Conditions: Spinal Muscular Atrophy Type 3
Keywords: Type 3
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 13
Healthy volunteers: no

Brief summary:
A long term safety study of amifampridine phosphate in patients with spinal muscular atrophy (SMA) Type 3.

Detailed description:
This open-label outpatient extension study was designed to evaluate the long-term safety and tolerability of amifampridine in patients diagnosed with SMA Type 3. In addition, the evaluation of the effects of amifampridine on the QoL was performed. The study was planned to enroll those patients who had completed the SMA-001 study and after all final evaluations for that study had been completed, or those who demonstrated benefit after completing the dose titration period but failed to meet the randomization criteria on Day 0 of SMA-001.

The duration of participation for each patient was expected to be at least 12 months as patients could continue in the study until amifampridine was approved by Regulatory Agencies or the clinical development of amifampridine was terminated for this indication. In addition to amifampridine, patients continued to receive previous concomitant medications, as needed.

Arms:
arm 1: The dose of amifampridine was based on optimal neuromuscular benefit determined from the Run-in Period from SMA-001 or could be modified as the discretion of the Investigator. The maximum single dose was 20 mg. The dose range for patients 6 to 16 years of age was 15 to 60 mg, and for those 17 years and older the range was from 30 to 80 mg daily.

Interventions: intervention 1: Amifampridine Phosphate 10 MG Oral Tablet
Intervention descriptions: intervention 1: Oral tablets

Protocol document:
SAP_002.pdf: 


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Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
 
 
 
 
PROTOCOL SMA-002 
 
Long Term Safety Study of Amifampridine Phosphate in Ambulatory 
Patients with Spinal Muscular Atrophy (SMA) Type 3 
 
STATISTICAL ANALYSIS PLAN 
Version 1.0 
29 June 2020 
 
 
CONFIDENTIAL 
 
 
Submitted to: 
 
Gary Ingenito, MD, PhD 
Chief Medical Officer 
Catalyst Pharmaceuticals, Inc. 
355 Alhambra Circle, Suite 1500 
Coral Gables, FL 33134 
 
 
 
 




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2 
Modification History 
 
Unique Identifier 
for this Version 
Date of the 
Document 
Version 
Author 
Significant Changes from  
Previous Authorized Version 
0.1 
15MAY2020 
Luisa D’Alonzo 
n.a. 
0.2 
01JUN2020 
Luisa D’Alonzo 
Previous version not yet approved. 
Minor change after Sponsor’s 
revision of version 0.1 
1.0 
29JUN2020 
Luisa D’Alonzo 
Approved version 
 
 
 
 
 
 


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3 
List of Abbreviations and Definitions of Terms 
Abbreviation 
Definition 
Abs 
Antibodies 
Ach 
Acetylcholine 
AChR 
Acetylcholine receptor 
ADL 
Activities of Daily Living 
AE(s) 
adverse event(s) 
ALT 
alanine aminotransferase  
AST 
aspartate aminotransferase 
ATU 
Autorisations Temporaires d'Utilisation Normative 
CFB 
Change from baseline 
CM 
Centimeter(s) 
CMS 
congenital myasthenia syndromes 
CRA(s) 
clinical research associate(s) 
CRF 
case report form 
CRO 
contract research organization 
CTFG 
Clinical Trial Facilitation Group 
DBP 
diastolic blood pressure 
ECG(s) 
electrocardiogram(s) 
eCRF 
electronic case report form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HCG 
human chorionic gonadotropin 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
ICH E6 
ICH Harmonised Tripartite Guideline: Guideline for Good Clinical 
Practice E6 
IEC 
independent ethics committee 
INQoL 
Individual quality of life 
IRB 
institutional review board 
ITT 
Intent-to-treat 
K+ 
potassium ion 
kg 
kilogram 
LEMS 
Lambert-Eaton myasthenic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 


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Abbreviation 
Definition 
mg 
milligram 
MG 
Myasthenia Gravis 
MI 
myocardial infarction 
mmHg 
millimeters of mercury 
MS 
multiple sclerosis 
MuSK 
muscle-specific receptor tyrosine kinase 
MuSK-MG 
muscle-specific receptor tyrosine Kinase-Myasthenia Gravis 
NMJ 
neuromuscular junction 
PEDSQLTM 
pediatric quality of life inventory 
PI 
Principal Investigator 
PK 
pharmacokinetic 
QoL 
Quality of life 
REB 
research ethics board 
SAE(s) 
serious adverse event(s) 
SAP 
statistical analysis plan 
SAS 
Statistical Analysis System (software) 
SBP 
systolic blood pressure 
SMA 
spinal muscular atrophy 
TEAE(s) 
treatment emergent adverse event(s) 
TESAE(s) 
treatment emergent serious adverse event(s) 
WHO-DD 
World Health Organization – Drug Dictionary 
 
 
 


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TABLE OF CONTENTS 
 
1 
Statistical Analysis Plan Signature Form 
2 
2 
Modification History 
3 
3 
List of Abbreviations and Definitions of Terms 
4 
4 
Introduction 
10 
4.1 
Background 
10 
5 
Trial Design 
11 
5.1 
Study Objectives 
11 
5.2 
Study Design 
11 
5.3 
Study Drug Dosage and Administration 
11 
6 
Sample Size, Randomization and Blinding 
12 
6.1 
Sample Size 
12 
6.2 
Randomization and Blinding 
12 
7 
Selection and Discontinuation of Patients 
12 
7.1 
Inclusion Criteria 
12 
7.2 
Exclusion Criteria 
12 
7.3 
Removal of Patients from Treatment or Assessment 
13 
8 
Schedule of Events 
13 
9 
Study Endpoints 
13 
9.1 
Efficacy Endpoints 
13 
9.1.1 
Quality of life assessment 
13 
9.2 
Safety Endpoints 
13 
10 
Data Analysis and Statistical Considerations 
13 
10.1 
Analysis Populations 
13 
10.2 
General Statistical Considerations 
14 
10.3 
Multiple Comparisons/ Multiplicity 
14 
10.4 
Examination of Subgroups 
14 
10.5 
Interim Analysis 
14 
10.6 
Final Analysis 
15 
10.7 
Retests, Unscheduled Visits and Early Termination Data 
15 
10.8 
Windowing Conventions 
15 
10.9 
Demographic Characteristics and Medical History 
15 
10.9.1 
Demographic Characteristics 
15 
10.9.2 
Medical History 
15 
10.10 Medication and Treatment Analysis 
16 
10.10.1 Patient Disposition and Accountability 
16 
10.10.2 Duration of Treatment and Compliance 
16 
10.10.3 Concomitant Medications 
16 
10.11 Efficacy Analyses 
16 


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10.12 Safety Data 
17 
10.12.1 Adverse Events 
17 
10.12.2 Vital Signs and Body Weight 
20 
10.12.3 12-Lead ECG 
20 
10.12.4 Physical Examination 
20 
10.12.5 Laboratory Tests 
21 
10.12.5.1 Laboratory Specific Derivations 
21 
10.13 Protocol Deviations 
23 
11 
Data Handling 
23 
11.1 
Multicenter Sites 
23 
11.2 
Handling of Missing Data 
23 
12 
Changes from the Protocol 
23 
13 
Table Shells and Specifications 
23 
13.1 
Table Specifications 
23 
13.1.1 Table Format Specification 
24 
13.2 
Line Listings Specifications 
24 
14 
Programming Conventions for Outputs 
24 
Appendix 1: Schedule of Events 
25 
Appendix 2: INQoL Scaling and Scoring 
26 
Table 14.1.1. Patients Enrolment by Site 
31 
Table 14.1.2.  Analysis Populations / All Enrolled Patients 
32 
Table 14.1.3.  Study Completion and Primary Reason for Premature Discontinuation of Study 
Medication / SAF 
33 
Table 14.1.4.  Protocol Deviations / SAF 
34 
Table 14.1.5.  Major Protocol Deviations / SAF 
35 
Table 14.1.6.  Demographic Characteristics / SAF 
36 
Table 14.1.7.  Childbearing Potential and Pregnancy Test at Screening / SAF 
37 
Table 14.1.8.  SMA History and SMN gene analysis / SAF 
38 
Table 14.1.9.  Medical History / SAF 
39 
Table 14.1.10.  Previous Diseases from Medical History by SOC and PT / SAF 
40 
Table 14.1.11.  Concomitant Diseases from Medical History by SOC and PT / SAF 
41 
Table 14.1.12.  Physical Examination / SAF 
42 
Table 14.1.13.  Physical Examination Abnormalities by SOC and PT / SAF 
43 
Table 14.2.1.  Duration of Treatment / SAF 
44 
Table 14.2.3.  Amifampridine Dosage by Visit / SAF 
45 
Table 14.2.4.  Treatment Compliance / SAF 
46 
Table 14.3.1.  Summary of Treatment Emergent Adverse Events (TEAEs) / SAF 
47 
Table 14.3.2.  Summary of TEAEs by SOC and PT / SAF 
48 
Table 14.3.3.  Summary of Related TEAEs by SOC and PT / SAF 
49 
Table 14.3.4.  Summary of TESAEs by SOC and PT / SAF 
50 
Table 14.3.5.  Summary of Related TESAEs by SOC and PT / SAF 
51 


