) Visit 10 at Week 24±3 days (End of the Efficacy Phase). The primary efficacy analysis will include 
the key primary/secondary efficacy data, all safety data available up to the data cut-off date of the last 
patient reaching Week 24±3 days, and PK parameter analysis. The reporting of Week 24±3 days data 
will allow for an early submission of an application for regulatory approval of Lojuxta® in the paediatric 
indication. The final statistical analysis will be performed when all patients have completed the 
Follow-up Visit (Visit 23) at Week 108±7 days. Efficacy, safety, and exploratory data collected during 
the Safety Phase and follow-up will be included. 
Tests of hypotheses and significance levels 
The primary and secondary efficacy parameters collected during the Efficacy Phase of the study will be 
statistically tested using a 2-sided test at the 5% significance level. 
To address the efficacy objectives, the efficacy parameters will be tested sequentially in a step-wise 
fashion, thereby controlling the overall type I error. First, the primary testing for percent change from 
Baseline in LDL-C at Week 24±3 days will be performed. If this test is statistically significant with a 
2-sided α = 0.05 and is statistically significant in a positive direction, then the tests of the secondary 
hypotheses will be performed in the following specified order at Week 24±3 days: (1) Non-HDL-C, (2) 
TC, (3) VLDL-C, (4) apo B, (5) TG, (6) Lp(a). 
If at any step of the testing procedure a non-significant p-value is reached, further tests in the sequence 
will be performed and p-values will be reported as a measure of the strength of effect without declaring 
statistical significance. 
Analysis of other secondary endpoints collected during the Efficacy Phase and of endpoints collected 
during the Safety Phase will be analysed without adjustment for multiplicity. 
Sample size of the study 
The study will have 92% power to declare a treatment effect (α = 0.05, 2-sided) in the reduction of 
LDL-C at Week 24±3 days compared to Baseline. The study sample size is based on the assumption 
that the true percent reduction from Baseline in LDL-C at Week 24±3 days would be 25%, with a 
standard deviation of 40%. As a conservative assumption, this estimated 25% reduction represents 
approximately 60% (relatively) of the 41% reduction from Baseline to Week 26 (End of Efficacy Phase) 
seen in the adult study UP1002/733-005, Intent-to-treat (ITT) population. This is the same assumption 
used for the sample size in the adult study. Further, the standard deviation (SD) represents an 
approximate 1/3 increase from the corresponding 31% SD seen in the adult study. This increase in SD 
was used to account for potentially increased variability across the 3 age groups.  
A total of 30 evaluable patients will be required; to allow for up to a 33% drop-out rate during the Efficacy 
Phase (prior to Week 24±3 days), approximately 45 patients will be enrolled. 


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C O N F I D E N T I A L  
1.2 
Flow Chart of Study and Follow-up 
Examination 
Screening 
Run-in Period 
Efficacy Phase 
Safety Phase 
EoTB 
Follow-upC 
Enrolment 
Compliance 
Baseline 
Efficacy 
Safety/Tolerability 
Visit 
1A 
2A 
3 
4 
5 to 10 
11 to 18 
19 to 21 
22 
23 
Week(s) 
Up to -12 
Minimum -6 
-2 
0 
(Day 0) 
4/8/12/16/ 
20/24 
28/32/36/40/ 
44/48/52/56 
68/80/92 
104 
108 
Window Procedure 
 
 
-1 week 
 
±3 days 
±3 days 
±1 week 
±1 week 
- 
Window Procedure for LA 
 
 
 
 
±3 days 
±3 days 
±3 days 
 
 
Eligibility & Safety Assessments 
 
 
 
 
 
 
 
 
 
 
Informed consent & assent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
X 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Physical exam (incl. xanthomas, height, weight, BMI, BSA)D 
X 
 
 
X 
X 
X 
X 
X 
X 
 
Tanner stagingD 
X 
 
 
X 
XD 
Week 56 
 
X 
 
 
12-Lead safety ECG (read locally) 
 
 
 
X 
Week 24 
Week 56 
Week 80 
X 
 
 
Most recent standard of care echocardiography on fileE (if available) 
 
 
 
X 
Week 24 
Week 56 
 
X 
 
 
Vital signs and blood pressure 
X 
 
 
X 
X 
X 
X 
X 
X 
 
Pulmonary function testF 
 
 
 
X 
Week 24 
Week 56 
 
X 
 
 
Lipid accumulation in liver (NMR or echography)G,H 
 
 
 
X 
Week 24 
Week 56 
 
XH 
XH 
 
Genetic testingI 
X 
 
 
 
 
 
 
 
 
Dietary CounsellingJ 
 
X 
X 
X 
Week 4 
 
 
 
 
 
2-Day Diet record 
 
XK 
X 
X 
X 
X 
X 
X 
 
Efficacy Assessments 
 
 
 
 
 
 
 
 
 
 
CIMT (mandatory) and FMD (whenever possible) 
 
 
 
X 
 
Week 56 
 
X 
 
Laboratory Tests 
 
 
 
 
 
 
 
 
 
 
CBC 
X 
 
 
X 
 
Week 56 
 
X 
X 
 
Metabolic panel (albumin, BG, BUN, Ca, carbon dioxide, Cl, 
creatinine, CRP, K, Na, total protein), CKL 
X 
 
 
X 
X 
X 
X 
X 
X 
 
LFTs: ALT, AST, GGT, AP, total bilirubin, (in)direct bilirubin 
X 
 
 
X 
X 
X 
X 
X 
X 
 
Fasting lipid panel: LDL-C, TC, HDL-C, Non-HDL-C, VLDL-C, TG, 
Lp(a), apo A-I, apo BM 
X 
 
X 
XN 
X 
X 
X 
X 
X 


Amryt Pharmaceuticals DAC 
Study Protocol APH-19 
 
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C O N F I D E N T I A L  
Examination 
Screening 
Run-in Period 
Efficacy Phase 
Safety Phase 
EoTB 
Follow-upC 
Enrolment 
Compliance 
Baseline 
Efficacy 
Safety/Tolerability 
Visit 
1A 
2A 
3 
4 
5 to 10 
11 to 18 
19 to 21 
22 
23 
Week(s) 
Up to -12 
Minimum -6 
-2 
0 
(Day 0) 
4/8/12/16/ 
20/24 
28/32/36/40/ 
44/48/52/56 
68/80/92 
104 
108 
Window Procedure 
 
 
-1 week 
 
±3 days 
±3 days 
±1 week 
±1 week 
- 
Window Procedure for LA 
 
 
 
 
±3 days 
±3 days 
±3 days 
 
 
Laboratory Tests (Continued) 
 
 
 
 
 
 
 
 
 
 
Serum levels of EFA: Linoleic acid, ALA, EPA, DHA, AA, and 
eicosatrienoic acid 
X 
 
 
X 
Week 24 
Week 56 
Week 80 
X 
X 
 
Serum lipase 
 
 
 
X 
Week 24 
Week 56 
 
X 
 
 
Fat-soluble vitamin levelsO (retinol, 25-hydroxy-D, alpha tocopherol, 
ratio alpha tocopherol/total lipids, ratio uncarboxylated 
osteocalcin/total osteocalcin) 
X 
 
 
X 
Week 24 
Week 56 
Week 80 
X 
X 
 
TSH, FSH, LH, ACTH, serum cortisol (between 6:00 and 08:00 a.m.)P 
X 
 
 
X 
 
Week 56 
 
X 
 
 
In patients who are Tanner Stage ≥2: Serum testosterone (males), 
serum oestradiol (females) 
X 
 
 
X 
 
Week 56 
 
X 
 
 
PharmacokineticsQ 
 
 
 
X 
X 
 
 
 
 
 
Urinalysis (bilirubin, blood, colour, glucose, ketones, pH, protein, 
turbidity, white blood cells) 
X 
 
 
X 
 
Week 56 
 
X 
X 
 
Urine pregnancy testR 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Investigational Medicinal Product 
 
 
 
 
 
 
 
 
 
 
AdministrationS, compliance checkS & palatability assessmentT 
 
 
 
X 
X 
X 
X 
 
 
Dietary SupplementsU 
 
 
X 
X 
X 
X 
X 
 
 
Adverse Events & Concomitant Medication 
 
 
 
Incidence, severity, and relatedness of AEs/SAEs 
 
Continuously throughout the study until resolution or stabilisation of the AE/SAE 
 
Review of concomitant medication 
Continuously throughout the study with date of onset until Follow-up Visit 23 
Withdrawal from Study 
End of Treatment Visit 22 Assessments (Week 104±1 week) should be conducted. 
 
Abbreviations 
AA 
Arachidonic acid 
ACTH 
Adrenocorticotrophic hormone 
AE 
Adverse event 
ALA 
Alpha linoleic acid 
ALT 
Alanine aminotransferase 
AP 
Alkaline phosphatase  
apo A-I  
apolipoprotein A-I  
apo B  
apolipoprotein B  
AST 
Aspartate aminotransferase 
BG 
Blood glucose 
BMI 
Body mass index 
BSA 
Body surface area 
BUN 
Blood urea nitrogen  
Ca 
Calcium 
CBC 
Complete blood count 
CIMT 
Carotid intima-media thickness 
CK 
Creatinine kinase 
Cl 
Chloride 
CRP 
C-reactive protein 
DHA 
Docosahexaenoic acid 
ECG 
Electrocardiogram 
EFA 
Essential fatty acids 
EoT 
End of Treatment 
EPA 
Eicosapentaenoic acid 


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Abbreviations (continued) 
FMD 
Flow-mediated dilatation 
FSH 
Follicle stimulating hormone 
GGT 
Gamma-glutamyl transferase 
HDL-C 
High-density lipoprotein cholesterol 
K 
Potassium 
LA 
Lipoprotein apheresis 
LDL-C 
Low-density lipoprotein cholesterol 
LFTs 
Liver function tests 
LH 
Luteinising hormone 
Lp(a) 
Lipoprotein(a) 
Na 
Sodium 
NMR 
Nuclear Magnetic Resonance 
Non-HDL-C 
Non high-density lipoprotein 
cholesterol 
PK 
Pharmacokinetic 
SAE 
Serious adverse event 
TC 
Total cholesterol 
TG 
Triglycerides 
TSH 
Thyroid stimulating hormone 
ULN 
Upper limit of normal 
VLDL-C 
Very low-density lipoprotein cholesterol 
 
A. There is no minimum timeframe between Screening, Enrolment and Start of the Run-in Period, as long as all results of diagnostic tests determining eligibility are available. 
B. In the event of early termination, EoT assessments should be performed. If a patient discontinues the study or the follow-up prematurely due to an AE/SAE, he/she will be followed up until the resolution 
or stabilisation of the AE/SAE.  
C. Patients entering the Expanded Access Programme (<18 years of age)/transitioning to commercial product (≥18 years of age) will have a follow-up phone call at Week 108±1 week to monitor safety 
including AE and concomitant medication reporting. Patients who have opted not to participate in or are unsuitable for the Expanded Access Programme (<18 years of age)/opted not to transition to 
commercial product (≥18 years of age) will return for an in person safety Follow-up Visit. 
D. A full physical exam, including growth and sexual maturation assessments, a genitourinary exam per the Principal Investigator’s judgment, but not rectal exam, will be performed at Screening, Baseline, 
Week 12±3 days, Week 24±3 days, Week 56±3 days, Week 104±1 week and/or at EoT. At all other time points shown, an abbreviated physical exam including measurement of height, weight, BMI 
and BSA may be performed. Please note that weight will be measured using a consistent approach at Screening and at each visit after the Run-in Period (i.e., child/adolescent always weighed in same 
amount of clothing, either in underwear, hospital gowns or by subtracting the weight of clothes). Xanthomas will be evaluated at every physical exam. 
E. It is anticipated that echocardiography will be performed annually as standard of care in this patient population. For this study, echocardiography is not mandated but data/results will be included as 
part of the study safety data. Information in relation to the most recent echocardiography on file (if available) will be documented in the electronic Case Report Form at the following visits: Baseline, 
Week 24±3 days; Week 56±3 days, and Week 104±1 week. 
F. Spirometry with DL,CO (diffusion capacity of the lung for carbon monoxide) will be performed to include: forced vital capacity (FVC); forced expiratory volume during 1 s (FEV1); maximal mid-expiratory 
flow (FEF25-75) 
G. All patients will undergo NMR imaging unless it is contraindicated or not feasible (e.g., due to the need for sedation or general anaesthesia in very young or anxious patients). In this case, echography 
(i.e., ultrasound scan) will be used at the discretion of the investigator. 
H. Lipid accumulation in the liver will only be determined at Week 104 in patients entering the Expanded Access Programme (<18 years of age)/transitioning to commercial product (≥18 years of age). In 
patients who have opted not to participate in or are unsuitable for the Expanded Access Programme (<18 years of age)/opted not to transition to commercial product (≥18 years of age), lipid accumulation 
in the liver will be determined at Week 108. 
I. 
Genetic testing is strongly encouraged, but not mandatory and not required for determining eligibility. Patients who have not previously had genetic testing, will be asked, whether they would consent 
to genetic testing. A separate informed consent will be obtained for genetic testing. A blood sample will be collected according to central laboratory procedures specified in the ‘Laboratory Manual’ for 
genotyping at Screening (Visit 1). If it is not possible to do this at Screening (Visit 1) it can be done at a later visit. 
J. The Principal Investigator can request additional dietary counselling as clinically indicated. 
K. The 2-day diet record collected at this visit will be used to make any necessary adjustments to the patient’s diet before starting study medication. A dietary compliance check will be performed at 
Week -2. 
L. CK monitoring and evaluation 
1. If CK values are found to be elevated >5 x ULN on routine testing, the patient should be questioned about muscle symptoms. 
2. A study site physician should be alerted to the occurrence of unexplained muscle symptoms and any CK values >5 x ULN, and must take immediate action if CK is >10 x ULN. 
3. If CK values are >5 x ULN with muscle symptoms or >10 x ULN with or without muscle symptoms the following steps should be taken: 
a. Clarify the nature, duration and intensity of any muscle symptoms. 
b. Review possible predisposing factors, such as: unaccustomed exercise, heavy alcohol intake, viral illness (consider performing serology), concomitant medication and consider diagnosis of 
other conditions which cause myopathy. 
c. Physical examination for muscle tenderness, weakness and rash. 
d. Measure CK again within a few days. 


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e. Measure serum creatinine. 
f. 
Urine dipstick. 
g. Arrange to review the patient again in 4 to 10 days, or earlier if symptoms of myopathy appear or worsen, or if the urine becomes very dark. 
4. Discontinue study medication for CK values >10 x ULN with or without muscle symptoms. 
5. For CK values 5 to 10 x ULN: 
a. If asymptomatic, or if symptomatic but alternative explanation exists, symptoms should be followed and CK levels tested weekly until it is no longer a medical concern or symptoms worsen and 
meet criteria for any of the above. 
b. If symptomatic, and no alternative explanation exists, withhold therapy. 
6. Throughout the study, patients should be instructed to promptly report any unexplained muscle pain or weakness, particularly if associated with malaise or fever. If this should occur, CK should be 
measured as soon as possible. 
M. Draw 2 blood samples for the fasting lipid panel, of which 1 will be analysed in the local hospital laboratory and 1 will be sent to the central laboratory specified in the ‘Laboratory Manual’. 
N. Baseline values of lipid and lipoprotein parameters will be obtained as the maximum concentration (Cmax) immediately prior to LA, if applicable before start of study treatment. 
O. Bone health and bone age will be assessed by measurement of 25-hydroxyvitamin D and total uncarboxylated osteocalcin levels (as a reflection of vitamin K levels).  
P. The blood sample for testing of serum cortisol must be obtained in the early morning (6:00 to 8:00 am). 
Q. A single PK sample will be collected at Baseline, at Visit 5 (Week 4±3 days), Visit 7 (Week 12±3 days), Visit 8 (Week 16±3 days), and Visit 10 (Week 24±3 days). Two PK samples will be collected at 
least 1 hour apart at Visit 6 (Week 8±3 days) and Visit 9 (Week 20±3 days); these samples must be collected as separate blood draws (time between separate blood draws might be used for undertaking 
other procedures scheduled for the respective visit(s)). 
R. Urine pregnancy tests will be conducted in postmenarchal female adolescent patients using test strips at every scheduled visit from Visit 1 through Visit 23 and every 4 weeks after Visit 18 at 
Week 56±3 days through Week 104±1 week. 
S. Patients will be instructed to refrain from taking study medication within 8 hours prior to their study visits. They will be asked to bring all unused study medication with them to the clinical site at every 
visit (including Safety/Tolerability Visits) for a compliance check.  
T. At Visit 4, a 5-point facial hedonic scale will be used to record the child’s assessment of palatability of study medication on the first occasion that any patient who is unable to swallow the intact 
capsule(s) opens the capsule(s) and sprinkles the capsule content on a small amount (1 tablespoon) of either apple sauce or mashed banana (i.e., if a patient tries both food media, assessment will 
be made at the first instance of taking the study medication with apple sauce and the first instance of taking the study medication with mashed banana). The type of food media (apple sauce or mashed 
banana) will be captured. At Visit 5, the investigator will ask the parent(s)/legal guardian(s) to evaluate the children’s reaction to investigational product and dietary supplement administration. A 3-point 
scale that assesses the parent(s)/legal guardian(s) interpretation of the child’s reaction/facial expression will be used to determine whether they find lomitapide “pleasant”, “unpleasant” or are “not 
sure”. In addition, an assessment of ease of administration will be incorporated by asking the parent(s)/legal guardian(s) the following question: “Do you sometimes have problems in giving the 
medication to your child because he/she refuses to take it or throws it up immediately after taking it? (Yes/No).” The same question will be asked for the administration of dietary supplements. Timing 
of the reaction relative to dosing will be recorded to help distinguish between palatability of the investigational product and gastrointestinal events that are a result of the investigational products 
mechanism of action.  
U. Dietary supplements will be dispensed at the Week -2 (Run-in Compliance) Visit and will be administered daily throughout the Efficacy and Safety Phases of the study. Dietary supplements should be 
taken in the morning. 
 


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2 
INTRODUCTION 
2.1 
Background 
2.1.1 
Homozygous Familial Hypercholesterolaemia 
Homozygous familial hypercholesterolaemia (HoFH) is a rare and life-threatening inherited 
disorder of lipid metabolism with an estimated prevalence of 1 per 160,000 to 300,000 in the 
European population (Cuchel, Bruckert et al. 2014, Sjouke, Kusters et al. 2015).  
The Consensus Panel on Familial Hypercholesterolaemia (FH) of the European 
Atherosclerosis Society (EAS) recommends the following criteria for the diagnosis of HoFH 
(Cuchel, Bruckert et al. 2014): 
• Genetic confirmation of 2 mutant alleles at the LDL receptor (LDLR), apolipoprotein B 
(apo B), proprotein convertase subtilisin/kexin type 9 (PCSK9), or LDL-receptor adapter 
protein 1 (LDLRAP1) gene locus or  
• An untreated low-density lipoprotein cholesterol (LDL-C) >500 mg/dL (13 mmol/L) and 
treated LDL-C ≥300 mg/dL (8 mmol/L), respectively together with either  
− Cutaneous or tendon xanthomas before the age of 10 years or  
− Untreated LDL-C levels consistent with heterozygous FH in both parents.  
Significantly elevated LDL-C levels lead to premature, severe, and progressive atherosclerosis 
and development of early cardiovascular disease (CVD). The average age of death is 18 years 
if untreated and effective lipid-lowering therapy (LLT) greatly improves survival in HoFH 
(Thompson, Blom et al. 2018).  
Based on the evidence that treatment can delay the onset of CVD, primary prevention is 
suggested to start as early as possible and mainly consists of lowering LDL-C levels to 
<135 mg/dL (<3.5 mmol/L) in paediatric HoFH patients and to <100 mg/dL (<2.5 mmol/L) in 
adults. Secondary prevention comprises a decrease of LDL-C levels to <70 mg/dL 
(<1.8 mmol/L) in adults with CVD as recommended by the EAS (Cuchel, Bruckert et al. 2014).  
2.1.2 
Treatment Options and Medical Need 
Lipid-lowering Medicinal Products 
Therapeutic options include 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase 
inhibitors or statins, cholesterol absorption inhibitors such as ezetimibe, bile-acid sequestrants, 
and PCSK9 inhibitors. Statins and ezetimibe reduce LDL-C levels by about 25%. The PCSK9 
inhibitor evolocumab decreases LDL-C beyond other lipid-lowering drugs by about 20% with 
wide variability depending on receptor status, as patients with receptor-negative mutations and 
less LDLR expression and activity respond less or not at all to PCSK9 inhibitors (Santos 2018, 
Thedrez, Blom et al. 2018).  
Lipoprotein Apheresis 
A current standard of care in HoFH includes lipoprotein apheresis (LA), a physical method of 
purging the plasma of LDL-C. The International Consensus Paper on integrating LA and new 
lipid-lowering drugs considers LA plus high dose statins and ezetimibe as first-line treatment 
in HoFH, as it reduces LDL-C, CVD, and prolongs life (Stefanutti, Julius et al. 2017). 
However, the rebound phenomenon after LA described by Thompsen and Thompson in 2006 
(Thompsen and Thompson 2006) makes it necessary to perform LA sessions weekly, since 
lipid-lowering drugs induce constantly low LDL-C levels (Julius 2016). In fact, time-averaged 
LDL-lowering ranges between 26% for biweekly LA treatment to 47%, if LA is done twice a 


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week (Thompson 2015). However, even weekly LA combined with high-dose statins and 
ezetimibe failed to prevent progression of CVD in HoFH patients (Graesdal, Bogsrud et al. 
2012). Despite combination of conventional LLT and weekly or biweekly LA, about 50% of 
HoFH patients suffer progressive atherosclerosis and major cardiovascular events 
(Giammanco, Cefalu et al. 2019).  
This fact has recently been confirmed by a publication on multimodal LLT in paediatric patients 
with HoFH, which revealed that 24% of children who started chronic LA before the age of 18 
suffered progressive CVD despite weekly LA including 1 death due to coronary and 
cerebrovascular disease. Of 17 patients with genetically proven HoFH or compound 
heterozygous (c-het) FH in this study, 12 patients underwent LA weekly and 5 patients twice a 
week. The authors concluded that early and intensified LLT including LA is needed to improve 
the outcome (Klaus, Taylan et al. 2018).  
Luirink et al. recently published a systematic review on the evidence for the safety and efficacy 
of LA in paediatric patients with HoFH. They evaluated 76 studies with 209 children starting 
LA at a mean age of 9.3 years (range 2 to 18 years). Mean pre-apheresis LDL-C levels were 
604 mg/dL (15.6 mmol/L) and were reduced by a mean of 67.2% per session using 
semiselective LA, by 63.3% using nonselective LA, and by 71.6% using selective LA. While 
xanthomas regressed or disappeared in 83% of patients, surrogate parameters of CVD 
remained stable in most patients. Of 123 patients, 24 experienced a CVD event of whom 
10 had experienced a CVD before LA onset. Six patients died at follow-up. The authors 
concluded that the impact of LA on the onset of CVD remains unclear and that more robust 
data was needed, particularly as LA is an invasive therapy with an important impact on daily 
life for children (Luirink, Determeijer et al. 2019).  
Liver Transplantation 
Liver transplantation is the only curative treatment for HoFH (Alim, Tokat et al. 2016), as it 
replaces the missing LDLR and normalises LDL-C. According to data from the European Liver 
Transplant Registry, 21 liver transplants for HoFH were performed between 1988 and 2009.  
Paediatric liver transplantation in HoFH patients has been shown to sustainably normalise 
LDL-C levels within 1 month following transplantation. However, due to the high 
transplantation-related morbidity and mortality, the shortage of donors, and the need for 
life-long immunosuppressive therapy, the EAS does not recommend liver transplantation as 
first-line therapy for HoFH (Cuchel, Bruckert et al. 2014). HEART UK even considers to 
balance the early use of lomitapide and evolocumab beyond current licensed age restriction in 
severely affected children and young adults against the risks of liver transplantation (France, 
Rees et al. 2016).  
In a longitudinal cohort of 31 molecularly defined HoFH patients enrolled in the Spanish HoFH 
registry, which is a subset of the SAFEHEART (Spanish Familial Hypercholesterolaemia 
Cohort Study, NCT02693548) registry, at inclusion 4 patients had received a liver transplant 
at a mean age of 13 years. Of these 4 patients, 2 withdrew LLT after the liver transplant, while 
2 still required moderate doses of statins. During follow-up, a further patient underwent liver 
transplant at the age of 15 years. Overall, 2 patients died, 1 because of septicaemia due to 
immunosuppression and 1 during the postoperative period (Alonso, Diaz-Diaz et al. 2016). 
One of the 31 HoFH patients started lomitapide as an adjunct to LLT and achieved an 
additional LDL-C reduction of 52% without significant AEs.  
Beyond the high transplantation-related morbidity and mortality and the need for life-long 
immunosuppressive therapy, there is some evidence that CVD is the leading cause of 
long-term morbidity and mortality in liver transplant recipients due to a proatherogenic 
lipoprotein profile (Chhatrala, Siddiqui et al. 2015) and that LDL-C independently predicts CVD 
events (Siddiqui, Arshad et al. 2019). This may contribute to the need for LLT treatment after 
liver transplant. 


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2.2 
Investigational Product 
Lomitapide is a first in class oral, selective inhibitor of microsomal transfer protein (MTP), an 
intracellular lipid-transfer protein that is found in the lumen of the endoplasmic reticulum and 
is responsible for binding and shuttling individual lipid molecules between membranes. MTP 
plays a key role in the assembly of apo B containing lipoproteins in the liver and intestines. 
Inhibition of MTP reduces lipoprotein secretion and circulating concentrations of 
lipoprotein-borne lipids including cholesterol and triglycerides. 
The European Commission (EC) granted authorisation for lomitapide under the trade name 
‘Lojuxta®’ in July 2013. Lomitapide is a “lipid modifying agent” according to the Anatomical 
Therapeutic Chemical (ATC) Classification System (ATC code C10AX12). It is indicated as an 
adjunct to a low-fat diet and other lipid-lowering medicinal products with or without LA in adult 
patients with HoFH. Genetic confirmation of HoFH should be obtained whenever possible. 
Other forms of primary hyperlipoproteinaemia and secondary causes of hypercholesterolaemia 
(e.g., nephrotic syndrome, hypothyroidism) must be excluded. 
Please refer to Section 6.1 Description of the Investigational Product for details regarding 
formulation, packaging, and labelling as well as storage of lomitapide. 
2.3 
Summary of Non-clinical Studies with Lomitapide 
Please refer to Section 2.3 of the European Public Assessment Report (EPAR) of the 
European Medicines Agency for Lojuxta® dated 30 May 2013 for a summary of non-clinical 
studies with lomitapide. 
2.4 
Summary of Clinical Studies with Lomitapide 
According to the EPAR of the European Medicines Agency for Lojuxta® dated 30 May 2013 
the clinical development programme for Lojuxta® included 15 phase I studies, 7 phase II 
studies and 3 phase III studies. In total, 1,145 healthy subjects and patients were treated, 
including 943 who received lomitapide, either as monotherapy or co-administered with other 
LLT. The majority of subjects (959 out of 1,145) were enrolled in placebo and/or 
active-controlled studies. The clinical studies were performed in accordance with Good Clinical 
Practice (GCP). Clinical studies conducted outside the community were carried out in 
accordance with the ethical standards of Directive 2001/20/EC. In support of the clinical studies 
in man, the marketing authorisation application also included 12 in vitro studies using human 
samples or human cell material. 
Please refer to Section 2.4 of the EPAR of the European Medicines Agency for Lojuxta® dated 
30 May 2013 for further details.  
2.4.1 
Clinical Pharmacology and Pharmacokinetics 
Please refer to Section 2.4 of the EPAR for Lojuxta® dated 30 May 2013 for a summary of 
clinical aspects of pharmacokinetics and pharmacodynamics of lomitapide. 
2.4.2 
Clinical Efficacy and Safety 
Global Phase III Study and Long-Term Extension Study 
The efficacy and safety of lomitapide as an adjunct to a low-fat diet and LLT with or without LA 
was investigated in a single-arm, multi-national phase III study (UP1002/AEGR-733-005, 
NCT00730236) in adult patients with HoFH. The study had a 26-week Efficacy Phase during 
which all background LLT including LA remained fixed and lomitapide was titrated to the 
maximum tolerated dose (MTD, range 5 to 60 mg, mean dose 40 mg) and a 52-week Safety 
Phase during which lomitapide dose was continued at the MTD and background LLT could be 
altered with physician discretion.  


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Overall, 23 of 29 patients (16 male, 13 female, mean age of 30.7 years) completed the Efficacy 
Phase of the study. By Week 26, mean LDL-C decreased significantly by 40% in the 
Intent-to-treat (ITT) and by 50% in the completer population. Reductions in LDL-C were 
maintained during the Safety Phase with a mean change from Baseline to Week 56 of 44.0% 
(p<0.001) and to Week 78 of 38.4% (p<0.001). Concurrent LLT was reduced in 
15 of 23 patients (65%); 6 of 13 patients (46%) who were receiving LA either permanently 
stopped LA (n=3) or permanently increased the interval in between LA treatments (n=3). LDL-C 
values of <100 mg/dL (<2.5 mmol/L) were observed at least once in 55%, LDL-C values of 
<70 mg/dL (<1.8 mmol/L) in 31% of patients (Cuchel, Meagher et al. 2013). 
Long-term data of the extension study (AEGR-733-012, NCT00943306) that enrolled 19 of the 
23 patients who completed the pivotal study with a mean age of 30.4 years (10 male, 9 female) 
confirmed efficacy and safety of lomitapide. The median treatment duration with lomitapide 
across both studies was 5.1 years (range, 2.1 to 5.7 years).  
From Baseline through Week 246, a total of 14 (74%) patients achieved LDL-C <100 mg/dL 
(<2.5 mmol/L), and 11 (58%) patients achieved LDL-C <70 mg/dL (<1.8 mmol/L) on at least 
1 occasion. One additional patient discontinued LA in the long-term extension study. The most 
common adverse events (AEs) reported were gastrointestinal, including diarrhoea, nausea, 
dyspepsia, and vomiting. For most drug-related AEs, the incidence was lower in the extension 
study compared with the pivotal study (42.1% versus 84.2%) (Blom, Averna et al. 2017) 
LOWER Registry 
The Lomitapide Observational Worldwide Evaluation Registry (LOWER, NCT02135705, 
European PAS register number ENCEPP/SDPP/5326) is an international, multi-centre, 
observational registry to prospectively assess long-term safety and efficacy of lomitapide. The 
LOWER Registry is an EU Risk Management Plan (RMP) Category 2 study following a specific 
obligation on the exceptional marketing authorisation of lomitapide dated 31 July 2013.  
As of 01 March 2018, a total of 178 patients with a mean age of 52.1 years have been enrolled. 
The duration of lomitapide exposure ranged from 0.3 to 60.1 months with a median exposure 
duration of 21.7 months and doses ranging from 2.5 mg to 40 mg daily. 
At any time after initiating lomitapide treatment, 104 (59.4%) patients experienced a reduction 
in LDL-C by at least 50%, 117 (66.9%) patients experienced an LDL-C value <100 mg/dL 
(<2.5 mmol/L) and 73 (41.7%) patients experienced an LDL-C value of <70 mg/dL 
(<1.8 mmol/L). Mean percent changes in LDL-C and other serum lipids and lipoproteins were 
consistent with mean percent changes reported in the phase III pivotal study (Cuchel, Meagher 
et al. 2013).  
Overall, 133 (76.0%) patients experienced at least 1 AE, with diarrhoea (n=57, 32.6%) and 
nausea (n=20, 11.4%) being the most commonly reported, consistent with the prescribing 
information and the phase III clinical study (Cuchel, Meagher et al. 2013). Events that were 
considered treatment-related by the investigator were reported in approximately half of the 
patients (n=97, 55.4%), the majority of which were mild (n=48, 27.4%) or moderate (n=38, 
21.7%) with the remaining considered severe (n=10, 5.7%). The most common 
treatment-related AEs were diarrhoea (n=49, 28.0%) and nausea (n=15, 8.6%) as expected. 
Serious AEs were reported in 34 (19.4%) patients, and the SAEs experienced by >2% of 
patients were acute myocardial infarction (n=4, 2.3%), angina pectoris (n=5, 2.9%), cardiac 
failure congestive (n=3, 1.7%), coronary artery disease (n=7, 4.0%), and pneumonia (n=4, 
2.3%). Overall, no new safety signals have been identified.  
In about a quarter of enrolled patients (n=41, 23.4%), permanent discontinuation of lomitapide 
was due to AEs, mostly due to GI events (n=25, 14.3%), specifically diarrhoea (n=15, 8.6%), 
which was slightly higher than the 10% (n=3/29) of patients discontinuing due to GI AEs in the 
phase III study and increases in hepatic enzymes/liver function tests (LFTs) (n=12, 6.9%).  


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Given the high risk associated with the extreme LDL-C levels experienced by patients with 
HoFH, the results of this analysis of data collected in the LOWER registry support the 
favourable benefit-risk profile of lomitapide when used as directed. 
Cohort Analyses and Case Studies 
There are several publications that report data in case studies and cohort analyses following 
treatment with lomitapide in the real world that show superior efficacy and similar or improved 
tolerability compared with the phase III study data that led to the exceptional approval by the 
European Medicines Agency (EMA).  
Van Lennep et al. reports data on 4 HoFH cases: Each patient was commenced on lomitapide 
according to the prescribed protocol and subjected to routine follow-up. All 4 patients 
experienced clinically meaningful reductions in LDL-C levels of 35 to 73% (Roeters van 
Lennep, Averna et al. 2015).  
Stefanutti et al. reports data on 7 patients with genetically determined HoFH who were treated 
with lomitapide in the normal course of their therapy. All patients received LA either weekly or 
biweekly. Lomitapide was administered according to the approved EU prescribing information. 
The LDL-C reductions ranged from 5% (early in treatment) to 83% with a mean reduction of 
40% (Stefanutti, Morozzi et al. 2016).  
The publication by deGoma reports in detail the case history of a patient receiving treatment 
with lomitapide in the US. The patient had a pre-apheresis LDL-C ranging from 146 to 
188 mg/dL prior to treatment with lomitapide. After 12 weeks and on a dose of 5 mg, his LDL-C 
reduced to 64 mg/dL and he stopped apheresis. The LDL-C increased slightly to 107 mg/dL 
and the lomitapide dose was increased to 10 mg. He was also able to stop treatment with 
colesevelam, ezetimibe and fenofibric acid (deGoma 2014).  
Comparably, 1 of 2 HoFH patients reported by Real et al. experienced a dramatic reduction of 
LDL-C values at lomitapide doses of 5 to 10 mg/day. The first patient maintained LDL-C levels 
<70 mg/dL (<1.8 mmol/L) and stopped LA. His brother received a dose of 20 mg/day and 
showed interapheresis LDL-C levels of <100 mg/dL(<2.5 mmol/L) (Real, Arbona et al. 2018).  
Kolovou et al. reviewed their experience in treating 4 HoFH patients with lomitapide as an 
adjunct to LLT including LA for 14 months. Two patients showed LDL-C reductions of 54% and 
65%, respectively (called hyper-responders), while LDL-C levels in 2 patients decreased by 
35% and 11% (called hypo-responders). Dr Kolovou reported the variability in response may 
be due to MTP gene expression (Kolovou, Kolovou et al. 2016).  
The biggest dataset in real world use comes from Italy and includes 15 HoFH patients treated 
for up to 3 years with mean Baseline LDL-C levels of 426.0±204.0 mg/dL despite receiving 
treatment with statins, ezetimibe and LA (in 10 of the 15 patients). With a rather low mean dose 
of 19±13.3 mg lomitapide/day as an adjunct to LLT, LDL-C was lowered by a mean of 
76.2%±16.7%. Overall, 8 of 10 patients on LA were able to discontinue LA completely, while 
the 2 remaining patients decreased the frequency of LA. After stopping LA and adjusting other 
LLT, the mean LDL-C reduction at the last timepoint was 68.2±24.8% versus Baseline. At their 
last visit, 60% of patients achieved LDL-C <100 mg/dL (<2.5 mmol/L), and 46.6% of patients 
achieved LDL-C <70 mg/dL (<1.8 mmol/L) (D'Erasmo, Cefalu et al. 2017). 
Evidence on Efficacy and Safety in Paediatric Patients 
Chacra et al. have published a case report describing a 49-month compassionate use of 
lomitapide in a 7.6-year old female child with HoFH. The patient presented with LDL-C values 
of 1,009 mg/dL at the age of 29 months. After 10 months of low-saturated fat/cholesterol diet, 
atorvastatin 5 mg/day and ezetimibe 10 mg/day were introduced. Atorvastatin was titrated to 
40 mg/day and the mean LDL-C reduction under this regimen was 44%. Due to the LDLR null 
mutations in this patient, the administration of PCSK9 inhibitors was not considered. 
Lomitapide was started at 5 mg/day at the age of 92 months when LDL-C was 428 mg/dL, as 


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the left ventricle-aortic peak gradient of the patient had increased and valve regurgitation was 
progressive. Lomitapide was gradually titrated up to the MTD of 20 mg/day and achieved a 
37% reduction in LDL-C on top of atorvastatin and ezetimibe. Lomitapide was safe and well 
tolerated and the patient presented with adequate growth and sexual maturation. However, 
despite the efficiency of lomitapide in reducing LDL-C levels, CVD was progressive, possibly 
due to the already established damage of the aortic valve at start of treatment. The authors 
concluded that further studies with lomitapide in this very high-risk population are urgently 
warranted to establish long-term safety and efficiency and to investigate whether lomitapide 
can retard the onset and progression of CVD (Chacra, Ferrari et al. 2019). 
Ben-Omran et al. have recently reported a case series of 11 paediatric HoFH patients at a 
mean age of 11.6±1.1 years who have received treatment with lomitapide on a named-patient 
basis, as their cases have been deemed ‘urgent to treat’ due to early CVD, lack of sufficient 
response to standard of care (SOC) treatment and inability to wait for study APH-19 to start. 
These patients have received lomitapide at a mean dose of 24.5±4.3 mg/day for 
20.0±2.9 months as an adjunct to their LLT (including LA in 5 patients). Mean Baseline LDL-C 
of 419±74.6 mg/dL was reduced by 58.4±6.8% to a nadir of 176.7±46.3 mg/dL. Six patients 
achieved EAS target levels of <135 mg/dL (3.5 mmol/L), 3 of whom reduced their LA 
frequency, and 2 stopped LA completely. Adverse events were consistent with those seen in 
the phase III study in adults and in real world use. The majority of AEs consisted of 
gastrointestinal (GI) complaints, presented early in the treatment course, and resolved with 
minimal active management. Transient increases in LFTs resolved either with brief dose 
reductions or without intervention. Overall, efficacy and safety were comparable to the results 
reported in adult HoFH patients. Consistent with real-world data from adult patients, efficacy 
was higher at a lower mean dose. The authors compared their approach of dose titration based 
on LDL-C levels as opposed to MTD with the results of D’Erasmo et al. who reported a mean 
LDL-C decrease of 76.2%±16.7% at a rather low mean dose of 19±13.3 mg lomitapide/day 
(D'Erasmo, Cefalu et al. 2017). According to Ben-Omran et al. an important and positive 
outcome for 5 children in this case series was the ability to reduce or stop LA, which was a 
benefit given increasing time commitments as age advanced (Ben-Omran, Masana et al. 
2019).  
In summary, global pivotal phase III study data and real world evidence for lomitapide as an 
adjunct to a low-fat diet and LLT with or without LA in both adult and paediatric patients confirm 
the feasibility to reach EAS targets of LDL-C levels <135 mg/dL (3.5 mmol/L) in children and 
<100 mg/dL (<2.5 mmol/L) in primary or <70 mg/dL (<1.8 mmol/L) in secondary prevention in 
adults (see Figure 1). 


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Figure 1 
Percentage of Patients Achieving EAS Treatment Goals with Lomitapide 
across Pivotal Studies and in Real-world Evidence 
 
Figure based on Underberg J, J Clin Lipidol 2018;12(2):561-562 (Underberg, Harada-Shiba et al. 2018) showing 
percentage of patients achieving EAS treatment goals (LDL-C <135 mg/dL [3.5 mmol/L] in paediatric patients and 
LDL-C <100 mg/dL [<2.5 mmol/L] in primary and <70 mg/dL [<1.8 mmol/L] in secondary prevention in adults) at 
≥1 time point after initiating treatment with lomitapide 
IT = Italy; JP = Japan; LOWER = Lomitapide Observational Worldwide Evaluation Registry; LDL-C = Low-density 
lipoprotein C; PAED = Paediatrics; RWE = Real world evidence 
1. Underberg J, J Clin Lipidol 2018;12(2):561-562 (Underberg, Harada-Shiba et al. 2018) 
2. Cuchel M, Atherosclerosis Suppl 2014;15(2):33-45 (Cuchel, Bruckert et al. 2014) 
3. Blom DJ, Circulation 2017;136(3):332-335 (Blom, Averna et al. 2017) 
4. Harada-Shiba M, J Atheroscler Thromb 2017;24(4):402-411 (Harada-Shiba, Ikewaki et al. 2017) 
5. Underberg J, Circulation 2016;134(suppl1): A12117-A12117 (Underberg, Cannon et al. 2016) 
6. Underberg J, J Clin Lipidol 2018;12(2):561-562 (Underberg, Cannon et al. 2018) 
7. D’Erasmo L, Adv Ther 2017;34(5):1200-1210 (D'Erasmo, Cefalu et al. 2017) 
8. Ben-Omran T, Adv Ther 2019; https://doi.org/10.1007/s12325-019-00985-8 (Ben-Omran, Masana et al. 2019) 
2.5 
Rationale for Dose Selection 
Paediatric starting doses, dose escalation regimens, and appropriate maximum doses for 
different age ranges were determined using allometric scaling and physiologically-based 
pharmacokinetic modeling (PBPK) as well as simulation approaches (see Section 18.1 Source 
Documents, Lomitapide Pediatric Trial Dose Selections Using Two Approaches: Allometric 
Scaling and Physiologically-based Pharmacokinetic (PBPK) Modeling; Final Report, 
26 June 2013). 
The calculation is based on the approved dosing regimen for adults. It takes into account the 
assumptions that disease progression, response to intervention and concentration-response 
(C-R) are similar in children and adults. These assumptions are considered reasonable due to 
the genetic cause of HoFH and the mechanism of action of lomitapide.  
Figure 2 displays the proposed paediatric dose (mg) by age group and method: The 
age-dependent doses calculated by allometric scaling were combined to calculate a mean 
dose for each age group specified in the PBPK modelling. The error bars represent the 
standard deviation of the calculated mean dose. As can be seen, the proposed mean paediatric 
doses were overall 0.5 to 1 mg higher using the allometric scaling approach compared to the 
PBPK approach except in the oldest age group (see Figure 2).  


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Figure 2 
Proposed 
Mean 
Lomitapide 
Paediatric 
Starting 
Dose 
Based 
on 
Physiologically-based Pharmacokinetic Modelling and Allometric Scaling 
 
Table 1 shows the recommended first-in-paediatric doses by age group, for which both the 
calculated doses based on PBPK modelling and allometric scaling and the availability of 
minimum dosage form strength (2 mg) and next higher dosage strength (5 mg) have been 
taken into consideration.  
Table 1 Suggested 
Lomitapide 
Starting 
Doses 
by 
Age 
Group 
Based 
on 
Physiologically-based Pharmacokinetic Modelling and Allometric Scaling 
Age Group (years) 
Suggested Starting Dose (mg) 
PBPK Modelling 
Allometric Scaling 
Recommendation 
5 to 10 
1.0 to 1.5 
1.9 to 2.5 
2.0 
11 to 15 
2.0 to 3.0 
3.3 to 4.2 
2.0 
16 to ≤17 
5.0 
4.0 to 4.5 
5.0 
PBPK = Physiologically-based Pharmacokinetic 
Please refer to Section 7.2 Treatment Schedule for corresponding starting doses, dose 
escalation regimens, and maximum doses of lomitapide by age group.  
2.6 
Known and Potential Benefits and Risks 
2.6.1 
Unmet Medical Need 
Due to their cumulative LDL-C burden, paediatric HoFH patients suffer early-onset 
atherosclerotic cardiovascular disease (ASCVD) at the age of 12.5 years and die at the age of 
18 years, if the disease is undetected or untreated (Nordestgaard, Chapman et al. 2013).  
Lipid-lowering medicinal products reduce LDL-C levels by up to 45% with wide variability 
depending on receptor status (Santos 2018, Thedrez, Blom et al. 2018). Time-averaged 
LDL-C-lowering of LA ranges between 26% for biweekly LA treatment to 47%, if LA is done 
twice a week (Thompson 2015). However, despite standard of care LLT including LA, 


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paediatric patients with HoFH rarely achieve EAS LDL-C target levels and suffer early 
progressive CVD (Klaus, Taylan et al. 2018, Luirink, Determeijer et al. 2019).  
Since the EAS does not recommend liver transplantation as first-line therapy for HoFH (Cuchel, 
Bruckert et al. 2014) and HEART UK considers to balance the early use of lomitapide in 
severely affected children against the risks of liver transplantation (France, Rees et al. 2016), 
lomitapide is a “last-resort” treatment for paediatric patients, who respond less or not at all to 
PCSK9 inhibitors due to receptor-negative mutations with less LDLR expression and activity 
(Thedrez, Blom et al. 2018) and for those who either do not have access to LA or suffer 
progressive CVD despite receiving LLT including LA (Ben-Omran, Masana et al. 2019). 
Please refer to Section 2.1.2 Treatment Options and Medical Need for further details.  
2.6.2 
Known and Potential Benefits 
Lomitapide is a first in class oral, selective MTP inhibitor that functions independently of the 
LDLR. It is administered orally and is subject to a high first-pass effect following ingestion 
resulting in a low systemic bioavailability of approximately 7% (see Section 2.3.3 of the EPAR 
for Lojuxta® dated 30 May 2013). The pharmacodynamic activity of lomitapide is not dependent 
on systemic exposure but is directly related to local concentrations achieved in the small 
intestine and liver.  
The high first-pass effect observed to limit systemic availability of lomitapide is likely to be 
dominated by significant metabolism by CYP 3A4 inhibitors. The parent molecule is cleaved 
into 2 primary metabolites (M1 and M3) that lack activity against MTP. Systemic concentrations 
of lomitapide are low following oral administration and there is a large apparent volume of 
distribution despite a high level of protein binding. This suggests loose binding to low-affinity 
sites, mitigating the likelihood of interactions by displacement of other protein-bound drugs. 
Excretion of unchanged lomitapide is minimal by any route, and the majority of the drug 
appears as water soluble (polar) metabolites in the bile.  
Therefore, strong or moderate CYP 3A4 inhibitors are not permitted during the study as 
described in Section 7.6.3 Non-Permitted Concomitant Medication, Food or Substances. Weak 
CYP 3A4 inhibitors are only permitted during the Safety Phase of the study and doses of 
lomitapide or concomitant medication should either be administered 12 hours apart or modified 
(see Section 7.3.3 Dose Modification for Concomitant Medication).  
The central role of LDL-C in the pathophysiology of ASCVD is well established. Every 1 mmol/L 
(38.6 mg/dL) reduction in LDL-C levels is associated with a corresponding 22% decrease in 
cardiovascular mortality and 12% reduction in total mortality over 5 years (Baigent, Blackwell 
et al. 2010).  
Published evidence shows lomitapide to reduce LDL-C consistently and significantly by a 
mean 40% to 50% across the whole spectrum of molecularly-defined adult HoFH patients 
irrespective of LA and independent of LDLR function. There was no loss of efficacy in patients 
with genotypes predicting the most severely compromised LDLR function, who tend to be 
non-responsive to other therapies like statins and PCSK9 inhibitors (Hegele, Shah et al. 2018). 
Global pivotal phase III study data and real world evidence for lomitapide as an adjunct to a 
low-fat diet and LLT with or without LA confirmed the feasibility to reach EAS targets of LDL-C 
levels <135 mg/dL (3.5 mmol/L) in 55% of paediatric and <100 mg/dL (<2.5 mmol/L) in 
51 to 74% or <70 mg/dL (<1.8 mmol/L) in 28 to 58% of adult HoFH patients (see Figure 1).  
This magnitude of LDL-C reduction is unprecedented in clinical experience within the HoFH 
patient population, in whom LDL-C levels have largely proven refractory to oral therapy, 
necessitating use of regular LA to effect further reductions. For the first time, it is now feasible 
to reach target LDL-C goals and maintain these levels during chronic treatment. 
According to a modelling analysis in 149 HoFH patients LDL-C lowering of lomitapide could 
increase median life expectancy by 11.6 years and delay time to the first major cardiovascular 


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event (MACE) by 5.7 years (Leipold, Raal et al. 2017). Correspondingly, Blom et al. have 
shown that the annualised MACE rates in HoFH patients treated with mipomersen, lomitapide 
and evolocumab were 11.4%, 2.0%, and 2.1% versus 26.1% in the pre-mipomersen exposure 
cohort of the mipomersen study (Blom, Cuchel et al. 2018). Of note, HoFH in patients in the 
lomitapide cohort was more severe as evidenced by a higher mean Baseline LDL-C value of 
336 mg/dL and a Baseline CVD rate of 93%. 
2.6.3 
Known and Potential Risks 
Inhibition of MTP is expected to cause accumulation of triglycerides in intestinal mucosa and 
hepatocytes, and malabsorption of fat and fat-soluble vitamins from the diet. Major histological 
findings from non-clinical toxicological experiments showed increased incidences of lipid 
vacuolation in small intestinal mucosal epithelium and hepatocytes.  
However, increased incidences of liver and small intestine tumours in mice were not noted in 
clinical studies and may not be expected to occur in clinical use due to the lack of genotoxicity, 
immunotoxicity, or other cellular injury associated with high levels of lomitapide exposure. In 
addition, unphysiological factors in the non-clinical experiments such as vitamin E depletion 
and severe hypocholesterolaemia will be prevented by administering dietary supplements (see 
Section 6.3 Dietary Supplements) and by closely monitoring LDL-C levels (see Section 1.2 
Flow Chart of Study and Follow-up).  
In the pivotal phase III study, 10 of 29 patients experienced elevations of ALT and/or AST 
>3 x ULN once or more during the study. Four of these patients exhibited ALT increases 
>5 x ULN. No patient discontinued treatment permanently due to LFT elevations and all 
elevations were managed either by dose reduction or temporary interruption of lomitapide as 
per protocol. Of note, 3 of 4 patients with LFT elevations >5 x ULN reported consuming 
quantities of alcohol higher than those allowed per protocol. No patient experienced elevations 
in bilirubin or AP levels (Cuchel, Meagher et al. 2013).  
During the extension study, 4 of 19 (21.1%) patients experienced a ≥5 x ULN increase in ALT 
or AST. Increases ≥5 x ULN were typically associated with concomitant use of CYP 3A4 
inhibitors or excess alcohol use. These events were successfully managed by discontinuing 
offending medication, lomitapide dose reductions or suspension, and reintroduction of 
lomitapide after normalisation of transaminases (Blom, Averna et al. 2017). 
Management of elevated hepatic aminotransferases in this study is carefully specified by an 
algorithm in Section 7.3.2 Dose Modification, Interruption or Discontinuation for Adverse 
Events. In addition, an independent DSMB will provide oversight of patient safety (see 
Section 4.3 Data Safety Monitoring Board).  
Due to the potential for lomitapide to cause elevations in ALT/AST levels, it should be used in 
caution in patients who consume alcohol. Further, caution should be exercised when 
lomitapide is co-administered with agents known to be hepatotoxic (see Section 7.6.3 
Non-Permitted Concomitant Medication, Food or Substances) and is contraindicated in 
patients with moderate to severe hepatic impairment and those with active liver disease, 
including patients with unexplained persistent abnormal liver function tests (see Section 5.2 
Exclusion Criteria). 
In the pivotal phase III study, hepatic fat was measured non-invasively using NMR. Mean 
hepatic fat content of 20 evaluable patients was 1.0% at Baseline, 8.6% at Week 26, 5.8% at 
Week 56 and 8.3% at Week 78 (Cuchel, Meagher et al. 2013). In the extension study, 
18 patients had ≥1 assessment of hepatic fat by NMR after Baseline. Median hepatic fat 
increased from 0.7% at Baseline to 6.5% at Week 78 and was 7.7%, 10.3%, and 10.2% at 
Weeks 126, 174, and 246, respectively (Blom, Averna et al. 2017). 
Clinical data suggest that hepatic fat accumulation is reversible after stopping treatment with 
lomitapide. For this reason, hepatic fat content will be measured 4 weeks after EoT in patients 
who opt not to participate in or are unsuitable for the Expanded Access Programme (EAP; 


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<18 years of age)/opt not to transition to commercial product (≥18 years of age; see 
Section 8.1.2 Safety Assessments). 
The most common AEs in the phase III study included abdominal pain or discomfort, nausea, 
vomiting, dyspepsia, diarrhoea, and constipation. Diarrhoea was the most common symptom. 
This finding is expected since MTP inhibition is known to cause fat malabsorption and 
steatorrhea. As the occurrence and severity of GI AEs associated with the use of lomitapide 
decreases in the presence of a low-fat diet, patients will start to follow a diet supplying <20% 
of energy from fat or <30 g fat, whichever is the lesser amount at the Start of the Run-in Period, 
and will continue this diet until the EoT or through the administration of lomitapide in the EAP 
(<18 years of age) or during administration of commercial lomitapide (≥18 years of age; see 
Section 8.6.1 Diet Instructions and Diet Records).  
In the pivotal phase III study, decreased body weight was reported as an AE in 6 of 29 patients. 
All cases were assessed as mild to moderate in severity, non-serious and none led to study 
drug discontinuation. The combination of gastrointestinal (GI) symptoms (e.g., diarrhoea, 
nausea), fat malabsorption, and adherence to a strict fat-restricted diet, may result in a calorie 
deficit relative to daily requirements. Appropriate dietary supervision and monitoring is an 
important component to improve GI tolerability and the maintenance of an adequate diet to 
avoid unintended weight loss. In this study, weight will be measured at each visit after the 
Run-in Period and patients of normal or below normal body weight based on gender and 
age-specific World Health Organization (WHO) growth charts with weight loss >3% since the 
last visit will be instructed by the dietitian on how to increase caloric intake based on individual 
needs (see Section 8.6.1 Diet Instructions and Diet Records). Patients with below normal body 
weight any time during the study who continue to lose weight while on study medication despite 
all appropriate measures taken to correct for the weight loss and who are deemed to be at 
clinical risk in the judgment of the treating investigator should discontinue study medication 
and should be followed until an acceptable stable weight is reached as judged by the 
investigator (see Section 7.3.2 Dose Modification, Interruption or Discontinuation for Adverse 
Events).  
MTP inhibition with lomitapide is likely to cause a deficiency in fat-soluble vitamins, particularly 
vitamin E. Therefore, all patients in this study will receive daily oral supplementation with 
vitamin E (200 IU for patients 5 to 8 years of age, 400 IU for patients 9 to ≤17 years of age) 
and an EFA supplement containing approximately 200 mg linoleic acid, 210 mg ALA, 110 mg 
EPA, and 80 mg DHA (see Section 6.3 Dietary Supplements). 
The SPC (included in the Lojuxta® SPC in lieu of an Investigator’s Brochure [IB]; see 
Section 18.1 Source Documents) provides guidance in key areas to minimise risk to patients 
during treatment with lomitapide, which is reflected in the design of this study. Use of lomitapide 
in patients with moderate or severe hepatic impairment, active liver disease, or pregnancy is 
contraindicated (see Section 5.2 Exclusion Criteria). Contraindications also include 
co-administration with strong or moderate inhibitors of CYP 3A4 and co-administration with 
doses of simvastatin >40 mg (see Section 7.6.3 Non-Permitted Concomitant Medication, Food 
or Substances). In the presence of atorvastatin (a weak CYP 3A4 inhibitor), lomitapide should 
be taken 12 hours apart. Since patients will be required to remain on their concomitant LLT 
(including LA when applicable) established during the 6-week Run-in Period during the Efficacy 
Phase of the study through Week 24±3 days, a potential concomitant treatment with 
atorvastatin will remain unchanged during the Efficacy Phase, when lomitapide dosing will 
start. If atorvastatin is given concomitantly, it should be administered in the morning to separate 
it from lomitapide dosing by 12 hours. If during the 80-week Safety Phase it is not possible to 
administer atorvastatin and lomitapide 12 hours apart, the lomitapide dose should be reduced 
by half. After a minimum period of 4 weeks following dose reduction the patient can be 
re-challenged with a higher dose of lomitapide once these issues resolve (i.e., if atorvastatin 
can be administered 12 hours apart or if atorvastatin is discontinued), but the dose during the 
Safety Phase cannot exceed the MTD established during the Efficacy Phase unless eligibility 
for exceptional dose escalation is met (described in Section 7.3.1 Dose Escalation, Dose 


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Reduction and Re-challenge). For patients on a stable maintenance dose of lomitapide who 
receive any other weak CYP 3A4 inhibitor, the dose of the medications should be separated 
by 12 hours (see Section 7.3.3 Dose Modification for Concomitant Medication). Use in patients 
with known significant or chronic bowel disease is also contraindicated since MTP inhibition is 
known to cause fat malabsorption and steatorrhea. Use in patients with rare hereditary 
problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose 
malabsorption, 
are 
contraindicated 
in 
accordance 
with 
EU 
guidance 
(EC Volume 3B Guidelines, Medicinal Products for Human Use, Safety, Environment and 
Information: Excipients in the Label and Package Leaflet of Medicinal Products for Human 
Use, July 2003) since the drug product contains lactose (see Section 5.2 Exclusion Criteria). 
Hepatic aminotransferase levels must be determined prior to initiating therapy, and then 
monitored prior to each dose escalation, and regularly during treatment (see Section 1.2 Flow 
Chart of Study and Follow-up). In the event that hepatic aminotransferases become elevated, 
a detailed algorithm for dose adjustment or treatment discontinuation is provided (see 
Section 7.3.2 Dose Modification, Interruption or Discontinuation for Adverse Events). This 
algorithm is based on the approach agreed with the DSMB hepatologist that was used 
successfully in the pivotal phase III study and is consistent with the FDA’s draft guidance Drug-
Induced Liver Injury: Premarketing Clinical Evaluation, October 2007. Dietary advice, including 
fat content (see Section 8.6.1 Diet Instructions and Diet Records) and supplementation with 
vitamin E and essential fatty acids (see Section 6.3 Dietary Supplements), is also specified, 
and dosing is escalated gradually to minimise GI side effects and allow for regular hepatic 
aminotransferase determination (see Section 7.2 Treatment Schedule). These elements of 
safety monitoring are designed to allow the optimum individualised dose to be selected for 
each patient in order to maximise the benefit of LDL-C reduction, ensure compliance with 
treatment, and avoid AEs. 
2.6.4 
Benefits and Risks Conclusions 
Patients with HoFH deal with a life-threatening disease every day in the absence of effective 
treatment to reduce their LDL-C to target levels. For the first time, it is now feasible to reach 
target LDL-C goals and maintain these levels during chronic treatment. LDL-C lowering of 
lomitapide was modelled to increase median life expectancy of HoFH patients by 11.6 years 
and delay time to the first MACE by 5.7 years (Leipold, Raal et al. 2017). 
Lomitapide treatment is a major advance in the treatment of a devastating disease through 
modification of a risk factor that is currently uncontrolled by available treatment interventions, 
supporting a favourable benefit-risk assessment for its use in this high-risk patient population.  
In this study, lomitapide will be carefully titrated to the MTD based upon safety, tolerability and 
LDL-C levels and safety will be monitored by an independent DSMB (see Section 4.3 Data 
Safety Monitoring Board). Therefore, the benefits will outweigh the risks. 
2.7 
Rationale of the Study and of the Study Design 
Lomitapide has been approved for use in adult patients with HoFH in the European Union (EU) 
and European Economic Area (EEA), United States of America (USA), Israel, Argentina, 
Canada, Colombia, and Japan. This study is designed to determine if lomitapide is effective 
and can be safely administered to paediatric patients with HoFH. If the efficacy and safety so 
far observed in adults is confirmed in paediatric patients, the potential exists to significantly 
lower LDL-C levels in paediatric patients with HoFH. Furthermore, the lower LDL-C levels may 
reduce atherosclerosis progression and would be expected to benefit these paediatric patients 
with HoFH. 
A single-arm, non-comparator design has been selected due to the rarity of the disease and 
because the evaluation of safety variables such as growth and sexual maturation requires 
longer term observation than would not be feasible in the context of a placebo-controlled study.  


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In addition, similar efficacy cannot reasonably be assumed in a 2-arm design with standard of 
care LLT including LA as comparator, and, as a result, randomisation of these very high risk 
patients to placebo for longer than 6 months would not be acceptable.  
Finally, the high incidence of GI AEs expected in lomitapide-treated patients and the 
corresponding inability to keep patients and physicians blinded to treatment would introduce 
an assessment bias. 
To mitigate the disadvantages of a single-arm design, the study includes a Run-in Period of at 
least 6 weeks during which current LLT (including LA, when applicable) will be stabilised to 
establish Baseline levels allowing each patient to serve as his/her own control. Patients will 
also remain on stable LLT (including LA, when applicable) during the Efficacy Phase of the 
study through Week 24±3 days. 
3 
STUDY OBJECTIVES 
3.1 
Primary Objective 
Evaluate the efficacy of lomitapide as defined by the percent change in LDL-C at the MTD at 
Week 24±3 days compared to Baseline when added to stable LLT (including LA when 
applicable) in paediatric patients (5 to ≤17 years of age) with HoFH. 
3.2 
Secondary Objectives 
• Evaluate the efficacy of lomitapide in paediatric HoFH patients as assessed by: 
− Percent change from Baseline at Week 24±3 days in lipid parameters, including total 
cholesterol (TC), non high-density lipoprotein cholesterol (Non-HDL-C), very low-density 
lipoprotein cholesterol (VLDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], and 
apolipoprotein B (apo B). 
− Percent change from Baseline in TC, non-HDL-C, LDL-C, TG, VLDL-C, Lp(a), and apo B 
at all other time-points through Week 104±1 week. 
− Change in LLT and LA from Week 24±3 days through Week 104±1 week. 
− Number (percent) of patients achieving the EAS recommended target LDL-C of 
<135 mg/dL (3.5 mmol/L) at Week 24±3 days and at any time on study. 
3.3 
Safety Objectives 
• Evaluate the long-term safety and tolerability of lomitapide in paediatric HoFH patients as 
assessed by: 
− Incidence in reported AEs and in clinically significant abnormal findings of physical 
examinations including weight and BMI, electrocardiogram (ECG), standard of care 
echocardiography (if available), vital signs, pulmonary function tests (PFT), and 
laboratory parameters including hepatic and renal function tests. 
− Effects on growth, bone health and bone age will be assessed using both measurements 
of children’s height and growth charts to track age-appropriate progress at Screening 
and from Baseline at every visit through Week 104±1 week and/or at EoT, together with 
analysis of Vitamin D and K levels at Screening, Baseline, Week 24±3 days, 
Week 56±3 days, Week 80±1 week, Week 104±1 week and/or at EoT (and at Week 108 
for patients who opt not to participate in or are unsuitable for the EAP [<18 years of 
age]/opt not to transition to commercial product [≥18 years of age]). 
− Potential effects on maturation, reproductive development, gonadotropins, and variables 
of the pituitary-adrenal axis at Screening, Baseline, Week 56±3 days, Week 104±1 week 


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and/or at EoT will be analysed; potential effects on the levels of sex steroids will be 
analysed for patients assessed as Tanner Stage ≥2. 
− Lipid accumulation in the liver as measured by nuclear magnetic resonance (NMR) 
imaging or echography (i.e., ultrasound scan) at Baseline and at Week 24±3 days, 
Week 56±3 days, and at Week 104±1 week (for patients who opt not to participate in or 
are unsuitable for the EAP [<18 years of age)/opt not to transition to commercial product 
[≥18 years of age], lipid accumulation in the liver will be measured at Baseline, at 
Week 24±3 days, Week 56±3 days, and at Week 108). All patients will undergo NMR 
imaging unless it is contraindicated or not feasible (e.g., due to the need for sedation or 
general anaesthesia in very young or anxious patients). In this case, ultrasound scans 
will be used at the discretion of the investigator. 
3.4 
Exploratory Objectives 
• Evaluate exploratory assessments of: 
− Change from Baseline at Week 56±3 days and Week 104±1 week in mean carotid 
intima-media thickness (CIMT, mandatory) and flow-mediated dilatation (FMD, 
whenever possible). 
− The resolution and/or regression of pre-existing xanthomas at Week 56±3 days and at 
Week 104±1 week. 
− Changes from Baseline through Week 24±3 days in cholesterol and triglyceride content 
of VLDL, intermediate density lipoprotein (IDL), LDL and HDL, particle number and size 
of VLDL, LDL, and HDL as well as particle number of their respective lipoprotein 
subclasses (large, medium, and small) as assessed based on 2D NMR (Liposcale® Test) 
of pharmacokinetics (PK) samples. 
3.5 
Palatability Objective 
• Assess the palatability of the study medication using a 5-point facial hedonic scale anchored 
with descriptors, to record the children’s assessment of palatability in terms of overall liking. 
• The parent(s)/legal guardian(s) interpretation of the child’s reaction/facial expression will be 
used to determine whether they find lomitapide “pleasant”, “unpleasant” or are “not sure”. 
• Ease of administration of the study medication and dietary supplements by the 
parent(s)/legal guardian(s) will be assessed using the following question at each visit during 
the treatment phase: “Do you sometimes have problems in giving the medication to your 
child because he/she refuses to take it or throws it up immediately after taking it? (Yes/No).” 
3.6 
Pharmacokinetic Objective 
• Evaluate the PK of lomitapide in paediatric HoFH patients through sparse blood sampling. 


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4 
INVESTIGATIONAL PLAN 
All references to “the investigator” throughout this document refer to “the investigator or a 
delegated sub-investigator”. 
4.1 
Study Endpoints 
4.1.1 
Primary Endpoint 
• Percent change from Baseline in LDL-C at Week 24±3 days. 
4.1.2 
Secondary Endpoints 
• Percent change from Baseline at Week 24±3 days for the following lipid parameters: TC, 
Non-HDL-C, VLDL-C, TG, Lp(a), and apo B. 
• Percent change from Baseline at all other time points through Week 104±1 week for the 
following lipid parameters: LDL-C, TC, Non-HDL-C, VLDL-C, TG, Lp(a), and apo B. 
• Total number and percent of patients with a change from Baseline in LLT and LA from 
Week 24±3 days through Week 104±1 week. 
• Total number and percent of patients achieving the EAS recommended target LDL-C of 
<135 mg/dL (3.5 mmol/L) in paediatric HoFH patients at Week 24±3 days and at any time 
on study. 
4.1.3 
Safety Endpoints 
• Incidence of AEs overall and by severity, and relatedness. 
• Physical examinations including regular measurements of height, weight, and BMI. 
• Sexual maturation (Tanner staging). 
− In patients with Tanner Stage ≥2: Change from Baseline in sex hormones (serum 
testosterone and serum oestradiol).  
• 12-Lead safety ECG (read locally), standard of care echocardiography (if available), vital 
signs and blood pressure. 
• PFT. 
• Laboratory tests: 
− Standard haematology (complete blood count [CBC]) and clinical chemistry panels).  
− Liver function tests: ALT, AST, gamma-glutamyl transferase (GGT), alkaline 
phosphatase (AP), total bilirubin, and serum albumin. 
− High-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apo A-I). 
− Creatinine kinase (CK). 
− Serum lipase. 
− Serum levels of essential fatty acids (EFA): Linoleic acid, alpha linoleic acid (ALA), 
eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and 
eicosatrienoic acid. 
− Serum concentrations of fat-soluble vitamins: Vitamin A (retinol), vitamin E (alpha 
tocopherol), ratio of vitamin E to total lipids (total cholesterol plus fasting triglycerides), 
and vitamin D (25-hydroxy-D). Levels of vitamin K will be assessed indirectly by 
measuring total and uncarboxylated levels of serum osteocalcin. (Bone health will be 


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assessed indirectly using growth to track age-appropriate progress, and measurement 
of 25-hydroxy-D as well as total and uncarboxylated osteocalcin levels.) 
− Pituitary-adrenal hormone levels (thyroid stimulating hormone [TSH], follicle stimulating 
hormone [FSH], luteinising hormone [LH], adrenocorticotrophic hormone [ACTH], and 
morning serum cortisol).  
− Urinalysis. 
• Lipid accumulation in the liver as measured by NMR imaging or echography (i.e., ultrasound 
scan) at Baseline and at Week 24±3 days, Week 56±3 days, and at Week 104±1 week (for 
patients who opt not to participate in or are unsuitable for the EAP (<18 years of age)/opt 
not to transition to commercial product (≥18 years of age), lipid accumulation in the liver will 
be measured at Baseline and at Week 24±3 days, Week 56±3 days, and at Week 108). All 
patients will undergo NMR imaging unless it is contraindicated or not feasible (e.g., due to 
the need for sedation or general anaesthesia in very young or anxious patients). In this 
case, ultrasound scans will be used at the discretion of the investigator. 
4.1.4 
Exploratory Endpoints 
• Percent change from Baseline at Week 56±3 days and Week 104±1 week in CIMT and 
FMD. 
• Total number and percent of patients with resolution and/or regression of pre-existing 
xanthomas at Week 56±3 days and at Week 104±1 week. 
• Changes from Baseline through Week 24±3 days in cholesterol and triglyceride content of 
VLDL, IDL, LDL and HDL, particle number and size of VLDL, LDL, and HDL as well as 
particle number of their respective lipoprotein subclasses (large, medium, and small) as 
assessed based on 2D NMR (Liposcale® Test) of PK samples at Week 4±3 days, 
Week 8±3 days, 
Week 12±3 days, 
Week 16±3 days, 
Week 20±3 days 
and 
at 
Week 24±3 days. 
4.1.5 
Palatability Endpoints 
• Total number and percent of patients for each response of palatability: 
− 
Able to swallow capsule (including food media responses if used). 
− 
Palatability rating (using a 5-point facial hedonic scale). 
− 
Parent/guardian interpretation of child’s reaction/facial expression (using a 3-point 
scale). 
− 
Parent/guardian experience problems in giving medication to child because they refuse 
to take or throw up immediately after taking. 
− 
Parent/guardian experience problems in giving dietary supplement to child because 
they refuse to take or throw up immediately after taking. 
4.1.6 
Pharmacokinetic Endpoint 
• The PK data from this study will be incorporated into an existing population PK model in 
adult HoFH patients. 
4.2 
Overall Study Design 
This is a single-arm, open-label, multi-centre phase III study to evaluate the efficacy and 
long-term safety of lomitapide in paediatric patients with HoFH receiving stable LLT (including 
LA, when applicable). Each patient will participate for up to 120 weeks (about 2.5 years) in the 
study (see Figure 3).  


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4.2.1 
Study 
The study will consist of 5 periods (see Figure 3):  
1. 
Screening Period (starting at Week -12, i.e., ≤12 weeks prior to Baseline for up to 
6 weeks). 
2. 
Stratified Enrolment and Start of Run-in Period (starting at minimum at Week -6, i.e., 
6 weeks prior to Baseline for a minimum of 6 weeks): 
• Enrolment will be stratified to ensure approximately equal numbers of patients in the 
following age groups: 5 to 10 years, 11 to 15 years, and 16 to ≤17 years (with 
≥8 patients in any individual age group). 
• Patients must be stabilised on current LLT (including LA, when applicable) and 
established on a diet supplying <20% of energy (calories) from fat or <30 g fat, 
whichever is the lesser amount. 
• Daily supplementation with vitamin E (200 international units [IU] for patients 5 to 
8 years of age, 400 IU for patients 9 to ≤17 years of age) and an EFA supplement 
containing approximately 200 mg linoleic acid, 210 mg ALA, 110 mg EPA, and 80 mg 
DHA starting at Week -2. 
3. 
Efficacy Phase (starting at Baseline, i.e., Day [D] 0 for 24 weeks±3 days): 
• Approximately 45 paediatric patients with HoFH will be treated with lomitapide given 
orally, added to their current, stable LLT (including LA, when applicable) established 
during the Run-in Period. 
• Assuming a withdrawal rate of approximately 33% by Week 24±3 days, this would 
result in 30 evaluable patients at Week 24±3 days (with ≥8 patients in any individual 
age group). 
• After stabilisation of the patient on his/her current MTD of LLT (including LA, when 
applicable) during the 6-week Run-in Period, treatment with lomitapide will be started 
as an add-on therapy on D0 of the Efficacy Phase. 
• Dosing will be initiated at the recommended starting dose and escalated to the 
maximum dose as applicable to the age groups based upon safety and tolerability in 
addition to LDL-C values (see Section 7.2 Treatment Schedule and Table 2). 
• The first dose of study medication will be administered at the study site on D0. 
• During the 24-week Efficacy Phase, patients will be required to remain on the stable 
LLT regimen (including LA, when applicable) established during the 6-week Run-in 
Period 
4. 
Safety Phase (starting at Week 24±3 days for 80±1 weeks) 
• Patients will enter the 80-week Safety Phase after the Week 24±3 days assessments 
have been completed. Each patient will continue receiving the MTD of lomitapide 
he/she achieved during the Efficacy Phase (unless criteria is met for reducing or 
increasing the dose) for an additional 80±1 weeks in the Safety Phase. 
• If after Week 24±3 days both the investigator and the sponsor consider a patient 5 to 
15 years of age to be eligible for further escalation of the lomitapide dose beyond the 
maximum recommended dose by the respective age group, the lomitapide dose can 
be increased to an extent defined by the investigator after consultation with the sponsor 
based on individual safety, efficacy, and concomitant LLT criteria. If the patient tolerates 
this new dose for ≥4 weeks, then this will be considered the new MTD. 
• If after Week 24±3 days, a patient has crossed over into the next age category, the 
study medication can be escalated to the maximum dose applicable for the new age 


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category. If the patient tolerates this new dose for ≥4 weeks, then this will be considered 
the new MTD. 
• During the 80-week Safety Phase, the lomitapide dose can be reduced from the MTD 
due to tolerability or safety issues, and the patient can be re-challenged after a 
minimum period of 4 weeks following dose reduction with a higher dose of lomitapide 
once these issues resolve, but the dose during the Safety Phase cannot exceed the 
MTD established during the Efficacy Phase unless eligibility for exceptional dose 
escalation described above is met. 
• Adjustments to background LLT (including LA, when applicable) will be allowed at the 
discretion of the investigator.  
5. 
Follow-up (starting at Week 104±1 week for 4 weeks): 
• At Week 104±1 week, eligible patients who complete the study per protocol and are 
<18 years of age may choose to enter the EAP. Patients ≥18 years of age may opt to 
transition to commercial product under the approved product label for adults. For both 
the patient groups, a follow-up phone call will be conducted at Week 108±1 week to 
monitor safety including AE and concomitant medication reporting.  
• For patients who opt not to participate in or are unsuitable for the EAP, or patients 
≥18 years of age who opt not to transition to commercial product will discontinue 
lomitapide treatment at Week 104±1 week and enter a 4-week Follow-up period during 
which they will remain on concomitant LLT (including LA, when applicable). These 
patients will then attend in person for a Week 108±1 week visit. 
 


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Figure 3 
Design of Study 
 
 
AE = adverse event; ALA = alpha-linoleic acid; DHA = docosahexaenoic acid; EFA = essential fatty acids; EPA = eicosapentaenoic acid; LA = lipoprotein apheresis; 
LDL-C = low-density lipoprotein cholesterol; LLT = lipid-lowering therapy; MTD = maximum tolerated dose 
1. Stabilise current LLT (including LA, when applicable), establish diet <20% energy from fat or <30 g fat, whichever is the lesser amount, dietary supplementation from Week -2 
(daily 200 IU [5 to 8 years of age] 400 IU [≥9 years of age] vitamin E and EFA supplement [approx. 200 mg linoleic acid, 210 mg ALA, 110 mg EPA, and 80 mg DHA]). 
2. During the 24-week Efficacy Phase, patients will be required to remain on the stable LLT regimen (including LA, when applicable) established during the 6-week Run-in Period.  
3. Based on safety, tolerability and efficacy parameters. 
4. Adjustments to background LLT (including LA, when applicable) will be allowed at the discretion of the investigator. 
5. Dose adjustment rules apply. 
6. Eligible patients who complete the study per protocol at Week 104 and are <18 years of age may choose to enter the Expanded Access Programme. Patients ≥18 years of age 
may opt to transition to commercial product under the approved product label for adults. For both these patient groups, a follow-up phone call will be conducted at Week 
108±1 week to monitor safety including AE and concomitant medication reporting. Patients who opt not to participate in or are unsuitable for the Expanded Access Programme, 
or patients ≥18 years of age who opt not to transition to commercial product will discontinue lomitapide treatment at Week 104±1 week and enter a 4-week Follow-up period 
during which they will remain on concomitant LLT (including LA, when applicable). These patients will attend in person for a Week 108±1 week visit. 
 
 


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4.2.2 
End of Study 
The End of Study is defined as completion of the last visit or assessment for the last patient. 
4.3 
Data Safety Monitoring Board 
An independent DSMB will be assigned to periodically review and evaluate study data for 
participant safety and to advise for continuation, modification or discontinuation in individual 
patients and of the study. Interim safety data reviews may be performed by the DSMB at their 
discretion, at any time, on an ‘as needed’ basis according to ongoing study results. 
The DSMB will have an initial organisational meeting at which time the composition, activities, 
and responsibilities of the DSMB will be detailed in a Charter as agreed upon by the sponsor 
and the DSMB members. The DSMB will be comprised of at least 3 members who are not 
otherwise involved in the conduct of the study, at least 1 of whom will be a statistician. The 
DSMB will meet at least 3 times during the conduct of the study.  
The DSMB in consultation with the sponsor will have the authority to stop the study for any 
reason including, but not limited to, unacceptable safety risks. If a patient discontinues 
treatment permanently due to a Hy’s law case or comparable signs of liver toxicity irrespective 
of origin, the DSMB will initiate an immediate recruitment stop as an urgent safety measure 
and will assess individual benefits and risks for the patients being treated with study medication 
regarding further therapy. 
5 
STUDY POPULATION 
5.1 
Inclusion Criteria 
A patient will be eligible for study participation only if all of the following criteria apply: 
1. 
Male and female patients aged 5 to ≤17 years with HoFH as defined by any of the following 
criteria recommended by the Consensus Panel on Familial Hypercholesterolaemia of the 
EAS (Cuchel, Bruckert et al. 2014): 
a. 
Genetic confirmation of 2 mutant alleles at the LDLR, apo B, PCSK9, or LDLRAP1 
gene locus OR 
b. 
An untreated LDL-C >500 mg/dL (13 mmol/L) or treated LDL-C ≥300 mg/dL 
(8 mmol/L) together with either 
− 
Cutaneous or tendon xanthoma before age 10 years or  
− 
Untreated LDL-C levels consistent with heterozygous FH in both parents 
2. 
Baseline LDL-C on LLT (Cmax of LDL-C immediately prior to LA, if applicable) of either: 
a. 
>160 mg/dL (4.1 mmol/L, no documented CVD) or 
b. 
>130 mg/dL (3.4 mmol/L, established CVD defined as aortic valve disease and/or 
coronary atherosclerosis) 
3. 
Body weight ≥15 kg or BMI and height both >10th percentile according to WHO Growth 
Charts for Boys and Girls 5 to 19 Years of Age (see Appendix 4 WHO Growth Charts). 
4. 
Patient and/or his/her legal representative has/have been informed, has/have read and 
understood the patient information/informed consent form, and has/have given written 
informed assent/consent. 
5. 
Patient and/or his/her legal representative must be able and willing to follow study 
procedures and instructions, particularly that: 


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a. 
LLT (including LA when applicable) must be stable for at least 6 weeks prior to 
Baseline (Run-in Period) and remain stable through Week 24±3 days (end of Efficacy 
Phase). 
b. 
The patient must be compliant with both the low-fat diet supplying <20% of energy 
(calories) from fat or <30 g fat, whichever is the lesser amount starting at the 
beginning of the Run-in Period and the dietary supplement regimen starting at 
Week -2 of the Run-in Period, both continuing until completion of the study (and during 
the EAP/administration of commercial product, when applicable). 
6. 
Postmenarchal female adolescents must be willing to use highly effective methods of birth 
control that, alone or in combination, result in a low failure rate (i.e., <1% per year) when 
used consistently and correctly (e.g., implant, injectable, combined oral contraceptive, 
intrauterine contraceptive device, sexual abstinence, vasectomy or vasectomised partner) 
during participation in the study (and at least 4 weeks thereafter). Postmenarchal female 
adolescent patients taking oestrogen-based oral contraceptives should be advised that 
diarrhoea and/or vomiting may reduce hormone absorption. In case of protracted or severe 
diarrhoea and/or vomiting lasting more than 2 days, the investigator should advise 
according to national practice, which additional contraceptive measures (such as sexual 
abstinence, barrier methods) should be used for 7 days after resolution of symptoms. 
7. 
Patient must be in stable physical and mental health at Screening. 
5.2 
Exclusion Criteria 
A patient will not be eligible to participate in this study, if any of the following criteria apply: 
1. 
Other 
forms 
of 
primary 
hyperlipoproteinaemia 
and 
secondary 
causes 
of 
hypercholesterolaemia (e.g., nephrotic syndrome, hypothyroidism). 
2. 
Contraindications for the use of lomitapide according to section 4.3 of the Summary of 
Product Characteristics (SPC included in the Lojuxta® SPC in lieu of an IB; see 
Section 18.1 Source Documents), such as hypersensitivity to the active substance or to 
any of the excipients listed in Section 6.1 of the SPC, known significant or chronic 
inflammatory bowel disease or malabsorption. 
3. 
Moderate (Child-Pugh B, see Appendix 1 Child-Pugh Score) or severe hepatic impairment 
(Child-Pugh C), active liver disease and/or abnormal liver function tests at Screening (AST 
or ALT >1.5 x ULN and/or total bilirubin >1.5 x ULN in the absence of Gilbert’s syndrome 
or AP >1.5 x ULN [based on appropriate age and gender normal values]).  
4. 
Serum CK >2 x ULN. 
5. 
Chronic renal insufficiency with glomerular filtration rate (GFR) <70 mL/min/1.73 m2 
calculated using the Schwartz formula (see Appendix 2 Schwartz Formula). 
6. 
Uncontrolled hypertension (defined as mean systolic and/or diastolic blood pressure ≥95% 
of normal for age and sex) despite medical therapy. 
7. 
New York Heart Association (NYHA) Class III or IV congestive heart failure. 
8. 
Precocious/delayed puberty or endocrine disorder affecting growth (e.g., hypothyroidism, 
premature adrenarche). 
9. 
History of drug abuse within the last 3 years or habitual alcohol consumption (defined as 
>1 ounce [28 g] of liquor or 4-ounce glass [113 g] of wine, or the equivalent, ≥3 times per 
week). 
10. Life expectancy predicted to be <5 years. 
11. History of a non-skin malignancy (with the exception of cervical cancer in situ) within 
3 years prior to enrolment. 