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Table 14.3.6.  Summary of TEAEs Leading to Hospitalization by SOC and PT / SAF 
52 
Table 14.3.7.  Summary of Life-Threatening TEAEs by SOC and PT / SAF 
53 
Table 14.3.8.  Summary of TEAEs Leading to Premature Discontinuation by SOC and PT / SAF54 
Table 14.3.9.  Summary of TEAEs by SOC and PT and Maximum Severity / SAF 
55 
Table 14.3.10.  Summary of TEAEs by SOC and PT and Relationship to Treatment / SAF 
56 
Table 14.4.1.  Summary of Clinical Laboratory Tests: Haematology / SAF 
57 
Table 14.4.2.  Summary of Clinical Laboratory Tests: Blood Chemistry / SAF 
58 
Table 14.4.3.  Summary of Haematology Shift Result Relative to the Normal Range / SAF 
59 
Table 14.4.4.  Summary of Blood Chemistry Shift Result Relative to the Normal Range / SAF 60 
Table 14.5.1.  Summary of Vital Signs: Systolic Blood Pressure / SAF 
61 
Table 14.5.2.  12-Lead ECG / SAF 
62 
Table 14.5.3.  Childbearing Potential and Pregnancy Test / SAF 
63 
Table 14.6.1.  Summary of INQoL: Weakness / ITTQOL 
64 
Table 14.6.2.  Summary of PEDSQL: About my Neuromuscular Disease / ITTQOL 
65 
Listing 16.2.1.  Completed and Discontinued Patients with Primary Reason for Discontinuation66 
Listing 16.2.2.1  Inclusion Criteria 
67 
Listing 16.2.2.2.  Exclusion Criteria 
69 
Listing 16.2.3.1.  Protocol Deviations 
71 
Listing 16.2.3.2.  Patients Excluded from the Analysis Populations 
72 
Listing 16.2.4.  Demographic Characteristics 
73 
Listing 16.2.4.2.1.  Medical History: SMA Characteristics 
74 
Listing 16.2.4.2.2.  Medical History: Previous and Concomitant Diseases 
75 
Listing 16.2.5.1.1.  Amifampridine Treatment at Screening 
76 
Listing 16.2.5.1.2.  Amifampridine Treatment Over the Study 
77 
Listing 16.2.5.2.1  Duration and Compliance over the Study 
78 
Listing 16.2.5.2.2  Study Drug Accountability 
79 
Listing 16.2.6.1.  Quality of Life (QoL): Type of Questionnaire 
80 
Listing 16.2.7.1.1  PEDSQL Parent Report for Young Child (5-7 years): About My Child’s 
Neuromuscular Disease (Items from 1 to 17) 
81 
Listing 16.2.7.1.2.  PEDSQL Parent Report for Young Child (5-7 years): Communication (Items from 
1 to 3), About our Family Resources (Items from 1 to 5) and Questionnaire Scores 
82 
Listing 16.2.7.2.1.  PEDSQL Parent Report for Child (8-12 years): About My Child’s Neuromuscular 
Disease (Items from 1 to 17) 
84 
Listing 16.2.7.2.2.  PEDSQL parent Report for Child (8-12 years): Communication (Items from 1 to 
3), About our Family Resources (Items from 1 to 5) and Questionnaire Scores 
85 
Listing 16.2.7.3.1. PEDSQL Teen Report (13-18 years): About My Neuromuscular Disease (Items 
from 1 to 17) 
87 
Listing 16.2.7.3.2.  PEDSQL Teen Report (13-18 years): Communication (Items from 1 to 3), About 
our Family Resources (Items from 1 to 5) and Questionnaire Scores 
88 
Listing 16.2.7.4.1.  INQOL: Items from Section 1-1 to Section 1-5C 
90 
Listing 16.2.7.4.2.  INQOL: Items from Section 1-6 to Section 2-Question 1.B2 
91 


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Listing 16.2.7.4.3.  INQOL: Items from Section 2-Question 2.A to Section 2-Question 3.B6 
92 
Listing 16.2.7.4.4.  INQOL: Items from Section 2-Question 4.A1 to Section 3-Question 1.A3 93 
Listing 16.2.7.4.5.  INQOL: Items from Section 3-Question 1.B1 to Section 3-Question 1.B3 and 
Comments 
94 
Listing 16.2.7.4.6.  INQOL: Questionnaire Scores 
95 
Listing 16.2.5.1.  Treatment Emergent Adverse Events 
99 
Listing 16.2.5.2.  Treatment Emergent Serious Adverse Events 
100 
Listing 16.2.5.3.  IMP Related Treatment Emergent Adverse Events 
101 
Listing 16.2.5.4.  IMP Related Treatment Emergent Serious Adverse Events 
102 
Listing 16.2.5.5.  Treatment Emergent Adverse Events Leading to Hospitalization 
103 
Listing 16.2.5.6.  Life-Threatening Treatment Emergent Adverse Events 
104 
Listing 16.2.5.7.  Treatment Emergent Adverse Events Leading to Premature Discontinuation 105 
Listing 16.2.5.8.  Treatment Emergent Adverse Events Leading to Death 
106 
Listing 16.2.5.9.  Adverse Events Started Before the First Dose of Study Drug for the Current Long-
Term Study 
107 
Listing 16.2.6.1.  Clinical Laboratory Evaluations: Blood Chemistry 
108 
Listing 16.2.6.2.  Clinical Laboratory Evaluations: Hematology 
109 
Listing 16.2.6.3.  Clinical Laboratory Evaluations: Urinalysis 
110 
Listing 16.2.7.1.  Pregnancy Test 
111 
Listing 16.2.7.2.  Vital Signs 
112 
Listing 16.2.7.3.  ECG 
113 
Listing 16.2.7.4.  Physical Examination 
114 
Listing 16.2.8.  Concomitant Medications 
115 
Listing 16.2.9.  End of Study 
116 
Listing 16.2.10.  Comments 
117 
 
 
 


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4 
Introduction  
This Statistical Analysis Plan (SAP) is based on study procedures and analyses from the protocol, 
Version 2.0, dated 24 July 2018. This SAP takes as well into account the following protocol 
version/amendment: 
- 
Version 3.0, dated 12 April 2019 (amendment) 
Table shells and mock listings corresponding to the contents of this document will be prepared and 
included with the final version. This document, with table shells and mock listings, will be reviewed 
prior to final analyses, and revised if necessary. 
4.1 Background 
Information on disease background, amifampridine, previously completed nonclinical and clinical 
studies of amifampridine, is described in the Introduction of SMA-001 and in the Investigator Brochure 
supplied by Catalyst (March 2019). Investigators are to review this document before initiating this study.  
Amifampridine is a non-specific voltage-dependent potassium (K+) channel blocker. Blockade of K+ 
channels causes depolarization of the presynaptic membrane and slows down or inhibits repolarization. 
Prolonged depolarization results in opening of slow voltage-dependent calcium (Ca2+) channels and 
allows a subsequent influx of Ca2+. The increased concentration of intracellular Ca2+ induces 
exocytosis of the synaptic vesicles containing acetylcholine (ACh), thus releasing an increased level of 
ACh into the synaptic cleft (Maddison, 1998a; Maddison, 1998b). The influx of ACh into the presynaptic 
cleft enhances neuromuscular transmission, providing improved muscle function. 
Mori et al. (2012) found that amifampridine improved neuromuscular transmission by predominantly 
increasing ACh release in the neuromuscular junction of in mice with MG induced by antibodies against 
muscle-specific kinase (MuSK).  Furthermore, a mouse model of MuSK-myasthenia gravis (MG), 
amifampridine significantly enhanced neuromuscular transmission after 1 week of treatment without 
exacerbating loss of endplate AChRs (Morsch et al. 2013).  
Multiple studies were conducted to evaluate the cardiac safety, pharmacokinetics and toxicity profile in 
rats and dogs. Reproductive and developmental toxicity studies with amifampridine were also conducted 
in rats and rabbit as well a variety of in vitro and in vivo genotoxicity studies, and in vitro 
metabolism/transporter studies. The main nonclinical findings related to amifampridine were central and 
autonomic nervous system effects, the development of Schwannomas, and histologic changes in muscle 
tissues. Below is an abbreviated summary of the effectiveness of amifampridine in MuSK-MG and 
overall safety in other patient populations. 
Spinal Muscular Atrophy (SMA), first described in the 1890s, is an autosomal recessive neuromuscular 
disease characterized by degeneration of alpha motor neurons in the anterior horn of spinal cord, leading 
to progressive denervation atrophy in the involved skeletal muscles, with weakness and paralysis. The 
disease is due to defects in the Survival Motor Neuron 1 (SMN1) gene in chromosome 5, with deficiency 
in the SMN protein, a ubiquitously expressed protein, critical to the health and survival of the motor 
neurons. 
Recent studies in SMA animal models and SMA patients have shown that the NMJ displays significant 
structural and functional defects that precede overt disease symptoms, suggesting that impaired NMJ 
function may contribute to SMA pathogenesis and symptoms. Defects in the NMJ appear to precede 
degeneration of motor neurons suggesting that abnormal formation and/or maintenance of this structure 
may be a key event in disease pathogenesis. These defects have been observed at both the pre- and 
postsynaptic components of the NMJ, which likely contribute to the failure to maintain the NMJ and 


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muscle innervation in mouse models of SMA. Finally, NMJ dysfunction has been also demonstrated in 
SMA patients, mainly in Type 3 subgroup, contributing to the symptoms associated with the disease. 
Small studies have demonstrated the beneficial effects of amifampridine in patients with muscle-specific 
receptor tyrosine kinase-myasthenia gravis (MuSK-MG) in 2 children, who achieved some benefit 
(Skjei, 2013) and 1 adult (Evoli, 2016).  Following 4 months of treatment, the authors report the adult 
patient had obvious improvement of ptosis, decreased neck weakness and arm fatigability. In an 
Investigator-Sponsored MuSK-MG randomized, double-blind, placebo-controlled, cross-over study 
conducted in Italy, 7 MuSK-MG patients demonstrated statistically significantly higher functional 
performance in all validated assessment scales when they were administered amifampridine compared 
to placebo. Tolerability to amifampridine was excellent (unpublished data). 
A review of the literature documents that amifampridine is a safe and effective treatment in multiple 
neurologic disorders and is recommended by the EFNS for first-line symptomatic treatment of patients 
with LEMS (Skeie, 2006; Skeie, 2010; Lindquist, 2011).  
5 
Trial Design  
5.1 Study Objectives  
The primary objectives of the study is to evaluate the long-term safety and tolerability of amifampridine 
in patients with SMA Type 3. 
The secondary objective of the study is to assess the clinical efficacy of amifampridine phosphate over 
time in patients with SMA Type 3 based on changes in QoL.  
5.2 
Study Design 
This is an open label outpatient extension study designed to evaluate the long-term safety, tolerability of 
amifampridine in patients diagnosed with SMA Type 3. In addition, evaluation of the effects of 
amifampridine on the QoL will be made. The study will enroll those patients who have completed the 
SMA-001 study and after all final evaluations for that study have been completed, or those who 
demonstrated benefit after completing the dose titration period but failed to meet the randomization 
criteria on Day 0 of SMA-001.  
The duration of participation for each patient is expected to be at least 12 months as patients may 
continue in the study until amifampridine is approved by Regulatory Agencies or the clinical 
development of amifampridine is terminated for this indication. In addition to amifampridine, patients 
will continue to receive previous concomitant medications, as needed.  
After a new informed consent is signed and inclusion / exclusion criteria for the current protocol are 
satisfied, eligible patients will be given the optimal dose and dosing schedule that was identified in the 
Run-in Period from Protocol SMA-001.   
The study will be completed when amifampridine is approved by Regulatory Agencies for Spinal 
Muscular Atrophy or the clinical development of amifampridine is terminated for this indication. 
5.3 Study Drug Dosage and Administration 
The IP is amifampridine, and it will be provided in round, white-scored tablets, containing 
amifampridine phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet. The 
product will be provided in bottles of bulk tablets to the Catalyst designee who will dispense to the site 
an amount for each portion of the study, in a patient-specific labeled bottle. 
The dose of amifampridine will be based on optimal neuromuscular benefit determined from the Run-in 
Period from SMA-001 or may be modified as the discretion of the Investigator. The maximum single 


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dose is 20 mg.  The dose range for patients 6 to 16 years of age is 15 to 60 mg and for those 17 years 
and older, the range is from 30 to 80 mg daily. The daily dose of amifampridine can be adjusted during 
this long-term at the discretion of the Investigator. 
6 
Sample Size, Randomization and Blinding 
6.1 Sample Size 
This study is not powered with respect to any endpoint and no hypothesis is being tested.  
The study will enroll those patients who have completed the SMA-001 study and after all final 
evaluations for that study have been completed, or those who demonstrated benefit after completing the 
dose titration period but failed to meet the randomization criteria on Day 0 of SMA-001.   
6.2 Randomization and Blinding 
Not applicable. This is an open label study. 
7 
Selection and Discontinuation of Patients 
7.1 Inclusion Criteria 
Individuals eligible to participate in this study must meet all the following inclusion criteria: 
1. Participated in the SMA-001 study 
2. Willing and able to provide written informed consent after the nature of the study has been 
explained and before the start of any research-related procedures. 
3. Female patients of childbearing potential defined according to the Clinical Trial Facilitation 
Group - CTFG guidelines* must have a negative pregnancy test (urine human chorionic 
gonadotropin [HCG] at the end of SMA-001 study); and must practice an effective, reliable 
contraceptive regimen during the study and for up to 30 days following discontinuation of 
treatment. 
4. Ability to participate in the study based on overall health of the patient and disease prognosis, 
as applicable, in the opinion of the Investigator; and able to comply with all requirements of the 
protocol, including completion of study questionnaires. 
* According to CTFG guidelines a woman is considered of childbearing potential, i.e. fertile, following 
menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation 
methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal 
state is defined as no menses for 12 months without an alternative medical cause. 
7.2 Exclusion Criteria  
Individuals who met any of the exclusion criteria in the original protocol or those listed below are not 
eligible to participate in the study: 
1. Epilepsy and currently on medication 
2. Uncontrolled asthma 
3. Concomitant use with sultopride 
4. Concomitant use with medicinal products with a narrow therapeutic window 
5. Clinically significant abnormalities in 12 lead ECG, in the opinion of the Investigator 
6. Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the 
study 