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12. Treatment with any Investigational Medicinal Product (IMP) within 6 months or 5 times the 
terminal half-life of the corresponding IMP, whichever is longer, before Screening (Visit 1).  
13. Patient is a dependent of the sponsor, of the investigational team or his/her immediate 
family. 
14. Pregnant or nursing women. 
6 
STUDY MEDICATION 
6.1 
Description of the Investigational Product 
6.1.1 
Formulation, Packaging and Labelling 
The investigational product will be supplied in high-density polyethylene bottles with polyester, 
aluminium foil, and cardboard induction seals and child-resistant polypropylene screw caps. It 
will be packed and labelled according to applicable regulatory requirements. 
Lomitapide is prepared as a crystalline methanesulfonate salt. The investigational product will 
be administered orally in opaque, hard gelatin capsules. Four bottle types will contain 
28 capsules each by 2 mg, 5 mg, 10 mg, and 20 mg strength. Each hard capsule contains 
lomitapide mesylate equivalent to its strength and the following inactive excipients: 
pregelatinised starch (maize), sodium starch glycolate (Type A), microcrystalline cellulose, 
lactose monohydrate, colloidal, anhydrous silica, and magnesium stearate.  
Please refer to the Lojuxta® SPC in lieu of an IB and to the Investigational Medicinal Product 
Dossier for the 2 mg lomitapide hard capsules regarding the excipients and colours of the 
capsule shells, which differ by strength (see Section 18.1 Source Documents). Further details 
regarding physical, chemical, and pharmaceutical properties and concerning the formulation, 
respectively are described in the EPAR Lojuxta® dated 30 May 2013, Section 2.2.  
Please refer to Section 2.2 Investigational Product for further details regarding the mechanism 
of action and therapeutic indication of lomitapide. 
6.1.2 
Storage and Stability 
Keep the bottle tightly closed in order to protect from moisture. Store below 30°C. 
6.1.3 
Drug and Dietary Supplements Accountability 
A sufficient number of lomitapide bottles will be provided to sites in bulk at appropriate intervals 
depending on the phase of the study and accrual of patients. Dietary supplements will be 
sourced locally, where possible (see Section 6.3 Dietary Supplements). The investigator, or 
the person designated by the investigator, will be responsible for dispensing the appropriate 
bottle or combination of bottles to a patient at each study visit. At each site, the investigator, or 
the person designated by the investigator, will be responsible for keeping accurate records of 
study medication accountability comprising the receipt, the dispensing, and the return of all 
used and partially unused study medication throughout the study. The drug accountability form 
should be kept up to date and will be reviewed periodically by the study monitor. Patients will 
be asked to keep all used and partially unused bottles of study medication and return them to 
the site during the scheduled visits. For drug accountability, the number of used and partially 
unused bottles and unused capsules will be counted. Compliance with dietary supplements is 
discussed with the patients at each visit and is documented in the electronic Case Report Form 
(eCRF). It is also verified by reviewing the patient Diet Records (see Section 8.6.1 Diet 
Instructions and Diet Records). After drug accountability is completed, all unused or partially 
used study medication may be returned to the sponsor or disposed of by the study site. The 
study monitor will instruct the site on the return of all study medication. A final inventory of the 
total amount of study medication and dietary supplements at each study site against the 


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amount used and returned must be recorded. Inventory records must be readily available for 
inspection by the study monitor and/or auditor, and open to government inspection at any time. 
6.2 
Investigational Product Compliance 
Patients and their parents/legal guardians will be instructed to return all unused study 
medication and dietary supplements to the clinical site at the visits indicated in Section 1.2 
Flow Chart of Study and Follow-up. Site study team members will count and record the number 
of capsules remaining in each of the bottles and record this information on the eCRF. Study 
drug compliance checks will be performed at all visits during the Efficacy and Safety Phases 
of the study. 
6.3 
Dietary Supplements 
Patients will be administered daily oral supplementation with vitamin E (200 IU for patients 
5 to 8 years of age, 400 IU for patients 9 to ≤17 years of age) and an EFA supplement 
containing approximately 200 mg linoleic acid, 210 mg ALA, 110 mg EPA, and 80 mg DHA. 
Dietary supplements will be dispensed during Visit 3 at Week -3 to Week -2 (Run-in 
Compliance), during Visit 4 at D0 (Baseline, Efficacy Phase), and at every visit thereafter until 
Visit 21 at Week 92±1 week. Please refer to Section 6.1.3 Drug and Dietary Supplements 
Accountability for dietary supplements accountability.  
7 
STUDY TREATMENT 
7.1 
Treatment Assignment, Blinding Procedure 
This is an open-label study, blinding of treatment is not applicable. 
7.2 
Treatment Schedule 
After stabilisation of the patient on his/her current MTD of LLT (including LA when applicable) 
during the 6-week Run-in Period, treatment with lomitapide will be started as add-on therapy 
on D0 of the Efficacy Phase.  
Lomitapide capsules will be provided in 4 dose strengths of 2 mg, 5 mg, 10 mg, and 20 mg. 
Dosing will be initiated at the recommended starting dose and escalated to the maximum dose 
as applicable to the age groups (see Table 2 and Figure 3) based upon safety and tolerability 
in addition to LDL-C values. 
Table 2 Lomitapide Starting Dose and Dose Escalation by Age Group 
Age Group 
(years) 
Lomitapide Dose (mg) 
D0 
Week 4 
±3 days 
Week 8 
±3 days 
Week 12 
±3 days 
Week 16 
±3 days 
Maximum 
5 to 10 
2 
2 
5 
10 
20 
20 (10, in Child-Pugh A) 
11 to 15 
2 
5 
10 
20 
40 
40 (20, in Child-Pugh A) 
16 to ≤17 
5 
10 
20 
40 
60 
60 (40, in Child-Pugh A) 
Each patient will take 1 to 3 capsule(s) once daily to achieve the doses specified in the titration 
scheme. The first dose of study medication will be administered at the study site on D0.  
As of D1, patients will self-administer (or the patient’s parent/legal guardian will administer to 
the patient) lomitapide orally, once daily, at approximately the same time each day. It is 
recommended to administer lomitapide at least 2 hours after the evening meal (e.g., at 
bedtime) with a glass of water on an empty stomach because the fat content of a recent meal 
may adversely impact GI tolerability. Patients who are unable to swallow the intact capsule(s) 


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may open the capsule(s) and sprinkle the capsule content on 1 tablespoon of apple sauce or 
mashed banana, which are fat-free.  
In case of a missed dose, patients should be instructed to take missed doses of lomitapide 
only if they can be taken at least 12 hours prior to the next scheduled dose. Dietary 
supplements are suggested to be taken in the morning. Patients taking bile acid sequestrants 
should be reminded that they should take lomitapide 4 hours before or 4 hours after this class 
of medications. If atorvastatin is given concomitantly, lomitapide should be administered 
12 hours apart. 
7.3 
Dose Modifications and Interruptions 
7.3.1 
Dose Escalation, Dose Reduction and Re-challenge 
Dose Escalation 
Patients will be categorised according to disease severity as determined by the presence or 
absence of clinically evident CVD, which will be defined by documented aortic valve disease 
or coronary atherosclerosis at Baseline.  
Lomitapide will not be escalated, if LDL-C is less than the target threshold: 
• LDL-C is <100 mg/dL (<2.5 mmol/L) in patients without CVD at Baseline 
• LDL-C is <70 mg/dL (<1.8 mmol/L) in patients with CVD at Baseline 
For each of the 3 age groups, lomitapide dosing will escalate following the applicable dose 
titration scheme in Table 2 at Week 4±3 days, Week 8±3 days, and Week 12±3 days to the 
maximum allowable dose by Week 16±3 days or the MTD by Week 20±3 days based upon 
acceptable safety and tolerability criteria in addition to LDL-C values.  
Each dose must be tolerated for ≥4 consecutive weeks before being escalated to the next 
higher dose in stepwise increments. The MTD is defined as the highest dose of lomitapide 
through Week 24±3 days that does not result in tolerability or safety concerns. This is the 
highest dose that does not result in dose reduction, dosing interruption, or discontinuation, but 
may include a re-challenged dose level. 
Each patient will continue receiving the MTD of lomitapide he/she achieved during the Efficacy 
Phase (unless criteria is met for reducing or increasing the dose) for an additional 80±1 weeks 
in the Safety Phase (for a total treatment period of 2 years). 
If after Week 24±3 days both the investigator and the sponsor consider a patient 5 to 15 years 
of age to be eligible for further escalation of the lomitapide dose beyond the maximum 
recommended dose by the respective age group, the lomitapide dose can be increased to an 
extent defined by the investigator after consultation with the sponsor based on individual 
safety, efficacy, and concomitant LLT criteria. If the patient tolerates this new dose for 
≥4 weeks, then this will be considered the new MTD. 
If after Week 24±3 days, a patient has crossed over into the next age category, the study 
medication can be escalated to the maximum dose applicable for the new age category. If the 
patient tolerates this new dose for a minimum of 4 weeks, then this will be considered the new 
MTD. 
Dose Reduction and Re-challenge 
If a dose reduction is required, dosage will either be reduced to the previous tolerated dose or 
to an intermediate dose. Please note that only down-titrations to intermediate doses are 
allowed, dose escalations need to follow the guidance provided in Table 2. After resolution of 
the cause for dose reduction, patients may be re-challenged after a minimum period of 4 weeks 
following dose reduction with prior doses in stepwise increments based on dose escalation 
guidelines, but may not exceed the MTD established during the Efficacy Phase until 


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Week 24±3 days, after which further increase is only possible if patients have crossed into the 
next age category or eligibility for exceptional dose escalation as described above is met.  
If the investigator determines that a patient is not tolerating any particular dose (per specified 
criterion), the investigator may request a dose reduction or a hold on the current dose until the 
next scheduled visit. Once the patient has stabilised on the reduced dose, the dose can be 
increased back to the next step again, and the patient may progress through subsequent dose 
increases at a minimum of 4-week intervals. If the patient does not tolerate the re-challenge 
dose, then the MTD is considered the reduced dose and will be the highest dose allowed for 
the remainder of the study. 
Weeks 0 through 24±3 days establish the MTD, Week 20±3 days is the last visit that the 
lomitapide dose can be increased, except when there has been a down-titration at/or after 
Week 16±3 days. Re-challenging will depend on the assessment of safety and tolerability 
criteria and the LDL-C value relative to the LDL-C goal of <135 mg/dL (3.5 mmol/L) and is at 
the discretion of the investigator except for Hy’s law cases or comparable signs of liver toxicity, 
irrespective of origin, in which no re-challenge will be allowed (see Section 7.4 Patient 
Discontinuation Criteria). 
The study medication can be escalated as a re-challenge dose during an unscheduled visit 
after the investigator consults with the study medical monitor, but any additional dose 
escalations, i.e., dose titration, must be made during a completed scheduled visit. In addition, 
a re-challenge with lomitapide will not be performed if the LDL-C is below the target threshold 
while the patient was receiving the reduced dose.  
During the 80-week Safety Phase, the lomitapide dose can be reduced from the MTD due to 
tolerability or safety issues, and the patient can be re-challenged with a higher dose of 
lomitapide once these issues resolve (after a minimum period of 4 weeks following dose 
reduction), but the dose during the Safety Phase cannot exceed the MTD established during 
the Efficacy Phase unless eligibility for exceptional dose escalation described above is met. 
Please refer to Section 7.3.2 Dose Modification and Interruption for Adverse Events for further 
details regarding dose reductions due to AEs and to Section 7.3.3 Dose Modification for 
Concomitant Medication for detailed information about dose reductions depending on 
concomitant medication. 
7.3.2 
Dose Modification, Interruption or Discontinuation for Adverse 
Events 
The investigator and/or DSMB have the authority to reduce study medication dosage or 
discontinue study medication in a patient if situations develop that, in the opinion of the 
investigator or DSMB, would compromise the patient's safety or successful participation in the 
study (see Section 4.3 Data Safety Monitoring Board and Section 7.4 Patient Discontinuation 
Criteria). In particular, modifications in dosage or discontinuation of treatment will be instituted 
if any of the situations below apply. 
HEPATOBILIARY GUIDELINES 
Dose Modification Based on Hepatobiliary Adverse Events 
If a patient matches the criteria referred to as “Hy’s law case” according to the European 
Association for the Study of the Liver (EASL) Clinical Practice Guidelines on Drug-induced 
Liver Injury (EASL 2019) and the FDA Guidance for Industry Drug-Induced Liver Injury 
Premarketing Clinical Evaluation (FDA 2009) or shows comparable signs of liver toxicity, 
irrespective of origin, treatment must be permanently discontinued and no re-challenge will be 
allowed. 
Upon the investigator’s discretion study medication will be discontinued permanently if a 
patient experiences any CTCAE Grade 3 or Grade 4 hepatobiliary AE (see Appendix 3 


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Common Terminology Criteria for Adverse Events, Hepatobiliary Disorders), regardless of 
relationship to study drug.  
Biochemical Hepatobiliary Guidelines 
Note: The toxicity “levels” described below are different and separate from CTCAE “grades”. 
The toxicity levels do NOT correlate to CTCAE grades nor should they be used for grading 
AEs. 
If aminotransferase elevations are accompanied by clinical symptoms of liver injury (such as 
nausea, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like symptoms), increases in 
bilirubin ≥2 x ULN, study drug will be discontinued, the event will be reported to the DSMB by 
the sponsor (or its designee) immediately upon notification and the patient referred to a 
hepatologist for further work up. 
Level 4 Hepatotoxicity 
Level 4 Hepatotoxicity is defined as follows: 
• ALT or AST levels reach ≥10 x ULN at 1 single time point. Patients should be referred to a 
hepatologist or gastroenterologist for further work up.  
• In symptomatic patients, ALT >5 x ULN AND total bilirubin >2 x ULN on 2 separate 
occasions and at least 7 days apart. 
• AP is >5 x ULN on 2 separate occasions and at least 7 days apart. 
• Total bilirubin is >2 x ULN on 2 separate occasions and at least 7 days apart in the absence 
of Gilbert’s syndrome or haemolysis. 
Patients who experience confirmed Level 4 Hepatotoxicity will immediately interrupt study 
medication. Patients will return to the study site weekly or sooner if clinically indicated until 
resolution. Any Level 4 Hepatotoxicity will be reported to the DSMB by the sponsor (or its 
designee) immediately upon notification. 
Following evaluation by a hepatologist, a patient may resume lomitapide treatment if the 
Level 4 Hepatotoxicity is resolved, and in the opinion of the investigator, DSMB and sponsor, 
the benefit of treatment justifies any risk of recurrent toxicity. 
Level 3 Hepatotoxicity 
Level 3 Hepatotoxicity is defined as follows: 
• Patients who experience ALT or AST ≥5 x ULN on 2 separate occasions and at least 7 days 
apart. 
Patients who experience confirmed Level 3 Hepatotoxicity will immediately interrupt study 
medication. The patient will return to the clinic for repeat blood tests including AP, bilirubin and 
International normalised ratio (INR) every 7 days until the aminotransferase levels have fallen 
<3 x ULN. Once this occurs, study drug dosing may be resumed at the dose level below that 
associated with Level 3 Hepatotoxicity.  
If this dose level is tolerated without elevation of ALT or AST >3 x ULN, then this dose will be 
defined as the MTD. If aminotransferases increase ≥3 x ULN further dose reduction or 
interruption may be necessary consistent with the guidance provided in this protocol. 
Elevations in ALT or AST >3 x ULN that persist despite dose reduction or interruption for 
≥4 weeks will be reported to the DSMB by the sponsor (or its designee) immediately upon 
notification. Patients will be referred to a hepatologist for further work up. 


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Level 2 Hepatotoxicity 
Level 2 Hepatotoxicity is defined as follows: 
• Patients who experience ALT or AST 3.0 to 4.9 x ULN on 2 separate occasions and at least 
7 days apart. 
Patients who experience confirmed Level 2 Hepatotoxicity will have the dose of study 
medication reduced to the previous tolerated dose. The patient will return to the clinic for repeat 
blood tests including AP, bilirubin and INR every 7 days until the aminotransferase levels have 
fallen to <3 x ULN. Once this occurs, lomitapide dosing may be resumed at the dose level 
below that associated with Level 2 Hepatotoxicity.  
If this dose level is tolerated without elevation of ALT or AST >3 x ULN, then this dose will be 
defined as the MTD. If aminotransferases increase >3 x ULN further dose reduction or 
interruption may be necessary consistent with the guidance provided in this protocol. 
Elevations in ALT or AST >3 x ULN that persist despite dose interruption for ≥4 weeks will be 
reported to the DSMB by the sponsor (or its designee) immediately upon notification. Patients 
will be referred to a hepatologist for further work up. 
Level 1 Hepatotoxicity 
Level 1 Hepatotoxicity is defined as follows: 
• Patients who experience ALT or AST 1.1 to 2.9 x ULN. 
No dose modification will be required. 
Considerations for Liver Biopsy and Histopathological Guidelines 
Considerations for Liver Biopsy 
A percutaneous liver biopsy should be considered for persistent Level 2 Hepatotoxicity defined 
as AST or ALT ≥3 x ULN for ≥6 months but can also be performed at the discretion of the 
investigator. 
Histopathological Hepatobiliary Guidelines 
If a patient undergoes a liver biopsy and the specimen shows the following features, the patient 
will be discontinued from the study and followed by a hepatologist:  
• Type 3 non-alcoholic steatohepatitis (NASH) characterised by fat accumulation and 
ballooning degeneration, or  
• Type 4 NASH characterised by fat accumulation, ballooning degeneration, and either 
Mallory’s hyaline or fibrosis. 
Patients with fatty liver alone (Type 1 NASH) or fat accumulation and lobular inflammation but 
without ballooning degeneration and/or Mallory’s hyaline or fibrosis (Type 2 NASH) will 
continue on study medication, and discontinuation will be dictated by biochemical criteria. 
Creatinine Kinase Monitoring and Evaluation 
If CK values are found to be elevated >5 x ULN on routine testing, the patient should be 
questioned about muscle symptoms.  
A study site physician should be alerted to the occurrence of unexplained muscle symptoms 
and any CK values >5 x ULN, and must take immediate action if CK is >10 x ULN. 
If CK values are >5 x ULN with muscle symptoms or >10 x ULN with or without muscle 
symptoms the following steps should be taken: 
• Clarify the nature, duration and intensity of any muscle symptoms. 


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• Review possible predisposing factors, such as: unaccustomed exercise, heavy alcohol 
intake, viral illness (consider performing serology), concomitant medication and consider 
diagnosis of other conditions which cause myopathy. 
• Physical examination for muscle tenderness, weakness and rash. 
• Measure CK again within a few days. 
• Measure serum creatinine. 
• Urine dipstick. 
• Arrange to review the patient again in 4 to 10 days, or earlier if symptoms of myopathy 
appear or worsen, or if the urine becomes very dark. 
Discontinue study medication for CK values >10 x ULN with or without muscle symptoms. 
For CK values 5 to 10 x ULN: 
If asymptomatic, or if symptomatic but alternative explanation exists, symptoms should be 
followed and CK levels tested weekly until it is no longer a medical concern or symptoms 
worsen and meet criteria for any of the above. 
If symptomatic, and no alternative explanation exists, withhold therapy. 
Throughout the study, patients should be instructed to promptly report any unexplained muscle 
pain or weakness, particularly if associated with malaise or fever. If this should occur, CK 
should be measured as soon as possible. 
Dose Modification Based on Weight Loss 
Weight will be measured using a consistent approach at Screening and at each visit after the 
Run-in Period (i.e., child/adolescent always weighed in same amount of clothing, either in 
underwear, hospital gowns or by subtracting the weight of clothes). Patients of normal or below 
normal body weight based on gender and age-specific WHO growth charts (see Appendix 4 
WHO Growth Charts) with weight loss >3% since the previous visit will meet with the dietitian 
for further instruction. Patients with below normal body weight any time during the study who 
continue to lose weight while on study medication despite all appropriate measures taken to 
correct for the weight loss and who are deemed to be at clinical risk in the judgment of the 
treating investigator should discontinue study drug and be followed until an acceptable stable 
weight is reached as judged by the investigator. 
7.3.3 
Dose Modification for Concomitant Medication 
Weak Cytochrome P450 (CYP) 3A4 Inhibitors 
Medicinal products that induce CYP 3A4 would be expected to increase the rate and extent of 
metabolism of lomitapide. CYP 3A4 inducers exert their effect in a time-dependent manner, 
and may take at least 2 weeks to reach maximal effect after introduction. Conversely, on 
discontinuation, CYP 3A4 induction may take at least 2 weeks to decline. 
Co-administration of a CYP 3A4 inducer is expected to reduce the effect of lomitapide. Any 
impact on efficacy is likely to be variable. When co-administering CYP 3A4 inducers (i.e., 
aminoglutethimide, nafcillin, non-nucleoside reverse transcriptase inhibitors, phenobarbital, 
rifampicin, carbamazepine, pioglitazone, glucocorticoids, modafinil and phenytoin) with 
lomitapide, the possibility of a drug-drug interaction affecting efficacy should be considered. 
Strong or moderate cytochrome CYP 3A4 inhibitors are not permitted during the study as 
described in Section 7.6.3 Non-Permitted Concomitant Medication, Food or Substances.  
Weak cytochrome CYP 3A4 inhibitors are only permitted during the Safety Phase of the study, 
but lomitapide should be administered 12 hours apart. If atorvastatin is given concomitantly, it 
should be administered in the morning to separate it from lomitapide dosing by 12 hours. In 
case it is not possible to administer atorvastatin and lomitapide 12 hours apart, the lomitapide 


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dose should be reduced by half, as the lomitapide dose can be reduced from the MTD due to 
tolerability or safety issues during the 80-week Safety Phase. After a minimum period of 
4 weeks following dose reduction the patient can be re-challenged with a higher dose of 
lomitapide once these issues resolve (i.e., if atorvastatin can be administered 12 hours apart 
or if atorvastatin is discontinued), but the dose during the Safety Phase cannot exceed the 
MTD established during the Efficacy Phase unless eligibility for exceptional dose escalation is 
met (described in Section 7.3.1 Dose Escalation, Dose Reduction and Re-challenge). 
HMG-CoA Reductase Inhibitors (‘Statins’) 
Lomitapide increases plasma concentrations of statins. Patients receiving lomitapide as 
adjunctive therapy to a statin should be monitored for AEs that are associated with the use of 
high doses of statins. Statins occasionally cause myopathy. In rare cases, myopathy may take 
the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and 
can lead to fatality. All patients receiving lomitapide in addition to a statin should be advised of 
the potential increased risk of myopathy and told to report promptly any unexplained muscle 
pain, tenderness, or weakness (see Section 7.3.2 Dose Modification, Interruption or 
Discontinuation for Adverse Events, Creatinine Kinase Monitoring and Evaluation). 
Concomitant administration of >40 mg simvastatin will not be permitted during the study as 
described in Section 7.6.3 Non-permitted Concomitant Medication, Food or Substances. 
Since patients will be required to remain on their concomitant LLT (including LA, when 
applicable) established during the 6-week Run-in Period during the Efficacy Phase of the study 
through Week 24±3 days, a potential concomitant treatment with atorvastatin will remain 
unchanged during the Efficacy Phase, when lomitapide dosing will start. If atorvastatin is given 
concomitantly, it should be administered in the morning to separate it from lomitapide dosing 
by 12 hours. If during the 80-week Safety Phase it is not possible to administer atorvastatin 
and lomitapide 12 hours apart, the lomitapide dose should be reduced by half. After a minimum 
period of 4 weeks following dose reduction the patient can be re-challenged with a higher dose 
of lomitapide once these issues resolve (i.e., if atorvastatin can be administered 12 hours apart 
or if atorvastatin is discontinued), but the dose during the Safety Phase cannot exceed the 
MTD established during the Efficacy Phase unless eligibility for exceptional dose escalation is 
met (described in Section 7.3.1 Dose Escalation, Dose Reduction and Re-challenge). 
Coumarin-based Anticoagulants 
Lomitapide increases the plasma concentrations of warfarin and increases INR. Increases in 
the dose of lomitapide may lead to supratherapeutic anticoagulation, and decreases in the 
dose may lead to subtherapeutic anticoagulation. Patients taking warfarin should undergo 
regular monitoring of the INR, especially after any changes in the dose of lomitapide. The dose 
of warfarin should be adjusted as clinically indicated. 
Hepatotoxic Agents 
Caution should be exercised when lomitapide is used with other medicinal products known to 
have potential for hepatotoxicity, such as isotretinoin, amiodarone, acetaminophen (>4 g/day 
for ≥3 days/week), methotrexate, tetracyclines, and tamoxifen. The effect of concomitant 
administration of lomitapide with other hepatotoxic medicine is unknown. More frequent 
monitoring of liver function tests may be warranted. 
7.4 
Patient Discontinuation Criteria 
Patients and/or their parents/legal guardians will have the right to withdraw from the study at 
any time for any reason without prejudice to their future medical care. A patient may be 
withdrawn from the study at any time at either the investigator’s, sponsor’s, or DSMB’s 
discretion.  


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A patient must be discontinued from the study for any of the following reasons:  
• The patient matches the criteria referred to as “Hy’s law case” according to the EASL 
Clinical Practice Guidelines on Drug-induced Liver Injury (EASL 2019) and the FDA 
Guidance for Industry Drug-Induced Liver Injury Premarketing Clinical Evaluation (FDA 
2009). Any Hy's law case or comparable signs of liver toxicity, irrespective of origin, must 
lead to permanent treatment discontinuation of the individual patient (no re-challenge 
allowed). 
• The patient and/or his/her parent/legal guardian withdraws assent/consent. 
• Pregnancy as evidenced by a positive pregnancy test. 
If a patient becomes pregnant during the study, during the follow-up, or 30 days within the 
last application of study medication, the sponsor will have to be informed within 24 hours. 
The investigator will be asked to complete a pregnancy report provided by the sponsor. 
He/she will be asked to obtain data on the course of the pregnancy, including perinatal and 
neonatal outcome (see Section 11.5.4 Other Reportable Information). 
• Any AE which, in the opinion of the investigator, places the patient at unacceptable risk, 
including intolerable AE(s) after attempted dose reduction (see Section 7.3.2 Dose 
Modification, Interruption, or Discontinuation for Adverse Events). 
The investigator will be able to withdraw patients from the study for the following reasons: 
• Hepatobiliary criteria for discontinuation 
• Hepatobiliary AE CTCAE Grade 4 (see Appendix 3 Common Terminology Criteria for 
Adverse Events, Hepatobiliary Disorders), regardless of relationship to study drug 
• Biochemical hepatobiliary guideline Level 4 Hepatotoxicity or Level 3 Hepatotoxicity that 
persists despite interruption of study drug 
• Histopathological diagnosis of Type 3 or Type 4 NASH 
• Patient is noncompliant with the study procedures or medications in the opinion of the 
investigator 
• Progression of a medical condition, which in the opinion of the investigator should preclude 
further participation of the patient in the study (e.g., excessive weight loss) 
• Administration of non-permitted concomitant medication(s), substances, or foods 
• Investigators’ decision that a change of therapy is in the patients’ best interest 
• Occurrence of an AE (including abnormal laboratory findings), which makes discontinuation 
desirable or necessary in the investigators’ and/or the patients’ opinion 
If a patient discontinues the study or the follow-up prematurely due to an AE/SAE, he/she will 
be followed up until the resolution or stabilisation of the AE/SAE. 
If a patient discontinues the study prematurely, the EoT visit assessments should be made 
(see Section 9.7 End of Treatment Visit).  
All data collected before premature discontinuation of the study will be used for analysis. 
Patients who drop out will not be replaced unless the assumptions for drop-out have been 
exceeded.  
7.5 
Overdose 
There is no specific treatment in the event of overdose. In the event of overdose, the patient 
should be treated symptomatically and supportive measures instituted as required. Liver 
function tests should be monitored. Haemodialysis is unlikely to be beneficial given that 


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lomitapide is highly protein-bound. Please refer to the SPC, Section 4.9 (included in the 
Lojuxta® SPC in lieu of an IB; see Section 18.1 Source Documents) for further details.  
7.6 
Concomitant Medication 
All medications that the patient is taking will be recorded in the eCRF. For each concomitant 
medication, the name of the medication, start and stop date, dose, indication, frequency of 
dosing and route of administration will be recorded. During the study, only changes of 
information from the previous visit at the time points indicated in Section 1.2 Flow Chart of 
Study and Follow-up will be recorded. 
7.6.1 
Concomitant Lipid-lowering Treatment 
Patients will be required to remain on their concomitant LLT (including LA, when applicable) 
established during the 6-week Run-in Period during the Efficacy Phase of the study through 
Week 24±3 days. Patients with HoFH are expected to be following different treatment 
regimens that usually include a statin together with additional LLT such as fibrates, bile acid 
sequestrant, and ezetimibe, as well as LA.  
Each patient’s individual therapeutic regimen should not be changed during the first 
24 weeks±3 days of lomitapide treatment (Efficacy Phase). After Week 24±3 days, 
adjustments to background LLT (including LA, when applicable) may be made as necessary 
for optimal standard of care. 
LA treatment causes a sharp drop in LDL-C, followed by a rebound phase. Therefore, in 
patients undergoing LA, it is important that lipid parameters are evaluated at a time that is as 
close as possible to and before the scheduled LA treatment. Once established, this time point 
for lipid profile blood draws should always be maintained, relative to the previous LA visit, so 
that lipid profiles are always performed at the same point on the LDL-C rebound curve.  
During the Run-in Period a stable frequency regimen (i.e., LA every X number of days) will be 
established. This frequency of LA needs to be maintained during the Efficacy Phase (through 
Week 24±3 days). The frequency of LA is usually personalised to meet the patient’s needs and 
the centre’s capacity. Therefore, windows are provided in Section 1.2 Flow Chart of Study and 
Follow-up for each visit to allow flexibility when patients can be seen. If a patient is unable to 
come for an LA per his/her usual regimen, LA should be rescheduled as soon as possible. If 
LA was missed at a time a study visit was scheduled, then blood for lipid profile should be 
drawn before the LA treatment and as close as possible to the LA regimen established during 
the Run-in Period or as revised if during the Safety Phase. 
However, for Visits 4 through 21 (i.e., during the Efficacy and Safety Phase) fasting lipids must 
be drawn just prior to the LA and LA must occur ±3 days from the regimen established during 
the Run-in Period. 
7.6.2 
Permitted Concomitant Medication 
The following medication will be permitted during study and follow-up: 
• Lipid-lowering medicinal products including statins, fibrates, bile acid sequestrants, and 
PCSK9 inhibitors 
Please note: Patients who receive atorvastatin, should separate the dose of the medicinal 
products by 12 hours, e.g., by taking atorvastatin in the morning and lomitapide in the 
evening (see Section 7.3.3. Dose Modification for Concomitant Medication). Patients who 
receive bile acid sequestrants, should separate the dose of the medicinal products by 
4 hours. Concomitant administration of >40 mg simvastatin is not permitted (see 
Section 7.6.3 Non-permitted Concomitant Medication, Food or Substances). 


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• Oestrogen-based oral contraceptives 
Please note: Postmenarchal female adolescent patients taking oestrogen-based oral 
contraceptives should be advised that diarrhoea and/or vomiting may reduce hormone 
absorption. In case of protracted or severe diarrhoea and/or vomiting lasting more than 
2 days, the investigator should advise according to national practice, which additional 
contraceptive measures (such as sexual abstinence, barrier methods) should be used for 
7 days after resolution of symptoms. 
• Supportive therapy upon the investigators’ discretion. 
The following medication will be permitted during the Safety Phase of the study: 
• If a weak CYP 3A4 inhibitor, e.g., aminoglutethimide, nafcillin, non-nucleoside reverse 
transcriptase 
inhibitors, 
phenobarbital, 
rifampicin, 
carbamazepine, 
pioglitazone, 
glucocorticoids, modafinil and phenytoin inhibitor is required during the Safety Phase, the 
dose of lomitapide should be reduced as described in Section 7.3.3 Dose Modification for 
Concomitant Medication. 
Please note: Patients who receive weak CYP 3A4 inhibitors, should separate the dose of 
the medicinal products by 12 hours.  
If atorvastatin is given concomitantly, it should be administered in the morning to separate 
it from lomitapide dosing by 12 hours. In case it is not possible to administer atorvastatin 
and lomitapide 12 hours apart, the lomitapide dose should be reduced by half (see 
Section 7.3.3 Dose Modification for Concomitant Medication). 
7.6.3 
Non-permitted Concomitant Medication, Food or Substances 
Non-permitted Concomitant Medication 
The following medication will not be permitted during the study: 
• Contraindications for the use of lomitapide according to section 4.3 of the SPC (included in 
the Lojuxta® SPC in lieu of an IB; see Section 18.1 Source Documents), such as  
− Concomitant administration of >40 mg simvastatin. 
− Concomitant use of strong or moderate CYP 3A4 inhibitors, e.g., antifungal azoles such 
as itraconazole, fluconazole, ketoconazole, voriconazole, posaconazole; macrolide 
antibiotics such as erythromycin or clarithromycin; ketolide antibiotics such as 
telithromycin; HIV protease inhibitors; the calcium channel blockers diltiazem and 
verapamil, and the anti-arrhythmic dronedarone. 
The following medication will not be permitted during the Efficacy Phase of the study: 
• Weak CYP 3A4 inhibitors, e.g., aminoglutethimide, nafcillin, non-nucleoside reverse 
transcriptase 
inhibitors, 
phenobarbital, 
rifampicin, 
carbamazepine, 
pioglitazone, 
glucocorticoids, modafinil and phenytoin. If a weak CYP 3A4 inhibitor is required during the 
Safety Phase, the dose of lomitapide should be reduced as described in Section 7.3.3 Dose 
Modification for Concomitant Medication. 
Non-permitted Concomitant Food or Substances 
The use of the following food or substances should be avoided with lomitapide: 
• Alcohol: Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury. 
• Grapefruit juice: Grapefruit juice is a moderate inhibitor of CYP 3A4 and is expected to 
substantially increase exposure to lomitapide. 
• Peppermint oil or Seville oranges. 
• St. John’s Wort (i.e., Hypericum perforatum). 


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8 
ASSESSMENTS 
Please refer to Section 1.2 Flow-Chart of Study and Follow-up for a tabular overview of 
assessments by visit.  
8.1 
Eligibility and Safety Assessments 
8.1.1 
Eligibility Assessments 
Informed Consent 
The investigator will obtain written informed assent (according to applicable local regulations) 
and/or consent from the patient and his/her parent/legal guardian before he/she will initiate any 
study-specific procedure.  
The following criteria will be assessed for eligibility prior to enrolment: 
Inclusion/Exclusion 
The investigator will assess the patient’s eligibility as outlined in Section 5.1 Inclusion Criteria 
and Section 5.2 Exclusion Criteria including confirmation of a negative urine pregnancy test in 
postmenarchal female adolescents. 
Demographics 
Age, gender, and ethnic origin will be recorded at Screening (Visit 1). 
Medical History/Current Medical Conditions 
The investigator will ask the patient and/or his/her parent/legal guardian for the patient’s 
general and disease-specific medical history and current medical conditions. Changes in 
current medical conditions, particularly cardiovascular procedures and events, will be recorded 
at each visit thereafter.  
For those patients who have had genetic testing in the past, information should be collected 
regarding the details of the alleles for the genes involved. 
Genetic Testing 
Genetic testing is strongly encouraged, but not mandatory and not required for determining 
eligibility. Patients who have not previously had genetic testing, will be asked, whether they 
would consent to genetic testing. A separate informed consent will be obtained for genetic 
testing. For those patients who have signed a separate informed consent form (ICF) for this 
procedure, a blood sample will be collected according to central laboratory procedures for 
genotyping specified in the ‘Laboratory Manual’ at Screening (Visit 1). If it is not possible to do 
this at Screening (Visit 1) it can be done at a later visit.  
Physical Examination 
The investigator will do a complete physical examination including growth and sexual 
maturation assessments of the patient (and a genitourinary, but not rectal exam at the 
investigator’s discretion) and will document height, weight, body mass index (BMI), body 
surface area (BSA) and all clinically relevant findings at Screening (Visit 1), at Visit 7 
(Week 12±3 days), Visit 10 (Week 24±3 days), Visit 18 (Week 56±3 days), at Visit 22 
(Week 104±1 week), and in case of premature discontinuation.  
At all other 4-week study visits, an abbreviated physical examination, to include a focused 
evaluation of general appearance, skin, thorax/lungs, CV, and abdomen, will be conducted. 
Xanthomas will be evaluated at every physical exam. 
Weight will be measured using a consistent approach at Screening and at each visit after the 
Run-in Period (i.e., child/adolescent always weighed in same amount of clothing, either in 
underwear, hospital gowns or by subtracting the weight of clothes):  


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• Patients of normal or below normal body weight (based on BMI with weight loss >1.5 kg 
since the previous visit) and their parent/legal guardian will meet with the dietitian for further 
instruction.  
• Patients with below normal body weight at any time during the study who continue to lose 
weight while on study medication despite all appropriate measures taken to correct for the 
weight loss and who are deemed to be at clinical risk in the judgment of the treating 
investigator should discontinue study medication and be followed until an acceptable stable 
weight is reached as judged by the investigator (see Section 7.3.2 Dose Modification, 
Interruption or Discontinuation for Adverse Events). 
Tanner Staging 
Tanner Staging is required for this study, and every attempt should be made to collect this 
information. Tanner Staging must be completed together with the physical exam by the same 
study-affiliated clinician (e.g., paediatrician) in the most inconspicuous manner for the patient 
as possible. When Tanner Staging is not completed at a required visit, it should be performed 
at the next study visit. 
Tanner Staging assessment consists of 2 domains (pubic hair and breast development) for 
girls and 3 domains (pubic hair, penis development, and testes development) for boys. The 
Tanner Staging assessment as a reference for the completing clinician is included in Appendix 
5 Tanner Staging. A patient who reaches Stage 5 (both in pubic hair and genitalia) does not 
need to continue with Tanner staging. 
Sites should make attempts to have examiners of both gender types available and to have the 
examination performed by the same gender as the patient, where possible. Otherwise, 
patient’s parent/guardian or a study-affiliated person (e.g., nurse) who is the same gender as 
the patient should be in the same examination room with the patient while the examination is 
performed. 
8.1.2 
Safety Assessments 
Concomitant Medication 
During the Screening and Run-in Period, at Baseline, during the Efficacy and Safety Phases 
as well as during the follow-up period, all concomitant medications and treatments (including 
LA, when applicable) will be recorded. The name, start and stop date, dosage, indication, 
frequency and route of administration of all medications as well as the name, start and stop 
date, indication, and frequency of all treatments will be recorded on the eCRF at first report 
and again only if anything has changed since the last visit. 
Adverse Events 
Adverse events occurring before the first administration of study medication will be recorded 
in the Medical History/Current Medical Conditions section of the eCRF. AEs occurring during 
the Efficacy and Safety Phases, and during the follow-up period until 30 days after the last 
administration of study medication will be recorded in the AE section of the eCRF. During the 
Screening and Run-in Period (<D0) and at Baseline (D0 of the Efficacy Phase) before study 
medication administration, AEs related to study procedures should also be reported. For 
reporting of AEs, please refer to Section 11.2 Recording of Adverse Events and Serious 
Adverse Events.  
Serious Adverse Events 
Serious AEs will be recorded in the SAE section of the eCRF during the Screening and Run-in 
Period, at Baseline, during the Efficacy and Safety Phases as well as during the follow-up 
period. For reporting of SAEs, please refer to Section 11.5 Immediately Reportable 
Information. 


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Vital Signs 
Vital signs, including systolic and diastolic blood pressure, heart rate, body temperature, and 
respiratory rate, will be measured at Screening (Visit 1), at Baseline (Visit 4), and at every visit 
thereafter (see Section 1.2 Flow Chart of Study and Follow-up). Blood pressure and heart rate 
will be measured after 5 minutes of rest in a sitting position. 
Electrocardiogram 
A 12-lead ECG will be recorded and read locally at Baseline (Visit 4), at Visit 10 
(Week 24±3 days), Visit 18 (Week 56±3 days), Visit 20 (Week 80±1 week), and at EoT 
(Week 104±1 week) (see Section 1.2 Flow Chart of Study and Follow-up).  
Electrocardiograms will be obtained after the patient has been supine for 5 minutes. The ECG 
recordings are to be reviewed by the investigator and classified as ‘normal’ or ‘abnormal’. 
Abnormal ECGs must in addition be classified as ‘abnormal, clinically significant’ or ‘abnormal, 
not clinically significant’. The reason(s) for ‘abnormal’ findings should be documented. 
Abnormal, clinically significant findings occurring after first administration of study medication 
should be reported as an AE (unless already pre-existing at Baseline with the same severity). 
Standard of Care Echocardiography 
It is anticipated that echocardiography will be performed annually as standard of care in this 
patient population. For this study, echocardiography is not mandated but data/results will be 
included as part of the study safety data. Information in relation to the most recent 
echocardiography on file (if available) will be documented in the eCRF at the following visits: 
Baseline (Visit 4), Visit 10 (Week 24±3 days), Visit 18 (Week 56±3 days), and at EoT 
(Week 104±1 week) (see Section 1.2 Flow Chart of Study and Follow-up). 
Pulmonary Function Test 
Pulmonary function tests, i.e., spirometry with DL,CO (diffusion capacity of the lung for carbon 
monoxide) will be performed to include: forced vital capacity (FVC); forced expiratory volume 
during 1 s (FEV1) and maximal mid-expiratory flow (FEF25-75) at Baseline (D0), Visit 10 
(Week 24±3 days), Visit 18 (Week 56±1 week), and at EoT (Week 104±1 week) (see 
Section 1.2 Flow Chart of Study and Follow-up).  
Nuclear Magnetic Resonance Imaging 
The terms Magnetic Resonance Imaging (MRI) and Nuclear Magnetic Resonance (NMR) are 
synonymous as are echography and ultrasound scan.  
Lipid accumulation in the liver (i.e., hepatic fat content) will be assessed at Baseline (D0), 
Visit 10 (Week 24±3 days), Visit 18 (Week 56±1 week), and at EoT (Week 104±1 week) in 
patients entering the EAP (<18 years of age)/transitioning to commercial product (≥18 years 
of age) or at Follow-up (Week 108) in patients who opt not to participate in or are unsuitable 
for the EAP (<18 years of age)/opt not to transition to commercial product (≥18 years of age; 
see Section 1.2 Flow Chart of Study and Follow-up). All patients will undergo NMR imaging 
unless it is contraindicated or not feasible (e.g., due to the need for sedation or general 
anaesthesia in very young or anxious patients). In this case, ultrasound scans will be used at 
the discretion of the investigator. The NMR images will be processed by a central reader, the 
ultrasound scans will be interpreted locally. 
Safety Laboratory Assessments 
The following safety laboratory tests are to be conducted as outlined in Section 1.2 Flow Chart 
of Study and Follow-up. See Appendix 6 Laboratory Tests for a comprehensive list of all 
laboratory tests to be performed. The total blood volume collected from each patient for the 
entire study is within the guidelines set forth by the WHO (Howie 2011). 


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Comprehensive Metabolic Panel and Liver Function Tests 
The comprehensive metabolic panel includes sodium (Na), potassium (K), calcium (Ca), 
carbon dioxide, chloride (Cl), blood glucose (BG), C-reactive protein (CRP), renal parameters 
(blood urea nitrogen [BUN], creatinine), creatinine kinase (CK), total protein, and albumin.  
Liver function tests include alanine aminotransferase (ALT), aspartate aminotransferase 
(AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (AP) and total bilirubin 
including direct and indirect bilirubin.  
Fasting Lipid Panel 
The patient should be fasting for at least 8 hours, except for water and medications, prior to 
drawing the fasting lipid panel. The fasting lipid panel includes the efficacy parameters TC, 
LDL-C, VLDL-C, calculated Non-HDL-C, TG, apo B, and Lp(a) (see Section 8.3.1 Fasting Lipid 
Panel) and the safety parameters high-density lipoprotein cholesterol (HDL-C) and 
apolipoprotein A-I (apo A-I). 
As the fasting lipid panel will be analysed at both the local hospital laboratory and the central 
laboratory, 2 separate samples must be drawn (see Section 10 Collection, Storage, and 
Shipment of Laboratory Samples). 
Complete Blood Count 
The complete blood count (CBC) includes white blood cell count, haemoglobin, haematocrit, 
platelet count, red blood cell count, red cell distribution width, mean corpuscular volume (MCV), 
mean corpuscular haemoglobin (MCH), and mean corpuscular haemoglobin concentration 
(MCHC). 
Fat-Soluble Vitamin Levels 
Vitamin A (retinol), vitamin E (alpha tocopherol), and vitamin D (25-hydroxy-D) will be 
assessed by measuring serum concentrations of the individual vitamins. In addition, vitamin E 
will also be reported as the ratio of alpha tocopherol/total lipids (TC + fasting TG). Levels of 
vitamin K will be assessed indirectly by measuring carboxylation of serum osteocalcin (ratio 
uncarboxylated osteocalcin/total osteocalcin). 
Fat-soluble vitamin levels will be analysed at the central laboratory specified in the ‘Laboratory 
Manual’ (see Section 10 Collection, Storage, and Shipment of Laboratory Samples). 
Serum Levels of Essential Fatty Acids (EFA) 
The Essential Fatty Acid (EFA) profile comprises serum levels of linoleic acid, alpha linoleic 
acid (ALA), arachidonic acid (AA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), 
and eicosatrienoic acid.  
Serum levels of EFA will be analysed at the central laboratory specified in the ‘Laboratory 
Manual’ (see Section 10 Collection, Storage, and Shipment of Laboratory Samples). 
Hormones 
Thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), serum cortisol, 
and sex hormones (serum follicle stimulating hormone [FSH] and luteinising hormone [LH]) will 
be assessed. The blood sample for testing of serum cortisol must be obtained in the early 
morning (6:00 to 8:00 a.m.). For patients who are Tanner Stage ≥2, serum oestradiol will be 
assessed for female patients and serum testosterone will be assessed for male patients. 
Urinalysis 
Urinalysis includes the assessment of urine colour, turbidity, pH, glucose, bilirubin, ketones, 
blood, protein, and white blood cells. 


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Pregnancy Tests 
Urine pregnancy tests will be conducted in postmenarchal female adolescent patients using 
test strips at every scheduled visit from Visit 1 through Visit 23 and every 4 weeks after Visit 18 
at Week 56±3 days through Week 104±1 week. 
If a patient becomes pregnant during the study, during the follow-up, or 30 days within the last 
application of study medication, the study medication must be discontinued immediately (see 
Section 7.4 Patient Discontinuation Criteria) and the sponsor will have to be informed within 
24 hours.  
The investigator will be asked to complete a pregnancy report provided by the sponsor. He/she 
will be asked to obtain data on the course of the pregnancy, including perinatal and neonatal 
outcome (see Section 11.5.4 Other Reportable Information). 
Bone Health 
Bone health will be assessed indirectly using growth to track age-appropriate progress, and 
measurement of 25-hydroxy-D and total and uncarboxylated osteocalcin levels (as reflection 
of vitamin K levels). Effects on growth, bone health and bone age will be assessed using both 
measurements of children’s height and growth charts to track age-appropriate progress at 
Screening and from Baseline at every visit through Week 104±1 week and/or at EoT, together 
with analysis of Vitamin D and K levels at Screening, Baseline, Week 24±3 days, 
Week 56±3 days, Week 80±1 week, Week 104±1 week and/or at EoT (and at Week 108 for 
patients who opt not to participate in or are unsuitable for the EAP [<18 years of age]/opt not 
to transition to commercial product [≥18 years of age]). 
8.2 
Pharmacokinetics 
Plasma levels of lomitapide will be measured. Baseline PK will be taken at D0. Steady-state 
PK from Visit 5 (Week 4±3 days) through Visit 10 (Week 24±3 days) will be evaluated. Single 
PK samples will be collected at Visit 5 (Week 4±3 days), Visit 7 (Week 12±3 days), Visit 8 
(Week 16±3 days), and at Visit 10 (Week 24±3 days). Two PK samples will be collected at 
least 1 hour apart at Visit 6 (Week 8±3 days) and at Visit 9 (Week 20±3 days); these samples 
must be collected as separate blood draws (time between separate blood draws might be used 
for undertaking other procedures scheduled for the respective visit(s)). 
All samples taken are trough samples of about 3.5 mL each (the volume of blood taken might 
be adjusted based on the body weight of the patient and central laboratory procedures). 
Samples will not be taken in duplicate. The date and time of the patient’s last lomitapide dose 
and the date and time of the sample(s) should be recorded in the eCRF.  
8.3 
Assessment of Efficacy 
8.3.1 
Fasting Lipid Panel 
The patient should be fasting for at least 8 hours, except for water and medications, prior to 
drawing the fasting lipid panel. The fasting lipid panel includes TC, LDL-C, VLDL-C, calculated 
Non-HDL-C, TG, apo B, and Lp(a) and the safety parameters HDL-C and apo A-I (see 
Section 8.1.2 Safety Assessments).  
At Screening (Visit 1), LDL-C may be estimated from the Friedewald formula if TG are 
<400 mg/dL; however, if TG are ≥400 mg/dL, LDL-C will be measured directly. 
Friedewald formula: 𝐿𝐿𝐿𝐿𝐿𝐿-𝐶𝐶= 𝑇𝑇𝑇𝑇−(𝐻𝐻𝐻𝐻𝐻𝐻-𝐶𝐶+
𝑇𝑇𝑇𝑇
5 ) 
At all other visits, LDL-C is measured directly. 


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For patients on LA, fasting lipid panels must be drawn at all assessments required by the 
protocol and (as applicable) are to be obtained immediately before the scheduled LA treatment 
(see Section 7.6.1 Concomitant Lipid-Lowering Treatment). 
As the fasting lipid panel will be analysed at both the local hospital laboratory and the central 
laboratory, 2 separate samples must be drawn (see Section 10 Collection, Storage, and 
Shipment of Laboratory Samples). 
8.3.2 
LDL-C Treatment Criteria 
The LDL-C values for Screening (Visit 1) and Week -3 to Week -2 (Visit 2) must be as follows 
for a patient to be eligible to begin treatment on D0. 
Baseline LDL-C on LLT (Cmax of LDL-C immediately prior to LA, if applicable) of either: 
a. 
>160 mg/dL (4.1 mmol/L, no documented CVD) or 
b. 
>130 mg/dL (3.4 mmol/L, established CVD defined as aortic valve disease and/or 
coronary atherosclerosis) 
8.4 
Exploratory Assessments 
8.4.1 
Regression or Resolution of Xanthomas 
The patient’s xanthomas (tendon and cutaneous, size and location) will be evaluated during 
physical examination at Screening (Visit 1), at Baseline (Visit 4, D0) and at every visit 
thereafter.  
8.4.2 
Assessment of Carotid Intima-Media Thickness and Flow-mediated 
Dilation 
Carotid intima-media thickness (CIMT, mandatory) and flow-mediated dilation (FMD, 
whenever possible) will be assessed using ultrasound scan to evaluate carotid atherosclerotic 
vascular disease and brachial artery dilation after a transient period of forearm ischaemia at 
Baseline (Visit 4, D0), at Visit 18 (Week 56±3 days), and at EoT (Week 104±1 week).  
8.4.3 
Liposcale® Test 
The Liposcale® Test will be used to assess changes from Baseline through Week 24±3 days 
in cholesterol and triglyceride content of VLDL, IDL, LDL and HDL, particle number and size 
of VLDL, LDL, and HDL as well as particle number of their respective lipoprotein subclasses 
(large, medium, and small), from PK samples at Week 4±3 days, Week 8±3 days, 
Week 12±3 days, Week 16±3 days, Week 20±3 days and Week 24±3 days. For this 2D NMR 
analysis, 200 µL aliquots will only be taken from each PK sample at the central laboratory 
specified in the ‘Laboratory Manual’, if sufficient sample material has been provided and would 
otherwise be discarded. No additional blood sampling from the patient at the site will be 
required (see Section 10 Collection, Storage and Shipment of Laboratory Samples). 


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8.5 
Palatability 
Palatability will be assessed using a 5-point facial hedonic scale, anchored with descriptors, to 
record the children’s assessment of palatability in terms of overall liking (see Figure 4). 
Figure 4 
Example of a 5-Point Facial Hedonic Scale Used for Hedonic Ratings by 
Children (Guinard 2000) 
 
Palatability will be assessed on the first occasion that any patient who is not able to swallow 
the intact capsule(s) takes lomitapide by opening and sprinkling the capsule onto either food 
media (i.e., if a patient tries both food media, assessment will be made at the first instance of 
taking the study medication with apple sauce and the first instance of taking the study 
medication with mashed banana).  
The investigator or a study team member will also ask the parent(s)/legal guardian(s) to 
evaluate the children’s reaction to investigational product and dietary supplement 
administration. A 3-point scale that assesses the parent(s)/legal guardian(s) interpretation of 
the child’s reaction/facial expression will be used to determine whether they find lomitapide 
“pleasant”, “unpleasant” or are “not sure”.  
In addition, an assessment of ease of administration will be incorporated by asking the 
parent(s)/legal guardian(s) the following question at each visit during the treatment phase: “Do 
you sometimes have problems in giving the medication to your child because he/she refuses 
to take it or throws it up immediately after taking it? (Yes/No).” The same question will be asked 
for the administration of dietary supplements. 
Timing of the reaction relative to dosing will be recorded to help distinguish between palatability 
of the investigational product and GI events that are a result of the investigational products 
mechanism of action.  
8.6 
Other Assessments 
8.6.1 
Diet Instructions and Diet Records 
The occurrence and severity of GI AEs associated with the use of lomitapide decreases in the 
presence of a low-fat diet. Patients will start to follow a diet supplying <20% of energy from fat 
or <30 g fat, whichever is the lesser amount at Visit 2 (Start of the Run-in Period) and will 
continue this diet until the EoT (and throughout the EAP [<18 years of age]/administration of 
commercial product [≥18 years of age], when applicable).  
A dietitian will provide dietary counselling to the patients and their parents/legal guardians from 
Visit 2 (Start of the Run-in Period) through Visit 5 (Week 4±3 days). Patients and parents/legal 
guardians will be instructed on how to consume <20% energy from fat or <30 g fat, whichever 
is the lesser amount. Instructions will include detailed information concerning the role of dietary 


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fat and GI-related symptoms and patients will be encouraged to pay special attention to foods 
they eat when/if they experience these symptoms. The dietitian will review current eating habits 
in order to point out needed changes and address potential adherence problems. The dietitian 
will provide diet instructions that are tailored to each patient’s caloric needs to promote healthy 
weight maintenance.  
The dietitian will also review compliance with the diet and discuss any issues or concerns the 
patient and his/her parents/legal guardians may have with the diet at Visit 3 (Week -3 to 
Week -2). The dietitian will inform patients and their parents/legal guardians to call him/her to 
discuss over the phone or schedule a meeting to address any diet-related questions or 
concerns at any time during the study. Additional resources pertaining to the diet will be 
available to the dietitian and the patient and his/her parent/legal guardian. 
Weight will be measured using a consistent approach at Screening and at each visit after the 
Run-in Period (i.e., child/adolescent always weighed in same amount of clothing, either in 
underwear, hospital gowns or by subtracting the weight of clothes). Patients of normal or below 
normal body weight with weight loss >3% since the last visit will be instructed by the dietitian 
on how to increase caloric intake based on individual needs. The standard recommended fat 
intake for children >2 years old is to follow a diet with <30% energy from fat, hence, decreasing 
dietary fat intake to <20% or <30 g fat, whichever is the lesser amount should not pose any 
risk to patients of any age that may be enrolled in this study. 
The investigator can request additional dietary counselling as clinically indicated. At the same 
visits, 2-Day Diet Records will be given to the patients and their parents/legal guardians.  
In order to assess dietary compliance and to provide information for interpreting possible GI 
AEs, patients will be instructed to document all food and beverages consumed periodically 
throughout the study, using Diet Records. A 2-Day Diet Record will be dispensed and returned 
from Visit 2 (Start of the Run-in Period) through Visit 21 (Week 92±1 week).  
If diet-related problems are noted during the study, e.g., weight loss or GI-related complaints 
such as diarrhoea, the patients may be requested to fill out additional Diet Records. Note that 
Diet Records collected during the Run-in Period do not get analysed, but are used by the 
dietitian on site to assess compliance before beginning lomitapide treatment. 
Patients treated with lomitapide and their parents/legal guardians should be advised of the 
potential risk of dehydration in relation to GI AEs and take precautions to avoid fluid depletion. 
Please refer to Section 6.3 Dietary Supplements for details regarding oral supplementation 
with vitamin E and essential fatty acids. 
9 
VISIT SCHEDULE 
The visit schedule is summarised in Section 1.2 Flow Chart of Study and Follow-up. The 
calculation of all study days is based on D0, which is defined as the day of the first application 
of study medication. 
9.1 
Screening Period (Starting at Week -12, i.e., ≤12 Weeks Prior to 
Baseline for a Minimum of 6 Weeks), Visit 1 
Study sites might contact patients who are registered in centre-specific databases to inform 
them about the study and to invite them for screening.  
The investigator will have to obtain written informed assent/consent (according to applicable 
local regulations) from the patient and written informed consent from his/her parent/legal 
guardian before any study-related procedure will be initiated (see Section 14.3 Patient and 
Parent/Legal Guardian Information and Informed Consent). If the patient and his/her 
parent/legal guardian consent to the optional genetic testing, written informed consent for 
genetic testing will also be obtained.  


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9.1.1 
Visit 1 (Up to Week -12) 
During Visit 1 up to Week -12, the following will be completed: 
• Confirmation of patient eligibility using the inclusion criteria (see Section 5.1 Inclusion 
Criteria) and exclusion criteria (see Section 5.2 Exclusion Criteria)  
• Record of general and disease-specific medical history and current medical conditions 
including cardiovascular procedures and events 
• Record of demographic data (age, gender, and ethnic origin) 
• Complete physical examination of the patient (and a genitourinary, but not rectal exam at 
the investigator’s discretion) including the documentation of height, weight, BMI, BSA and 
all clinically relevant findings, such as xanthomas (see Section 8.1.1 Eligibility 
Assessments) 
• Determination of sexual maturation based on Tanner staging (see Section 8.1.1 Eligibility 
Assessments and Appendix 5 Tanner Staging) 
• Measurement of vital signs and blood pressure (see Section 8.1.1 Eligibility Assessments) 
• Record of concomitant medication including LLT and/or LA when applicable (see 
Section 7.6.1 
Concomitant 
Lipid-lowering 
Treatment 
and 
Section 8.1.2 
Safety 
Assessments) 
• Collection of blood samples for the following tests (see Section 8.1.2 Safety Assessments): 
− Complete blood count 
− Comprehensive metabolic panel 
− Liver function tests 
− Fasting lipid panel (see Section 8.3.1 Fasting Lipid Panel) 
− Serum level of essential fatty acids 
− Fat-soluble vitamin levels 
− Hormones (TSH, ACTH, serum cortisol [to be measured between 06:00 and 08:00 a.m.], 
FSH, LH) 
− In patients who are Tanner Stage ≥2, serum oestradiol will be assessed for female 
patients and serum testosterone will be assessed for male patients 
• Urinalysis (urine colour, turbidity, pH, glucose, bilirubin, ketones, blood, protein, and white 
blood cells) 
• A urine pregnancy test in all postmenarchal female adolescents (see Section 8.1.2 Safety 
Assessments) 
• Genetic testing in patients who have not previously had genotyping and who have 
consented to this procedure (collection of a blood sample according to central laboratory 
procedures specified in the ‘Laboratory Manual’, see Section 8.1.1 Eligibility Assessments). 
If it is not possible to do genetic testing at Screening (Visit 1) it can be done at a later visit. 
9.2 
Re-screening 
If the patient is a screen failure, he/she can be re-screened on 2 separate occasions within 
2 weeks of the previous (re-)screening. The patient can only be re-screened for the purpose 
of repeating LDL-C (inclusion criterion 2), serum CK (exclusion criterion 4) or blood pressure 
(exclusion criterion 6) measurement(s), as deemed appropriate by the investigator, since these 
parameters might change within a short timeframe. A new screening for eligibility based on all 
other inclusion and exclusion criteria is not possible, because they are not expected to change 


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within a short timeframe. The patient must be reconsented for the re-screening procedure(s); 
however, to reduce study burden and blood draws in this paediatric patient population, other 
screening procedures must not be repeated. The patient will be assigned a new patient 
number. 
9.3 
Stratified Enrolment and Start of Run-in Period (Starting at 
Minimum at Week -6, i.e., 6 Weeks Prior to Baseline for a 
Minimum of 6 Weeks, Visits 2 to 3 
9.3.1 
Visit 2 (Stratified Enrolment and Start of Run-in Period, at Minimum 
Week -6) 
Upon confirmation of eligibility, patients will come back to the study site for Visit 2 (at minimum 
Week -6) for stratified enrolment and to start the Run-in Period. At Visit 2, the following 
procedures will be conducted: 
• Dietary counselling (see Section 8.6.1 Diet Instructions and Diet Records) 
• Dispensing of 2-Day Diet record (used to enable adjustments to the patient’s diet before 
starting study drug; see Section 8.6.1 Diet Instructions and Diet Records) 
• A urine pregnancy test in all postmenarchal female adolescents (see Section 8.1.2 Safety 
Assessments) 
• Record of concomitant medication including LLT and/or LA when applicable (see 
Section 7.6.1 
Concomitant 
Lipid-lowering 
Treatment 
and 
Section 8.1.2 
Safety 
Assessments) 
• Enquiry about any AEs/SAEs and record in the AE section of the eCRF. 
9.3.2 
Visit 3 (Compliance, Week -3 to Week -2) 
The patient will visit the study site for Visit 3 (Week -3 to Week -2) and must present in fasting 
state. The following procedures will be conducted:  
• Dietary counselling (see Section 8.6.1 Diet Instructions and Diet Records) 
• Dispensing of new and collection of old 2-Day Diet records (see Section 8.6.1 Diet 
Instructions and Diet Records) 
• Collection of blood samples for fasting lipid panel (see Section 8.3.1 Fasting Lipid Panel) 
• Dispensing of dietary supplements (see Section 6.3 Dietary Supplements) 
• A urine pregnancy test in all postmenarchal female adolescents (see Section 8.1.2 Safety 
Assessments) 
• Record of concomitant medication including LLT and/or LA when applicable (see 
Section 7.6.1 
Concomitant 
Lipid-lowering 
Treatment 
and 
Section 8.1.2 
Safety 
Assessments) 
• Enquiry about any AEs/SAEs and record in the AE section of the eCRF. 
9.4 
Efficacy Phase (Baseline, D0 to Week 24±3 days), Visits 4 to 10 
9.4.1 
Visit 4 (Baseline, D0) 
The patient will visit the study site for the Baseline assessment of the Efficacy Phase at Visit 4 
(D0) and must present in fasting state. The following procedures will be conducted:  
• Confirmation of patient eligibility using the inclusion criteria (see Section 5.1 Inclusion 
Criteria) and exclusion criteria (see Section 5.2 Exclusion Criteria)  


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• Abbreviated physical examination (including a focused evaluation of general appearance, 
skin, thorax/lungs, CV, abdomen, and xanthomas) and record of height, weight, BMI, and 
BSA (see Section 8.1.1 Eligibility Assessments) 
• Determination of sexual maturation based on Tanner staging (see Section 8.1.1 Eligibility 
Assessments and Appendix 5 Tanner Staging) 
• Record of 12-lead ECG (read locally, see Section 8.1.2 Safety Assessments) 
• Collection of information in relation to the most recent standard of care echocardiography 
on file (if available, see Section 8.1.2 Safety Assessments) 
• Measurement of vital signs and blood pressure (see Section 8.1.1 Eligibility Assessments) 
• Pulmonary Function Test (see Section 8.1.2 Safety Assessments) 
• NMR imaging of liver for hepatic fat assessment; if NMR imaging is contraindicated or not 
feasible (e.g., due to the need for sedation or general anaesthesia in very young or anxious 
patients), ultrasound scans will be used at the discretion of the investigator (see 
Section 8.1.2 Safety Assessments) 
• Dietary counselling (see Section 8.6.1 Diet Instructions and Diet Records) 
• Dispensing of new and collection of old 2-Day Diet records (see Section 8.6.1 Diet 
Instructions and Diet Records) 
• Carotid intima-media thickness (CIMT, mandatory) and flow-mediated dilation (FMD, 
whenever possible) using ultrasound scan (see Section 8.4.2 Assessment of Carotid 
Intima-Media Thickness and Flow-mediated Dilation) 
• Collection of blood samples for the following tests (see Section 8.1.2 Safety Assessments): 
− Complete blood count 
− Comprehensive metabolic panel 
− Liver function tests 
− Fasting lipid panel (see Section 8.3.1 Fasting Lipid Panel) 
− Serum level of essential fatty acids 
− Serum lipase 
− Fat-soluble vitamin levels 
− Hormones (TSH, ACTH, serum cortisol [to be measured between 06:00 and 08:00 a.m.], 
FSH, LH) 
− In patients who are Tanner Stage ≥2, serum oestradiol will be assessed for female 
patients and serum testosterone will be assessed for male patients 
− Pharmacokinetics (single trough sample, date and time of the patient’s last lomitapide 
dose and time of the sample should be recorded in the eCRF) 
• Urinalysis (urine colour, turbidity, pH, glucose, bilirubin, ketones, blood, protein, and white 
blood cells) 
• A urine pregnancy test in all postmenarchal female adolescents (see Section 8.1.2 Safety 
Assessments) 
• Dispensing of dietary supplements and collection of used dietary supplement bottles as 
needed (see Section 6.3 Dietary Supplements) 
• Dispensing of study medication (see Section 7.2 Treatment Schedule): The first dose of 
study medication will be administered at the study site.  


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• Palatability assessment: A 5-point facial hedonic scale will be used to record the child’s 
assessment of palatability of study medication on the first occasion that any patient who is 
unable to swallow the intact capsule(s) and opens the capsule(s) and sprinkles the capsule 
content on a small amount (1 tablespoon) of either apple sauce or mashed banana (i.e., if 
a patient tries both food media, assessment will be made at the first instance of taking the 
study medication with apple sauce and the first instance of taking the study medication with 
mashed banana). The type of food media (apple sauce or mashed banana) will be captured 
(see Section 8.5 Palatability) 
• Record of concomitant medication including LLT and/or LA when applicable (see 
Section 7.6.1 
Concomitant 
Lipid-lowering 
Treatment 
and 
Section 8.1.2 
Safety 
Assessments) 
• Enquiry about any AEs/SAEs and record in the AE section of the eCRF. 
9.4.2 
Visits 5, 6, 8, and 9 (Week 4±3 days, Week 8±3 days, Week 16±3 days, 
and Week 20±3 days) 
The patient will visit the study site for Visits 5, 6, 8 and 9 of the Efficacy Phase and must present 
in fasting state. The following procedures will be conducted:  
• Abbreviated physical examination (including a focused evaluation of general appearance, 
skin, thorax/lungs, CV, abdomen, and xanthomas) and record of height, weight, BMI, and 
BSA (see Section 8.1.1 Eligibility Assessments) 
• Measurement of vital signs and blood pressure (see Section 8.1.1 Eligibility Assessments) 
• Dietary counselling (see Section 8.6.1 Diet Instructions and Diet Records) at Visit 5 
(Week 4±3 days) only and as clinically indicated thereafter 
• Dispensing of new and collection of old 2-Day Diet records (see Section 8.6.1 Diet 
Instructions and Diet Records) 
• Collection of blood samples for the following tests (see Section 8.1.2 Safety Assessments): 
− Comprehensive metabolic panel 
− Liver function tests 
− Fasting lipid panel (see Section 8.3.1 Fasting Lipid Panel) 
− Pharmacokinetics (single trough samples at Visit 5 [Week 4±3 days] and Visit 8 
[Week 16±3 days]; date and time of the patient’s last lomitapide dose and time of the 
sample should be recorded in the eCRF) 
− Two PK samples will be collected at least 1 hour apart at Visit 6 (Week 8±3 days) and 
Visit 9 (Week 20±3 days); date and time of the patient’s last lomitapide dose and time of 
the samples should be recorded in the eCRF; these samples must be collected as 
separate blood draws (time between separate blood draws might be used for undertaking 
other procedures scheduled for the respective visit(s)). 
• A urine pregnancy test in all postmenarchal female adolescents (see Section 8.1.2 Safety 
Assessments) 
• Dispensing of dietary supplements and collection of used dietary supplement bottles as 
needed (see Section 6.3 Dietary Supplements) 
• Dispensing of study medication and collection of used study medication bottles as needed 
(see Section 7.2 Treatment Schedule). 
• Study medication compliance check (see Section 6.2 Investigational Product Compliance) 
• Palatability assessment (see Section 8.5 Palatability):  


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− The investigator will ask the parent(s)/legal guardian(s) to evaluate the children’s 
reaction to investigational product and dietary supplement administration. A 3-point scale 
that assesses the parent(s)/legal guardian(s) interpretation of the child’s reaction/facial 
expression will be used to determine whether they find lomitapide “pleasant”, 
“unpleasant” or are “not sure”.  
− In addition, an assessment of ease of administration will be incorporated by asking the 
parent(s)/legal guardian(s) the following question at each visit during the treatment 
phase: “Do you sometimes have problems in giving the medication to your child because 
he/she refuses to take it or throws it up immediately after taking it? (Yes/No).” The same 
question will be asked for the administration of the dietary supplements. 
− Timing of the reaction relative to dosing will be recorded to help distinguish between 
palatability of the investigational product and GI events that are a result of the 
investigational products mechanism of action.  
• Record of concomitant medication including LLT and/or LA when applicable (see 
Section 7.6.1 
Concomitant 
Lipid-lowering 
Treatment 
and 
Section 8.1.2 
Safety 
Assessments) 
• Enquiry about any AEs/SAEs and record in the AE section of the eCRF. 
9.4.3 
Visit 7 (Week 12±3 days) 
The patient will visit the study site for Visit 7 of the Efficacy Phase and must present in fasting 
state. The following procedures will be conducted:  
• Complete physical examination of the patient (and a genitourinary, but not rectal exam at 
the investigator’s discretion) including the documentation of height, weight, BMI, BSA and 
all clinically relevant findings, such as xanthomas (see Section 8.1.1 Eligibility 
Assessments) 
• Determination of sexual maturation based on Tanner staging (see Section 8.1.1 Eligibility 
Assessments and Appendix 5Tanner Staging) 
• Measurement of vital signs and blood pressure (see Section 8.1.1 Eligibility Assessments) 
• Dietary counselling (see Section 8.6.1 Diet Instructions and Diet Records) as clinically 
indicated 
• Dispensing of new and collection of old 2-Day Diet records (see Section 8.6.1 Diet 
Instructions and Diet Records) 
• Collection of blood samples for the following tests (see Section 8.1.2 Safety Assessments): 
− Comprehensive metabolic panel 
− Liver function tests 
− Fasting lipid panel (see Section 8.3.1 Fasting Lipid Panel) 
− Pharmacokinetics (single trough sample, date and time of the patient’s last lomitapide 
dose and time of the sample should be recorded in the eCRF) 
• A urine pregnancy test in all postmenarchal female adolescents (see Section 8.1.2 Safety 
Assessments) 
• Dispensing of dietary supplements and collection of used dietary supplement bottles as 
needed (see Section 6.3 Dietary Supplements) 
• Dispensing of study medication and collection of used study medication bottles as needed 
(see Section 7.2 Treatment Schedule). 
• Study medication compliance check (see Section 6.2 Investigational Product Compliance) 


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• Record of concomitant medication including LLT and/or LA when applicable (see 
Section 7.6.1 
Concomitant 
Lipid-lowering 
Treatment 
and 
Section 8.1.2 
Safety 
Assessments) 
• Enquiry about any AEs/SAEs and record in the AE section of the eCRF. 
9.4.4 
Visit 10 (Week 24±3 days) 
The patient will visit the study site for Visit 10 of the Efficacy Phase and must present in fasting 
state. The following procedures will be conducted:  
• Complete physical examination of the patient (and a genitourinary, but not rectal exam at 
the investigator’s discretion) including the documentation of height, weight, BMI, BSA and 
all clinically relevant findings, such as xanthomas (see Section 8.1.1 Eligibility 
Assessments) 
• Determination of sexual maturation based on Tanner staging (see Section 8.1.1 Eligibility 
Assessments and Appendix 5Tanner Staging) 
• Record of 12-lead ECG (read locally, see Section 8.1.2 Safety Assessments) 
• Collection of information in relation to the most recent standard of care echocardiography 
on file (if available, see Section 8.1.2 Safety Assessments) 
• Measurement of vital signs and blood pressure (see Section 8.1.1 Eligibility Assessments) 
• Pulmonary Function Test (see Section 8.1.2 Safety Assessments) 
• NMR imaging of liver for hepatic fat assessment; if NMR imaging is contraindicated or not 
feasible (e.g., due to the need for sedation or general anaesthesia in very young or anxious 
patients), ultrasound scans will be used at the discretion of the investigator (see 
Section 8.1.2 Safety Assessments) 
• Dietary counselling (see Section 8.6.1 Diet Instructions and Diet Records) as clinically 
indicated 
• Dispensing of new and collection of old 2-Day Diet records (see Section 8.6.1 Diet 
Instructions and Diet Records) 
• Collection of blood samples for the following tests (see Section 8.1.2 Safety Assessments): 
− Comprehensive metabolic panel 
− Liver function tests 
− Fasting lipid panel (see Section 8.3.1 Fasting Lipid Panel) 
− Serum levels of essential fatty acids 
− Serum lipase 
− Fat-soluble vitamin levels 
− Pharmacokinetics (single trough sample, date and time of the patient’s last lomitapide 
dose and time of the sample should be recorded in the eCRF) 
• A urine pregnancy test in all postmenarchal female adolescents (see Section 8.1.2 Safety 
Assessments) 
• Dispensing of dietary supplements and collection of used dietary supplement bottles as 
needed (see Section 6.3 Dietary Supplements) 
• Dispensing of study medication and collection of used study medication bottles as needed 
(see Section 7.2 Treatment Schedule). 
• Study medication compliance check (see Section 6.2 Investigational Product Compliance) 


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• Record of concomitant medication including LLT and/or LA when applicable (see 
Section 7.6.1 
Concomitant 
Lipid-lowering 
Treatment 
and 
Section 8.1.2 
Safety 
Assessments) 
• Enquiry about any AEs/SAEs and record in the AE section of the eCRF. 
9.5 
Safety Phase (Week 28±3 Days to Week 92±1 Week), Visits 11 to 
21 
9.5.1 
Visits 11 to 17 (Week 28±3 days, Week 32±3 days, Week 36±3 days, 
Week 40±3 days, Week 44±3 days, Week 48±3 days, and 
Week 52±3 days) 
The patient will visit the study site for Visits 11 through 17 of the Safety Phase and must present 
in fasting state. The following procedures will be conducted:  
• Abbreviated physical examination (including a focused evaluation of general appearance, 
skin, thorax/lungs, CV, abdomen, and xanthomas) and record of height, weight, BMI, and 
BSA (see Section 8.1.1 Eligibility Assessments) 
• Measurement of vital signs and blood pressure (see Section 8.1.1 Eligibility Assessments) 
• Dietary counselling (see Section 8.6.1 Diet Instructions and Diet Records) as clinically 
indicated 
• Dispensing of new and collection of old 2-Day Diet records (see Section 8.6.1 Diet 
Instructions and Diet Records) 
• Collection of blood samples for the following tests (see Section 8.1.2 Safety Assessments): 
− Comprehensive metabolic panel 
− Liver function tests 
− Fasting lipid panel (see Section 8.3.1 Fasting Lipid Panel) 
• A urine pregnancy test in all postmenarchal female adolescents (see Section 8.1.2 Safety 
Assessments) 
• Dispensing of dietary supplements and collection of used dietary supplement bottles as 
needed (see Section 6.3 Dietary Supplements) 
• Dispensing of study medication and collection of used study medication bottles as needed 
(see Section 7.2 Treatment Schedule). 
• Study medication compliance check (see Section 6.2 Investigational Product Compliance) 
• Record of concomitant medication including LLT and/or LA when applicable (see 
Section 7.6.1 
Concomitant 
Lipid-lowering 
Treatment 
and 
Section 8.1.2 
Safety 
Assessments) 
• Enquiry about any AEs/SAEs and record in the AE section of the eCRF. 
9.5.2 
Visit 18 (Week 56±3 days) 
The patient will visit the study site for Visit 18 of the Safety Phase and must present in fasting 
state. The following procedures will be conducted:  
• Complete physical examination of the patient (and a genitourinary, but not rectal exam at 
the investigator’s discretion) including the documentation of height, weight, BMI, BSA and 
all clinically relevant findings, such as xanthomas (see Section 8.1.1 Eligibility 
Assessments) 


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• Determination of sexual maturation based on Tanner staging (see Section 8.1.1 Eligibility 
Assessments and Appendix 5 Tanner Staging) 
• Record of 12-lead ECG (read locally, see Section 8.1.2 Safety Assessments) 
• Collection of information in relation to the most recent standard of care echocardiography 
on file (if available, see Section 8.1.2 Safety Assessments) 
• Measurement of vital signs and blood pressure (see Section 8.1.1 Eligibility Assessments) 
• Pulmonary Function Test (see Section 8.1.2 Safety Assessments) 
• NMR imaging of liver for hepatic fat assessment; if NMR imaging is contraindicated or not 
feasible (e.g., due to the need for sedation or general anaesthesia in very young or anxious 
patients), ultrasound scans will be used at the discretion of the investigator (see 
Section 8.1.2 Safety Assessments) 
• Dietary counselling (see Section 8.6.1 Diet Instructions and Diet Records) as clinically 
indicated 
• Dispensing of new and collection of old 2-Day Diet records (see Section 8.6.1 Diet 
Instructions and Diet Records) 
• Carotid intima-media thickness (CIMT, mandatory) and flow-mediated dilation (FMD, 
whenever possible) using ultrasound scan (see Section 8.4.2 Assessment of Carotid 
Intima-Media Thickness and Flow-mediated Dilation) 
• Collection of blood samples for the following tests (see Section 8.1.2 Safety Assessments): 
− Complete blood count 
− Comprehensive metabolic panel 
− Liver function tests 
− Fasting lipid panel (see Section 8.3.1 Fasting Lipid Panel) 
− Serum levels of essential fatty acids 
− Serum lipase 
− Fat-soluble vitamin levels 
− Hormones (TSH, ACTH, serum cortisol [to be measured between 06:00 and 08:00 a.m.], 
FSH, LH) 
− In patients who are Tanner Stage ≥2, serum oestradiol will be assessed for female 
patients and serum testosterone will be assessed for male patients 
• Urinalysis (urine colour, turbidity, pH, glucose, bilirubin, ketones, blood, protein, and white 
blood cells) 
• A urine pregnancy test in all postmenarchal female adolescents (see Section 8.1.2 Safety 
Assessments) 
• Dispensing of dietary supplements and collection of used dietary supplement bottles as 
needed (see Section 6.3 Dietary Supplements) 
• Dispensing of study medication and collection of used study medication bottles as needed 
(see Section 7.2 Treatment Schedule). 
• Study medication compliance check (see Section 6.2 Investigational Product Compliance) 
• Record of concomitant medication including LLT and/or LA when applicable (see 
Section 7.6.1 
Concomitant 
Lipid-lowering 
Treatment 
and 
Section 8.1.2 
Safety 
Assessments) 


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• Enquiry about any AEs/SAEs and record in the AE section of the eCRF. 
9.5.3 
Visits 19 to 21 (Week 68±1 week, Week 80±1 week, and 
Week 92±1 week) 
The patient will visit the study site for Visits 19 through 21 of the Safety Phase and must present 
in fasting state. The following procedures will be conducted:  
• Abbreviated physical examination (including a focused evaluation of general appearance, 
skin, thorax/lungs, CV, abdomen, and xanthomas) and record of height, weight, BMI, and 
BSA (see Section 8.1.1 Eligibility Assessments) 
• Record of 12-lead ECG (read locally, Visit 20 only, see Section 8.1.2 Safety Assessments) 
• Measurement of vital signs and blood pressure (see Section 8.1.1 Eligibility Assessments) 
• Dietary counselling (see Section 8.6.1 Diet Instructions and Diet Records) as clinically 
indicated 
• Dispensing of new and collection of old 2-Day Diet records (see Section 8.6.1 Diet 
Instructions and Diet Records) 
• Collection of blood samples for the following tests (see Section 8.1.2 Safety Assessments): 
− Comprehensive metabolic panel 
− Liver function tests 
− Fasting lipid panel (see Section 8.3.1 Fasting Lipid Panel) 
− Serum levels of essential fatty acids (Visit 20 only) 
− Fat-soluble vitamin levels (Visit 20 only) 
• A urine pregnancy test in all postmenarchal female adolescents (see Section 8.1.2 Safety 
Assessments) 
• Dispensing of dietary supplements and collection of used dietary supplement bottles as 
needed (see Section 6.3 Dietary Supplements) 
• Dispensing of study medication and collection of used study medication bottles as needed 
(see Section 7.2 Treatment Schedule). 
• Study medication compliance check (see Section 6.2 Investigational Product Compliance) 
• Record of concomitant medication including LLT and/or LA when applicable (see 
Section 7.6.1 
Concomitant 
Lipid-lowering 
Treatment 
and 
Section 8.1.2 
Safety 
Assessments) 
• Enquiry about any AEs/SAEs and record in the AE section of the eCRF. 
9.6 
Unscheduled Visits 
Unscheduled visits should be performed whenever necessary, e.g., in case of AEs or SAEs. 
Evaluations and/or assessments should be performed, as deemed appropriate by the 
investigator based on the nature of the event prompting an unscheduled visit. 
The results of all examinations during an unscheduled visit should be documented in the 
patient’s file and should be recorded in the eCRF. If a patient is withdrawn from the study, all 
examinations scheduled for the EoT visit should be performed. 