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7. Intolerable amifampridine-related side effects   
8. Treatment with an investigational drug (other than amifampridine) or device while 
participating in this study 
9. Any medical condition that, in the opinion of the Investigator, might interfere with the patient’s 
participation in the study, poses an added risk for the patient, or confound the assessment of the 
patient 
10. History of drug allergy to any pyridine-containing substances or any amifampridine 
excipient(s) 
For inclusion/exclusion criteria of protocol version 2.0 please refer to paragraphs 8.2.1 and 8.2.2 of 
study protocol. 
7.3 Removal of Patients from Treatment or Assessment 
Patients may withdraw their consent to participate in the study or to receive treatment at any time without 
prejudice. The investigator or Catalyst may withdraw a patient from the treatment or from the study at 
any time. 
8 
Schedule of Events 
The schedule of clinical procedures and assessments conducted during the study is presented in 
Appendix 1. 
9 
Study Endpoints 
9.1 Efficacy Endpoints 
The QoL questionnaire will be performed as described in the Schedule of Events (Appendix 1). 
9.1.1 Quality of life assessment 
The Individualized Quality of Life for neuromuscular disease (INQoL) or the Pediatric Quality of Life 
(PEDSQLTM) will be assessed for adult or pediatric patients, respectively. 
9.2 Safety Endpoints 
Safety endpoints include the evaluation of treatment-emergent AE, vital signs, clinical laboratory 
assessments (hematology, chemistry, and urinalysis), ECGs, and physical examinations. Pregnancy 
testing is also required for females of childbearing potential. The timing of the required evaluations is 
described in the Schedule of Events (Appendix 1). 
10 Data Analysis and Statistical Considerations 
Statistical tables and by-patient data listings will be prepared using SAS System (SAS Institute, Cary, 
North Carolina, USA), Version 9.4 under Windows 10 PRO. 
10.1 Analysis Populations 
The following analysis populations have been defined for this clinical study: 
a) Enrolled Population: all patients who provided informed consent for this study. 
b) Safety Population (SAF): this population will consist of all patients who are enrolled in this 
Long-Term study and have received at least one dose of amifampridine 


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c) Efficacy Analysis Set (ITTQOL): this population consists of all patients who receive at least 1 
dose of amifampridine and have at least one post-treatment efficacy assessment 
The safety population will be used for the analysis of all safety variables and baseline characteristics. 
The ITTQOL population will be used for efficacy analyses on Quality of Life Questionnaires (QoL). 
10.2 General Statistical Considerations 
The following standards will be applied for the analyses unless otherwise specified.  
Simple summary statistics (descriptive statistics) for continuous data will be n (number of non-missing 
observations), mean, median, standard deviation, minimum, and maximum.  
The frequency count and percentage will be used to summarize categorical data. Summary statistics will 
be presented.  
Summary statistics for all safety and efficacy variables will be presented.  
All data collected will be presented in the by-patient data listings, sorted by site, patient and, where 
applicable, by study visit. 
Change From Baseline (CFB) will be summarized by post-dose time point for efficacy and safety 
assessments, where Baseline for this Long-Term study is defined as follow: 
- 
Safety Baseline values (physical exam, ECG, Labs, vitals)  
o Day 0 for patient not randomized in SMA-001 study 
o Day 28 for patient randomized in SMA-001 study 
o If the screening visit for SMA-002 will be performed on different day from SMA-001 
study last visit (i.e. not on Day 0 or Day 28 or on Early termination visit with the full 
panel of assessments performed), assessments have to be repeated and they will be the 
baseline values for SMA-002 
- 
Efficacy Baseline values (QoL) 
o Day 0 for patients that completed SMA-001 study 
o Day 0 for patients randomized but that not completed SMA-001 study (for example 
discontinued on Day 7) 
o Day 0 for patients who had QoL for SMA-001 study, however, did not qualify  for 
randomization; however, based on PI discretion, the patient had benefit and were allowed 
to enrol in the SMA-002 study  
o SMA-001 screening for patients who had QoL performed at Screening visit of the SMA-
001 study, and no QoL was performed on  Day 0 or thereafter.) 
10.3 Multiple Comparisons/ Multiplicity 
No multiple comparisons are foreseen for this study. 
10.4 Examination of Subgroups 
No subgroup analyses are foreseen for this study. 
10.5 Interim Analysis  
There will be no Interim Analysis for this study. 


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10.6 Final Analysis  
All final, planned analyses identified in this SAP will be performed by SPARC Consulting, Milan, Italy 
on behalf of Catalyst Pharmaceuticals following Sponsor Authorization of this Statistical Analysis Plan, 
Database Lock, and Sponsor Authorization of Analysis Sets. 
10.7 Retests, Unscheduled Visits and Early Termination Data 
In general, for by-visit summaries, data recorded at the nominal visit will be presented. Unscheduled 
measurements will not be included in by-visit summaries.  
Listings will include scheduled, unscheduled, and early discontinuation data. 
10.8 Windowing Conventions  
Actual dates of visits will be used for calculations of time intervals. No visit windowing will be 
performed for this study. Out-of-window visits will not be reallocated to the nearest timepoint. 
10.9 Demographic Characteristics and Medical History 
10.9.1 
Demographic Characteristics 
Demographic parameters, including age, gender, race, body weight, height, and BMI, at Screening, 
will be summarized for the SAF analysis set. 
10.9.2 
Medical History  
Summary analysis will involve the SAF analysis set. 
SMA history parameters, including time (years) from onset of SMA symptoms and SMN gene analysis 
results will be summarized. Time from onset of SMA symptoms will be calculated as the difference in 
years from the year of the date of the informed consent and the year of onset of SMA symptoms 
reported in CRF. 
All verbatim terms reported in the Medical History form will be assigned to a Preferred Term (PT) and 
will be classified by the primary System Organ Class (SOC) according to the Medical Dictionary for 
Regulatory Activities (MedDRA) thesaurus, version 23. 
Previous diseases are those reported in the “Medical History” form of the eCRF with item “Present at 
study start?” flagged as “No”. 
Concomitant diseases are those reported in the “Medical History” form of the eCRF with item “Present 
at study start?” flagged as “Yes” or “Unknown”. 
The following data will be presented: 
a) A default frequency table showing the number and percentage of patients who exhibited an 
abnormality by single body system; 
b) A default frequency table showing the number and percentage of patients who exhibited at least 
one previous disease and the previous diseases by primary SOC and PT; 
c) A default frequency table showing the number and percentage of patients who exhibited at least 
one concomitant disease and the concomitant diseases by primary SOC and PT; 
Medical history will be listed for all enrolled patients. 


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10.10 
Medication and Treatment Analysis 
10.10.1 Patient Disposition and Accountability 
The number and percentage of patients who are enrolled, in the SAF and ITTQOL analysis set, and who 
complete Long-term study will be presented. The number and percentage of patients who discontinue 
dosing prematurely, along with the primary reason that dosing was discontinued prematurely, will be 
presented. 
10.10.2  Duration of Treatment and Compliance 
Duration of treatment will be summarized for the SAF analysis set.   
The duration of treatment is the (date of the last study drug dose intake minus the date of administration 
of the first dose of study drug) +1.  
Compliance is 100%*(Number consumed)/(Number prescribed). “Number consumed” is from Study 
Drug Accountability and “Number prescribed” is number of tablets to have been taken daily duration. 
Compliance will be summarized for the SAF analysis set. 
10.10.3  Concomitant Medications  
All prescription and over-the-counter medications and herbal and nutritional supplements taken during 
the Long-Term study will be recorded on the designated CRF. All prior medications taken within 14 
days of initiation of this study are to be recorded on the CRF which is also recorded in the appropriate 
CRF pages of Study SMA-001 as concomitant medications. 
The Investigator may prescribe additional medications during the study if the prescribed medication is 
not prohibited by the protocol. In the event of an emergency, any needed medications may be prescribed 
without prior approval, but the medical monitor must be notified of the use of any contraindicated 
medications immediately thereafter. Any concomitant medications added or discontinued during the 
study should be recorded on the CRF. 
Concomitant medications will be only listed for all enrolled patients. 
10.11 
Efficacy Analyses 
Efficacy will be assessed by changes in QoL over time. 
Assessments of efficacy will be performed using the following endpoints: 
1. CFB in the INQoL subscales scores: 
Symptoms (section 1): 
a) Weakness 
b) Muscle “locking”  
c) Pain 
d) Fatigue 
e) Droopy eyelids 
f) Double vision 
g) Swallowing difficulties 
Life domains (section 2): 
a) Activities 
b) Independence 