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9.7 
End of Treatment (Week 104±1 week), Visit 22 
The EoT visit should be performed for all patients at Week 104 and should also be performed 
at any time if the patient is prematurely discontinued from the study. The patient must present 
in fasting state. The following procedures will be conducted: 
• Complete physical examination of the patient (and a genitourinary, but not rectal exam at 
the investigator’s discretion) including the documentation of height, weight, BMI, BSA and 
all clinically relevant findings, such as xanthomas (see Section 8.1.1 Eligibility 
Assessments) 
• Determination of sexual maturation based on Tanner staging (see Section 8.1.1 Eligibility 
Assessments and Appendix 5 Tanner Staging) 
• Record of 12-lead ECG (read locally, see Section 8.1.2 Safety Assessments) 
• Collection of information in relation to the most recent standard of care echocardiography 
on file (if available, see Section 8.1.2 Safety Assessments) 
• Measurement of vital signs and blood pressure (see Section 8.1.1 Eligibility Assessments) 
• Pulmonary Function Test (see Section 8.1.2 Safety Assessments) 
• NMR imaging of liver for hepatic fat assessment; if NMR imaging is contraindicated or not 
feasible (e.g., due to the need for sedation or general anaesthesia in very young or anxious 
patients), ultrasound scans will be used at the discretion of the investigator (see 
Section 8.1.2 Safety Assessments) 
• Dietary counselling (see Section 8.6.1 Diet Instructions and Diet Records) as clinically 
indicated 
• Collection of old 2-Day Diet records (see Section 8.6.1 Diet Instructions and Diet Records) 
• Carotid intima-media thickness (CIMT, mandatory) and flow-mediated dilation (FMD, 
whenever possible) using ultrasound scan (see Section 8.4.2 Assessment of Carotid 
Intima-Media Thickness and Flow-mediated Dilation) 
• Collection of blood samples for the following tests (see Section 8.1.2 Safety Assessments): 
− Complete blood count 
− Comprehensive metabolic panel 
− Liver function tests 
− Fasting lipid panel (see Section 8.3.1 Fasting Lipid Panel) 
− Serum levels of essential fatty acids 
− Serum lipase 
− Fat-soluble vitamin levels 
− Hormones (TSH, ACTH, serum cortisol [to be measured between 06:00 and 08:00 a.m.], 
FSH, LH) 
− In patients who are Tanner Stage ≥2, serum oestradiol will be assessed for female 
patients and serum testosterone will be assessed for male patients 
• Urinalysis (urine colour, turbidity, pH, glucose, bilirubin, ketones, blood, protein, and white 
blood cells) 
• A urine pregnancy test in all postmenarchal female adolescents (see Section 8.1.2 Safety 
Assessments) 


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• Collection of used dietary supplement bottles as needed (see Section 6.3 Dietary 
Supplements) 
• Collection of used study medication bottles as needed (see Section 7.2 Treatment 
Schedule). 
• Record of concomitant medication including LLT and/or LA when applicable (see 
Section 7.6.1 
Concomitant 
Lipid-lowering 
Treatment 
and 
Section 8.1.2 
Safety 
Assessments) 
• Enquiry about any AEs/SAEs and record in the AE section of the eCRF. 
9.8 
Follow-up (Week 108), Visit 23 
9.8.1 
Visit 23 (Week 108) 
Patients entering the EAP (<18 years of age)/transitioning to commercial product (≥18 years 
of age) will have a follow-up phone call at Week 108±1 week to monitor safety including AE 
and concomitant medication reporting. Patients who have opted not to participate in or are 
unsuitable for the EAP (<18 years of age)/opted not to transition to commercial product (≥18 
years of age) will return for an in person safety Follow-up Visit at Week 108. The patient must 
present in fasting state. The following procedures will be conducted: 
• Abbreviated physical examination (including a focused evaluation of general appearance, 
skin, thorax/lungs, CV, abdomen, and xanthomas) and record of height, weight, BMI, and 
BSA (see Section 8.1.1 Eligibility Assessments) 
• Measurement of vital signs and blood pressure (see Section 8.1.1 Eligibility Assessments) 
• NMR imaging of liver for hepatic fat assessment; if NMR imaging is contraindicated or not 
feasible (e.g., due to the need for sedation or general anaesthesia in very young or anxious 
patients), ultrasound scans will be used at the discretion of the investigator (see 
Section 8.1.2 Safety Assessments) 
• Collection of blood samples for the following tests (see Section 8.1.2 Safety Assessments): 
− Complete blood count 
− Comprehensive metabolic panel 
− Liver function tests 
− Fasting lipid panel (see Section 8.3.1 Fasting Lipid Panel) 
− Serum levels of essential fatty acids 
− Fat-soluble vitamin levels 
• Urinalysis (urine colour, turbidity, pH, glucose, bilirubin, ketones, blood, protein, and white 
blood cells) 
• A urine pregnancy test in all postmenarchal female adolescents (see Section 8.1.2 Safety 
Assessments) 
• Record of concomitant medication including LLT and/or LA when applicable (see 
Section 7.6.1 
Concomitant 
Lipid-lowering 
Treatment 
and 
Section 8.1.2 
Safety 
Assessments) 
• Enquiry about any AEs/SAEs and record in the AE section of the eCRF. 


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10 
COLLECTION, STORAGE AND SHIPMENT OF 
LABORATORY SAMPLES 
The following laboratory tests will be performed at the local hospital laboratories to allow for 
taking therapeutic decisions upon availability of results:  
1. 
Comprehensive Metabolic Panel: Na, K, Ca, carbon dioxide, Cl, BG, CRP, BUN, 
creatinine, CK, total protein, and albumin 
2. 
Serum Lipase 
3. 
Liver Function Tests: ALT, AST, GGT, AP, and total bilirubin including direct and indirect 
bilirubin 
4. 
Fasting Lipid Panel: TC, LDL-C, VLDL-C, calculated Non-HDL-C, TG, apo B, Lp(a), 
HDL-C, and apo A-I 
Please note: Fasting lipid panels will also be analysed in the central laboratory specified 
in the ‘Laboratory Manual’. As the fasting lipid panel will be analysed at both the local 
hospital laboratory and the central laboratory, 2 separate samples must be drawn. 
5. 
Complete Blood Count: White blood cell count, haemoglobin, haematocrit, platelet count, 
red blood cell count, red cell distribution width, MCV, MCH, and MCHC 
6. 
Hormones: TSH, ACTH, serum cortisol, FSH and LH; the blood sample for testing of 
serum cortisol must be obtained in the early morning (6:00 to 8:00 a.m.) 
7. 
Sex hormones (in patients who are Tanner Stage ≥2): serum oestradiol for female patients 
and serum testosterone for male patients 
8. 
Urinalysis: urine colour, turbidity, pH, glucose, bilirubin, ketones, blood, protein, and white 
blood cells 
9. 
Pregnancy Test: Urine pregnancy test strips will be provided to the sites for conducting 
urine pregnancy tests in female postmenarchal adolescent patients. 
The following laboratory tests will be performed at the central laboratories specified in the 
‘Laboratory Manual’:  
1. 
Genetic Testing: For those patients who have signed a separate ICF for genetic testing, a 
blood sample will be collected according to central laboratory procedures for genotyping 
specified in the ‘Laboratory Manual’ at Screening (Visit 1) or at a later visit. 
2. 
Fasting Lipid Panel: TC, LDL-C, VLDL-C, calculated Non-HDL-C, TG, apo B, Lp(a), 
HDL-C, and apo A-I 
Please note: As the fasting lipid panel will be analysed at both the local hospital laboratory 
and the central laboratory, 2 separate samples must be drawn. All samples will be kept for 
up to 2 years after the study is completed. 
3. 
Fat-Soluble Vitamin Levels: Retinol, alpha tocopherol, 25-hydroxy-D, ratio of alpha 
tocopherol/total lipids (TC + fasting TG), ratio uncarboxylated osteocalcin/total osteocalcin 
4. 
Serum Levels of EFA: Linoleic acid, ALA, AA, DHA, EPA, and eicosatrienoic acid 
5. 
Pharmacokinetics: Lomitapide; pharmacokinetics will be sampled, processed and shipped 
to the central pharmacokinetics laboratory as described in the ‘Laboratory Manual’.  
6. 
Liposcale® Test: The central laboratory specified in the ‘Laboratory Manual’ will take 
aliquots from each PK sample for the exploratory Liposcale® Test, if sufficient sample 
material has been provided and would otherwise be discarded (see ‘Laboratory Manual’ 
for further details). Neither additional blood sampling nor processing or shipping of 
separate samples for the Liposcale® Test will be required at the site.  


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11 
DRUG SAFETY 
The investigator is responsible for the detection and documentation of events meeting the 
definition of an AE or an SAE as provided in Section 11.1 Definitions. This includes the 
evaluation of its seriousness, its severity, and the causal relationship to the investigational 
product and/or concomitant therapy (see Section 11.2 Recording of Adverse Events and 
Serious Adverse Events). 
At each visit, the patient and parent/legal guardian will be asked whether any AEs have 
occurred. A diagnosis of the event based on signs, symptoms and/or other clinical information 
should be established if possible. The diagnosis should be recorded as an AE and/or SAE in 
the corresponding section of the eCRF rather than the individual symptoms. If no diagnosis is 
known and neither clinical signs nor symptoms are present, the abnormal finding should be 
recorded. 
The patient should be observed and monitored carefully until the AE has resolved, the 
condition has stabilised or its cause has been identified. The investigator will be responsible 
to ensure that follow-up will include any supplemental investigations that may be indicated to 
elucidate the nature and/or the cause of the event. 
11.1 
Definitions 
The definitions in this section follow the tripartite harmonised International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) 
Guidelines E6 ‘Good Clinical Practice (GCP)’ and E2A ‘Clinical Safety Data Management: 
Definitions and Standards for Expedited Reporting’. 
11.1.1 
Adverse Event 
An AE is defined as any untoward medical occurrence in a patient administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment. 
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of the medicinal 
product, whether or not considered related to the medicinal product. 
11.1.2 
Adverse Drug Reaction 
Adverse Drug Reactions (ADRs) are all noxious and unintended responses to a medicinal 
product related to any dose. The phrase ‘responses to a medicinal product’ means that a 
causal relationship between a medicinal product and an AE is at least a reasonable possibility, 
i.e., the relationship cannot be ruled out. 
All AEs judged by the reporting investigator or the sponsor as having a reasonable causal 
relationship to the study medication qualify as ADRs. 
11.1.3 
Unexpected Adverse Drug Reaction 
If the nature or severity of the ADR is not consistent with the Lojuxta® SPC in lieu of an IB 
(Serious Adverse Reactions Expected in the Paediatric Population Table Page 1; see 
Section 18.1 Source Documents), it is an unexpected ADR. 
11.1.4 
Serious Adverse Event or Adverse Drug Reaction 
Special medical or administrative criteria are needed to define reactions that, either due to their 
nature (‘serious’) or due to the significant, unexpected information they provide, justify 
expedited reporting. 


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Please refer to Section 11.2.2 Assessment of Severity for the difference between the terms 
‘serious’ and ‘severe’.  
An SAE or serious ADR (SADR) is any untoward medical occurrence or effect that at any dose: 
• Results in death (death is an outcome, the condition leading to death is the SAE) 
• Is life-threatening 
The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which the patient 
was at risk of death at the time of the event; it does not refer to an event, which hypothetically 
might have caused death if it were more severe. 
• Requires inpatient hospitalisation or prolongation of existing hospitalisation 
• Results in persistent or significant disability or incapacity 
• Is a congenital anomaly or birth defect 
Medical and scientific judgment should be exercised in deciding whether an AE is serious in 
other situations. Important AEs may not be immediately life-threatening, result in death or 
hospitalisation, but may jeopardise the patient or may require intervention to prevent one of 
the other outcomes listed above. These should also be considered serious.  
11.1.5 
Suspected Unexpected Serious Adverse Reaction 
A Suspected Unexpected Serious Adverse Reaction (SUSAR) is a suspected adverse reaction 
related to the study medication that is both unexpected and serious.  
The nature or severity of the unexpected ADR is not consistent with the Lojuxta® SPC in lieu 
of an IB (Serious Adverse Reactions Expected in the Paediatric Population Table Page 1; see 
Section 18.1 Source Documents). 
If the investigator or the Medical Monitor judges an SAE not previously documented in the 
Lojuxta® SPC in lieu of an IB (Serious Adverse Reactions Expected in the Paediatric 
Population Table Page 1; see Section 18.1 Source Documents) to be related to study 
medication, the event will qualify as SUSAR and will be subject to expedited regulatory 
reporting. 
11.1.6 
Adverse Events of Special Interest 
Adverse events of special interest (AESI) include the following: 
• Hepatic, small bowel/intestinal, pancreatic and colorectal tumours 
• Hepatic abnormalities 
– Elevations of hepatic transaminases resulting in discontinuation of lomitapide 
– Elevations of hepatic transaminases >3 x ULN that persist despite dose reduction or 
interruption 
– Elevations of hepatic transaminases ≥5 x ULN 
– Symptomatic liver injury 
– Other hepatic evaluation and testing or any histology obtained from liver biopsy and 
imaging evaluations 
• Gastrointestinal effects 
– Events leading to permanent treatment discontinuations 
– Hospitalisation due to gastrointestinal events 
– Events triggering additional investigations such as endoscopy 


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• Major congenital anomalies 
Enhanced Pharmacovigilance will include systematically collecting and reviewing AESIs. In 
addition to reporting AESIs within 15 calendar days (see Section 11.5.2 Reporting of Adverse 
Events of Special Interest), they will be discussed in relevant safety aggregate reports.  
The AESIs will also be diligently followed-up with the investigators using specialised query 
follow-up forms and they will also be identified as potential signals that will be reviewed during 
routine monthly signal detection activities (see Section 11.5.2 Reporting of Adverse Events of 
Special Interest). 
11.2 
Recording of Adverse Events and Serious Adverse Events 
The definitions in this section follow the ‘Detailed Guidance on the Collection, Verification and 
Presentation of Adverse Event/Reactions Reports Arising from Clinical Trials on Medicinal 
Products for Human Use (CT-3)’ of the EC and the EMA ‘Note for Guidance – EudraVigilance 
Human – Processing of Safety Messages and Individual Case Safety Reports (ICSRs).  
11.2.1 
Assessment of Seriousness 
See Section 11.1.4 Serious Adverse Event or Adverse Drug Reaction for the definition of SAEs 
and SADRs. 
11.2.2 
Assessment of Severity 
The severity of AEs will be evaluated according to the Common Terminology Criteria for 
Adverse Events (CTCAE), version 5.0 (Section 18.1 Source Documents). 
The terms ‘severe’ and ‘serious’ are not synonymous:  
• Severity: The term ‘severe’ is often used to describe the intensity of a specific event (as in 
mild, moderate, or severe myocardial infarction); the event itself, however, may be of 
relatively minor medical significance (such as severe headache).  
• Seriousness: The term ‘serious’ is based on patient/event outcome or action criteria 
usually associated with events that pose a threat to a patient's life or functioning. 
Seriousness (not severity) serves as a guide for defining regulatory reporting obligations. 
If an AE term is not listed in the CTCAE classification, the severity of the event should be 
assessed as follows: 
• Grade 1 (mild): The AE is noticeable to the patient but does not interfere with routine 
activity. 
• Grade 2 (moderate): The AE interferes with routine activity but responds to symptomatic 
therapy or rest. 
• Grade 3 (severe): The AE significantly limits the patient's ability to perform routine activities 
despite symptomatic therapy. 
• Grade 4 (life-threatening): The patient is at immediate risk of death. 
• Grade 5 (death): Death related to the AE. 
11.2.3 
Assessment of Causality 
Careful medical judgment of the investigator is necessary to determine if there is a causal 
relationship between an AE and the investigational product.  
If there are facts (evidence) or arguments to suggest a reasonable relationship between the 
AE and the investigational product, the investigator will make a determination of a ‘reasonable 
causal relationship’. In all other cases, there is a ‘non-reasonable causal relationship’ 
between the AE and the investigational product. 


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To provide sufficient guidance for the investigator, which previously known assessments of 
causality now fall under the categories of ‘reasonable causal relationship’ and ‘non-reasonable 
causal relationship’, the former assessments of causality are listed below for information only. 
Please note that both the SAE forms and the eCRF will only offer the choice between 
‘reasonable causal relationship’ and ‘non-reasonable causal relationship’. 
Former assessments of causality qualifying for ‘reasonable causal relationship’ (for guidance 
and information only): 
• Certain: A clinical event, including laboratory test abnormality occurring in a plausible time 
relationship to drug administration, which cannot be explained by concurrent disease or 
other drugs or chemicals. The response to withdrawal of the drug (de-challenge) should be 
clinically plausible. The event must be pharmacologically or phenomenologically definitive, 
using a satisfactory re-challenge procedure if necessary. 
• Probable: A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the drug, unlikely to be attributed to concurrent disease or 
other drugs or chemicals, which follows a clinically reasonable response on withdrawal 
(de-challenge). Re-challenge information is not required to fulfil this definition. 
• Possible: A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the drug, but which could also be explained by concurrent 
disease or other drugs or chemicals. Information on drug withdrawal may be lacking or 
unclear. 
Former assessment of causality qualifying for ‘non-reasonable causal relationship’ (for 
guidance and information only): 
• Unlikely: A clinical event, including laboratory test abnormality, with a temporal relationship 
to drug administration, which makes a causal relationship improbable, and in which other 
drugs, chemicals or underlying disease provide plausible explanations. 
11.3 
Monitoring Laboratory Assessments 
Please refer to Section 10 Collection, Storage and Shipment of Laboratory Samples for 
laboratory tests that will be performed at the local hospital laboratories to allow for taking 
therapeutic decisions upon availability of results. The clinical laboratory values are to be 
reviewed by the investigator and classified as ‘normal’ or ‘abnormal’. Abnormal laboratory 
values must in addition be classified as ‘abnormal, clinically significant’ or ‘abnormal, not 
clinically significant’. The reason(s) for ‘abnormal’ findings should be documented. Abnormal, 
clinically significant findings occurring after first administration of study medication should be 
reported as an AE (unless already pre-existing at Baseline with the same severity). 
Please note that fasting lipid panels will also be analysed in the central laboratory specified in 
the ‘Laboratory Manual’ (see Section 10 Collection, Storage and Shipment of Laboratory 
Samples). 
11.4 
Documenting of Adverse Events and Serious Adverse Events 
All information regarding AEs and SAEs, whether reported by the patient/parent/legal guardian 
or observed by the investigator, must be documented in the patient’s medical record and 
recorded in the AE/SAE section of the eCRF. For SAEs, the paper SAE form in the investigator 
site file must also be completed (see Section 11.5.1 Reporting of Serious Adverse Events). 
The investigator is responsible for recording and reporting AEs observed from the first dose of 
study medication (D0) until follow-up at Week 108.  
All AEs occurring during Screening (i.e., after obtaining the patient’s written consent, but before 
starting study medication) should be recorded in the Medical History/Current Medical 


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Conditions section of the eCRF, except those resulting from a protocol-mandated procedure, 
which should be reported in the AE/SAE section of the eCRF. 
All patients will be followed-up for AEs/SAEs until the resolution or stabilisation of the 
AEs/SAEs. At the end of the study, the Medical Monitor will review all ongoing AEs/SAEs. For 
patients who enter the EAP, all ongoing AEs/SAEs will be followed up during the EAP. For all 
other patients, the Medical Monitor will determine appropriate follow-up required for any 
ongoing AEs/SAEs with the corresponding investigator for the respective patient.  
If an investigator learns of an SAE to be reasonably related to study medication any time after 
study medication dosing has stopped, he/she should promptly notify the sponsor. 
11.5 
Immediately Reportable Information 
11.5.1 
Reporting of Serious Adverse Events 
All SAEs should be reported immediately, i.e., within 24 hours of learning that the event meets 
the definition of an SAE. The investigator should complete the SAE report form in the 
investigator site file and send the initial SAE report within 24 hours to the Pharmacovigilance 
Department at APH-19-Safety@emmes.com. 
If the SAE is fatal or life-threatening and is considered at least possibly related to the study 
medication, the completed SAE form should be sent to the Safety and Pharmacovigilance 
Department immediately. 
The minimum information required for the initial SAE report is: 
• Identifiable patient 
• Identifiable reporter 
• Investigational product 
• Description of the event 
If relevant information is missing at the time of the initial SAE report, the reporter should provide 
it in follow-up SAE report(s) upon availability. The follow-up report should contain new, updated 
or corrected information. It should further describe whether the event has resolved or 
continues, and if and how it was treated including documentation of all supportive actions 
taken.  
11.5.2 
Reporting of Adverse Events of Special Interest 
All AESIs (see Section 11.1.6 Adverse Events of Special Interest) should be reported within 
15 calendar days. The investigator should complete the AESI report form in the investigator 
site file and send the initial AESI report to the Pharmacovigilance Department at 
APH-19-Safety@emmes.com. 
The minimum information required for the initial AESI report is: 
• Identifiable patient 
• Identifiable reporter 
• Investigational product 
• Description of the event 
If relevant information is missing at the time of the initial AESI report, the reporter should 
provide it in follow-up AESI report(s) upon availability. The follow-up report should contain new, 
updated or corrected information. It should further describe whether the event has resolved or 


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continues, and if and how it was treated including documentation of all supportive actions 
taken.  
All AESIs will be diligently followed-up using specialised query follow-up forms. They will be 
systematically collected, reviewed, and discussed in relevant safety aggregate reports. AESIs 
will be identified as potential signals that will be reviewed during routine monthly signal 
detection activities.  
Specific hepatic and gastro-intestinal abnormalities, hepatic fibrosis, primary hepatic tumours, 
small bowel/intestinal or pancreatic tumours and major congenital abnormalities will be 
reported expeditedly.  
11.5.3 
Reporting Safety Observations by the Investigator to the IEC/IRB 
At each clinical site, the Principal Investigator is responsible for promptly notifying the relevant 
IEC/IRB of the following information, as applicable: 
• All SAEs and subsequent follow-up information. 
• Any SAE reports and follow-up reports received from the sponsor or the sponsor’s 
designee. 
11.5.4 
Other Reportable Information: Pregnancy 
In the event that a patient is confirmed to be pregnant during the study or during follow-up, the 
investigational product must be discontinued immediately and permanently.  
Any pregnancy or fathering of a child, which occurs up to 30 days within the last application of 
study medication should immediately be reported. The investigator will be asked to complete 
a pregnancy report provided by the sponsor. In addition, the investigator should provide 
follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome. 
12 
STATISTICAL ANALYSIS 
12.1 
Statistical Methods 
The primary efficacy analysis will be conducted once all patients have completed (or withdrawn 
prior to Visit 10) at Week 24±3 days (End of the Efficacy Phase). The primary efficacy analysis 
will include the key primary/secondary efficacy data, all safety data available up to the data 
cut-off date of the last patient reaching Week 24±3 days, and PK parameter analysis. The 
reporting of Week 24±3 days data will allow for an early submission of an application for 
regulatory approval of Lojuxta® in the paediatric indication. The final statistical analysis will be 
performed when all patients have completed the Follow-up Visit (Visit 23) at Week 108±7 days. 
Efficacy, safety, and exploratory data collected during both the Safety Phase and follow-up will 
be included.  
No interim efficacy analyses for efficacy and/or futility will be performed as outlined in 
Section 12.3.3 Interim Analysis. 
12.1.1 
Tests of Hypotheses and Significance Levels 
The primary and secondary efficacy parameters collected during the Efficacy Phase of the 
study will be statistically tested using a 2-sided test at the 5% significance level. 
To address the efficacy objectives, the efficacy parameters will be tested sequentially in a 
step-wise fashion, thereby controlling the overall type I error. First, the primary testing for 
percent change from Baseline in LDL-C at Week 24±3 days will be performed. If this test is 
statistically significant with a 2-sided α = 0.05 and is statistically significant in a positive 


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direction, then the tests of the secondary hypotheses will be performed in the following 
specified order at Week 24±3 days: 
1. 
Non-HDL-C 
2. 
TC 
3. 
VLDL-C 
4. 
apo B 
5. 
TG 
6. 
Lp(a) 
If at any step of the testing procedure a non-significant p-value is reached, further tests in the 
sequence will be performed and p-values will be reported as a measure of the strength of effect 
without declaring statistical significance. 
Analysis of other secondary endpoints collected during the Efficacy Phase and of endpoints 
collected during the Safety Phase will be analysed without adjustment for multiplicity. 
12.1.2 
Determination of Sample Size 
At least 30 evaluable patients (≥8 patients in each of the following age groups, determined by 
age at Baseline: 5 to 10 years, 11 to 15 years, and 16 to ≤17 years) are required at 
Week 24±3 days to provide 92% power, assuming a 25% reduction from Baseline in LDL-C 
with a standard deviation (SD) of 40% and a 2-sided α of 0.05. To allow for up to 33% dropout 
during the Efficacy Phase (prior to Week 24±3 days), an additional 15 patients will be enrolled, 
resulting in a total sample size of approximately 45 patients. Enrolment will be stratified to 
ensure approximately equal numbers of patients in the following age groups: 5 to 10 years, 
11 to 15 years, and 16 to ≤17 years.  
As a conservative assumption, the estimated 25% mean reduction represents approximately 
60% of the 41% mean reduction from Baseline to Week 26/End of Efficacy Phase seen in the 
adult study UP1002/733-005, Intent-to-Treat (ITT) Population. This is the same assumption 
that was used for the sample size in the adult study. The SD represents an approximate 1/3 
increase from the 31% SD observed in the adult study. This increase in SD was used to 
account for potentially increased variability across the 3 age groups. 
12.2 
Definition of Study Populations 
The statistical analysis will be based on the following study populations: 
• The safety analysis set (SAF) will include all patients treated with at least 1 dose of study 
medication. The SAF will be used for all safety analyses.  
• The full analysis set (FAS) will include all patients in the SAF who receive at least 1 dose of 
study medication and who have a Baseline and at least 1 post-Baseline measurement of 
LDL-C. The FAS will be used for all efficacy analyses.  
• All patients from the FAS will be assigned to a completer analysis set (CAS), if they have 
not discontinued the study during the Efficacy Phase (up to Week 24) irrespective of the 
reason for discontinuation. The CAS will be used for all efficacy analyses during the Efficacy 
Phase. 
• Patients who reasonably adhered to all protocol conditions i.e., who have met the eligibility 
criteria and will have received planned study medication without important protocol 
deviations considered to have a serious impact on the efficacy results with the Efficacy 
Phase of the study, will constitute the per-protocol analysis set (PP). The PP will be used 
for supplementary efficacy analyses during the Efficacy Phase. 


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The data obtained will be used to check whether the study protocol was adhered to (e.g., 
inclusion and exclusion criteria, time windows, concomitant medication). Case-by-case 
decisions regarding exclusions of patients from the PP analysis will be made in a data review 
meeting. 
Patients who are not treated will not be assigned to any of these analysis sets. All participants 
who pass Screening and enter the run-in period, irrespective of whether they received study 
medication, will be included in the Enrolled Set. 
The FAS will serve as the primary population for the analysis of efficacy data in this study. 
Specifically, the primary, confirmatory endpoint analysis will be done using the FAS. In 
addition, efficacy analyses will be done using the PP and the CAS, serving as sensitivity 
analyses. Safety analyses will be conducted using the SAF. 
12.3 
Planned Analysis 
Full details of the planned analyses will be documented in a Statistical Analysis Plan prior to 
database lock. The primary estimand will be a ‘treatment policy’ estimand which will be defined 
in the Statistical Analysis Plan. 
12.3.1 
Disposition and Exposure 
Patient disposition, medical history, prior and concomitant medication use including current 
LLT and LA, and study medication exposure will be summarised. 
12.3.2 
Demographic Data and other Baseline Characteristics 
Demographics and other Baseline characteristics will be summarised in total and by age group 
by means of summary statistics (number of patients, mean, standard deviation, minimum, 
median, maximum) for continuous variables and by absolute and relative frequencies for 
categorical variables. Baseline characteristics are defined as all results of the examinations 
performed prior to the first administration of study medication. 
Relevant demographic and Baseline characteristics will be summarised using descriptive 
statistics. These variables include: 
• Demographic variables: Age, gender, race, and ethnicity 
• Baseline: 
− Height, weight, BMI, and BSA 
− LDL-C, TC, Non-HDL-C, VLDL-C, Lp(a), TG, and apo B 
− Disease characteristics 
12.3.3 
Interim Analysis 
No interim efficacy analyses for efficacy and/or futility will be performed. 
The primary efficacy analysis and final statistical analysis will be performed as described in 
Section 12.1 Statistical Methods. 
An independent DSMB will periodically review the safety data as described in Section 4.3 Data 
Safety Monitoring Board. 
12.3.4 
Planned Analysis for Primary Endpoint 
The primary efficacy endpoint, percent change from Baseline in directly measured LDL-C at 
Week 24±3 days, will be analysed using the one-sample t-test to test the null hypothesis that 
the percentage change from Baseline is equal to zero against the alternative hypothesis the 
percentage change from Baseline is not equal to zero. The percentage change at 


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Week 24±3 days, together with the corresponding 2-sided 95% confidence interval and 
p-value will be presented. Missing data will be imputed using last observation carried forward 
(LOCF). The analysis will be based on the FAS Population.  
A sensitivity analysis will be performed using a Mixed Model Repeated Measures (MMRM) 
model with the missing at random assumption (i.e., missing data will not be imputed using 
LOCF or any other method). The analysis will be based on the FAS Population. 
Supplementary analyses will include the one-sample t-test and summaries based on the PP 
and CAS. 
Sub-group analyses will be conducted using an Analysis of Covariance (ANCOVA) model to 
estimate the mean percentage change and 2-sided 95% confidence intervals within each 
sub-group at Week 24±3 days. Sub-group analyses will be performed for the 3 age groups and 
also based on documented CVD history, established CVD history, concomitant LLT 
medication, and dose reduction of study medication. These analyses will be based on the FAS 
Population. 
12.3.5 
Planned Analysis for Secondary Endpoints 
The secondary lipid parameter endpoints will be analysed as described for the primary 
endpoint in Section 12.3.4 Planned Analysis for Primary Endpoint. 
As secondary analyses of the pattern of LDL-C and lipid parameter change over time, a MMRM 
model will be used, including all available data (all visits from Baseline through 
Week 104±1 week). Observed changes and percent changes from Baseline at each timepoint 
will be summarised. 
Number and percentage of patients treated with standard LLT (including LA when applicable) 
will be summarised overall and by age group. Any dose increases of standard LLT/increased 
frequency of LA will be summarised. 
Number and percentage of patients with LDL-C falling below the target level will be 
summarised by study visit at any time up to Week 24±3 days and at any time up to Week 104 
by age group and overall. 
12.3.6 
Planned Analysis for Safety Endpoints 
Safety will be assessed using the SAF Population, including all patients who receive any 
amount of study medication, and will be based on evaluation of AEs, laboratory data, vital signs 
and physical examination findings, height, weight, BSA and BMI, ECG, echocardiography (if 
available) and hepatic fat. Safety data summary statistics will be presented overall and by age 
group. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
for purposes of summarisation. All AEs occurring during the study will be included in by-patient 
data listings and will be summarised overall and by age group. Events leading to death, SAEs, 
and events resulting in study discontinuation will be summarised. Adverse events of special 
interest, such as hepatobiliary AEs and hepatotoxicity of different levels, will be summarised 
(see Section 11.1.6 Adverse Events of Special Interest). 
Reported clinical laboratory results and changes from Baseline will be summarised using 
descriptive statistics overall and by age group. Shift tables and summaries of potentially 
clinically significant findings will be presented. Reported values and changes from Baseline for 
vital signs, ECG findings, and echocardiography (if available) will be summarised by time point 
overall and by age group. For lipid accumulation in the liver, the number and percentage of 
patients with liver fat content ≤10%, >10% and ≤20%, and >20% will be summarised overall 
and by age group. Changes from Baseline over time will be presented in shift tables for ECG 
results, echocardiography (if available) and lipid accumulation in the liver. 


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To assess sexual maturation, changes from Baseline in Tanner staging results will be 
presented in shift tables and graphically. 
12.3.7 
Planned Analysis for Exploratory Endpoints 
The percentage change from Baseline in mean CIMT and mean FMD at Week 56±3 days and 
at Week 104±1 week will be assessed overall and by age group. 
The number and percentage of patients with (tendon/cutaneous) xanthomas present, and 
locations, will be summarised overall and by age group at Baseline, Week 56±3 days and 
Week 104±1 week. The number and percentage of patients with resolution and regression of 
pre-existing xanthoma (Baseline) to Week 56±3 days and Week 104±1 week will be 
summarised overall and by age group. 
Changes from Baseline in parameters assessed by the Liposcale® Test will be summarised at 
Week 4±3 days, Week 8±3 days, Week 12±3 days, Week 16±3 days, Week 20±3 days and at 
Week 24±3 days. 
12.3.8 
Planned Analysis for Palatability Endpoints 
The number and percentage of patients responding to each question regarding palatability will 
be presented over time overall and by age group. 
12.3.9 
Planned Analysis for Pharmacokinetic Endpoint 
PK data will be used in population PK/PD modelling for the lomitapide program. This will be 
described in a separate document. 
12.4 
Statistical Criteria for Study Termination 
No interim analysis for futility will be performed. Therefore, no criteria for early termination of 
the study from a statistical perspective are considered. 
12.5 
Handling of Missing Data 
Care will be taken during the conduct of this study to minimise the amount of missing data. 
The FAS will be used for the primary analysis of all efficacy endpoints. Each patient in the FAS 
will have a Baseline value and at least one post-Baseline value. Because this is a single-arm 
study, for patients who have missing data at the time point of interest, the LOCF approach will 
be used in all Efficacy Phase analyses. However, for the fasting lipid panel, it is not appropriate 
to carry forward Screening/run-in period values if a Baseline value is missing as this value 
would be obtained prior to stabilisation of the patient on LLT so LOCF will not be used for these 
analyses. 
12.6 
Time Windows 
Data as evaluated during regular visits will be analysed in accordance to the respective visit. 
Time window violations will only be considered for lipid data analyses and for analyses using 
the PP. Visit windows will be defined in the Statistical Analysis Plan. A data review meeting 
will be performed prior to data base lock and it may be decided to exclude single visits from 
the PP analyses due to time window violation. For time to event analyses, the exact visit dates 
and D0 will be taken for calculating the time to event.  


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13 
QUALITY CONTROL AND QUALITY ASSURANCE 
13.1 
Pre-study Documentation 
Prior to enrolment of patients at a study site, specific regulatory documents must be available, 
such as Independent Ethics Committee (IEC)/Institutional Review Board (IRB) approval and 
curricula vitae of investigators and study staff. Amryt Pharmaceuticals DAC will inform the 
investigator which documents need to be provided according to the applicable regulatory 
requirements. 
13.2 
Monitoring 
Amryt Pharmaceuticals DAC will appoint qualified and appropriately trained persons to monitor 
the study and the FU. Monitors will periodically contact the site and perform site visits in 
accordance with applicable regulations, GCP and Amryt Pharmaceuticals DAC approved 
procedures. Study objectives, study design, and enrolment rate will determine the extent, 
nature and frequency of site visits. 
The monitor will contact the site before the start of the study to discuss the protocol and data 
collection procedures with the site study team members. 
During site visits, the monitor will: 
• Check and assess the progress of the study 
• Review study data collected 
• Perform source data verification 
• Identify any issues and address their resolution 
Aim of the site visits is to verify that: 
• The data are authentic, accurate and complete 
• The safety and rights of patients are being protected 
• The study is conducted in accordance with the approved protocol (and any subsequent 
amendment), GCP and all applicable regulatory requirements 
The investigator agrees to allow the monitor direct access to all relevant documents and to 
allocate his/her time and the time of his/her staff to the monitor to discuss findings and any 
relevant issues. 
The study monitor will record any protocol deviations identified, including, but not limited to, 
patients that were enrolled even though they did not meet all eligibility criteria, patients who 
took concomitant medications specifically prohibited by the protocol, patients who received an 
incorrect dose of study medication, and patients who failed to comply with the protocol-defined 
dietary restrictions. The Investigator and study team members will collaborate with the study 
monitor to identify the reason for each protocol deviation.  
At study closure, the monitor will conduct all activities as indicated in Section 13.4 Study and 
Site Closure. 
13.3 
Data Management and Processing 
Amryt Pharmaceuticals DAC is responsible for data quality control. Each study site is 
responsible for the data documentation and for the maintenance of patient files. 


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13.3.1 
Data Collection 
The investigator or an authorised delegate from the study staff will have to complete an eCRF 
for each patient enrolled including patients who discontinue prematurely. If a patient withdraws 
from the study, the reason should be noted in the eCRF if possible. If a patient is withdrawn 
from the study because of a treatment-limiting AE, thorough efforts should be made to clearly 
document the outcome. 
The investigator should ensure the accuracy, completeness, legibility, and timeliness of the 
data reported to the sponsor in the eCRFs and in all required reports. 
13.3.2 
Data Management Procedures 
A separate ‘Data Management Plan’ will detail data management vendors, systems and 
processes. 
13.3.3 
Data Verification Procedures 
Data will be checked systematically according to a pre-specified ‘Data Validation Plan’ after 
they have been entered into the study database. Queries will be created for errors or missing 
data and clarified by the study monitor at the investigational site.  
13.3.4 
Coding 
All AEs and concomitant diseases will be coded according to MedDRA and all concomitant or 
previous medication based on the World Health Organization (WHO) Drug Dictionary. 
13.3.5 
Procedures for Analysis of Consistency and Medical Plausibility 
A data review meeting will be conducted as soon as all data of the study and the follow-up 
period has been entered into the eCRF and the database has been confirmed as ‘clean’. After 
resolution of all remaining queries, the Statistical Analysis Plan will be finalised and the 
database will be locked. All changes to the data will be kept in an audit trail. 
13.3.6 
Data to be Recorded Directly into the Electronic Case Report Form 
The eCRF will serve as source document for the ethnic origin, which will only be recorded for 
the study.  
13.4 
Study and Site Closure 
Upon completion of the study or premature study (site) closure, the monitor and the investigator 
will be responsible for 
• Return of all study data to Amryt Pharmaceuticals DAC 
• Data clarification and/or resolution 
• Accounting, reconciliation and return of used and unused study medication 
• Review of study site records for completeness 
• Return of all study specific equipment to Amryt Pharmaceuticals DAC 
Amryt Pharmaceuticals DAC reserves the right to suspend or prematurely discontinue this 
study at either a single site or at all sites at any time for any reason. Amryt 
Pharmaceuticals DAC will inform the investigator(s), the IECs/IRBs, and the regulatory 
authorities if the study will be suspended or stopped prematurely.  


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13.5 
Audits and Inspections 
Amryt Pharmaceuticals DAC or its designee may conduct a quality assurance audit of this 
study to evaluate compliance with the protocol and the principles of GCP. The investigator 
agrees to allow the auditor direct access to all relevant documents and to allocate his/her time 
and the time of his/her staff to the auditor to discuss findings and any relevant issues. 
Regulatory agencies may conduct a regulatory inspection of this study. If a regulatory authority 
requests an inspection, the investigator must inform Amryt Pharmaceuticals DAC immediately 
about this request. The investigator agrees to allow the inspector(s) direct access to all relevant 
documents and to allocate his/her time and the time of his/her staff to the inspector(s) to 
discuss findings and any relevant issues. 
14 
LEGAL AND ETHICAL REQUIREMENTS 
This study will be conducted in accordance with the harmonised tripartite ICH Guidelines for 
GCP and all applicable laws and regulations, including the Declaration of Helsinki, June 1964, 
as modified by the 64th World Medical Association General Assembly, Fortaleza, Brazil, 
October 2013 (see Appendix 7 Declaration of Helsinki). 
14.1 
Regulatory Authority Approval 
Documents required for the application of this study will be submitted to the responsible 
competent authority according to the applicable country-specific laws and regulations. The 
study will not start until the competent authority authorises the study. 
14.2 
Independent Ethics Committee/Institutional Review Board 
This protocol, any amendments if applicable, any material provided to the patient (such as 
patient information, informed consent form and patient questionnaires) as well as additional 
documents, which may be required by national regulations and the IEC/IRB, will be submitted 
to the competent IEC/IRB for review and approval.  
Written approval from the IEC/IRB must be obtained before starting the study, and must be 
documented in a letter specifying the date on which the IEC/IRB met and granted the approval. 
The IEC/IRB approval letter must identify all documents approved by listing the study number, 
study title, study sites/investigators, date and version of study protocol, date and version of 
patient information/informed consent form. A list of IEC/IRB members should be attached to 
the approval letter. 
Any subsequent modifications made to the protocol or to any other documents that must be 
reviewed by the IEC/IRB must also be submitted to the IEC/IRB in accordance with local 
procedures and regulatory requirements. 
14.3 
Patient and Parent/Legal Guardian Information and Informed 
Consent 
In addition to information sheets and consent/assent forms for patients (according to applicable 
local regulations), parent/legal guardian information sheets and consent forms will be 
prepared. 
The investigator will explain the aims, methods, objectives and potential risks and benefits of 
the study to the patient and the parent/legal guardian and will obtain written informed 
consent/assent from the patient (according to applicable local regulations) and written informed 
consent from the parent/legal guardian before he/she will initiate any study-specific procedure.  
The patient and the parent/legal guardian will have sufficient time to ask and resolve any 
questions pertaining to participation in the study, and to consider study participation. In the 


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event that a patient is unable to read or will only be able to provide verbal informed consent, 
the parent/legal guardian may act on the patients’ behalf. 
The investigator will also explain to the patient and the parent/legal guardian that the patient 
will be free to refuse entering the study or to withdraw from it at any time for any reason. Neither 
the refusal to give consent nor the withdrawal of consent will result in discrimination of the 
patient, in particular regarding his/her subsequent medical treatment.  
The patient (according to applicable local regulations) and the parent/legal guardian will be 
asked to review, sign, and date the informed consent form. He/she will receive a copy of the 
signed informed consent form, including the investigator’s signature. The investigator will retain 
the original document. 
The eCRF for this study will contain a section for documenting informed patient consent, which 
needs to be completed appropriately. The consent form will be reviewed and updated if the 
risk/benefit assessment changes or if amendments to the protocol affect the patients’ 
participation in the study. All patients (including those already being treated) and their 
parents/legal guardians will be informed about the new information. Patients are only allowed 
to further participate in the study if they and their parents/legal guardians agree to sign the 
amended form, indicating that they reconsent to participate in the study.  
14.4 
Data Protection 
Medical information about individual patients obtained in the course of this study is confidential 
and may not be disclosed to third parties, except authorised monitors, auditors or inspectors. 
Confidentiality will be ensured by the use of patient numbers for the identification of each 
patient; these patient numbers will also be used for patient data in the patient files and eCRFs. 
The investigator should keep a patient enrolment log showing codes, names and addresses 
and should maintain documents, e.g., patients’ written consent forms, in strict confidence. 
14.5 
Notification of Primary Care Physician 
The investigator should notify the patients’ primary care physician of the patients’ participation 
in the study, if applicable and agreed by the patient and his/her parent/legal guardian. 
14.6 
Investigator Reporting Requirements 
The investigator will ensure that site study team members will promptly bring AEs/SAEs to 
his/her attention. He/she will report all AEs/SAEs as described in Section 11.4 Documenting 
of Adverse Events and Serious Adverse Events and Section 11.5 Immediately Reportable 
Information. The investigator will inform his/her IEC/IRB of any SAE in accordance with the 
local reporting requirements. 
14.7 
Record Retention 
Upon closure of the study, the investigator/study site will maintain a copy of all study records 
in a safe and designated location at the study site in accordance with applicable regulatory 
requirements. Amryt Pharmaceuticals DAC will inform the investigator/study site of the time for 
retaining these records to comply with applicable regulatory requirements. 
Essential documents as defined in the ICH E6 Guideline of GCP must be retained until 
• 2 years after the last approval of a marketing application in an ICH region 
• There are no pending or contemplated marketing applications in an ICH region 
• 2 years will have elapsed since the formal discontinuation of clinical development of the 
investigational product 
• Longer if required by the applicable regulatory requirement(s)/the sponsor 


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Unless other Union law (outside of the EU) requires archiving for a longer period, the sponsor 
and the investigator will archive the content of the clinical trial master file for at least 25 years 
after the completion or discontinuation of the study. The medical files of patients will be 
archived in accordance with local regulations. 
15 
PROTOCOL AMENDMENTS 
All protocol amendments must be submitted to the competent IECs/IRBs and Regulatory 
Agencies for information and/or approval in accordance with local requirements. If applicable, 
approval must be awaited before changes can be implemented, except for changes necessary 
to eliminate an immediate hazard to patients. 
16 
DISCLOSURE OF INFORMATION 
All data and records generated during the study except for patient medical records and all 
inventions discovered in the course of conducting the study, whether patentable or not, are the 
sole and exclusive property of Amryt Pharmaceuticals DAC. 
The investigator and site study team members will keep strictly confidential any information 
provided by Amryt Pharmaceuticals DAC related to this study and all data and records 
generated in the course of conducting the study. They will not use the information, data or 
records for any other purpose than conducting the study without prior written approval of Amryt 
Pharmaceuticals DAC. 
Amryt Pharmaceuticals DAC will prepare an integrated clinical study report in accordance with 
the harmonised tripartite ICH E3 Guideline ‘Structure and Content of Clinical Study Reports’ 
after completion of the study. 
16.1 
Publication of Study Findings 
Negative and positive results of this study will be presented at scientific meetings and/or will 
be published in a peer reviewed scientific or medical journal. By signing the clinical study 
agreement, the investigator agrees that the results of the clinical study may be used for 
publication. The first publication or disclosure shall be a complete, joint multi-centre publication 
or disclosure. Authorship will be discussed with all parties involved, depending on such 
considerations as recruitment. A premature publication or disclosure of partial results is not 
possible. 
The investigator(s) may use the scientific data generated during the study for non-commercial 
purposes, e.g., for scientific publications of any kind only after prior written consent of Amryt 
Pharmaceuticals DAC. The investigator(s) will allow Amryt Pharmaceuticals DAC to review the 
proposed publication or disclosure prior to submission for publication, presenting, using for 
instructional purposes or otherwise disclosing the results of the study. 
If Amryt Pharmaceuticals DAC supposes the proposed publication or disclosure to risk Amryt’s 
ability to patent any invention related to the study, the publication or disclosure will be modified 
or delayed to allow Amryt Pharmaceuticals DAC to file a patent application.  
17 
COMPENSATION FOR INJURIES 
Insurance coverage for damages emerging from the study and involving study patients treated 
with the study medication will be provided according to applicable legal requirements. The 
investigator must inform the patient and parent/legal guardian accordingly and must point out 
that the patient should seek the investigators’ consent before undergoing other medical 
treatment, whenever possible. The investigator will advise patients and parents/legal 
guardians that they must inform the investigator immediately of any injury that might have been 
caused by study participation. 
 


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18 
REFERENCES 
18.1 
Source Documents 
Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 dated 
27 November 2017, U.S. Department of Health and Human Services, National Institutes of 
Health, National Cancer Institute, 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick
_Reference_8.5x11.pdf, accessed 19 July 2019 
European Medicines Agency, Lojuxta®, European Public Assessment Report, 30 May 2013, 
https://www.ema.europa.eu/en/documents/assessment-report/lojuxta-epar-public-
assessment-report_en.pdf (accessed 19 July 2019) 
Lojuxta® Summary of Product Characteristics in lieu of an Investigator’s Brochure including the 
Lojuxta® Summary of Product Characteristics, 23 April 2018; Final Report, 17 September 2020 
Investigational Medicinal Product Dossier, Lomitapide 2 mg hard gelatin capsules, Version 1.0, 
July 2019 
Lomitapide Observational Worldwide Evaluation Registry (LOWER, NCT02135705, 
https://clinicaltrials.gov/ct2/show/NCT02135705?cond=Lomitapide+Observational+Worldwide
+Evaluation+Registry+LOWER%2C+NCT02135705&rank=1 
[accessed 
19 July 2019], 
European 
PAS register 
number 
ENCEPP/SDPP/5326 
http://www.encepp.eu/encepp/viewResource.htm?id=20494 [accessed 19 July 2019]) 
Lomitapide Pediatric Trial Dose Selections Using Two Approaches: Allometric Scaling and 
Physiologically-based Pharmacokinetic (PBPK) Modeling; Final Report, 26 June 2013 
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G. F. Watts, K. G. Parhofer, G. K. Hovingh, P. T. Kovanen, C. Boileau, M. Averna, J. Boren, 
E. Bruckert, A. L. Catapano, J. A. Kuivenhoven, P. Pajukanta, K. Ray, A. F. Stalenhoef, E. 
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Underberg, J., C. P. Cannon, D. Larrey, L. Makris, A. Jurecka and D. Blom (2018). "Long-term 
Safety and Efficacy of Lomitapide in Patients with Homozygous Familial Hypercholesterolemia: 
Three-Year Data from LOWER." Atherosclerosis Suppl 32: 24. 
Underberg, J., M. Harada-Shiba, R. Hegele, P. McCullough, K. DiGioia, A. Jurecka, C. 
Stefanutti and D. Blom (2018). "LDL-C Therapeutic Target Attainment in Patients with 
Homozygous Familial Hypercholesterolemia treated with Lomitapide." Journal of Clinical 
Lipidology 12(2): 561-562. 
 
 
 


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C O N F I D E N T I A L  
19 
APPENDICES 
Appendix 1 Child-Pugh Score 
 
Parameter 
Points 
1 
2 
3 
Encephalopathy 
None 
Mild to moderate 
(CTCAE Grade 1/2) 
Severe 
(CTCAE Grade 3/4) 
Ascites 
None 
Mild to moderate 
(Diuretics responsive) 
Severe  
(Diuretics refractory) 
Bilirubin (mg/dL) 
<2 
2 to 3 
>3 
Albumin (g/dL) 
>3.5 
2.8 to 3.5 
<2.8 
Prothrombin time 
 
 
 
• 
Seconds prolonged 
<4 
4 to 6 
>6 
• 
International normalised ratio 
<1.7 
1.7 to 2.3 
>2.3 
Child-Turcotte-Pugh Class obtained by adding score for each parameter (total points) 
Class A 
5 to 6 points 
(least severe liver disease) 
Class B 
7 to 9 points 
(moderately severe liver disease) 
Class C 
10 to 15 points 
(most severe liver disease) 
Sources:  
C. G. Child, J. G. Turcotte: Surgery and portal hypertension. In: C. G. Child (Editor): The liver and portal 
hypertension. Saunders, Philadelphia 1964, P. 50–64. 
R. N. Pugh, I. M. Murray-Lyon, J. L. Dawson, M. C. Pietroni, R. Williams: Transection of the oesophagus for bleeding 
oesophageal varices. In: British Journal of Surgery. Volume 60, Issue 8, August 1973, P. 646–649, ISSN 0007-
1323. PMID 4541913. 
 
 
 


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C O N F I D E N T I A L  
Appendix 2 Schwartz Formula 
 
𝐺𝐺𝐺𝐺𝐺𝐺 (𝑚𝑚𝑚𝑚/ min 𝑝𝑝𝑝𝑝𝑝𝑝 1.73 𝑚𝑚2) = 39.1 ቎ℎ𝑒𝑒𝑒𝑒𝑒𝑒ℎ𝑡𝑡 (𝑚𝑚)
𝑆𝑆𝑆𝑆𝑆𝑆 (𝑚𝑚𝑚𝑚
𝑑𝑑𝑑𝑑)
቏
0.516
𝑥𝑥 ቎
1.8
𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝐶𝐶 (𝑚𝑚𝑚𝑚
𝐿𝐿)
቏
0.294 
[1.099]𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚 ൤ℎ𝑒𝑒𝑒𝑒𝑒𝑒ℎ𝑡𝑡 (𝑚𝑚)
1.4
൨
0.188
 
 
Bedside calculation of 0.413*(height/serum creatinine) provides a good approximation to the 
estimated GFR formula. 
 
Source: G. J. Schwartz, A. Munoz, M. F. Schneider, R. H. Mak, F. Kaskel, B. A. Warady, S. L. Furth: New Equations 
to Estimate GFR in Children with CKD. Journal of the American Society of Nephrology 2009, Volume 20, Issue 3, 
P. 629-637. 
 
 


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C O N F I D E N T I A L  
Appendix 3 Common Terminology Criteria for Adverse Events (CTCAE), 
Hepatobiliary Disorders 
 
 


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C O N F I D E N T I A L  
 
Source: Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 dated 27 November 2017, U.S. 
Department of Health and Human Services, National Institutes of Health, National Cancer Institute, 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.p
df, accessed 01 September 2020 
 
 


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C O N F I D E N T I A L  
Appendix 4 WHO Growth Charts for Boys and Girls 5 to 19 Years of Age 
Appendix-Figure 1 BMI-For-Age, Boys, 5 to 19 Years of Age 
 
Source: https://www.who.int/growthref/cht_bmifa_boys_perc_5_19years.pdf, accessed 01 September 2020 
Appendix-Figure 2 BMI-For-Age, Girls, 5 to 19 Years of Age 
 
Source: https://www.who.int/growthref/cht_bmifa_girls_perc_5_19years.pdf, accessed 01 September 2020 
 
 


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Appendix-Figure 3 Height-For-Age, Boys, 5 to 19 Years of Age 
 
Source: https://www.who.int/growthref/cht_hfa_boys_perc_5_19years.pdf, accessed 01 September 2020 
Appendix-Figure 4 Height-For-Age, Girls, 5 to 19 Years of Age 
 
Source: https://www.who.int/growthref/cht_hfa_girls_perc_5_19years.pdf, accessed 01 September 2020 


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Appendix 5 Tanner Staging 
Appendix-Table 1 Classification of Sex Maturity Stages in Girls 
Stage 
Pubic Hair 
Breasts 
1 
Preadolescent 
Preadolescent 
2 
Sparse, lightly pigmented, straight, medial 
border of labia 
Breast and papilla elevated as small 
mound, areolar diameter increased 
3 
Darker, beginning to curl, increased amount 
Breast and areola enlarged, no contour 
separation 
4 
Coarse, curly, abundant but amount less 
than adult 
Areola and papilla form secondary mound 
5 
Adult feminine triangle, spread to medial 
surface of thighs 
Mature, nipple projects, areola part of the 
general breast contour 
Appendix-Table 2 Classification of Sex Maturity Stages in Boys 
Stage 
Pubic Hair 
Penis 
Testes 
1 
None 
Preadolescent 
Preadolescent 
2 
Scanty, long, slightly 
pigmented 
Slight enlargement 
Enlarged scrotum, pink 
texture altered 
3 
Darker, starts to curl, small 
amount 
Longer 
Larger 
4 
Resembles adult type but 
less in quantity; coarse, 
curly 
Larger, glans and breadth 
increase in size 
Larger, scrotum dark 
5 
Adult distribution, spread to 
medial surface of thighs 
Adult size 
Adult size 
Sources:  
W. A. Marshall, J. M. Tanner: Variations in pattern of pubertal changes in girls. In: Archives of Disease in Childhood 
1969, Volume 44, P. 291–303. 
W. A. Marshall, J. M. Tanner: Variations in pattern of pubertal changes in boys. In: Archives of Disease in Childhood 
1970, Volume 45, P. 13–23. 
 
 
 


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Page 105 of 111 
C O N F I D E N T I A L  
Appendix 6 Laboratory Tests 
 
Category, Panel 
Parameters 
Haematology 
 
• Complete Blood Count (CBC) 
Haematocrit 
 
Haemoglobin 
 
Mean corpuscular haemoglobin (MCH) 
 
Mean corpuscular haemoglobin concentration (MCHC) 
 
Mean corpuscular volume (MCV) 
 
Platelet count 
 
Red blood cell count 
 
Red cell distribution width 
 
White blood cell count 
Serum chemistry 
 
• Metabolic panel 
Albumin 
 
Blood glucose (BG) 
 
Blood urea nitrogen (BUN) 
 
Calcium (Ca) 
 
Carbon dioxide 
 
Chloride (Cl) 
 
Creatinine 
 
Creatinine kinase (CK) 
 
C-reactive protein (CRP) 
 
Potassium (K) 
 
Sodium (Na) 
 
Total protein 
 
Serum lipase 
• Fasting lipid panel 
apolipoprotein A-I (apo A-I) 
 
apolipoprotein B (apo B) 
 
High-density lipoprotein cholesterol (HDL-C) 
 
Lipoprotein(a) [Lp(a)] 
 
Low-density lipoprotein cholesterol (LDL-C) 
 
Non high-density lipoprotein cholesterol (Non-HDL-C) 
 
Total cholesterol (TC) 
 
Triglycerides (TG) 
 
Very low-density lipoprotein cholesterol (VLDL-C) 
• Liver function tests (LFTs) 
Alanine aminotransferase (ALT) 
 
Aspartate aminotransferase (AST) 
 
Alkaline phosphatase (AP) 
 
Gamma-glutamyl transferase (GGT) 
 
Total bilirubin 
 
Direct bilirubin 
 
Indirect bilirubin 
• Essential fatty acids (EFA) 
Arachidonic acid (AA) 


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C O N F I D E N T I A L  
Category, Panel 
Parameters 
• Essential fatty acids (EFA) 
Alpha linoleic acid (ALA) 
 
Docosahexaenoic acid (DHA) 
 
Eicosapentaenoic acid (EPA) 
 
Eicosatrienoic acid 
 
Linoleic acid 
• Fat-soluble vitamin levels 
Retinol (Vitamin A) 
 
25-hydroxy-D (Vitamin D) 
 
Alpha tocopherol (Vitamin E) 
 
Ratio alpha tocopherol/total lipids 
 
Ratio uncarboxylated osteocalcin/total osteocalcin 
• Hormones 
Thyroid stimulating hormone (TSH) 
 
Adrenocorticotrophic hormone (ACTH) 
 
Serum cortisolL 
 
Follicle stimulating hormone (FSH) 
 
Luteinising hormone (LH) 
• Sex hormones (Tanner Stage ≥2) 
Serum testosterone 
 
Serum oestradiol 
• Pharmacokinetics 
Lomitapide 
Urine 
 
• Urinalysis 
Bilirubin 
 
Blood 
 
Colour 
 
Glucose 
 
Ketones 
 
pH 
 
Protein 
 
Turbidity 
 
White blood cells 
• Urine pregnancy test 
 
 
 
 
 
 


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C O N F I D E N T I A L  
Appendix 7 Declaration of Helsinki 
World Medical Association Declaration of Helsinki 
Ethical Principles for Medical Research 
Involving Human Subjects 
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the: 
29th WMA General Assembly, Tokyo, Japan, October 1975 
35th WMA General Assembly, Venice, Italy, October 1983 
41st WMA General Assembly, Hong Kong, September 1989 
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 
52nd WMA General Assembly, Edinburgh, Scotland, October 2000 
53rd WMA General Assembly, Washington, DC, USA, October 2002 (Note of Clarification added) 
55th WMA General Assembly, Tokyo, Japan, October 2004 (Note of Clarification added) 
59th WMA General Assembly, Seoul, Republic of Korea, October 2008 
64th WMA General Assembly, Fortaleza, Brazil, October 2013 
Preamble 
1. The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of 
ethical principles for medical research involving human subjects, including research on identifiable 
human material and data.  
The Declaration is intended to be read as a whole and each of its constituent paragraphs should be 
applied with consideration of all other relevant paragraphs. 
2. Consistent with the mandate of the WMA, the Declaration is addressed primarily to physicians. The 
WMA encourages others who are involved in medical research involving human subjects to adopt 
these principles. 
General Principles 
3. The Declaration of Geneva of the WMA binds the physician with the words, “The health of my patient 
will be my first consideration,” and the International Code of Medical Ethics declares that, “A 
physician shall act in the patient's best interest when providing medical care.” 
4. It is the duty of the physician to promote and safeguard the health, well-being and rights of patients, 
including those who are involved in medical research. The physician's knowledge and conscience 
are dedicated to the fulfilment of this duty. 
5. Medical progress is based on research that ultimately must include studies involving human subjects. 
6. The primary purpose of medical research involving human subjects is to understand the causes, 
development and effects of diseases and improve preventive, diagnostic and therapeutic 
interventions (methods, procedures and treatments). Even the best proven interventions must be 
evaluated continually through research for their safety, effectiveness, efficiency, accessibility and 
quality. 
7. Medical research is subject to ethical standards that promote and ensure respect for all human 
subjects and protect their health and rights. 
8. While the primary purpose of medical research is to generate new knowledge, this goal can never 
take precedence over the rights and interests of individual research subjects. 
9. It is the duty of physicians who are involved in medical research to protect the life, health, dignity, 
integrity, right to self-determination, privacy, and confidentiality of personal information of research 
subjects. The responsibility for the protection of research subjects must always rest with the physician 


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C O N F I D E N T I A L  
or other health care professionals and never with the research subjects, even though they have given 
consent.  
10. Physicians must consider the ethical, legal and regulatory norms and standards for research 
involving human subjects in their own countries as well as applicable international norms and 
standards. No national or international ethical, legal or regulatory requirement should reduce or 
eliminate any of the protections for research subjects set forth in this Declaration. 
11. Medical research should be conducted in a manner that minimizes possible harm to the environment. 
12. Medical research involving human subjects must be conducted only by individuals with the 
appropriate ethics and scientific education, training and qualifications. Research on patients or 
healthy volunteers requires the supervision of a competent and appropriately qualified physician or 
other health care professional. 
13. Groups that are underrepresented in medical research should be provided appropriate access to 
participation in research. 
14. Physicians who combine medical research with medical care should involve their patients in research 
only to the extent that this is justified by its potential preventive, diagnostic or therapeutic value and 
if the physician has good reason to believe that participation in the research study will not adversely 
affect the health of the patients who serve as research subjects. 
15. Appropriate compensation and treatment for subjects who are harmed as a result of participating in 
research must be ensured. 
Risks, Burdens and Benefits 
16. In medical practice and in medical research, most interventions involve risks and burdens.  
Medical research involving human subjects may only be conducted if the importance of the objective 
outweighs the risks and burdens to the research subjects. 
17. All medical research involving human subjects must be preceded by careful assessment of 
predictable risks and burdens to the individuals and groups involved in the research in comparison 
with foreseeable benefits to them and to other individuals or groups affected by the condition under 
investigation.  
Measures to minimise the risks must be implemented. The risks must be continuously monitored, 
assessed and documented by the researcher. 
18. Physicians may not be involved in a research study involving human subjects unless they are 
confident that the risks have been adequately assessed and can be satisfactorily managed.  
When the risks are found to outweigh the potential benefits or when there is conclusive proof of 
definitive outcomes, physicians must assess whether to continue, modify or immediately stop the 
study. 
Vulnerable Groups and Individuals 
19. Some groups and individuals are particularly vulnerable and may have an increased likelihood of 
being wronged or of incurring additional harm.  
All vulnerable groups and individuals should receive specifically considered protection. 
20. Medical research with a vulnerable group is only justified if the research is responsive to the health 
needs or priorities of this group and the research cannot be carried out in a non-vulnerable group. In 
addition, this group should stand to benefit from the knowledge, practices or interventions that result 
from the research. 
Scientific Requirements and Research Protocols 
21. Medical research involving human subjects must conform to generally accepted scientific principles, 
be based on a thorough knowledge of the scientific literature, other relevant sources of information, 
and adequate laboratory and, as appropriate, animal experimentation. The welfare of animals used 
for research must be respected. 


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C O N F I D E N T I A L  
22. The design and performance of each research study involving human subjects must be clearly 
described and justified in a research protocol.  
The protocol should contain a statement of the ethical considerations involved and should indicate 
how the principles in this Declaration have been addressed. The protocol should include information 
regarding funding, sponsors, institutional affiliations, potential conflicts of interest, incentives for 
subjects and information regarding provisions for treating and/or compensating subjects who are 
harmed as a consequence of participation in the research study. 
In clinical trials, the protocol must also describe appropriate arrangements for post-trial provisions. 
Research Ethics Committees 
23. The research protocol must be submitted for consideration, comment, guidance and approval to the 
concerned research ethics committee before the study begins. This committee must be transparent 
in its functioning, must be independent of the researcher, the sponsor and any other undue influence 
and must be duly qualified. It must take into consideration the laws and regulations of the country or 
countries in which the research is to be performed as well as applicable international norms and 
standards but these must not be allowed to reduce or eliminate any of the protections for research 
subjects set forth in this Declaration.  
The committee must have the right to monitor ongoing studies. The researcher must provide 
monitoring information to the committee, especially information about any serious adverse events. 
No amendment to the protocol may be made without consideration and approval by the committee. 
After the end of the study, the researchers must submit a final report to the committee containing a 
summary of the study’s findings and conclusions. 
Privacy and Confidentiality 
24. Every precaution must be taken to protect the privacy of research subjects and the confidentiality of 
their personal information. 
Informed Consent 
25. Participation by individuals capable of giving informed consent as subjects in medical research must 
be voluntary. Although it may be appropriate to consult family members or community leaders, no 
individual capable of giving informed consent may be enrolled in a research study unless he or she 
freely agrees. 
26. In medical research involving human subjects capable of giving informed consent, each potential 
subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts 
of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the 
study and the discomfort it may entail, post-study provisions and any other relevant aspects of the 
study. The potential subject must be informed of the right to refuse to participate in the study or to 
withdraw consent to participate at any time without reprisal. Special attention should be given to the 
specific information needs of individual potential subjects as well as to the methods used to deliver 
the information.  
After ensuring that the potential subject has understood the information, the physician or another 
appropriately qualified individual must then seek the potential subject’s freely-given informed 
consent, preferably in writing. If the consent cannot be expressed in writing, the non-written consent 
must be formally documented and witnessed.  
All medical research subjects should be given the option of being informed about the general 
outcome and results of the study. 
27. When seeking informed consent for participation in a research study the physician must be 
particularly cautious if the potential subject is in a dependent relationship with the physician or may 
consent under duress. In such situations the informed consent must be sought by an appropriately 
qualified individual who is completely independent of this relationship. 
28. For a potential research subject who is incapable of giving informed consent, the physician must 
seek informed consent from the legally authorised representative. These individuals must not be 
included in a research study that has no likelihood of benefit for them unless it is intended to promote 
the health of the group represented by the potential subject, the research cannot instead be 


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C O N F I D E N T I A L  
performed with persons capable of providing informed consent, and the research entails only minimal 
risk and minimal burden. 
29. When a potential research subject who is deemed incapable of giving informed consent is able to 
give assent to decisions about participation in research, the physician must seek that assent in 
addition to the consent of the legally authorised representative. The potential subject’s dissent should 
be respected. 
30. Research involving subjects who are physically or mentally incapable of giving consent, for example, 
unconscious patients, may be done only if the physical or mental condition that prevents giving 
informed consent is a necessary characteristic of the research group. In such circumstances the 
physician must seek informed consent from the legally authorised representative. If no such 
representative is available and if the research cannot be delayed, the study may proceed without 
informed consent provided that the specific reasons for involving subjects with a condition that 
renders them unable to give informed consent have been stated in the research protocol and the 
study has been approved by a research ethics committee. Consent to remain in the research must 
be obtained as soon as possible from the subject or a legally authorised representative. 
31. The physician must fully inform the patient which aspects of their care are related to the research. 
The refusal of a patient to participate in a study or the patient’s decision to withdraw from the study 
must never adversely affect the patient-physician relationship. 
32. For medical research using identifiable human material or data, such as research on material or data 
contained in biobanks or similar repositories, physicians must seek informed consent for its 
collection, storage and/or reuse. There may be exceptional situations where consent would be 
impossible or impracticable to obtain for such research. In such situations the research may be done 
only after consideration and approval of a research ethics committee. 
Use of Placebo 
33. The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of 
the best proven intervention(s), except in the following circumstances:  
Where no proven intervention exists, the use of placebo, or no intervention, is acceptable; or  
Where for compelling and scientifically sound methodological reasons the use of any intervention 
less effective than the best proven one, the use of placebo, or no intervention is necessary to 
determine the efficacy or safety of an intervention  
and the patients who receive any intervention less effective than the best proven one, placebo, or no 
intervention will not be subject to additional risks of serious or irreversible harm as a result of not 
receiving the best proven intervention.  
Extreme care must be taken to avoid abuse of this option. 
Post-Trial Provisions 
34. In advance of a clinical trial, sponsors, researchers and host country governments should make 
provisions for post-trial access for all participants who still need an intervention identified as beneficial 
in the trial. This information must also be disclosed to participants during the informed consent 
process. 
Research Registration and Publication and Dissemination of Results 
35. Every research study involving human subjects must be registered in a publicly accessible database 
before recruitment of the first subject.  
36. Researchers, authors, sponsors, editors and publishers all have ethical obligations with regard to the 
publication and dissemination of the results of research. Researchers have a duty to make publicly 
available the results of their research on human subjects and are accountable for the completeness 
and accuracy of their reports. All parties should adhere to accepted guidelines for ethical reporting. 
Negative and inconclusive as well as positive results must be published or otherwise made publicly 
available. Sources of funding, institutional affiliations and conflicts of interest must be declared in the 
publication. Reports of research not in accordance with the principles of this Declaration should not 
be accepted for publication. 


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C O N F I D E N T I A L  
Unproven Interventions in Clinical Practice 
37. In the treatment of an individual patient, where proven interventions do not exist or other known 
interventions have been ineffective, the physician, after seeking expert advice, with informed consent 
from the patient or a legally authorised representative, may use an unproven intervention if in the 
physician's judgement it offers hope of saving life, re-establishing health or alleviating suffering. This 
intervention should subsequently be made the object of research, designed to evaluate its safety and 
efficacy. In all cases, new information must be recorded and, where appropriate, made publicly 
available. 
 

SAP_001.pdf: 
Veristat study no: OCH19003
AMRYT Pharmaceuticals DAC study no: APH-19
Date: 28JUN2024
Page
of
Version: Final 5.0
ST/form/010/15
Phase III, Single-arm, Open-label, International, Multi-
centre Study to Evaluate the Efficacy and Safety of 
Lomitapide in Paediatric Patients with Homozygous 
Familial Hypercholesterolaemia (HoFH) on Stable Lipid-
lowering Therapy
AMRYT Pharmaceuticals DAC Study No: APH-19
Veristat Study No: OCH19003
Statistical Analysis Plan 
Version: FINAL 5.0
Date: 28th June 2024
Author
Sig1sig
Sig1role
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
(
DocuSigned by: 
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j{,St.- Ct,.,..pbS 
ll(J 
Signer Name: Jose Campos 
L
Signing Reason: I am the author of this document 
Signing Time: 28 June 202418:16:34 AM EDT 
1595A5A423AC411 DB7FDCA76941375DF 
46 


Veristat study no: OCH19003
AMRYT Pharmaceuticals DAC study no: APH-19
Date: 28JUN2024
Page
of
Version: Final 5.0
ST/form/010/15
Approved By Amryt Pharma
Ruth Nallen
Associate Director Clinical Operations
Zsuzsanna Tamas
Senior Director / Project Physician Leader
Global Rare Diseases
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
( 
DocuSigned by: 
I 
(J 
Signer Name: Ruth Nallen 
L
Signing Reason: I approve this document 
Signing Time: 28 June 2024 I 2:48:43 PM BST 
828F1C51 C8114629957A317DF4ABD0B4 
(
DocuSigned by: 
I 
(J 
Norn du signataire : Zsuzsanna Tamas 
L 
Motif de la signature : J'approuve ce document 
Heure de signature : 28 juin 2024 I 2:24:32 PM GEST 
90EC66709B83407BBA1B8362CEB092AB 
2 
46 


Veristat study no: OCH19003 
 
AMRYT Pharmaceuticals DAC study no: APH-19 
 
Date: 28JUN2024 
Page of 
Version: Final 5.0 
ST/form/010/15 
 
Modification History 
 
Version Change 
History 
Reason 
Date 
1.0 
First Version 
N/A 
 
14APR2022 
2.0 
Updated to 
Second 
Version 
 
To accommodate protocol version no 6 and PIP 
modification approved 01 August 2022. 
 
Add additional palatability objectives from the 
protocol that were omitted in error from the SAP.  
 
Added age group definition for clarity so now 2 
groups (age 5 to 10 years; 11 to 17 years) for 
analyses.  
 
Added profile plots for displaying adverse events. 
 
Added profile plots for liver function tests. 
 
Added scatter plots for lipid accumulation in the 
liver. 
 
Added waterfall and spaghetti plots for BMI / 
weight over time. 
 
Added additional subgroup analysis for reach MTD 
/ not reach MTD. 
 
Amend subgroup analysis for LLT to LLT meds 
(excluding LA) vs LLT meds (including LA). 
 
01SEP2022 
3.0 
Updated to 
Third Version 
 
Update analysis visit windows (section 5.3) to 
define analysis study weeks and nominal study 
visit. 
 
Update patient disposition (section 5.6) to include 
summary of subject study visits. 
 
Update demography and baseline (section 5.8.1) 
to include summary for country, HDL and Apo A1, 
 
Update prior and concomitant medications (section 
-
 
 
Update study treatment exposure (section 5.10) to 
define average daily exposure (mg/day). 
 
Update primary analysis (section 5.11.1.1) to 
clarify methods for analysis study week window 
and additional sensitivity analysis using nominal 
study visit. 
02DEC2022 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
5.9) to combine prior and 'run in' period . 
• 
• 
3 
46 


Veristat study no: OCH19003 
 
AMRYT Pharmaceuticals DAC study no: APH-19 
 
Date: 28JUN2024 
Page of 
Version: Final 5.0 
ST/form/010/15 
 
4.0 
Updated to 
Fourth Version 
 
Minor typo and format corrections.  
 
To accommodate protocol version no 7 approved 
09 February 2023. 
 
Updated visit windows to add window for the 
follow-up visit. 
 
Amended definition of completer analysis set 
(section 5.4). 
 
Addition of TC/HDL-C ratio as secondary endpoint. 
 
Add additional exploratory endpoints for the 2023 
EAS and 2018 American College of Cardiology 
LDL-C recommended target levels. 
 
Clarification of the process of determination of 
compliance with LLT. 
 
Update demography and baseline lipids (section 
5.8.1) to include TC/HDL-C ratio and LDL receptor 
function classification. 
 
Update exposure (section 5.10) to include 
summaries of duration on maintenance dose, IMP 
distribution over time, compliance to IMP and time 
to first dose interruption and discontinuation 
analyses. 
 
Addition of a summary of Lipoprotein apheresis 
regimen and days from LA to LDL-C assessment. 
 
Update primary and secondary endpoint (section 
5.11.1 and 5.11.2) to include sensitivity analysis 
using baseline observation carried forward, 
responder analysis and an additional subgroup 
analysis based on sex. 
 
Update adverse events (section 5.13.1) to include 
additional summaries for most frequent TEAEs 
and by AESI group. Addition of analysis for time to 
first gastrointestinal and hepatic TEAE. Addition of 
subgroups based on sex and compliance with low-
fat diet. 
 
Update clinical laboratory evaluation (section 5.14) 
to add additional summaries for liver function test. 
 
Update vital signs (section 5.15) to include 
percentage change and plots over time. 
 
Addition of summary of number of subjects with 
worsening from baseline in echocardiography 
(section 5.17) assessment. 
 
Update lipid accumulation in the liver (section 
5.18) to include additional analyses based on NMR 
data and analysis of number of subjects with 
increases in hepatic fat. Addition of scatter plots to 
assess correlation between liver function tests and 
hepatic fat. Addition of sensitivity analyses to 
assess the impact of a different NMR scan on Site 
12. 
 
Update physical examination (section 5.19) to 
include waterfall plots of change in BMI-Z-score by 
baseline BMI for age Z score, maximum weight 
loss and maximum z-score and spaghetti plots to 
assess the evolution of weight and Z-scores over 
time. 
 
Update diet and dietary supplement compliance 
(section 5.21) to include a summary of compliance 
with diet and dietary supplement compliance by 
study phase. 
04MAR2024 
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Update Xanthoma assessment (section 5.24.1) to 
include a cumulative summary of changes to pre-
existing xanthoma by dose group. 
5.0 
Updated to 
Fifth Version 
 
Addition of HDL-C as secondary endpoint (section 
2.3.2 and 5.11.2.2). 
 
Section 5.9, cosmetic updates and addition of a 
summary for subjects taking >= 2 and >=3 LLT 
during run-in. 
 
Addition of Wilcoxon-Signed rank test as a 
sensitivity analysis for primary and secondary 
efficacy endpoints (section 5.11.1.1). 
 
Addition of a summary of related TEAEs for 
elevated serum transaminases (section 5.13.1). 
 
Update to present summaries based on nominal 
(protocol) visits. Addition of percentage change to 
support safety evaluation of serum clinical 
chemistry parameters (section 5.14). 
 
Update Lipid accumulation in the liver (section 
5.18) to include Spearman  rank correlation 
coefficient for Ultrasound scans. 
28JUN2024 
 
 
 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
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Contents 
 
LIST OF ABBREVIATIONS..................................................................................................................... 8
1 
INTRODUCTION ........................................................................................................................... 10
2 
STUDY OBJECTIVES AND DESIGN ........................................................................................... 10
2.1 
Study Objectives ....................................................................................................................... 10
2.1.1 
Primary Objective .................................................................................................................. 10
2.1.2 
Secondary Objectives ............................................................................................................ 10
2.1.3 
Exploratory Objectives ........................................................................................................... 11
2.1.4 
Safety Objectives ................................................................................................................... 11
2.1.5 
Palatability Objective ............................................................................................................. 12
2.1.6 
PK Objective .......................................................................................................................... 12
2.2 
Study Estimands ....................................................................................................................... 12
2.3 
Study Endpoints ........................................................................................................................ 13
2.3.1 
Primary Endpoint ................................................................................................................... 13
2.3.2 
Secondary Endpoints ............................................................................................................. 13
2.3.3 
Exploratory Endpoints ............................................................................................................ 13
2.3.4 
Safety and Tolerability Endpoints .......................................................................................... 14
2.3.5 
Palatability Endpoints ............................................................................................................ 15
2.3.6 
PK Endpoints ......................................................................................................................... 15
2.4 
Study Design ............................................................................................................................. 15
2.5 
Visit Structure ............................................................................................................................ 17
3 
Sample Size .................................................................................................................................. 18
4 
ANALYSIS timings, SAFETY REVIEWS and publications ........................................................... 18
5 
Analysis Plan ................................................................................................................................. 19
5.1 
General ..................................................................................................................................... 19
5.2 
Data Review Meeting ................................................................................................................ 19
5.3 
General Derivations .................................................................................................................. 19
5.4 
Analysis Sets ............................................................................................................................ 24
5.5 
Data presentations .................................................................................................................... 24
5.6 
Disposition of participants ......................................................................................................... 25
5.7 
Protocol Deviations ................................................................................................................... 25
5.8 
Background and Demographic Characteristics ........................................................................ 26
5.8.1 
Demography and Baseline Characteristics ........................................................................... 26
5.8.2 
Diagnosis of HoFH ................................................................................................................. 26
5.8.3 
Medical and Cardiovascular History ...................................................................................... 27
5.9 
Prior and Concomitant Medications and Procedures ............................................................... 27
5.10 
Administration of Study Treatment and Exposure .................................................................... 28
5.11 
EFFICACY EVALUATION ........................................................................................................ 30
5.11.1 
Primary Endpoint ................................................................................................................... 30
5.11.2 
Secondary Endpoints ............................................................................................................. 33
5.12 
Multiplicity ................................................................................................................................. 36
5.13 
SAFETY EVALUATION ............................................................................................................ 36
5.13.1 
Adverse Events ...................................................................................................................... 36
5.14 
Clinical Laboratory Evaluation .................................................................................................. 39
5.15 
Vital Signs ................................................................................................................................. 40
5.16 
Electrocardiogram ..................................................................................................................... 41
5.17 
Echocardiography ..................................................................................................................... 41
5.18 
Lipid Accumulation in the Liver ................................................................................................. 41
5.19 
Physical Examination and Tanner Staging ............................................................................... 42
5.20 
Pulmonary Function Tests ........................................................................................................ 43
5.21 
Diet and Dietary Supplement Compliance ................................................................................ 43
5.22 
Pregnancy test .......................................................................................................................... 43
5.23 
Visit Dates ................................................................................................................................. 43
5.24 
Exploratory Assessments ......................................................................................................... 44
5.24.1 
Xanthoma Assessment .......................................................................................................... 44
5.24.2 
Carotid Intima-Media Thickness and Flow-mediated Dilation ............................................... 44
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5.24.3 
Palatability ............................................................................................................................. 44
5.25 
Changes from the Protocol Planned Analysis .......................................................................... 44
6 
References .................................................................................................................................... 46
 
 
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LIST OF ABBREVIATIONS 
 
AA  
Arachidonic acid  
ACTH  
Adrenocorticotrophic hormone  
AE  
Adverse event  
AESI  
Adverse Event of Special Interest  
AIC 
Akaike Information Criterion 
ALA  
Alpha-linolenic acid  
ALT  
Alanine transaminase  
ANCOVA  
Analysis of covariance  
AP  
Alkaline phosphatase  
apo A-I  
Apolipoprotein A-I  
apo B  
Apolipoprotein B  
AST  
Aspartate transaminase  
BMI  
Body mass index  
BOCF 
Baseline observation carried forward 
BSA  
Body surface area  
CAS 
Completer analysis set 
CBC  
Complete blood count  
CDF 
Cummulative distribution function 
CK  
Creatinine kinase  
CI 
Confidence interval 
CIMT  
Carotid intima-media thickness  
CSR 
Clinical Study Report 
D  
Day(s)  
DHA  
Docosahexaenoic acid  
DRM 
Data Review Meeting 
DSMB  
Data Safety Monitoring Board  
EAP 
Expanded Access Programme 
EAS  
European Atherosclerosis Society  
ECG  
Electrocardiogram  
eCRF  
Electronic Case Report Form  
EFA  
Essential fatty acids  
EPA  
Eicosapentaenoic acid  
EoT  
End of Treatment  
FAS  
Full analysis set  
FH  
Familial Hypercholesterolaemia  
FMD  
Flow-mediated dilatation  
FSH  
Follicle stimulating hormone  
FU  
Follow-up  
GGT  
Gamma-glutamyl transferase  
HDL-C  
High-density lipoprotein cholesterol  
HoFH  
Homozygous familial hypercholesterolaemia  
IDL  
Intermediate density lipoprotein  
ITT  
Intent-to-treat (analysis set)  
IU  
International units  
LA  
Lipoprotein apheresis  
LDL  
Low-density lipoprotein  
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LDL-C  
Low-density lipoprotein cholesterol (conventional mg/dL units 
can be converted to SI [mmol/L] units using the factor 0.0259)  
LDLR 
LDL receptor 
LDLRAP1 
LDL receptor adapter protein 1 
LFT  
Liver function test  
LH  
Luteinising hormone  
LLT  
Lipid-lowering therapy (including LA, where applicable)  
Lp(a)  
Lipoprotein a  
LOCF  
Last observation carried forward  
LSMean 
Least squares mean 
MACE  
Major adverse cardiac events  
MAR 
Missing at random 
MedDRA  
Medical Dictionary for Regulatory Activities  
MMRM 
Mixed Model Repeated Measures 
MTD  
Maximum tolerated dose  
N 
Non-missing observations 
NMR  
Nuclear magnetic resonance  
Non-HDL-C  
Non-high-density lipoprotein cholesterol  
NTEAE 
Non-treatment emergent adverse event 
PCSK9 
Proprotein convertase subtilisin/kexin type 9 
PDC 
Protocol deviation criteria 
PFT  
Pulmonary function test  
PIP 
Paediatric Investigation Plan 
PK  
Pharmacokinetics  
PPS  
Per-protocol (analysis set)  
PT 
Preferred Term 
SAE  
Serious adverse event  
SAF  
Safety analysis set  
SAP 
Statistical Analysis Plan 
SD  
Standard deviation  
SE 
Standard error 
SOC  
System Organ Class 
SMQ 
Standardized MedDRA Query 
TC  
Total cholesterol  
TC/HDL-C 
Total cholesterol: high-density-lipoprotein ratio 
TEAE 
Treatment emergent adverse event 
TFL 
Table, figure and listing 
TG  
Triglycerides  
TSH  
Thyroid stimulating hormone  
VLDL-C  
Very low-density lipoprotein cholesterol  
WHO  
World Health Organization  
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
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AMRYT Pharmaceuticals DAC study no: APH-19 
 
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1 INTRODUCTION 
This document details the statistical analysis of the data that will be performed for the 
Amryt Pharmaceuticals DAC study: Phase III, Single-arm, Open-label, International, 
Multi-centre Study to Evaluate the Efficacy and Safety of Lomitapide in Paediatric 
Patients with Homozygous Familial Hypercholesterolaemia (HoFH) on Stable Lipid-
lowering Therapy. 
The proposed analysis is based on the contents of the Final Version 7.0 of the protocol 
(dated 09 February 2023). The Statistical Analysis Plan (SAP) should be read in 
conjunction with the study protocol, electronic case report form (eCRF) and the table, 
figure and listing (TFL) shell. In the event of future amendments to the protocol and/or 
eCRF this SAP may be modified to account for changes relevant to the statistical 
analysis.  
The table, listing and figure shells are supplied in a separate document. 
2 STUDY OBJECTIVES AND DESIGN 
This is a prospective, single-arm, open-label study. 
2.1 Study Objectives 
2.1.1 
Primary Objective 
The primary objective of the study is:  
 To evaluate the efficacy of lomitapide as defined by the percent change in Low-
density lipoprotein cholesterol (LDL-C) at the maximum tolerated dose (MTD) 
at Week 24±3 days compared to baseline when added to stable Lipid-lowering 
therapy (LLT), (including lipoprotein apheresis [LA] when applicable) in 
 
2.1.2 
Secondary Objectives 
The secondary objectives of the study are to: 
 Evaluate the efficacy of lomitapide in paediatric HoFH patients as assessed 
by: 
 Percent change from baseline at Week 24±3 days in lipid parameters, 
including total cholesterol (TC), non-high-density lipoprotein cholesterol 
(Non-HDL-C), very low-density lipoprotein cholesterol (VLDL-C), 
triglycerides (TG), lipoprotein(a) [Lp(a)], and apolipoprotein B (apo B).  
 Percent change from baseline in TC, non-HDL-C, LDL-C, TG, VLDL-C, 
Lp(a) and apo B, at all other time-points through Week 104±1 week.  
 Change in LLT and LA from Week 24±3 days through Week 
104±1 week.  
Number (percent) of patients achieving the European Atherosclerosis 
Society (EAS) recommended target LDL-C of <135 mg/dL (3.5 mmol/L) 
at Week 24±3 days and at any time on study.  
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
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paediatric patients (5 to :517 years of age) with HoFH . 
• 
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 Percent change from baseline in total cholesterol: high-density-
lipoprotein cholesterol ratio (TC/HDL-C)* and high-density-lipoprotein 
cholesterol (HDL-C)*  at all timepoints upto Week 104±1 week.  
* HDL-C and TC/HDL-C are  non-key secondary endpoints. 
 