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c) Social relationship 
d) Emotions 
e) Body image 
Life domains (section 3): 
a) Perceived treatment effects 
b) Expected treatment effects 
Quality of Life 
2. CFB in the PEDSQL score (where applicable). 
The individual domain scores in INQoL will be calculated using the scoring algorithms outlined in 
Appendix 2. 
Results from INQoL questionnaires and PEDSQL inventory of disease specific symptoms will be 
summarized with descriptive statistics (n, mean, standard deviation, minimum, median, and maximum) 
per time point (Months 3, 6, 9, 12, 15, 21 and 27) and CFB, using the Day 0 [in the case where patient 
completed SMA-001 study, was randomized but not completed SMA-001 study, was not randomized; 
however based on PI discretion, the patient had benefits and were allowed to enroll in the SMA-002] or 
the screening visit for the SMA-001 study [in the case where patient had QoL performed at Screening 
visit of the SMA-001 study, and No QoL was performed on Day 0 or thereafter] response as the baseline 
level.  
The subscales of the INQoL questionnaires will be similarly summarized. 
Efficacy analysis will be conducted on ITTQOL analysis set. The efficacy analysis will be descriptive and 
will be presented on observed data only. Means with standard deviations of INQoL and PEDSQL scores 
will be also presented. 
10.12 
Safety Data 
Summaries of safety data will be presented for the SAF analysis set using observed data only, i.e. without 
imputation. All observed safety data will be listed. 
10.12.1 Adverse Events 
For this protocol, a reportable AE is any untoward medical occurrence (e.g. sign, symptom, illness, 
disease or injury) in a patient administered the IP or other protocol-imposed intervention, regardless of 
attribution. This includes: 
 AEs not previously observed in the patient, that emerge during the study. 
 Pre-existing medical conditions judged by the Investigator to have worsened in severity or 
frequency or changed in character during the study. 
 Complications that occur as a result of non-drug protocol-imposed interventions. 
An adverse drug reaction is any AE for which there is a reasonable possibility that the IP caused the AE. 
“Reasonable possibility” means there is evidence to suggest a causal relationship between the IP and the 
AE. 
Whenever possible, it is preferable to record a diagnosis as the AE term rather than a series of terms 
relating to a diagnosis. 
All ongoing non-serious AEs, even those which began under SMA-001 study, will be reported from the 
end of the double-blind study (SMA-001) or from Day 0 for those not randomized to double blind 
medication in SMA-001 study through the termination visit or at the early termination visit and will be 


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recorded on the AE page of the eCRF. All ongoing SAEs from SMA-001 study will be reported. The 
criteria for determining, and the reporting of new SAEs is provided in Study Protocol Section 11.2. 
The Investigator should follow all unresolved AEs until the events are resolved or stabilized, the patient 
is lost to follow-up, or it has been determined that the study treatment or participation is not the cause of 
the AE. Resolution of AEs (with dates) should be documented on the appropriate CRF page(s) and in 
the patient’s medical record. 
The Investigator responsible for the care of the patient or qualified designee will assess AEs for severity, 
relationship to IP, and seriousness (refer to Protocol Section 11.2 for SAE definition). Severity (as in 
mild, moderate or severe headache) is not equivalent to seriousness, which 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.  
The Investigator will determine the severity of each AE using grades defined in Table 1 (the event will 
be recorded on the source documents and AE CRF). Events that are Grades 4 and 5 are serious events 
and require completion of both an SAE form and AE CRF. 
Table 1 - Categories of Severity for Adverse Events 
Severity 
Description 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental ADL*. 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL**. 
Grade 4 
Life-threatening consequences; urgent 
intervention indicated. 
Note: Grade 4 and 5 
adverse events should 
always be reported as 
serious adverse events 
Grade 5 
Death related to AE. 
Activities of Daily Living (ADL) 
* Instrumental ADLs refer to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
** Self-care ADLs refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 
 
A Treatment-Emergent Adverse Event (TEAE) is any AE that emerges after the first dose of study drug for 
the current Long-Term Study. All AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA), Version 23.0. All TEAEs will be summarized. Counts and percentages will be presented 
for each observed System Organ Class (SOC) and Preferred Term (PT) as defined in MedDRA. A patient 
having more than one TEAE with the same PT will be counted only once in the incidence calculation 
for that PT.  Similarly, if a patient has more than one TEAE in the same SOC, the patient will be counted 
only once in the total number of patients with a TEAE for that SOC. Each TEAE will be assessed with 
respect to severity and relationship to treatment. All AEs will be listed, regardless of whether they were 
study treatment related. 


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The relationship of an AE will be recorded using the specified relationship categories described in Table 
2.  
Table 2 - Description of relationship to adverse events categories 
Relationship 
Category 
Description 
Not Related 
Exposure to the IP has not occurred 
OR 
The administration of the IP and the occurrence of the AE are not 
reasonably related in time  
OR 
The AE is considered likely to be related to an etiology other than the use 
of the IP; that is, there are no facts [evidence] or arguments to suggest a 
causal relationship to the IP. 
Possibly 
Related 
The administration of the IP and the occurrence of the AE are reasonably 
related in time 
AND 
The AE could be explained equally well by factors or causes other than 
exposure to the IP. 
Probably 
Related 
The administration of IP and the occurrence of the AE are reasonably 
related in time  
AND 
The AE is more likely explained by exposure to the IP than by other factors 
or causes. 
 
The following summary tables will be provided: 
1. An overview of TEAEs including the number of TEAEs, related TEAEs, TESAEs, related 
TESAEs, TEAEs leading to premature discontinuation, TEAEs leading to hospitalization, life-
threatening TEAEs, number of patients with at least one TEAE, at least one related TEAE, at 
least one TESAE, at least one related TESAE, at least one TEAE leading to premature 
discontinuation, at least one TEAE leading to hospitalization, at least one life-threatening TEAE, 
and at least one TEAE leading to death 
2. Summary of all TEAEs by Primary SOC and PT 
3. Summary of all related TEAEs by Primary SOC and PT 
4. Summary of all TESAEs by Primary SOC and PT 
5. Summary of all related TESAEs by Primary SOC and PT 
6. Summary of all TEAEs leading to hospitalization by Primary SOC and PT 
7. Summary of all life-threatening TEAEs by Primary SOC and PT 
8. Summary of all TEAEs leading to premature discontinuation by Primary SOC and PT 
9. Summary of all TEAEs by Primary SOC and PT and maximum severity 
10.  Summary of all TEAEs by Primary SOC and PT and relationship to treatment. 
The following individual data listings will be produced: 


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1. A listing of all TEAEs 
2. A listing of all TESAEs 
3. A listing of all IMP related TEAEs 
4. A listing of all IMP related TESAEs 
5. A listing of all TEAEs leading to hospitalization 
6. A listing of all life-threatening TEAEs 
7. A listing of TEAEs leading to premature discontinuation 
8. A listing of all TEAEs leading to death 
9. A listing of all AEs started before the first dose of study drug for the current Long-Term Study 
10.12.2   Vital Signs and Body Weight 
Analysis will be performed in the SAF analysis set. 
Vital signs, including sitting blood pressure (systolic and diastolic; mmHg), sitting heart rate 
(beats/minute), body temperature (oC), respiration rate (breaths/minute), and weight (kg) will be 
summarized by time point using descriptive statistics. Changes from baseline will also be summarized 
by post-dose time point. 
Height is recorded at Screening visit only. 
BMI will be calculated at Screening visit according to the following formula: 
BMI (kg/m^2) = ((body weight (kg)/(height (m))^2). 
Height and BMI will be summarized using descriptive statistics. 
10.12.3   12-Lead ECG 
Analysis will be performed in the SAF analysis set. 
A standard 12-lead ECG will be recorded at Screening, Months 3, 6, 9, 12, 15, 21 and 27 visit.  
Each tracing will be classified as “Normal tracing”, “Abnormal tracing (not clinically significant)”, 
“Abnormal tracing (clinically significant)”, or “Unknown”. 
ECG results will be summarized in a shift table with the following shifts presented (baseline versus post 
dose time point): normal/normal, normal/abnormal NCS, normal/abnormal CS, abnormal NCS/normal, 
abnormal NCS/abnormal NCS, abnormal NCS/abnormal CS, abnormal CS/normal, abnormal 
CS/abnormal NCS and abnormal CS/abnormal CS. 
Clinically significant changes from baseline will be recorded as AEs. 
Abnormalities reported will be coded using MedDRA thesaurus version 23.0, and the terms listed for all 
enrolled patients. 
10.12.4   Physical Examination 
Summary analysis will involve the SAF analysis set. 
A complete physical examination is to be performed at each clinic visit or, if applicable, at early 
discontinuation from the study. 
These assessments will be summarized by visit using counts and percentages.  
All verbatim terms reported in the Physical Examination form will be assigned to a Preferred Term (PT) 
and will be classified by the primary System Organ Class (SOC) according to the Medical Dictionary 
for Regulatory Activities (MedDRA) thesaurus, version 23. 


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A summary table containing the frequency and percentage of patients who exhibited at least one 
abnormality as well as of the abnormalities reported at each clinic visit by primary SOC and PT will be 
prepared. 
Physical examination abnormalities will be listed for all patients. 
10.12.5   Laboratory Tests 
For blood chemistry and hematology, descriptive statistics will be presented for the observed value and 
CFB by time point. In addition, a shift table will be constructed to show the shifts in laboratory results 
by parameter relative to the normal ranges. The number and percentage of patients with the following 
shifts will be presented by time point: normal/normal, normal/low, normal/high, low/low, low/normal, 
low/high, high/low, high/normal, and high/high. The laboratory parameters to be collected are given 
below in Table 3. 
Table 3 - Clinical Laboratory Tests  
Blood Chemistry 
Hematology 
Urine Tests 
Albumin  
Hemoglobin  
Appearance 
Alkaline phosphatase  
Hematocrit  
Color 
ALT (SGPT) 
WBC count 
pH 
AST (SGOT) 
RBC count 
Specific gravity 
Direct bilirubin 
Platelet count 
Ketones 
Total bilirubin 
Differential cell count  
Protein  
BUN 
 
Glucose  
Calcium 
 
Bilirubin 
Chloride 
 
Nitrite 
Total cholesterol 
 
Urobilinogen 
CO2 or bicarbonate 
 
Blood in urine 
Creatine phosphokinase 
 
 
Creatinine 
 
 
Glucose 
 
 
GGT 
 
 
LDH 
 
 
Phosphorus 
 
 
Potassium 
 
 
Total protein  
 
 
Sodium  
 
 
Uric acid 
 
 
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CO2, carbon dioxide; GGT, 
gamma-glutamyl transferase; LDH, lactate dehydrogenase; RBC, red blood cell; SGOT, serum glutamic-oxaloacetic 
transaminase; SGPT, serum glutamic-pyruvic transaminase; WBC, white blood cell. 
Urinalysis parameters will not be included in summary tables.  
All laboratory parameters will be listed for all patients. 
10.12.5.1 
Laboratory Specific Derivations 
For each laboratory parameter, where appropriate, the reported values will be converted into SI units 
and if needed boundary values for reference ranges will be converted as well. 
Conversion to SI will be provided using textbook ranges: SI Unit Conversion Guide, M. Laposata, 
NEJM, 1992. To convert from the conventional unit to the SI unit, multiply by the conversion factor:  


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Table 4 - Clinical Laboratory Tests SI Conversion Factors 
Component 
Conventional  
Unit 
Conversion 
Factor 
SI Unit 
Hematology 
RBC count 
x 106/µL 
1 
x 1012/L 
WBC count 
x 103/µL 
1 
x 109/L 
Neutrophils  
x 103/µL 
1 
x 109/L 
Lymphocytes 
x 103/µL 
1 
x 109/L 
Monocytes 
x 103/µL 
1 
x 109/L 
Eosinophils 
x 103/µL 
1 
x 109/L 
Basophils 
x 103/µL 
1 
x 109/L 
Platelet count 
x 103/µL 
1 
x 109/L 
Hemoglobin  
g/dL 
10 
g/L 
Hematocrit 
% 
0.01 
Proportion of 1.0 
 
 
 
 
Biochemistry 
 
 
 
Albumin 
g/dL 
10 
g/L 
Alkaline phosphatase (ALP) 
U/L 
1 
U/L 
ALT (SGPT) 
U/L 
1 
U/L 
AST (SGOT) 
U/L 
1 
U/L 
Direct Bilirubin 
mg/dL 
17.104 
µmol/L 
Total Bilirubin 
mg/dL 
17.104 
µmol/L 
BUN 
mg/dL 
0.357 
mmol/L 
Calcium 
mg/dL 
0.25 
mmol/L 
Chloride 
mEq/L 
1.0 
mmol/L 
Total cholesterol 
mg/dL 
0.02586 
mmol/L 
CO2 or bicarbonate 
mEq/L 
1 
mmol/L 
Creatinine phosphokinase 
U/L 
0.01667 
µkat/L 
Creatinine 
mg/dL 
88.4 
µmol/L 
Glucose 
mg/dL 
0.05551 
mmol/L 
Gamma-GT (GGT) 
U/L 
1 
U/L 
LDH 
U/L 
0.01667 
µkat/L 
Phosphorus 
mg/dL 
0.3229 
mmol/L 
Potassium 
mEq/L 
mg/dL 
1.0 
0.2558 
mmol/L 
 
Total protein 
g/dL 
10 
g/L 
Sodium  
mEq/L 
1.0 
mmol/L 
Uric acid 
mg/dL 
59.48 
µmol/L 


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10.13 
Protocol Deviations 
All the protocol deviations will be discussed case by case by the clinical team during the review of the 
data before the lock of the study database and described in the Data Review Report.  
However, the following protocol deviations are anticipated to be considered as major: 
 Inclusion and exclusion criteria not respected; 
 Missing information on IMP administration that does not allow calculation of IMP 
exposure/compliance;  
 Overall study treatment compliance < 80%;  
 Use of prohibited medications during study (see Protocol Section 10.4). 
The number and percentage of patients with each type of protocol deviation will be presented. 
11 Data Handling 
11.1 Multicenter Sites 
This study is conducted by multiple Investigators in two investigational sites.  
Site-related differences will not be evaluated and presented in the statistical output as the study does 
not foresee a stratification by Site. 
11.2 Handling of Missing Data 
Missing data due to discontinuation will not be imputed. Missing safety data will not be imputed.  
Handling of missing data in INQoL is provided in the Appendix 2. 
12 Changes from the Protocol 
No changes from the statistical analyses planned in the study protocol have been introduced in this 
SAP. 
13 Table Shells and Specifications  
13.1 Table Specifications 
Tables will be provided as defined by the table shells.  
All output will be generated by means of SAS System and exported into a Microsoft Word document in 
RTF format. All output will be in landscape orientation. Left and right margins will be 2 cm from the 
side; the top and bottom margins will be 2.5 cm. Font size will be Courier New 7 pt.   
The header containing the sponsor name (Catalyst Pharmaceuticals) and protocol number will appear on 
the top left corner of each page of the output. The page number, in the format of “Page x of y”, will 
appear on the top right corner of the output, where y = last page of corresponding output.  
Column headers in tables include the total possible numbers to be included in summaries for that table, 
designated as “(N=XX)”.  
The SAS program name, the date of the creation of the output (run date) and the listings from which the 
tables were derived will appear on the bottom left corner as follows: 
Source: [program name].sas, Run on ddmmmyyyy 
Source: Listing(s) xx.x.x, xx.x.x 


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13.1.1 
Table Format Specification 
Maximum and minimum values will be reported with the same number of decimal places as collected.  
Means and medians will be reported to one additional decimal place. Standard deviations and standard 
errors will be reported to two decimal places more than the collected data. Percentages will be reported 
with one decimal place.  
Data in the tables are formatted as follows: 
Text fields in the body of the tables and listings will be left-justified. 
When no data are available for a table, an empty page with the title will be produced with suitable text. 
Example:  THERE WERE NO SERIOUS ADVERSE EVENTS. 
13.2 Line Listings Specifications 
Individual line listings will be provided as defined by the listing shells.    
All output will be generated by SAS System and exported into a Microsoft Word document in RTF 
format. All output will be in landscape orientation. Left and right margins will be 2 cm from the side; 
the top and bottom margins will be 2.5 cm. Font size will be Courier New 7 pt.   
The header containing the sponsor name (Catalyst Pharmaceuticals) and protocol number will appear on 
the top left corner of each page of the output. The page number, in the format of “Page x of y”, will 
appear on the top right corner of the output, where y = last page of corresponding output.  
The SAS program name, and the date of the creation of the output (run date) will appear on the bottom 
left corner as follows: 
Source: [program name].sas, Run on ddmmmyyyy. 
 