2.1.3 
Exploratory Objectives 
 Evaluate exploratory assessments of: 
 The change from baseline at Week 56±3 days and Week 104±1 week in 
mean carotid intima-media thickness (CIMT, mandatory) and flow-
mediated dilatation (FMD, whenever possible). 
 The resolution and/or regression of pre-existing xanthomas at 
Week 56±3 days and at Week 104±1 week. 
 Changes from baseline through Week 24±3 days in cholesterol and 
triglyceride content of VLDL, intermediate density lipoprotein (IDL), LDL 
and HDL, particle number and size of VLDL, LDL, and HDL as well as 
particle number of their respective lipoprotein subclasses (large, 
medium, and small) as assessed based on 2D nuclear magnetic 
resonance (NMR) (Liposcale® Test) of pharmacokinetics (PK) samples. 
2.1.4 
Safety Objectives 
 Evaluate the long-term safety and tolerability of lomitapide in paediatric HoFH 
patients as assessed by: 
 Incidence in reported (treatment-emergent) adverse events [(TE)AEs] 
and in clinically significant abnormal findings of physical examinations 
including weight and body mass index (BMI), electrocardiogram (ECG), 
standard of care echocardiography (if available) and vital signs, 
pulmonary function tests (PFT), and laboratory parameters including 
hepatic and renal function tests.  
 Effects on growth, bone health and bone age will be assessed using both 
-
appropriate progress at screening and from baseline at every visit 
through Week 104±1 week and/or at end of treatment (EoT), together 
with analysis of Vitamin D and K levels at screening, baseline, Week 
24±3 days, Week 56±3 days, Week 80±1 week, Week 104±1 week 
and/or at EoT (and at Week 108 for patients who opt not to participate in 
or are unsuitable for the EAP [<18 years of age]/opt not to transition to 
 years of age]). 
 Potential 
effects 
on 
maturation, 
reproductive 
development, 
gonadotropins, and variables of the pituitary-adrenal axis at screening, 
baseline, Week 56±3 days, Week 104±1 week and/or at EoT will be 
analysed; potential effects on the levels of sex steroids will be analysed 
 
 Lipid accumulation in the liver as measured by NMR imaging or 
echography (i.e., ultrasound scan) at baseline and at Week 24±3 days, 
Week 56±3 days, and at Week 104±1 week (for patients who opt not to 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
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0 
measurements of children's height and growth charts to track age 
commercial product [~18 
0 
for patients assessed as Tanner Stage ~2. 
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participate in or are unsuitable for the EAP [<18 years of age)/opt not to 
transition to commercial product [ 18 years of age], lipid accumulation 
in the liver will be measured at baseline, at Week 24±3 days, Week 56±3 
days, and at Week 108). All patients will undergo NMR imaging unless 
it is contraindicated or not feasible (e.g., due to the need for sedation or 
general anaesthesia in very young or anxious patients). In this case, 
ultrasound scans will be used at the discretion of the investigator. 
2.1.5 
Palatability Objective 
 Assess the palatability of the study medication using a 5-point facial hedonic 
palatability in terms of overall liking. 
 
expression will be used to determine whether the
 
 Ease of administration of the study medication and dietary supplements by the 
parent(s)/legal guardian(s) will be assessed using the following question at 
each visit during the treatment phase: 
giving the medication to your child because he/she refuses to take it or throws 
 
2.1.6 
PK Objective 
Evaluate the PK of lomitapide in paediatric HoFH patients through sparse blood 
sampling. 
2.2 Study Estimands 
The primary estimand 
. 
The primary estimand components are as follows: 
A. Population: The population is defined by the inclusion/exclusion criteria to 
reflect the targeted patient population. 
B. Variable: The primary variable is the percentage change from baseline in LDL-
C at week 24±3 days. 
C. Intercurrent Events: The following intercurrent events and strategy have been 
defined for this study: 
a. Dose adjustment of study drug: All data collected will be used in the 
analysis, irrespective of any dose adjustments to the investigational 
study drug. 
b. Use of alternative treatments/change in background LLT: All data 
collected will be used in the analysis, irrespective of any use of 
alternative treatments or changes in background LLTs. 
c. Study drug discontinuation: All data collected will be used in the analysis, 
irrespective of study drug discontinuation. If a subject does not have any 
data post study drug discontinuation, the data will be considered missing 
and imputed. 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
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scale anchored with descriptors, to record the children's assessment of 
• 
The parent(s)/legal guardian(s) interpretation of the child's reaction/facial 
y find lomitapide "pleasant", 
"unpleasant" or are "not sure" . 
• 
"Do you sometimes have problems in 
it up immediately after taking it? (Yes/No)." 
is defined as a 'treatment policy' estimand 
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D. Population-level Summary: The population-level summary measure is the 
mean percentage change from baseline in LDL-C at week 24±3 days.  
2.3 Study Endpoints  
The study endpoints are as follows. Note that t
be used interchangeably throughout this SAP to refer to the measurement of interest. 
The following efficacy endpoints: LDL-C, Non-HDL-C, TC, VLDL-C, apo B, TG and 
Lp(a), will be based on centralized core lab data from the fasting lipid panel, with the 
exception of Lp(a), which will be based on local labs as Lp(a) was not collected by the 
central lab at the beginning of the study. 
2.3.1 
Primary Endpoint 
The primary efficacy endpoint of the study is:  
 Percent change from baseline in LDL-C at Week 24±3 days. 
2.3.2 
Secondary Endpoints 
The secondary efficacy endpoints of the study are: 
 Percent change from baseline at Week 24±3 days for the following lipid 
parameters: Non-HDL-C, TC, VLDL-C, apo B, TG and Lp(a). 
 Percent 
change 
from 
baseline 
at 
all 
other 
time 
points 
through 
Week 104±1 week for the following lipid parameters: LDL-C, Non-HDL-C, TC, 
VLDL-C, apo B, TG and Lp(a). 
 Total number and percent of patients with a change from baseline in LLT and 
LA from Week 24±3 days through Week 104±1 week. 
 Total number and percent of patients achieving the 2014 EAS recommended 
target LDL-C of <135 mg/dL (3.5 mmol/L) in paediatric HoFH patients at 
Week 24±3 days and at any time on study. 
 Percent change from baseline at all timepoints upto Week 104±1 week for HDL-
C* and TC/HDL-C*. 
* HDL-C and TC/HDL-C are non-key secondary endpoints. 
2.3.3 
Exploratory Endpoints 
The exploratory efficacy endpoints of the study are: 
 Percent change from baseline at Week 56±3 days and Week 104±1 week in 
CIMT and FMD. 
 Total number and percent of patients with resolution and/or regression of pre-
existing xanthomas at Week 56±3 days and at Week 104±1 week. 
 Total number and percent of patients achieving the 2023 EAS recommended 
target LDL-C of <115 mg/dL (3.0 mmol/L) in paediatric HoFH patients at 
Week 24±3 days and at any time on study. 
 Total number and percent of patients achieving the 2018 American College of 
Cardiology/American Heart Association Task Force recommended target LDL-
C of <110 mg/dL (i.e. 2.9 mmol/L) in paediatric HoFH patients at week 24+/- 3 
days and at any time on the study  
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
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The Liposcale® Test exploratory endpoint will be reported separately.  
2.3.4 
Safety and Tolerability Endpoints 
 Incidence of (TE)AEs overall and by severity and relatedness. 
 Physical examinations including regular measurements of height, weight and 
BMI. 
 Sexual maturation (Tanner staging). 
 In patients with Tanner stage 2: change from baseline in sex hormones 
(serum testosterone and serum oestradiol). 
 12-Lead safety ECG (read locally), standard of care echocardiography (if 
available), vital signs and blood pressure. 
 Pulmonary function test. 
 Laboratory tests: 
 Standard haematology (complete blood count [CBC]) and clinical 
chemistry panels (including comprehensive metabolic panel).  
 Liver 
function 
tests: 
Alanine 
transaminase 
(ALT), 
aspartate 
transaminase (AST), gamma-glutamyl transferase (GGT), alkaline 
phosphatase (AP), total bilirubin, and serum albumin. 
 HDL-C and apolipoprotein A-I (apo A-I). 
 Creatinine kinase (CK). 
 Serum lipase. 
 Serum levels of essential fatty acids (EFA): Linoleic acid, alpha linoleic 
acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), 
arachidonic acid (AA), and eicosatrienoic acid. 
 Serum concentrations of fat-soluble vitamins: Vitamin A (retinol), vitamin 
E (alpha tocopherol), ratio of vitamin E to total lipids (total cholesterol 
plus fasting triglycerides), and vitamin D (25-hydroxy-D). Levels of 
vitamin K will be assessed indirectly by measuring total and 
uncarboxylated levels of serum osteocalcin. (Bone health will be 
assessed indirectly using growth to track age-appropriate progress, and 
measurement of 25-hydroxy-D as well as total and uncarboxylated 
osteocalcin levels). 
 Pituitary-adrenal hormone levels (thyroid stimulating hormone [TSH], 
follicle 
stimulating 
hormone 
[FSH], 
luteinising 
hormone 
[LH], 
adrenocorticotrophic hormone [ACTH], and morning serum cortisol). 
 Urinalysis 
 Lipid accumulation in the liver as measured by NMR imaging or echography 
(i.e., ultrasound scan) at Baseline and at Week 24±3 days, Week 56±3 days, 
and at Week 104±1 week (for patients who opt not to participate in or are 
unsuitable for the expanded access programme (EAP) (<18 years of age)/opt 
not to transition to commercial product ( 18 years of age), lipid accumulation in 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
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• 
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• 
• 
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0 
0 
0 
0 
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the liver will be measured at Baseline and at Week 24±3 days, 
Week 56±3 days, and at Week 108)). All patients will undergo NMR imaging 
unless it is contraindicated or not feasible (e.g., due to the need for sedation or 
general anaesthesia in very young or anxious patients). In this case, ultrasound 
scans will be used at the discretion of the investigator.  
2.3.5 
Palatability Endpoints 
 Total number and percent of patients for each response of palatability: 
 Able to swallow capsule (including food media responses if used). 
 Palatability rating (using a 5-point facial hedonic scale). 
 
(using a 3-point scale). 
 Parent/guardian experience problems giving medication to child 
because they refuse to take or throw up immediately after taking. 
 Parent/guardian problems in giving dietary supplement to child 
because they refuse to take or throw up immediately after taking. 
2.3.6 
PK Endpoints 
The PK endpoints will be reported separately.  
2.4 Study Design 
The APH-19 study is a single-arm, open-label, multi-centre phase III study to evaluate 
the efficacy and long-term safety of lomitapide in paediatric patients with HoFH 
receiving stable LLT (including LA, when applicable).  
The study will consist of 5 distinct periods: 
1. Screening Period (starting at Week -
 baseline for up 
to 6 weeks). 
2. Stratified Enrolment and Start of Run-in Period (starting at minimum at 
Week -6, i.e., 6 weeks prior to baseline for a minimum of 6 weeks): 
 Enrolment will be stratified to ensure approximately equal numbers of 
patients in the following age groups: 5 to 10 years, 11 to 15 years, and 
 
 Patients must be stabilized on current LLT (including LA, when 
applicable) and established on a diet supplying <20% of energy 
(calories) from fat or <30 g fat, whichever is the lesser amount. 
 Daily supplementation with vitamin E (200 international units [IU] for 
patients 5 to 8 years of age, 400 IU for patients 9 
and an EFA supplement containing approximately 200 mg linoleic acid, 
210 mg alpha linolenic acid (ALA), 110 mg EPA, and 80 mg DHA starting 
at Week -2. 
3. Efficacy phase (starting at baseline, i.e. Day [D] 0 for 24 weeks±3 days): 
 Approximately 45 paediatric patients with HoFH will be treated with 
lomitapide given orally, added to their current, stable LLT (including LA, 
when applicable) established during the Run-in Period. 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
• 
0 
0 
o 
Parent/guardian interpretation of child's reaction/facial expression 
0 
0 
12, i.e. ::;12 weeks prior to 
0 
16 to ::;17 years (with ~8 patients in any individual age group). 
0 
0 
to ::;17 years of age) 
0 
15 
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AMRYT Pharmaceuticals DAC study no: APH-19 
 
Date: 28JUN2024 
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 Assuming a withdrawal rate of approximately 33% by Week 24±3 days, 
this would result in 30 evaluable patients at Week 24±3 days (with 
 patients in any individual age group). 
 After the stabilization of the patient on his/her current MTD of LLT 
(including LA, when applicable) during the 6-week Run-in Period, 
treatment with lomitapide will be started as an add-on therapy on D0 of 
the efficacy phase. 
 Dosing will be initiated at the recommended starting dose and escalated 
to the maximum dose as applicable to the age groups based upon safety 
and tolerability in addition to LDL-C values. 
 The first dose of study medication will be administered at the study site 
on D0. 
 During the 24-week efficacy phase, patients will be required to remain 
on the stable LLT regimen (including LA, when applicable) established 
during the 6-week Run-in Period. 
4. Safety Phase (starting at Week 24±3 days for 80±1 weeks): 
 Patients will enter the 80-week Safety Phase after the Week 24±3 days 
assessments have been completed. Each patient will continue receiving 
the MTD of lomitapide he/she achieved during the efficacy phase (unless 
criteria is met for reducing or increasing the dose) for an additional 80±1 
weeks in the Safety Phase. 
 If after Week 24±3 days both the investigator and the sponsor consider 
a patient 5 to 15 years of age to be eligible for further escalation of the 
lomitapide dose beyond the maximum recommended dose by the 
respective age group, the lomitapide dose can be increased to an extent 
defined by the investigator after consultation with the sponsor based on 
individual safety, efficacy, and concomitant LLT criteria. If the patient 
new MTD. 
 If after Week 24±3 days, a patient has crossed over into the next age 
category, the study medication can be escalated to the maximum dose 
applicable for the new age category. If the patient tolerates this new dose 
  
 During the 80-week Safety Phase, the lomitapide dose can be reduced 
from the MTD due to tolerability or safety issues, and the patient can be 
re-challenged after a minimum period of 4 weeks following dose 
reduction with a higher dose of lomitapide once these issues resolve, but 
the dose during the Safety Phase cannot exceed the MTD established 
during the efficacy phase unless eligibility for exceptional dose 
escalation described above is met. 
 Adjustments to background LLT (including LA, when applicable) will be 
allowed at the discretion of the investigator. 
5. Follow-up (starting at Week 104±1 week for 4 weeks) or participation in the 
EAP of this study: 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
0 
0 
0 
0 
0 
0 
0 
tolerates this new dose for ~4 weeks, then this will be considered the 
0 
for ~4 weeks, then this will be considered the new MTD. 
0 
0 
16 
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AMRYT Pharmaceuticals DAC study no: APH-19 
 
Date: 28JUN2024 
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 At Week 104±1 week, eligible patients who complete the study per 
protocol and are <18 years of age may choose to enter the EAP. 
under the approved product label for adults. For both the patient 
groups, a follow-up phone call will be conducted at Week 108±1 week 
to monitor safety including AE and concomitant medication reporting.  
 For patients who opt not to participate in or are unsuitable for the EAP, 
 not to transition to commercial 
product will discontinue lomitapide treatment at Week 104±1 week and 
enter a 4 week Follow up period during which they will remain on 
concomitant LLT (including LA, when applicable). These patients will 
then attend in person for a Week 108±1 week visit. 
See Figure 1 below for further information on the study periods.  
Figure 1: Design of Study 
 
 
AE = adverse event; ALA = alpha-linoleic acid; DHA = docosahexaenoic acid; EFA = essential fatty acids; 
EPA = eicosapentaenoic acid; IU = International unit(s); LA = lipoprotein apheresis; LDL-C = low-density lipoprotein 
cholesterol; LLT = lipid-lowering therapy; MTD = maximum tolerated dose  
1. Stabilize current LLT (including LA, when applicable), establish diet <20% energy from fat or <30 g fat, 
whichever is the lesser amount, dietary supplementation from Week -2 (daily 200 IU [5 to 8 years of age] 400 
and 80 mg DHA])  
2. During the 24-week efficacy phase, patients will be required to remain on the stable LLT regimen (including LA, 
when applicable) established during the 6-week run-in period  
3. Based on safety, tolerability and efficacy parameters  
4. Adjustments to background LLT (including LA, when applicable) are allowed at the discretion of the investigator  
5. Dose adjustment rules apply  
6. Eligible patients who complete the study per protocol at Week 104 and are <18 years of age may choose to 
enter the Expanded Access Pr
under the approved product label for adults. For both these patient groups, a follow-up phone call will be 
conducted at Week 108±1 week to monitor safety including AE and concomitant medication reporting. Patients 
age who opt not to transition to commercial product will discontinue lomitapide treatment at Week 104±1 week 
and enter a 4 week Follow up period during which they will remain on concomitant LLT (including LA, when 
applicable). These patients will attend in person for a Week 108±1 week visit. 
 
2.5 Visit Structure 
The visit structure and scheduled assessments are detailed in Section 1.2 of the study 
protocol.   
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
Hill+ 
Screening 
0 
Patients ~18 years of age may opt to transition to commercial product 
0 
or patients ~18 years of age who opt 
stratified by 
agegroup, 
years 
24-week 
treaunant 
pe,iocP 
Starting dose, 
mg{day 
MTO, 
mg{day 
End of = 
El)tlyto 
safety 
JIil-
·EMF 
80-week 
lf9alna\t---. 
: : : 
period4 
. . . 
: : 
_ 
.... _: __ _ 
End of 
: 
Fol!Qw-
= ; upl 
___ i __ _ 
IU [~9 years of age] vitamin E and EFA supplement [approx. 200 mg linoleic acid, 210 mg ALA, 110 mg EPA, 
ogramme. Patients ~18 years of age may opt to transition to commercial product 
who opt not to participate in or are unsuitable for the Expanded Access Programme, or patients ~18 years of 
17 
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AMRYT Pharmaceuticals DAC study no: APH-19 
 
Date: 28JUN2024 
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3 SAMPLE SIZE 
determined by age at baseline
required at Week 24±3 days to provide 92% power, assuming a 25% reduction from 
baseline in LDL-C with a standard deviation (SD) of 40% and a 2-
allow for up to 33% dropout during the efficacy phase (prior to Week 24±3 days), an 
additional 15 patients will be enrolled, resulting in a total sample size of approximately 
45 patients. Enrolment will be stratified to ensure approximately equal numbers of 
patients in the following age groups: 5 to 10 years, 11 to 15 years, and 
 
As a conservative assumption, the estimated 25% mean reduction represents 
approximately 60% of the 41% mean reduction from baseline to Week 26/End of 
efficacy phase seen in the adult study UP1002/733-005, Intent-to-Treat (ITT) 
Population; as well, it is the same assumption that was used for the sample size in the 
adult study. The SD represents an approximate 1/3 increase from the 31% SD 
observed in the adult study. This increase in SD was used to account for potentially 
increased variability across the 3 age groups.  
On 25 April 2022, Amryt Pharmaceuticals DAC submitted an application for 
modification of the agreed Paediatric Investigation Plan (PIP) to the European 
Medicines Agency (EMA). On 01 August 2022, the EMA Paediatric Committee agreed 
with the proposed change for the number of study participants by paediatric subset 
at least 30 evaluable patients at Week 24 (with at least 8 patients in the following 
age groups: 5 to 10 years, 11 to 15 years and 16 to less than 18 years of age)
at 
least 30 evaluable patients at Week 24 (with at least 12 patients in each of the 
following age groups: 5 to 10 years and 11 to less than 18 years of age)
the due date for completion (last patient, last visit) has been extended from April 2023 
to August 2024. 
As the PIP amendment was approved, age groups for statistical analysis are now 
based on the 2 age groups (i.e. 5 to 10 years and 11 to 17 years) as detailed below. 
4 ANALYSIS TIMINGS, SAFETY REVIEWS AND PUBLICATIONS 
The primary efficacy analysis will be conducted when all patients have completed (or 
withdrawn prior to) Visit 10 at Week 24±3 days (end of efficacy phase), for reporting 
in a Clinical Study Report (CSR). The primary efficacy analysis will include the key 
primary / secondary efficacy data, all safety data available up to the data cut-off date 
of the last patient reaching week 24±3 days and PK parameter analyses.  
No planned interim analyses for efficacy and/or futility will be performed, as detailed 
in the protocol.  
An independent Data Safety Monitoring Board (DSMB) will be periodically reviewing 
the safety data, as described in Section 4.3 of the study protocol as described within 
the DSMB Statistical Analysis Plan.  
The final statistical analysis will occur when all patients have completed follow-up 
Visit 23 at Week 108, and the CSR will be updated to include the final analysis. 
Efficacy, safety and exploratory data collected during the Safety phase and follow-up 
phase will be included. 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
At least 30 evaluable patients (~8 patients in each of the following age groups, 
: 5 to 10 years, 11 to 15 years, and 16 to :517 years) are 
sided a of 0.05. To 
16 to :517 years. 
from' 
> to I 
'. In addition, 
18 
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AMRYT Pharmaceuticals DAC study no: APH-19 
 
Date: 28JUN2024 
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of 
Version: Final 5.0 
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5 ANALYSIS PLAN 
5.1 General 
Summary statistics for continuous variables will consist of number of non-missing 
observations (n), mean, SD, minimum, median, maximum, 25th and 75th percentiles 
unless specified otherwise. The precision of these variables is defined in the table, 
figure and listing shells document.  
For categorical variables the number and percentage of subjects in each category will 
be presented, based on the number of subjects in the analysis set, unless otherwise 
specified.  
 
Tests of Hypotheses and Significance Levels  
The primary and secondary efficacy parameters collected during the efficacy phase of 
the study will be statistically tested using a 2-sided test at the 5% significance level. 
5.2 Data Review Meeting  
The Sponsor will convene a data review meeting (DRM) after the data for the 
Week 24±3 days lock has been cleaned and before the study is locked. The DRM will 
make decisions that will include, but will not be limited to: 
 the determination of whether protocol deviations are 'major' or 'minor', or not a 
protocol deviation at all; 
 the allocation of subjects to the per protocol analysis set (PPS); 
If required, after the DRM and prior to database lock, a SAP amendment will be issued 
and all changes based on the DRM will be documented in the SAP, including the 
reason for the change. 
On November 2022 the DRM was performed and subject allocation to PPS was 
performed. No changes were made in the SAP based on the DRM. 
5.3 General Derivations 
This section provides details of general derivations. Derivations specific to the 
parameter of interest are detailed within the specific SAP section. 
 
Definition of Baseline 
Baseline is defined as the last non-missing value (including scheduled and 
unscheduled assessments) prior to the subject receiving study treatment in the 
efficacy phase (Visit 4). If a baseline value is missing, it is not appropriate for this 
study, to carry forward screening / run-in period values for the fasting lipid panel 
prior to stabilisation of the patient on LLT. Thus, if baseline is missing, then it 
should remain as missing. 
 
Definition of Study Day 
-specified visits 
defined in the protocol. Data listings will additionally present study days. Study day 
will be calculated relative to the first date of administration of study treatment, Day 
0 (study day 1). Any calculations referencing study day are calculated as (end 
date- start date) +1. 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
• 
• 
• 
• 
Throughout this SAP any references to "Visit XX" refer to the pre 
19 
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Definition of Study Duration 
Study duration will be derived as the number of days between first 
-
 and date of study completion or the date of early study withdrawal (i.e. 
(date of study completion or date of early study withdrawal - date of starting the 
-
) +1).  
 
Definition of Treatment Duration 
Treatment duration will be derived as the number of days between the first 
administration of study drug and the date of the last administration of study drug 
(i.e. date of last administration of study drug  date of first administration of study 
drug) +1). 
 
-
 
-
s Visit 2 to Visit 4. If a subject drops out during the 
Run in  
-
 
 
Age at Screening 
Age at screening is recorded in years and months, but will be calculated for 
summary measures as age in years, defined as [years + (months) / 12] (e.g. 12 
years 6 months = 12.5 years)].  
 
Age groups 
Children will be divided into two age groups, based on their age at screening. The 
two age groups will be defined as:  
 Age 5 to 10 years (i.e. >=5 years to <=10 years);  
 Age 11 to 17 years (i.e. >=11 years to <=17 years). 
 
Body Mass Index 
BMI is calculated as (weight (kg) / height (m)²). 
 
z-scores and percentile 
The z-scores and percentiles for BMI and height will be calculated using the World 
Health Organization (WHO) growth reference data for 5-19 years in the following 
indicators: BMI-for-age (5-19 years), Height-for-age (5-19 years), Weight-for-age 
(5-10 years).  
Note: According to the WHO, weight-for-age reference data are not available 
beyond age 10 because this indicator does not distinguish between height and 
body mass in an age period where many children are experiencing the pubertal 
growth spurt and may appear as having excess weight (by weight-for-age) when 
in fact they are just tall. 
 
Body Surface Area 
Body Surface Area (BSA) is calculated using the Mosteller formula: 
 
BSA(m2) = 
 
 
(Mosteller RD. Simplified calculation of body surface area. N Engl J Med. 
1987;317:1098). 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
• 
in' period 
'run in' period 
• 
• 
Definition of 'Run in' 
The 'Run in' period is defined a 
' 
' period they are considered a 'Run in failure' . 
• 
• 
• 
• 
• 
..,/ c8eight ( cm)x Weight (kg)) 
3600 
day of the 'run 
20 
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AMRYT Pharmaceuticals DAC study no: APH-19 
 
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Ratios 
The following ratios will be calculated (if possible) at each timepoint: 
 Vitamin E to total lipids ratio 
Vitamin E : total lipid ratio = [Vitamin E (µmol/L) / total lipid (mmol/L) 
(where total lipids is the defined as total cholesterol (mmol/L) plus fasting 
triglycerides (mmol/L)) 
 Vitamin E to total cholesterol 
Vitamin E : total cholesterol ratio = [Vitamin E (µmol/L) / total cholesterol 
(mmol/L) 
 Vitamin E to triglycerides 
Vitamin E : triglycerides ratio = [Vitamin E (µmol/L) / triglycerides (mmol/L) 
TC : HDL-C ratio = [TC (mmol/L) / HDL-C (mmol/L)] 
 
Incomplete dates 
For calculation purposes, incomplete dates will be completed using worst case, 
the most conservative value possible. Further details are detailed in the relevant 
sections as required. 
 
Non-numeric values 
In the case where a variable is 
purposes a value of x will be taken. Where a range of values is quoted the midpoint 
of the range will be taken. For example, if a laboratory safety parameter is reported 
as being below the limit of quantification or <x, the value of the limit will be used 
in the calculation of summary statistics. The recorded value will be reported in 
listings. 
 
Methods for handling withdrawals and missing data 
As this is a single-arm study, for patients who have missing data at the timepoint 
of interest, the last observation carried forward (LOCF) approach will be used in 
the efficacy phase analyses of primary and key secondary endpoints. If a baseline 
value is missing, it is not appropriate to carry forward screening / run-in period 
values for the fasting lipid panel prior to stabilisation of the patient on LLT. Thus, 
if efficacy phase baseline is missing, then it should remain as missing. 
 
Analysis Study Week Windows and Analysis Study Visit  
Analysis study week windows will be applied to the Fasting Lipid panel data for 
the analysis of the primary endpoint and secondary endpoints. The study protocol 
(Final Version 7.0, dated 09 February 2023) stated Fasting Lipid panel data should 
be collected within +/- 3 days of the target assessment date for Week 4 to Week 
56 inclusive and +/- 7 days of the target assessment date for Week 68 to Week 
104 inclusive).  
However, it was not always possible to adhere to the tight study window of ±3 days 
of the target assessment date for the following reasons: In 5 subjects, visits were 
either missed or out of window due to infections including COVID-19 (n=4), in 2 
subjects, visits had to be postponed due to malfunction of lipoprotein apheresis 
machines, 1 subject had to travel abroad for a case of death in the family and 1 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
• 
• 
• 
recorded as ">x", "~x", "<x" or "sx", then for analysis 
• 
• 
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subject could not visit the site in time due to bad weather conditions and a distance 
of 317 km to the site. The majority of visits out of window occurred in the Middle 
East, where subjects had to travel a median distance of 296 km to the sites 
(minimum of 30 km, maximum of 985 km) and could not attend the sites in time, 
because their father could not accompany them, the visit did not match the 
lipoprotein apheresis schedule, or the visit fell into a period of cultural holidays, 
such as Ramadan. To allow for these various reasons the Analysis Visit Window 
for the Lipid Panel data has been adapted to accommodate.  
The Analysis study week window will be defined so study visits are mapped onto 
the relevant study week, as defined by the corresponding study day the study 
assessment occurred for scheduled and unscheduled visits. If more than one 
scheduled / unscheduled visit falls within a study week window, then the study 
assessment visit closest to the intended target day of assessment should be used 
for that study week window. If more than one scheduled / unscheduled visit falls 
within a study week window and are equal distance from the target day of 
assessment then the average of the two study assessment visits should be used 
for that study week window.     
In addition to the Analysis study week windows, the Nominal Analysis Study Visit 
will be defined as the nominal study visit attached to the corresponding study 
assessment. The nominal study visit will only be applied to the Lipid panel data for 
statistical analyses. 
Study 
Week 
Target day of 
assessment 
(according to 
protocol) 
Analysis study day 
window  
(Lipid panel data) 
Analysis study day 
window  
(All Non-Lipid data for 
secondary objectives)
Baseline 
1 
-1 to 1 
-1 to 14 
Week 4 
28±3 
15 to 42 
15 to 42 
Week 8  
56±3 
43 to 70 
43 to 70 
Week 12  
84±3 
71 to 98 
71 to 98 
Week 16  
112±3 
99 to 126 
99 to 126 
Week 20  
140±3 
127 to 154 
127 to 154 
Week 24  
168±3 
155 to 182 
155 to 182 
Week 28  
196±3 
183 to 210 
183 to 210 
Week 32  
224±3 
211 to 238 
211 to 238 
Week 36  
252±3 
239 to 266 
239 to 266 
Week 40  
280±3 
267 to 294 
267 to 294 
Week 44  
308±3 
295 to 322 
295 to 322 
Week 48  
336±3 
323 to 350 
323 to 350 
Week 52  
364±3 
351 to 378 
351 to 378 
Week 56  
392±3 
379 to 434 
379 to 434 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
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AMRYT Pharmaceuticals DAC study no: APH-19 
 
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Study 
Week 
Target day of 
assessment 
(according to 
protocol) 
Analysis study day 
window  
(Lipid panel data) 
Analysis study day 
window  
(All Non-Lipid data for 
secondary objectives)
Week 68  
476±7 
435 to 518 
435 to 518 
Week 80  
560±7 
519 to 602 
519 to 602  
Week 92  
644±7 
603 to 686 
603 to 686 
Week 104 
728±7 
687 to 748 
687 to 748 
Week 108 
756±7 
749 to LPLV 
749 to LPLV 
 
Study Visit / Week  
(according to protocol) 
Nominal analysis study visit 
(Lipid panel data) 
Visit 4, Baseline, Day 0 
Visit 4 
Visit 5, Week 4 
Visit 5 
Visit 6, Week 8  
Visit 6 
Visit 7, Week 12  
Visit 7 
Visit 8, Week 16  
Visit 8 
Visit 9, Week 20  
Visit 9 
Visit 10, Week 24  
Visit 10 
Visit 11, Week 28  
Visit 11 
Visit 12, Week 32  
Visit 12 
Visit 13, Week 36  
Visit 13 
Visit 14, Week 40  
Visit 14 
Visit 15, Week 44  
Visit 15 
Visit 16, Week 48  
Visit 16 
Visit 17, Week 52  
Visit 17 
Visit 18, Week 56  
Visit 18 
Visit 19, Week 68  
Visit 19 
Visit 20, Week 80  
Visit 20 
Visit 21, Week 92  
Visit 21 
Visit 22, EOT / Week 104 
Visit 22 
Visit 23, Follow-Up Week 108 
Visit 23 
 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
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5.4 Analysis Sets 
The following analysis set definitions will be used in the data presentations: 
The Enrolled Set is defined as all participants who pass screening and enter onto the 
Run-in period, irrespective of whether they receive the study treatment. 
The Safety Analysis Set (SAF) is defined as all participants who are treated with at 
least one dose of the IMP. The SAF will be used for all safety analyses. 
The Full Analysis Set (FAS) is defined as all participants who receive at least one 
dose of the IMP and who have a baseline and at least one post-baseline measurement 
of LDL-C. The FAS will be used for all efficacy analyses. 
The Completer Analysis Set (CAS) is defined as a subset of the FAS and will include 
all participants who have not discontinued the efficacy phase (up to Week 24) of the 
study early irrespective of the reason for discontinuation. The CAS will be used for 
supplementary efficacy analyses during the efficacy phase. 
The Per-Protocol Set (PPS) will be a subset of the Full Analysis Set consisting of 
those participants who reasonably adhere to all protocol conditions i.e., who have met 
the eligibility criteria and will have received planned study medication without important 
protocol deviations considered to have a serious impact on the efficacy results within 
the efficacy phase of the trial. The PPS will be used for supplementary efficacy 
analyses during the efficacy phase. 
The Analysis Set Planning form will indicate which analysis data sets (e.g. PPS) 
require individual subject assignments to be listed for review and agreement at the 
final DRM prior to final analysis. The Analysis Set Planning form will document the 
timing of the data reviews. Where analysis sets do not require data review of individual 
subject assignments, the definitions are considered sufficient to determine the 
subjects included within these analysis sets without listing and data review. 
5.5 Data presentations 
All data are unblinded due to the nature of the study (i.e., open-label). 
-
, has entered the study but not received study 
treatment), the 
 
The data will be summarised in tabular form for all treated subjects. 
All post-baseline laboratory, vital signs, ECG, echocardiography and NMR scan values 
will be tabulated and listed; in particular all clinically significant values will be noted. 
Eligibility and analysis set listings will be based on the enrolled set and all other listings 
will be based on the SAF set. 
Listings will be sorted by subject number and date/time of assessment. Graphical 
presentations of the data will also be provided where appropriate. 
Analysis sets will be summarised using the enrolled set. Study disposition will be 
summarised using the enrolled set and SAF. Protocol deviations will be listed using 
the SAF. Background and demographic characteristics will be summarised using the 
SAF set. The primary efficacy endpoint will be summarised using the FAS, CAS and 
PPS sets. The secondary efficacy endpoints (i.e. fasting lipid panel at week 24±3 days) 
that are adjusted for multiplicity (as defined in section 5.12) will be summarised using 
the FAS, CAS and PPS sets. All other secondary efficacy endpoints will be 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
If a participant is a 'run in failure' (i.e. 
treatment variable will be labelled as 'Not Treated'. 
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summarised using the FAS. Prior/concomitant medications, administration of study 
treatment exposure and safety will be summarised using the SAF. 
5.6 Disposition of participants 
The number and percentages of all participants will be presented for the following: 
 Screen failures. 
 Run-in failures. 
 
Run-in P
. 
 Analysis sets (i.e. Enrolled, FAS, CAS, PPS, SAF). 
 Completed the efficacy phase of the study.  
 Completed the safety phase of the study. 
 Prematurely discontinued from the study. 
 Reason for study withdrawal. 
run-
-
the Enrolled set. All other percentages for the analysis sets (FAS, CAS, PPS, SAF), 
completed study, prematurely discontinued study will be based off the SAF.  
 
The following parameters will be presented as summary statistics, with weeks as the 
unit of measure: 
 Study duration. 
 Treatment duration.  
The number and percentage of participants will be summarised by their reason for 
withdrawal from study / treatment. 
Run-in failures  are defined as subjects who enter the Run-in Period  and discontinue 
the study before receiving a first dose of study treatment.  
Subjects who prematurely discontinue from the study due to a reason relating to 
COVID-19 are identified as either of the following:  
 Reason for withdrawal 
-
 
 
-19 
related AE reported on the AE eCRF page.  
Patients who prematurely discontinue from study due to a reason relating to COVID-
19 will be classified during the DRM. The number and percentage of subjects who 
prematurely discontinue due to either of these definitions will be presented as a reason 
-
 
Eligibility for each of the analysis sets and reasons for exclusion will be listed. Eligibility 
criteria, informed consent and assent, study completion/withdrawal and Visit dates 
data will be listed. The number of subjects attending each study visit will also be 
summarised.  
5.7 Protocol Deviations 
All protocol deviations will be assessed and documented on a case-by-case basis prior 
to the database lock. Major protocol deviations are a subset of protocol deviations that 
may significantly impact the completeness, accuracy, and/or reliability of the study 
-being. Major 
protocol deviations and their impact on the analysis sets for this study are decided by 
the study team.  
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
• 
• 
• 
Completed the' 
• 
• 
• 
• 
• 
eriod' 
The percentages for ' 
in' failures and completed the 'run in' period will be based off 
• 
• 
• 
of 'Other' with a corresponding free text reason 
containing a text version of 'COVID 19'. 
• 
Reason for withdrawal of 'Adverse Event' with a corresponding COVID 
for withdrawal of 'COVID 19'. 
data or that may significantly affect a subject's rights, safety, or well 
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Prior to database lock, Amryt may review the individual deviations to confirm that major 
protocol deviations have been captured correctly and to agree impact to analysis sets 
as indicated in the Protocol Deviation Criteria (PDC) form.   
Details of all major protocol deviations (date, deviation type, deviation category and 
specific details) and participant eligibility will be listed. Details of all minor protocol 
deviations will also be listed. 
Missing data and protocol deviations are expected as a result of COVID-19. All 
protocol deviations regarding visits and assessments due to the COVID-19 pandemic 
will be presented in a separate listing. 
Compliance with lipid lowering therapy will be determined through manual review of 
protocol deviations. 
5.8 Background and Demographic Characteristics 
5.8.1 
Demography and Baseline Characteristics 
Demographic characteristics (age, sex, race and ethnicity), body measurements 
(height, weight, BMI, and BSA), height percentile, height z-score, BMI percentile, and 
BMI z-score collected at Baseline will be summarised overall and by age group.  
Baseline lipids (i.e. LDL-C, TC, Non-HDL-C, VLDL-C, Lp(a), TG, apo B, HDL-C, 
TC/HDL-C ratio, and apo A1) will be summarised overall and by age group.  
Age at screening (in years) will be presented as a summary measure (as defined in 
section 5.3) and will be summarised overall and by age group.  
All subject demographic and baseline characteristic data, including informed consent, 
will be listed. 
5.8.2 
Diagnosis of HoFH 
Details regarding the diagnosis of HoFH will be summarised overall and by age group:  
 Duration of HoFH diagnosis. 
 Genetic confirmation of 2 mutant alleles (including mutant alleles). 
 LDL receptor (LDLR) gene locus 
 apo B gene locus 
 Proprotein convertase subtilisin/kexin type 9 (PCSK9) gene locus 
 LDL receptor adapter protein 1 (LDLRAP1) gene locus 
 Unknown 
 Other (please specify) 
 Classification of mutations in LDL receptor. 
 An untreated LDL-C value >500 mg/dL (13 mmol/L) or treated LDL-C value 
300 mg/dL (8 mmol/L) AND cutaneous or tendon xanthoma before age of 
10 years. 
 An untreated LDL-C value >500 mg/dL (13 mmol/L) or treated LDL-C value 
300 mg/dL (8 mmol/L) AND untreated LDL-C levels consistent with 
heterozygous FH in both parents. 
Duration of HoFH diagnosis (months) will be calculated as: 
12 * [date of baseline  date of HoFH diagnosis + 1] / 365.25 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
• 
• 
0 
0 
0 
0 
0 
0 
• 
• 
• 
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Mutations in LDLR can impair LDLR activity at different levels and therefore are 
classified according to their phenotypic behaviour (Galicia-Garcia 2020; Gidding 2015) 
as: 
 Class 1: Synthesis of receptor or precursor protein is absent, 
 Class 2: Absent or impaired formation of receptor protein, partial or complete 
retention of LDLR in the endoplasmic reticulum, 
 Class 3: Normal synthesis of receptor protein, but abnormal or defective binding 
to apo B, 
 Class 4: Defective endocytosis, clustering in coated pits, and internalization of 
the receptor complex does not take place, 
 Class 5: Diminished LDLR recycling capacity, receptors are not recycled and 
are rapidly degraded. 
According to Gidding et al. the functional defects in the LDLR are complex, and a 
mutation can belong to more than one class. Therefore, LDLR mutations will be 
classified upon medical review into 4 groups: subjects with the LDLR variant category 
, 
 and subjects with 
unknown LDLR variant category. 
All diagnosis of HoFH data will be listed. 
5.8.3 
Medical and Cardiovascular History 
Medical history events and cardiovascular disease history events will be coded using 
the latest MedDRA dictionary version. The version used will be indicated in the data 
summaries and listings. The number and percentage of participants will be presented 
for ongoing conditions and previous conditions separately by system organ class 
(SOC), and preferred term (PT), where SOC and PT will be presented in decreasing 
frequency of the total number of participants with medical history / cardiovascular 
disease history events.  
Medical history will be summarised overall and by age group. 
Cardiovascular disease history collected at Screening will be summarised overall and 
by age group. Established cardiovascular disease history will be defined as aortic 
valve disease and/or coronary atherosclerosis. 
All medical history / cardiovascular disease history events will be listed. 
5.9 Prior and Concomitant Medications and Procedures 
Medications will be coded using the latest World Health Organization Drug dictionary 
(WHO Drug) version. The version used will be indicated in the data summaries and 
listings.  
Procedures will be coded using the latest MedDRA version. The version used will be 
indicated in the data summaries and listings. 
Prior medications and procedures are defined as those that started and ended prior to 
the enrolment date visit (Visit 2) 
Run-in P
.  
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
• 
• 
• 
• 
• 
'defective/defective', subjects with the LDLR variant category 'defective/negative' 
subjects with the LDLR variant category 'negative/negative' 
(i.e. start of the ' 
eriod') 
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-
 and procedures are defined as those that are ongoing at the time 
of s
Run-in Period
Run-in 
Period
.  
Concomitant medications / procedures are defined as those that are: 
 Ongoing at the time of first administration of study treatment or  
 Started or ended on or after the time of first administration of study treatment 
or  
 Started prior to the end/last dose of study treatment.  
Prior LLT medications and procedures (including LA) are defined as those that started 
-
  
-
LLT medications and procedures (including LA) are defined as any LLT or 
procedure that are ongoing at the enrolment vi
Run-in 
P
and 
Run-in Period
administration of study treatment. 
(including LA) (efficacy phase) are 
defined as any LLT or procedure that are ongoing at the time of first administration of 
study treatment or started on or after the time of first administration of study treatment 
or started prior to the end/last dose of study treatment within the efficacy phase.  
defined as any LLT or procedure that are ongoing at the start of the safety phase or 
started on or after the start of the safety phase or started prior to the end/last dose of 
study treatment within the safety phase.  
If medication / procedure dates are incomplete and it is not clear whether the 
medication / procedure was concomitant, it will be assumed to be concomitant. 
All medications / procedures will be medically reviewed for accurate classification of 
LLT medications / procedures. 
The number and percentage of participants (overall and by age group) taking the 
following will be summarised by medication class and standardised medication name:  
 Prior 
-
medications and procedures (except for LLT),  
 Concomitant medications and procedures (except for LLT), 
 Prior 
-
LLT medications and procedures, 
 Concomitant LLT medications and procedure (efficacy phase and safety 
phase). 
In the summary tables, the medication class and standardised medication name will 
be presented in decreasing frequency of the total number of participants with 
medications. Participants taking multiple medications in the same medication class or 
having the same standardised medication recorded multiple times in the study will be 
counted only once for that specific medication class and standardised medication 
name. For LLT medications, the number of subjects taking at least 2 and at least 3 
medications during Run-in will be presented. 
Medication and procedure data will be listed. 
5.10  Administration of Study Treatment and Exposure 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
'Run in' medications 
tarting the ' 
' (i.e. Visit 2) or started after the start of the ' 
• 
• 
• 
', but before the time of first administration of study treatment 
and ended prior to the enrolment date visit (Visit 2) (i.e. start of the 'Run in Period'). 
'Run in' 
sit (visit 2) date (i.e. start of the ' 
eriod') 
or started after the start of the ' 
', but before the time of first 
'Concomitant' LL T medications and procedures 
'Concomitant' LL T medications and procedures (including LA) (safety phase) are 
• 
and 'Run in' 
• 
• 
and 'Run in' 
• 
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After the stabilization of the participant on their current LLT (including LA when 
applicable) during the 6-week Run-in Period , treatment with lomitapide will be started 
as add-on therapy on baseline (Day 0, D0) of the efficacy phase. 
The age of the child at baseline (D0) will be used to determine their age group for the 
starting dosing of lomitapide. 
Lomitapide capsules will be provided in 4 dose strengths of 2 mg, 5 mg, 10 mg, and 
20 mg. Dosing will be initiated at the recommended starting dose and escalated to the 
maximum dose as applicable to the age groups (see Table 1) based upon safety and 
tolerability in addition to LDL-C values.  
 