14 Programming Conventions for Outputs 
Outputs will be presented according to the standard SPARC’s layout of tables and line listings. 
Dates & Times: depending on data available, dates and times will take the form ddmmmyyyy hh:mm 
(i.e. 01JAN2019 10:20) 
Spelling Format: English US.  
Listings: all listings will be ordered by the following (unless otherwise indicated in the template): 
 Site ID 
 Patient number  
 Study visit 
 Date and hours (where applicable) 
In all listings missing data will be reported, according to the variable type, as follows: 
- 
Character variables and dates will be presented as empty fields 
- 
Numerical variables will be presented with a “-“ 
 


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Appendix 1: Schedule of Events 
Study Assessment or Event  
Screening 
and 
Enrollment* 
End of Study Month ± 1 week 
3 
6 
9 
12 
15 
21 
27 
EoSg 
Informed consent a 
x 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
x 
 
 
 
 
 
 
 
 
Complete physical exam b 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Vital signs  
x 
x 
x 
x 
x 
x 
x 
x 
x 
12-Lead ECG  
x 
x 
x 
x 
x 
x 
x 
x 
x 
Clinical laboratory tests c 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Pregnancy test d 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Amifampridine Treatment 
 
x 
x 
x 
x 
x 
x 
x 
 
QoL  
x 
x 
x 
x 
x 
x 
x 
x 
x 
Dispense IP e 
x 
x 
x 
x 
x 
x 
x 
 
 
IP accountability 
 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse events/SAEs f 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Concomitant medications 
x 
x 
x 
x 
x 
x 
x 
x 
x 
EoS= End of Study is the patients last visit to the site and discontinuation of study medication; IP=investigational product; QoL=quality of life; SAE=serious 
adverse event.  
a Informed consent must be obtained before any study procedures are performed. 
b Complete physical examination includes evaluation of all major body systems, including weight at all visits. 
c Clinical laboratory tests include serum chemistry, hematology, and urinalysis. 
d Urine pregnancy tests will be obtained from female patients of childbearing potential. 
e Pharmacist will dispense sufficient amount of medication until the next clinic visit. All unused medication must be returned to the clinic for drug accountability. 
f SAE reporting commences after informed consent is signed. Non-serious adverse event reporting commences after the first dose of study drug for the current 
Long-Term Study. 
g EoS or early termination visit if the last visit does not coincide the scheduled 3- or 6-month visit. 
*These data may be obtained from Study SMA-001. If data not available, then the assessment should be repeated. 


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Appendix 2: INQoL Scaling and Scoring 
 
Scaling and scoring 
INQoL_English.pdf  
 
Scaling and scoring 
of PedsQL English.pdf 


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Table 
Number 
 
Title of Table 
Analysis 
Population
Listing Source 
14.1.1. 
Patients Enrollment by Site 
Enrolled 
16.2.1 
14.1.2 
Analysis Populations / All Enrolled Patients 
Enrolled 
16.2.1 
14.1.3 
Study Completion and Primary Reason for Premature Discontinuation of Study Medication 
SAF 
16.2.1. 
14.1.4. 
Protocol Deviations 
SAF 
16.2.3.1. 
14.1.5. 
Major Protocol Deviations 
SAF 
16.2.3.1. 
14.1.6. 
Demographic Characteristics 
SAF 
16.2.4. 
14.1.7. 
Childbearing Potential and Pregnancy Test at Screening 
SAF 
16.2.7.1. 
14.1.8. 
SMA History and SMN Gene Analysis 
SAF 
16.2.4.2.1 
14.1.9. 
Medical History 
SAF 
16.2.4.2.2. 
14.1.10. 
Previous Diseases from Medical History by SOC and PT 
SAF 
16.2.4.2.2. 
14.1.11. 
Concomitant Diseases from Medical History by SOC and PT 
SAF 
16.2.4.2.2. 
14.1.12. 
Physical Examination  
SAF 
16.2.7.4.  
14.1.13. 
Physical Examination Abnormalities by SOC and PT 
SAF 
16.2.7.4. 
14.2.1. 
Duration of Treatment  
SAF 
16.2.5.2.1. 
14.2.3. 
Amiframpridine Dosage by Visit 
SAF 
16.2.5.1.2. 
14.2.4. 
Treatment Compliance  
SAF 
16.2.5.2.1. 
14.3.1. 
Summary of Treatment Emergent Adverse Events (TEAEs) 
SAF 
16.2.5.1. 
14.3.2. 
Summary of TEAEs by SOC and PT 
SAF 
16.2.5.1. 
14.3.3. 
Summary of Related TEAEs by SOC and PT 
SAF 
16.2.5.3. 
14.3.4. 
Summary of TESAEs by SOC and PT 
SAF 
16.2.5.2. 
14.3.5. 
Summary of Related TESAEs by SOC and PT 
SAF 
16.2.5.4. 
14.3.6. 
Summary of TEAEs Leading to Hospitalization by SOC and PT 
SAF 
16.2.5.5. 
14.3.7. 
Summary of Life-Threatening TEAEs by SOC and PT 
SAF 
16.2.5.6. 
14.3.8. 
Summary of TEAEs Leading to Premature Discontinuation by SOC and PT 
SAF 
16.2.5.7. 
14.3.9. 
Summary of TEAEs by SOC and PT and Maximum Severity  
SAF 
16.2.5.1. 


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Version Date: 29JUN2020  
 
Table 
Number 
 
Title of Table 
Analysis 
Population
Listing Source 
14.3.10. 
Summary of TEAEs by SOC and PT and relationship to Treatment 
SAF 
16.2.5.1. 
14.4.1. 
Summary of Clinical Laboratory Tests: Haematology 
SAF 
16.2.6.2. 
14.4.2. 
Summary of Clinical Laboratory Tests: Blood Chemistry 
SAF 
16.2.6.1. 
14.4.3. 
Summary of Hematology Shift Results Relative to the Normal Range 
SAF 
16.2.6.2. 
14.4.4. 
Summary of Blood Chemistry Shift Results Relative to the Normal Range 
SAF 
16.2.6.1. 
14.5.1. 
Summary of Vital Signs: Systolic Blood Pressure 
SAF 
16.2.7.2. 
14.5.2. 
12-Lead ECG  
SAF 
16.2.7.3. 
14.5.3. 
Childbearing Potential and Pregnancy Test  
SAF 
16.2.7.1. 
14.6.1. 
Summary of INQoL: Weakness  
ITTQOL 
16.2.7.4.1.  
16.2.7.4.2. 
16.2.7.4.3. 
16.2.7.4.4. 
16.2.7.4.5. 
16.2.7.4.6. 
14.6.2. 
Summary of PEDSQL: About my Neuromuscular Disease 
ITTQOL 
16.2.7.1.1.  
16.2.7.1.2. 
16.2.7.2.1. 
16.2.7.2.2. 
16.2.7.3.1. 
16.2.7.3.2. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 29 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 
Number 
 