Table 1 Lomitapide Starting Dose and Dose Escalation by Age Group  
Age 
Group 
(years) 
Lomitapide Dose (mg) 
D0 
Week 4 
±3 days 
Week 8 
±3 days 
Week 12 
±3 days 
Week 16 
±3 days 
Maximum 
5 to 10 
2 
2 
5 
10 
20 
20 (10, in Child-
Pugh A) 
11 to 15 
2 
5 
10 
20 
40 
40 (20, in Child-
Pugh A) 
 
5 
10 
20 
40 
60 
60 (40, in Child-
Pugh A) 
Each patient will take 1 to 3 capsule(s) once daily to achieve the doses specified in 
the titration scheme. The first dose of study medication will be administered at the 
study site on D0.  
As of D1, patients will self-
egal guardian will 
administer to the patient) lomitapide orally, once daily, at approximately the same time 
each day. 
Full details of permitted dose escalation, dose reduction and re-challenge are provided 
in the protocol (section 7.3.1). Full details of permitted dose modification, interruption 
or drug discontinuation for adverse events are provided in the protocol (section 7.3.2) 
and details for permitted dose modification for concomitant medication are provided in 
the protocol (section 7.3.3).  
If a participant changes dose, they will be analysed according to the dose cohort 
assigned at D0 (start of efficacy phase). 
 
The total number of weeks of exposure to the study treatment will be calculated as: 
[(last date of dosing  first date of dosing) + 1] / 7 
The average daily exposure (mg/day) to the study treatment will be calculated as: 
(Number of doses received * treatment dose (mg)) / (number of days exposed) 
Study drug exposure to the maintenance dose (i.e., not including the time the subject 
was titrating the dose to reach the maintenance dose) (mean, median, and range of 
exposure) will also be summarised. The total number of weeks of exposure to the 
maintenance dose will be calculated as:  
 
[(last date of dosing  date when maintenance dose is reached) + 1]/7 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
16toS17 
administer (or the patient's parent/I 
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Study treatment, exposure (weeks and mg/day), maximum tolerated dose (mg), 
number of doses received, number of dose increases, number of dose reductions, 
number of dose interruptions, number of dose reductions due to concomitant 
medication, number of dose reductions due to adverse events, number of dose 
interruptions due to concomitant medication, number of dose interruptions due to 
adverse events, number of drug discontinuations due to adverse events and dose at 
drug discontinuation due to adverse events will be summarised by study phase and 
listed using the Safety population. In the listings, the reason for dose change will also 
be given.  
In addition, a summary of the time to first dose interruption and first dose reduction will 
be presented for the efficacy phase, the safety phase and overall, using the Safety 
population. The summary will use the Kaplan-Meier method to estimate the time to 
each event, with results displayed using a Kaplan-Meier plot and in tabular form. For 
the safety phase summary, time 0 will be set as the start of the safety phase (i.e., the 
date of the week 24 visit). Additionally, patients who do not enter the safety phase will 
be censored at time 0. If a patient discontinues study drug they will be counted as an 
event for both dose interruption and dose reduction at the time of study drug 
discontinuation. If a patient has not had a dose interruption or reduction and is still on 
study drug, they will be censored at their last visit assessment date.  
Compliance with IMP dosing during the study will be reviewed medically on a patient 
level basis. The proportion of patients compliant with IMP dosing during the efficacy 
phase will be reported as yes/no (n(%)). The proportion of patients compliant with IMP 
dosing during the safety phase will also be reported as yes/no (n(%)), with patients 
who do not enter the safety phase, excluded from the summary. 
The number and percentage of subjects with the achieved doses at Week 24, Week 
56 and Week 104 will be provided by age group. 
 
5.11  EFFICACY EVALUATION 
Unless specified otherwise, all listings will be based on the FAS set. 
All hypothesis tests will be two-sided and conducted at the 5% significance level, 
unless otherwise specified. 
Analysis of all lipid panel data will be based on data from the Central Lab, with the 
exception of Lp(a), which will be based on Local Labs as Lp(a) was not collected by 
the central lab at the beginning of the study.  
5.11.1 Primary Endpoint 
5.11.1.1 
Percent change in LDL-C at Week 24±3 days  
Primary Analysis 
The primary endpoint is percent change in LDL-C at Week 24±3 days compared to 
baseline.  
Analysis Study Weeks will be used as specified in the visit window table (see 
Section 5.3). 
The observed values at baseline and Week 24 and observed change and percentage 
change from baseline at Week 24 will be summarised overall and by age group.  
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
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Percentage change = [ (Week 24  baseline) / baseline ] * 100% 
The primary efficacy endpoint (i.e. percentage change at Week 24) will be analysed 
using the one-sample t-test to test the null hypothesis that the percentage change from 
baseline is equal to zero against the alternative hypothesis the percentage change 
from baseline is not equal to zero. The percentage change at Week 24, together with 
the corresponding two-sided 95% confidence interval (CI) and p-value will be 
presented. 
Percent change from baseline data will be presented by age-group using a waterfall 
plot. 
Missing data will be imputed using LOCF as described in Section 5.3. 
The primary efficacy analysis will be based on the FAS.  
Sensitivity Analysis  using Nominal study visit number 
Nominal Study Visit will be used as specified in Section 5.4 above. 
The percentage change at Visit 10 will be analysed using the one-sample t-test to test 
the null hypothesis that the percentage change from baseline is equal to zero against 
the alternative hypothesis the percentage change from baseline is not equal to zero. 
The percentage change at Visit 10, together with the corresponding two-sided 95% 
confidence interval and p-value will be presented. 
Missing data will be imputed using LOCF as described in Section 5.3. 
The analysis will be based on the FAS only.   
Sensitivity Analysis  using MMRM model 
Analysis Study Weeks will be used as specified in the visit window table (see 
Section 5.3). 
A sensitivity analysis using a Mixed Model Repeated Measures (MMRM) model with 
the missing at random (MAR) assumption (i.e. missing data will not be imputed using 
LOCF or any other method) will be conducted. The MMRM model will estimate the 
mean percentage change and 95% CI at Week 24 and will include the percentage 
change as the dependent variable and visit as a categorical fixed effect. An 
unstructured covariance structure will be used. If the model does not converge, 
alternative covariance structures for repeated visits within a subject will be evaluated, 
including compound symmetry, 1st order autoregressive, and Toeplitz. The Akaike 
Information Criterion (AIC) will be used to assess model fit for the alternative 
covariance structures. The covariance structure resulting in the smallest AIC indicating 
the best model will be selected.  
The primary efficacy sensitivity analysis will be based on the FAS only.   
Sensitivity Analysis  using baseline observation carried forward (BOCF) 
Analysis Study Weeks will be used as specified in the visit window table (see 
Section 5.3). Missing data at week 24 will be imputed using BOCF. If a baseline value 
is missing, it is not appropriate to carry forward screening / run-in period values for the 
fasting lipid panel prior to stabilisation of the patient on LLT. Thus, if efficacy phase 
baseline is missing, then it should remain as missing. 
Sensitivity Analysis  using Wilcoxon Signed-Rank test 
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Analysis Study Weeks will be used as specified in the visit window table (see 
Section 5.3). A sensitivity analysis using a non-parametric approach, Wilcoxon 
Signed-Rank test, will be conducted.  
Missing data will be imputed using LOCF as described in Section 5.3. 
The analysis will be based on the FAS. 
Supplementary Analysis 
Supplementary analysis for the primary efficacy endpoint will include the one-sample 
t-test, Wilcoxon Signed-Rank test and summaries based on the PPS and the CAS. 
Analysis Study Weeks will be used as specified in the visit window table (see 
Section 5.3). 
 
Responder Analysis 
Supplementary responder analyses for the primary efficacy endpoint (overall and by 
age-group) will also be provided using the following cut-offs for a responder: 
 >15% reduction in LDL-C at Week 24 
 >25% reduction in LDL-C at Week 24 
 >50% reduction in LDL-C at Week 24 
Number and percentage of subjects achieving the above cut-offs will be presented. If 
a patient discontinued study medication early, they will be considered a non-
responder. A cumulative distribution function (CDF)plot for the percent reduction will 
also be provided by age group and overall (early discontinuations will be assigned a 
percent change of 0). These analyses will also be repeated based on achieving the 
above targets anytime on or after Week 8 (if a patient discontinued study medication 
prior to Week 8 they will be considered a non-responder and assigned a percent 
change of 0 for the CDF plot.) 
 
 
Sub-group Analysis 
Analysis Study Weeks will be used as specified in the visit window table (see 
Section 5.3). 
Additional supplementary analysis will be conducted using sub-group analysis. For 
each sub-group analysis, an analysis of covariance (ANCOVA) model will be 
conducted using the sub-group as a fixed effect and estimating the mean percentage 
change and two-sided 95% CI within each sub-group at Week 24±3 days. The 
following sub-group analyses will be performed:  
 Age groups (i.e. 5 to 10 years; 11 to 17 years); 
 Sex (male; female);  
 Subjects with documented cardiovascular disease history vs no documented 
cardiovascular disease history at screening (pooled across age groups); 
 Subjects with established cardiovascular disease history (defined as aortic 
valve 
disease 
and/or 
coronary 
atherosclerosis) 
vs 
no 
established 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
• 
• 
• 
• 
• 
• 
• 
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cardiovascular disease history (as defined previously) at screening (pooled 
across age groups);  
 Subjects who have taken concomitant LLT medications (excluding LA) vs those 
who have taken concomitant LLT medications (including LA) (pooled across 
age groups);  
 Subjects who have no dose reductions / no dose interruptions vs at least one 
dose reduction / dose interruption (pooled across age groups);  
 Subjects who reach MTD within age group vs subjects who do not reach MTD 
within age group (pooled across age groups;  
 Subjects with the LDLR variant category 
 vs subjects with 
the LDLR variant category 
 vs subjects with the  variant 
category 
, if there are at least 3 subjects, in each sub-group. 
  
Results for the sub-group analysis will be presented in tables and displayed using a 
forest plot. 
Subgroup analysis will only be based on the FAS. 
The subgroup analysis will be repeated using the Nominal Study Visit as specified in 
Section 5.3 above. Results for the additional sub-group analysis will be presented in 
tables only. 
Results for the sub-group analysis (based on Nominal Study Visit) will also be 
displayed using a forest plot. 
Fasting Lipid Panel data will be listed fully by age group using the SAF population set, 
as detailed in section 5.14. 
Sensitivity analyses will be conducted to determine the impact (if any) of COVID-19 
on the primary endpoint and will be described in the CSR  
5.11.2 Secondary Endpoints 
The primary analysis of all secondary endpoints will be based on the FAS. 
Supplementary analyses on the key-secondary efficacy endpoints will be conducted 
using the PPS and CAS. Adjustment for multiplicity among key-secondary efficacy 
endpoints are outlined in Section 5.12 
5.11.2.1 
Percent change at Week 24 ± 3 days  
The key-secondary efficacy endpoint analyses will use the same methods as outlined 
for the primary efficacy endpoint. The same sensitivity analysis, supplementary 
analyses and sub-group analyses as the primary endpoint will also be conducted. 
Key-secondary efficacy endpoints are the percent change from baseline at Week 24±3 
days for the following lipid parameters: 
Non-HDL-C, TC, VLDL-C, apo B, TG, and Lp(a). 
Fasting Lipid Panel data will be listed fully by age group using the SAF population set, 
as detailed in section 5.14. Lp(a) data will be listed for the local labs only. 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
• 
• 
• 
• 
• 
'defective/defective' 
'defective/negative' 
'negative/negative' 
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5.11.2.2 
Percent change at all other time points to Week 104 ± 1 week  
Additional secondary efficacy endpoints are the percent change from baseline at all 
other time points through to EOT / Week 104 for the following lipid parameters: 
LDL-C,  Non-HDL-C, TC, VLDL-C, apo-B, TG and Lp(a). 
Scheduled study visits (based on analysis study visit) conducted between specific 
study days will be included in the secondary efficacy analysis, as detailed in the table 
of study visits in Section 5.3. 
A summary of the observed change and percentage change from baseline at each 
timepoint, will be presented overall and by age group. In addition, the mean and 
median dose at each timepoint will be presented alongside these results. 
A MMRM model will be used to estimate the mean change at each timepoint. The 
model will include visit as a categorical fixed effect. An unstructured covariance 
structure will be used.  If the model does not converge alternative covariance 
structures for repeated visits within a subject, will be evaluated including compound 
symmetry, spatial spherical, spatial power, spatial Gaussian. The AIC will be used to 
assess model fit for the alternative covariance structures. The covariance structure 
resulting in the smallest AIC indicating the best model will be selected. Missing data 
will be maintained as missing. Least Squares means (LSMeans), standard error (SE), 
two-sided 95% CI and associated p-value will be presented at each timepoint.  
Figures showing the raw percent change from baseline and SD and estimated 
LSMeans percent change from baseline and SE, over time, for each endpoint will also 
be provided. In addition, the number of subjects, mean and median dose at each 
timepoint will be presented in the figures. 
Fasting Lipid Panel data will be listed fully by age group using the SAF population set, 
as detailed in section 5.14. 
5.11.2.3 
Change in LLT (and LA) from Week 24 ± 3 days through Week 56 
and week 104 ± 1 week  
The number and percentage of patients treated with standard LLT (including LA when 
applicable) at any post-baseline assessment will be summarised overall and by age 
group (based on analysis study visit). For this summary the percentages will be 
calculated using the number of patients attending the post-baseline visit as a 
denominator.  
Changes to the standard LLT from week 24 through Week 56 and 104 will be 
summarised, cumulatively, including the number and percentage of patients treated 
with LA, when applicable. 
The following changes to standard LLT are of notable interest and will be summarised, 
including the reason of change: 
 Dose reduction of standard LLT  
 Reduced frequency of / extended interval between LA 
 Discontinuation of LLT  
 Discontinuation of LA 
Any dose increases of standard LLT / increased frequency of LA will also be 
summarised. 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
• 
• 
• 
• 
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The percentage of changes to standard LLT and LA (i.e., dose reduction of standard 
LLT; reduced need for LA; discontinuation of LLT / LA; dose increase of LLT; increased 
need for LA) will use the number of patients treated with standard LLT (including LA) 
at Week 24 (end of efficacy phase). 
For subjects who were on apheresis at baseline, the apheresis regimen established 
during run-in and the weighted average of the days since previous LA will be 
presented. The weighted average will be derived as: 
 
Additionally, the duration in days between the most recent apheresis and the LDL-C 
assessment at Baseline (Week 0) and Week 24 will be presented. For subjects 
discontinuing the study before Week 24, the duration between the most recent 
apheresis and the last LDL-C assessment will be presented.  
Lipoprotein Apheresis history and treatment data will be fully listed by age group using 
the Safety set.  
5.11.2.4 
Recommended target of LDL-C at Week 24 ± 3 days and at any 
time on study 
The 2014 EAS recommends a target LDL-C of <135 mg/dL (i.e. 3.5 mmol/L) in 
paediatric HoFH patients (secondary endpoint). 
The number and percentage of patients with LDL-C falling below the target level of 
135 mg/dL (i.e. 3.5 mmol/L) will be summarised by study visit (based on analysis visit), 
at any time up to Week 24 and at any time up to Week 104 by age group and overall. 
Within each age group, the lomitapide dose at the time when LDL-C fell below the 
target level of 135 mg/dL (i.e. 3.5 mmol/L) will be summarised by study visit. 
The above analyses will also be repeated using the 2023 EAS recommended target 
LDL-C of <115 mg/dL (i.e. 3.0 mmol/L) in paediatric HoFH patients. 
Finally, the above analyses will be repeated using the 2018 American College of 
Cardiology/American Heart Association Task Force recommended target LDL-C of 
<110 mg/dL (i.e. 2.9 mmol/L) in paediatric HoFH patients.  
A CDF plot showing the cumulative distribution function of the LDL-C data for all 
patients will be plotted. A reference line at 135 mg/dL will be added indicting the EAS 
recommended target LDL-C of <135 mg/dL. A CDF plot will be plotted (using the 
analysis visit data) for Week 24 and for at any time on study. 
 
5.11.2.5 
Percent change from baseline upto Week 104 ± 1 week for HDL-C 
and TC/HDL-C (non-key secondary)  
Scheduled study visits (based on analysis study visit) conducted between specific 
study days will be included in the non-key secondary efficacy analysis, as detailed in 
the table of study visits in Section 5.3. 
A summary of the observed change and percentage change from baseline at each 
timepoint, will be presented overall and by age group. In addition, the mean and 
median dose at each timepoint will be presented alongside these results. 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
I(Days since previous LA x Number of days) 
L Number of days 
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A MMRM model will be used to estimate the mean change at each timepoint. The 
model will include visit as a categorical fixed effect. An unstructured covariance 
structure will be used.  If the model does not converge alternative covariance 
structures for repeated visits within a subject, will be evaluated including compound 
symmetry, spatial spherical, spatial power, spatial Gaussian. The AIC will be used to 
assess model fit for the alternative covariance structures. The covariance structure 
resulting in the smallest AIC indicating the best model will be selected. Missing data 
will be maintained as missing. LSMeans, SE, two-sided 95% CI and associated p-
value will be presented at each timepoint.  
Figures showing the raw percent change from baseline and SD and estimated 
LSMeans percent change from baseline and SE, over time, for each endpoint will also 
be provided. In addition, the number of subjects, mean and median dose at each 
timepoint will be presented in the figures. 
Fasting Lipid Panel data will be listed fully by age group using the SAF population set, 
as detailed in section 5.14. 
 
5.12  Multiplicity 
To address the efficacy objectives, the primary and key-secondary efficacy 
parameters will be tested sequentially in a step-wise fashion, thereby controlling the 
overall type I error. First, the primary testing for percent change from baseline in LDL-
C at Week 24 will be performed. If this test is statistically significant with a 2-
0.05 and is statistically significant in a positive direction, then the tests of the secondary 
hypotheses will be performed in the following specified order at Week 24: 
1. Non-HDL-C  
2. TC  
3. VLDL-C  
4. Apo B  
5. TG  
6. Lp(a)  
If at any step of the testing procedure a non-significant p-value is reached, further tests 
in the sequence will be performed and p-values will be reported as a measure of the 
strength of effect without declaring statistical significance.  
Analysis of other secondary endpoints collected during the efficacy phase and of 
endpoints collected during the safety phase will be analysed without adjustment for 
multiplicity and thus should be interpreted with this in mind. 
5.13  SAFETY EVALUATION 
The safety and tolerability of lomitapide will be based on adverse events, and safety 
evaluations including clinical laboratory evaluations, vital signs and ECGs. 
5.13.1 Adverse Events 
AEs will be coded using the latest MedDRA dictionary version. The version used will 
be indicated in the data summaries and listings.  
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
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A TEAE is defined as an AE that started on or after the start of the administration of 
study treatment up to 30 days post last dose. If adverse event dates are incomplete 
and it is not clear whether the adverse event was treatment-emergent, it will be 
assumed to be treatment-emergent. 
A non-treatment emergent adverse event (NTEAE) is defined as an AE that started on 
or after the start of the Run-in Period but before the administration of study treatment. 
A treatment-related TEAE is defined as a TEAE with a reasonable causal relationship 
to the study treatment. If the TEAE has a missing relationship it is assumed to be 
related to the study treatment for analysis purposes.  
Adverse events of special interest (AESI) are defined as follows and will be identified 
by medical review: 
 
Hepatic, small bowel/intestinal, pancreatic and colorectal tumours  
 
Hepatic abnormalities  
 
Elevations of hepatic transaminases resulting in discontinuation of lomitapide  
 
Elevations of hepatic transaminases >3 x ULN that persist despite dose 
reduction or interruption  
 
 
 
Symptomatic liver injury  
 
Other hepatic evaluation and testing or any histology obtained from liver 
biopsy and imaging evaluations  
 
Gastrointestinal effects 
 
Events leading to permanent treatment discontinuations 
 
Hospitalisation due to gastrointestinal events 
 
Events triggering additional investigations such as endoscopy  
 
Major congenital anomalies 
 
Musculoskeletal adverse events and muscle-related biochemical abnormalities 
(e.g., creatinine kinase)  
 
A summary table will present the following:  
 TEAEs.  
 Serious TEAEs (SAEs).  
 Serious Related TEAEs. 
 TEAEs leading to study discontinuation.  
 Serious TEAEs leading to study discontinuation. 
 Serious Related TEAEs leading to study discontinuation. 
 Study treatment-related TEAEs leading to discontinuation of study. 
 TEAEs leading to death. 
 TEAEs by severity (mild/moderate/severe/life-threatening/death). 
 TEAEs by relationship to study treatment category (unrelated/related).  
 NTEAEs leading to death 
 Treatment emergent AESI   
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Elevations of hepatic transaminases ~5 x ULN 
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 leading to study discontinuation.  
 Related 
 
 Major Adverse Cardiac Events (MACE) as defined by the medical team. 
 Action taken with study treatment. 
 
The following tables will be presented: 
 TEAEs by SOC and PT 
 TEAEs by SOC, PT and severity grade. 
 TEAEs by SOC, PT and relationship to study treatment and the pooled related 
categories (related/unrelated).  
 Most frequent TEAEs by SOC and PT defined as 2 patients reporting an AE 
 
 
 Elevated serum transaminases related TEAEs, by country, SOC and PT 
Summaries will be presented by study phase (including follow-up) and overall. TEAEs 
will be presented in the study phase corresponding to their start date. For all of the 
above, SOC and PT will be presented in decreasing frequency of the total number of 
subjects with TEAEs, SAEs, and AESIs separately. If a subject experienced more than 
one TEAE, the subject will be counted once for each SOC and once for each PT. If a 
subject experienced more than one TEAE, the subject will be counted once using the 
 
For gastrointestinal and hepatic AEs the time to the first hastrointestinal and first 
hepatic TEAE will be summarized using the Kaplan-Meier method. Gastrointestinal 
hepatic disorders  
comprehensive search. In addition, for all gastrointestinal and hepatic AEs a histogram 
showing the time of onset from the first dose will be provided and a tabular summary 
of the duration of the events will be provided. 
Adverse event data will be listed in full using the Enrolled population set and this will 
also include a treatment-emergent flag, a run-in flag, a flag to identify gastrointestinal 
and hepatic TEAEs, the time of onset and cessation of event relative to first dosing of 
study treatment and duration of AE. 
All tables and listings will be presented separately for each age group. Subject profile 
plot for the distribution of TEAEs and dose at time of TEAE will be plotted. 
Age profile for the distribution of TEAEs and MTD will be plotted. Two age profile plots 
will be displayed for (i) overall; (ii) related TEAEs. 
Both subject profile and age profile graphics will be displayed for: (i) all subjects; (ii) 
each age group.  
The following sub-group analyses for TEAEs and AESIs will be provided 
(presentations for SAEs, TEAEs leading to discontinuation and Grade 3 or higher 
TEAEs may also be provided): 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
• 
Treatment emergent AESl's 
• 
Treatment emergent AESl's 
• 
• 
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• 
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• 
Treatment emergent AESl's by AESI grouping, SOC and PT 
• 
most related event for the "by relationship to study treatment", "related to study 
treatment" summaries and the worst severity for the "by severity" summary. 
TEAEs will be defined as the SOC 'Gastrointestinal disorders'. Hepatic TEAEs will be 
based on the Standardized MedDRA Query (SMQ) 'Drug related 
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 Age group (5-10 and 11-17) 
 Sex (male, female) 
  
5.14  Clinical Laboratory Evaluation 
Clinical laboratory evaluation testing will include the following: 
 Standard Haematology (CBC) 
 Serum Clinical Chemistry 
 Metabolic panel 
 Liver Function Tests 
 Essential Fatty Acids 
 Fat-Soluble Vitamin levels 
 Hormones 
 Sex hormones 
 Serum Lipase 
 Urinalysis 
The observed change from baseline, and additionally, for serum clinical chemistry 
parameters, percentage change from baseline, will be summarised overall and by age 
group over time (using the nominal visit data).  
Clinically significant observed values and clinically significant changes from baseline 
in haematology, biochemistry, and urinalysis assessments will be marked. If the test 
results are reported in categorical format, the results will be summarised by subject 
counts and percentage for each category. 
Each haematology, biochemistry, and urinalysis parameter will be classed as low, 
normal, high, missing based on the reference ranges. Shift tables in relation to the 
normal range from baseline over time will be presented.  
A descriptive summary of the maximum observed values for ALT, AST, total bilirubin, 
and alkaline phosphatase during the Efficacy Phase (Weeks 0-24), Safety Phase 
(After Week 24), and overall will also be provided. In addition, a figure of the maximum 
AST and ALT values vs the corresponding Total Bilirubin value will be provided during 
the Efficacy Phase (Weeks 0-24), Safety Phase (After Week 24), and overall.  
A summary table will be produced for the number and percentage of subjects who 
have values of AST (>3, >5, >10, >20 x ULN), ALT (>3, >5, >10, >20 x ULN), AP 
(>1.5 x ULN), or TBL (>1.5, >2 x ULN) at each post baseline timepoint. 
Time to Onset and Duration of Liver Function Test (LFT) Abnormalities (for AST and 
ALT) will also be summarized. The time to first LFT abnormality will be calculated as 
the date of the first LFT assessment that is 3 x ULN subtracted from the first dose 
date, plus 1. Duration will be calculated as the date of resolution of the first LFT 
abnormality (resolution defined as <3 x ULN) minus the date of the first LFT 
assessment that is 3 x ULN. Subjects with an ongoing elevation will be censored at 
their last laboratory assessment date containing both AST and ALT results.  
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A subject profile plot for the duration of LFT abnormalities and dose at time of LFT 
abnormality will be plotted, identifying hepatic TEAEs. 
Haematology, biochemistry, and urinalysis will be listed separately including change 
from baseline, reference ranges flagging all out-of-range values and their clinical 
significance (using analysis visit data). 
Listings of clinically significant haematology, biochemistry, and urinalysis laboratory 
measurements recorded throughout the study will be provided. 
All tables and listings will be presented separately for each age group using the SAF 
population. 
The following LFT profiles will be displayed: 
 Individual subject profiles of liver function data will be displayed with all liver 
function data for a given subject on one graphic. 
 AST and ALT profiles over time, by subject age, will be displayed. 
 AST and ALT profiles over time, by subject MTD, will be displayed. 
The following lipid profile plots will be displayed: 
 Individual subject profiles of LDL-C over time. 
 LDL-C profiles over time, by subject age. 
 LDL-C profiles over time, by subject MTD.  
 Spaghetti plots with individual lipid profiles, overall and by age group. 
The AST, ALT and LDL-C profile plots will be displayed for: (i) all subjects; (ii) each 
age group. The individual subject profiles of LDL-C will present different symbols 
identifying dose adjustments and/or lipoprotein apheresis. 
5.15  Vital Signs 
Vital sign observed values, change and percentage change from baseline by 
parameter (unit) will be summarised over time (using analysis visit data).  
The vital signs parameters to be presented are: weight, height, BMI, BSA, heart rate, 
respiration rate, systolic blood pressure, diastolic blood pressure and body 
temperature. Height and weight collected at baseline will be reported with the 
demography data.  
The change from baseline in height / BMI percentile will be reported. Maximum, 
minimum and last post-baseline values will also be presented. 
The change from baseline in height / BMI z-score will be reported. Maximum, minimum 
and last post-baseline values will also be presented. 
Parameters will be presented in the same order as the CRF. 
All vital sign data (observed values and change from baseline values) will also be 
plotted over time using boxplots to display the distribution over time. A waterfall plot of 
the percent change in BMI, by age group and sex, at Week 24, Week 56 and Week 
104 will be presented. All vital sign data will be listed including change and percentage 
change from baseline (using analysis visit data). Subjects who just met inclusion 
criterion #3 of having a 
, while being below the 10th percentile for 
Height and BMI, will be flagged. 
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All tables and listings will be presented separately for each age group using the SAF 
population. 
5.16  Electrocardiogram 
A 12-lead ECG will be recorded and read locally. The ECG recordings will be reviewed 
further classifi
abnormal findings will be documented. 
Findings from the 12-lead ECG examinations will be summarised overall and by age 
group over time (using analysis visit data). Shift tables from baseline over time will also 
be presented.  
All tables and listings will be presented separately for each age group using the SAF 
population. 
5.17  Echocardiography 
It is anticipated that echocardiography will be performed annually as standard of care 
in this patient population. For this study, echocardiography is not mandated but 
data/results will be included as part of the study safety data.  
Information in relation to the most recent echocardiography on file (if available) will be 
documented in the eCRF. Findings from the standard of care echocardiography 
examination will be summarised overall and by age group (using analysis visit data). 
The number and percentage of subjects with a worsening from baseline (defined as a 
new condition or a progression of a current condition) will be summarised cumulatively 
over time overall and by age group. 
Parameters will be presented in the same order as the CRF.   
All tables and listings will be presented separately for each age group using the SAF 
population. 
5.18 Lipid Accumulation in the Liver 
Lipid accumulation in the liver will be assessed using NMR or ultrasound. All patients 
will undergo NMR imaging unless it is contraindicated or not feasible (e.g., due to the 
need for sedation or general anaesthesia in very young or anxious patients). In this 
case, ultrasound scans will be used at the discretion of the investigator. The NMR 
images will be processed by a central reader, the ultrasound scans will be interpreted 
locally. 
The observed values and percent change from baseline values for hepatic fat will be 
summarised over time overall and by age group.  
The number and percentage of patients with (i)  10% liver fat; (ii) >10% and 20% 
liver fat; (iii) >20% liver fat will be summarised overall and by age group over time 
(using analysis visit data), separately for ultrasound and NMR scan results. Shift tables 
from baseline over time will also be presented.  
In addition, the number and percentage of patients with an increase of hepatic fat 
 5 from baseline and 
the maximum post-baseline increase in hepatic fat will be summarized by timepoint 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
by the investigator and classified as 'normal' or 'abnormal'. Abnormal ECGs will be 
ed as 'clinically significant' and 'not clinically significant'. Reasons for 
::5 
::55%, 
>5 to ::510%, >10 to ::515%, >15 to ::520%, >20 to ::525%, and >25%. 
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overall and by age group for NMR scan results. CDF plots of the change from baseline 
will also be provided by timepoint overall and by age group. 
NMR scan at Site 12 failed and the assessments performed on Week 56 for 7 Site 12 
subjects failed. The scans were repeated, approximately on Week 80, with a different 
scan. To explore the impact of the new scan used on Site 12 for the unscheduled 
Week 80 assessment and the Week 104 assessment, sensitivity analyses of the 
summaries outlined above, excluding Site 12 will be provided. Site 12 results will also 
be presented. 
Tables and listings will be presented using the SAF population.   
Scatter plot of the change in hepatic fat up to Week 56 and Week 104 with change in 
BMI Z-score up to Week 56, by subject age will be plotted. 
Scatter plot of the change in hepatic fat up to Week 56 and Week 104 with changes in 
BMI Z-score up to Week 56, by subject MTD will be plotted. 
Scatter plot of change in hepatic fat up to Week 56 and Week 104 and time from 
lomitapide administration, by subject age will be plotted. 
Scatter plot of change in hepatic fat up to Week 56 and Week 104 and time from 
lomitapide administration, by subject MTD will be plotted. 
All scatter plots will be displayed for: (i) all subjects; (ii) each age group. 
To examine the relationship between liver steatosis and AST/ALT, scatter plots of ALT 
(and AST) versus hepatic fat at baseline, Week 24, Week 56 and Week 104 will be 
produced overall, grouped by age group, separately by imaging technology. Pears
 
(for NMR) and Spearman  rank (for Ultrasound) correlation coefficient (and 95% 
confidence limit) will be included on the scatter plots. 
5.19  Physical Examination and Tanner Staging 
Individual subject physical examination and Tanner staging data will be listed (using 
analysis visit data).  
To assess sexual maturation (Tanner staging) in patients with a Tanner stage 2, the 
observed values and change from baseline in sex hormones (i.e. serum testosterone 
and serum oestradiol) will be summarised overall and by age group over time.  
Shift tables in Tanner staging results (1 to 5 and missing) from baseline over time will 
be summarised. 
Spaghetti plots will be plotted to assess:  
 sexual maturation development (i.e. Tanner staging) of each subject.  
 growth development (i.e. BMI percentile) of each subject  
Separate spaghetti plots for each age group and sex will be presented.  
The following waterfall plots will be displayed: 
 Change in BMI Z-score (baseline to Week 24, Week 56 and Week 104), by 
patient age;  
 Change in BMI Z-score (baseline to Week 24, Week 56 and Week 104), by sex; 
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 Change in BMI Z-score (baseline to Week 24, Week 56 and Week 104), by 
baseline BMI for Age Z-score. 
 Change from baseline to maximum weight loss (minimum post-baseline change 
from baseline) observed up to and including week 104, by age and gender 
 Change from baseline to the minimum BMI z-score observed up to and 
including week 104, by age and gender 
The following spaghetti plots will be displayed: 
 Spaghetti plots of BMI Z-score over time by age, sex and baseline BMI-for-Age 
Z-score;  
 Spaghetti plots of BMI absolute value over time by age and sex;  
 Spaghetti plots of weight absolute value over time by age and sex. 
Individual spaghetti plots of weight and BMI Z-scores over time, by subject. All plots 
will be displayed for: (i) all subjects; (ii) each age group.  
All tables and listings will be presented separately for each age group using the SAF 
population. 
5.20  Pulmonary Function Tests 
Pulmonary function test observed values and change from baseline by parameter 
(unit) will be summarised over time (using analysis visit data). Parameters will be 
presented in the same order as the CRF. Shift tables from baseline over time will also 
be presented.  
All pulmonary function test data will be listed including change from baseline. All tables 
and listings will be presented separately for each age group using the SAF population.  
5.21  Diet and Dietary Supplement Compliance 
Diet and dietary supplement compliance data will be listed. 
A summary of the number and percentage of patients compliant with their low-fat diet 
and dietary supplement regimen overtime will be provided and compliance for the 
efficacy phase, the safety phase up to Week 56, and the safety phase up to Week 
104 will be presented.   
A patient will be considered compliant if during the respective phase, they indicated 
they were compliant with a low fat diet or dietary supplement regimen at least 80% of 
the time. 
5.22  Pregnancy test 
Pregnancy test details will be listed. 
5.23  Visit Dates 
Visit dates will be listed. 
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5.24  Exploratory Assessments 
5.24.1 
Xanthoma Assessment 
during the physical examination.  
The number and percentage of patients with (tendon/cutaneous) xanthomas present, 
and locations, will be summarised overall and by age group at baseline, week 56 and 
EOT / week 104 (using nominal visit data).  
The number and percentage of patients with resolution and regression of pre-existing 
xanthoma (baseline) to Week 56 and EOT / Week 104 will be summarised overall and 
by age group. 
The number and percentage of subjects with changes on pre-existing xanthoma from 
baseline (apparition of new xanthomas, increases in size, decreases in size or 
resolution) will be summarised cumulatively over time up to Week 104. 
Tables and listings will be presented using the SAF population. 
5.24.2 
Carotid Intima-Media Thickness and Flow-mediated Dilation 
CIMT (mandatory) and FMD (whenever possible) will be assessed using ultrasound 
scan and brachial artery dilation after a transient period of forearm ischaemia to 
evaluate carotid atherosclerotic vascular disease.  
The percentage change from baseline in mean CIMT and mean FMD at Week 56 and 
EOT / Week 104 will be assessed overall and by age group (using nominal visit data). 
Percentage change = [ (Week X  baseline) / baseline ] * 100% 
Tables and listings will be presented using the SAF population. 
5.24.3 
Palatability 
Palatability will be assessed using a 5-point facial hedonic scale, anchored with 
In addition, a 3-point scale will be used to assess the parent(s)/legal guardian(s) 
An assessment of ease of 
administration of medication and dietary supplements will also be asked of the 
parents(s)/legal guardian(s). 
Palatability will be assessed on the first occasion that the patient is not able to swallow 
the intact capsule(s) and takes lomitapide by opening and sprinkling the capsule onto 
food media. 
The number and percentage of patients will be presented over time for each question 
overall and by age group (using nominal visit data). 
Tables and listings will be presented using the SAF population. 
5.25  Changes from the Protocol Planned Analysis 
The following is a list of changes and additional analyses after database lock for the 
Efficacy phase (Week 24) analysis and prior to the final analysis: 
 
Changes: 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
The patient's xanthomas (tendon and cutaneous, size and location) will be evaluated 
descriptors, to record the children's assessment of palatability in terms of overall liking. 
interpretation of the child's reaction/facial expression. 
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1) Lp(a) data was missing from central lipid panels for all subjects (except Site 12) 
who had their baseline visits before January 2022. Lp(a) data was analysed 
based on local lab data in two different units (mass and molar). Given the 
limitations on conversion from mass to molar units, data were analysed 
separately by unit (either mg/dL or nmol/L; g/dL was converted to mg/dL). 
Statistical testing (t-test) as for the other endpoints was performed by unit and 
the p-values were combined 
 
 
Additions: 
2) Addition of HDL-C and TC/HDL-C ratio as non-keysecondary efficacy 
endpoints.   
3) New recommended target LDL-C levels added as exploratory endpoints. 
4) Addition of additional sensitivity analyses based on BOCF, Wilcoxon Signed-
Rank test, subgroup analysis based on sex and responder analyses for primary 
and key secondary endpoints. 
 
 
 
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using Fisher's method. 
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6 REFERENCES 
1. Galicia-Garcia, U. et al. 
assignment of sixteen missense variants located in the EGF-precursor 
-
020-58734-9.  
2. Gidding, S.S. et al. 
Circulation, 132(22), pp. 2167 2192. doi:10.1161/cir.0000000000000297. 
DocuSign Envelope ID: A18FEEF9-59CA-4D21-B668-F2E37C0A9EAE 
(2020) 'Mutation type classification and pathogenicity 
homology domain of the LDLR', Scientific Reports, 10(1). doi:10.1038/s41598 
(2015) 'The agenda for familial hypercholesterolemia', 
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