Title of Listing 
16.2.1 
Completed and Discontinued Patients with Primary Reason for Discontinuation 
16.2.2.1 
Inclusion Criteria 
16.2.2.2 
Exclusion Criteria  
16.2.3.1 
Protocol Deviations 
16.2.3.2 
Patients Excluded from the Analysis Populations 
16.2.4. 
Demographic Characteristics 
16.2.4.2.1 
Medical History: SMA Characteristics 
16.2.4.2.2 
Medical History: Previous and Concomitant Diseases 
16.2.5.1.1 
Amifampridine Treatment at Screening 
16.2.5.1.2 
Amifampridine Treatment Over the Study 
16.2.5.2.1 
Duration and Compliance Over the Study 
16.2.5.2.2 
Study Drug Accountability  
16.2.6.1 
Quality of Life (QoL): Type of Questionnaire 
16.2.7.1.1 
PEDSQL Parent Report for Young Child (5-7 years): About My Child’s Neuromuscular Disease (Items from 1 to 17) 
16.2.7.1.2 
PEDSQL Parent Report for Young Child (5-7 years): Communication (Items from 1 to 3), About our Family Resources (Items from 1 
to 5) and Questionnaire Scores 
16.2.7.2.1 
PEDSQL Parent Report for Child (8-12 years): About My Child’s Neuromuscular Disease (Items from 1 to 17) 
16.2.7.2.2 
PEDSQL Parent Report for Child (8-12 years): Communication (Items from 1 to 3), About our Family Resources (Items from 1 to 5) 
and Questionnaire Scores 
16.2.7.3.1 
PEDSQL Teen Report (13-18 years): About My Neuromuscular Disease (Items from 1 to 17) 
16.2.7.3.2 
PEDSQL Teen Report (13-18 years): Communication (Items from 1 to 3), About our Family Resources (Items from 1 to 5) and 
Questionnaire Scores 
16.2.7.4.1 
INQOL: Items from Section 1-1 to Section 1-5C 
16.2.7.4.2 
INQOL: Items from Section 1-6 to Section 2-Question 1.B2 
16.2.7.4.3 
INQOL: Items from Section 2-Question 2.A to Section 2-Question 3.B6 
16.2.7.4.4 
INQOL: Items from Section 2-Question 4.A1 to Section 3-Question 1.A3 


Catalyst Pharmaceuticals, Inc. 
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16.2.7.4.5 
INQOL: Items from Section 3-Question 1.B1 to Section 3-Question 1.B3 and Comments 
16.2.7.4.6 
INQOL: Questionnaire Scores 
16.2.5.1 
Treatment Emergent Adverse Events 
16.2.5.2 
Treatment Emergent Serious Adverse Events 
16.2.5.3 
IMP Related Treatment Emergent Adverse Events 
16.2.5.4 
IMP Related Treatment Emergent Serious Adverse Events 
16.2.5.5 
Treatment Emergent Adverse Events Leading to Hospitalization 
16.2.5.6 
Life-Threatening Treatment Emergent Adverse Events 
16.2.5.7 
Treatment Emergent Adverse Events Leading to Premature Discontinuation 
16.2.5.8 
Treatment Emergent Adverse Events Leading to Death 
16.2.5.9 
Adverse Events started Before First Dose of Study Drug for the Current Long-Term Study 
16.2.6.1 
Clinical Laboratory Evaluations: Blood Chemistry 
16.2.6.2 
Clinical Laboratory Evaluations: Hematology 
16.2.6.3 
Clinical Laboratory Evaluations: Urinalysis 
16.2.7.1 
Pregnancy Test 
16.2.7.2 
Vital Signs 
16.2.7.3 
ECG 
16.2.7.4 
Physical Examination 
16.2.8 
Concomitant Medications 
16.2.9 
End of Study 
16.2.10 
Comments 


Catalyst Pharmaceuticals, Inc. 
Page 31 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
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Table 14.1.1. Patients Enrolment by Site 
 
 
 
Statistic 
N = XX 
  
Number of Enrolled Patients 
          
         
Site 01 
n (%)      
xx (xx.x%)       
Site 02 
n (%)      
xx (xx.x%)       
Total 
n (%)      
xx (xx.x%)       
 
 
 
Number of Screening Failures 
          
         
Site 01 
n (%)      
xx (xx.x%)       
Site 02 
n (%)      
xx (xx.x%)       
Total 
n (%)      
xx (xx.x%)       
 
 
 
Percentages are calculated relative to the total number of patients enrolled. 
a) FPFV: DDMONYYYY Patient XX.   
b) LPLV: DDMONYYYY Patient YY. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listing: 16.2.1. 
 
 
 


Catalyst Pharmaceuticals, Inc. 
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Table 14.1.2.  Analysis Populations / All Enrolled Patients 
  
 
 
N = XX 
 
 
 
Patients Enrolled  
xx 
 
 
Safety Population (SAF) 
xx (xx.x) 
 
 
Efficacy Population (ITTQOL) 
xx (xx.x) 
 
 
 
Percentages are calculated on the number of enrolled patients. 
 
a) 
Safety Population (SAF) consists of all patients who were enrolled in the Long-Term 
study and had received at least one dose of amifampridine.   
b) 
Efficacy Population (ITTQOL) consists of all patients who receive at least 1 dose of 
amifampridine and have at least one post-treatment efficacy assessment 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listing: 16.2.1. 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 33 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.1.3.  Study Completion and Primary Reason for Premature Discontinuation of Study Medication / SAF  
 
 
Amifampridine 
(N=xx) 
 
 
No. patients who prematurely discontinued study medication 
xx (xx.x) 
 
 
Primary Reason for Discontinuation 
 
Drug inefficacy 
xx (xx.x) 
Adverse event 
xx (xx.x) 
Investigator’s decision 
xx (xx.x) 
Consent withdrawal (not due to AE)  
xx (xx.x) 
Non study drug compliance 
xx (xx.x) 
Major protocol deviation 
xx (xx.x) 
Lost to follow-up during the study 
xx (xx.x) 
Disease progression 
xx (xx.x) 
Screening failure 
xx (xx.x) 
Other reason 
xx (xx.x) 
Total 
xx 
Percentages are calculated on the number of patients (N). 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listing: 16.2.1. 
 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 34 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.1.4.  Protocol Deviations / SAF  
 
 
Amifampridine 
(N=xx) 
 
 
No. of patients with at least one protocol deviation 
xx (xx.x) 
 
 
Deviation 1 
xx (xx.x) 
Deviation 2 
xx (xx.x) 
… 
xx (xx.x) 
Deviation n 
xx (xx.x) 
 
 
 
A patient may have more than one deviation. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.1. 
 


Catalyst Pharmaceuticals, Inc. 
Page 35 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.1.5.  Major Protocol Deviations / SAF  
 
 
Amifampridine 
(N=xx) 
 
 
No. of patients with at least one major protocol 
deviation 
xx (xx.x) 
 
 
Deviation 1 
xx (xx.x) 
Deviation 2 
xx (xx.x) 
… 
xx (xx.x) 
Deviation n 
xx (xx.x) 
 
 
A patient may have more than one more deviation. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.3.1. 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 36 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.1.6.  Demographic Characteristics / SAF 
 
 
Statistic 
Amifampridine 
(N=xx) 
 
 
 
Age (years) 
n 
xx 
 
Mean (SD) 
xx.x (xx.xx) 
 
Median 
xx.x 
 
Min, Max 
xx, xx 
 
 
 
Gender 
 
 
Male 
n (%) 
xx (xx.x) 
Female 
n (%) 
xx (xx.x) 
 
 
 
Race 
 
xx (xx.x) 
Caucasian 
n (%) 
xx (xx.x) 
Black 
n (%) 
xx (xx.x) 
Asian 
n (%) 
xx (xx.x) 
Other 
n (%) 
xx (xx.x) 
Unknown 
n (%) 
xx (xx.x) 
 
 
 
Height (cm) 
n 
xx 
 
Mean (SD) 
xx.x (xx.xx) 
 
Median 
xx.x 
 
Min, Max 
xx, xx 
 
 
 
Weight (kg) 
n 
xx 
 
Mean (SD) 
xx.x (xx.xx) 
 
Median 
xx.x 
 
Min, Max 
xx, xx 
 
 
 
BMI (kg/cm^2) 
n 
xx 
 
Mean (SD) 
xx.x (xx.xx) 
 
Median 
xx.x 
 
Min, Max 
xx, xx 
 
 
 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.4. 
 


Catalyst Pharmaceuticals, Inc. 
Page 37 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.1.7.  Childbearing Potential and Pregnancy Test at Screening / SAF 
________________________________________________________________________ 
 
   Statistic  Amifampridine         
                (N=xx)         
________________________________________________________________________ 
 
Childbearing potential  
 Patient male                         n (%)      xx (xx.x%)    
 Menopause                            n (%)      xx (xx.x%)    
 Sterilized                           n (%)      xx (xx.x%)    
 Total hysterectomy                   n (%)      xx (xx.x%)    
 No contraception protection          n (%)      xx (xx.x%)    
 Contraception protection             n (%)      xx (xx.x%)    
 Child                                n (%)      xx (xx.x%)    
 Unknown                              n (%)      xx (xx.x%)    
 
Serum pregnancy test performed? 
 No                                   n (%)      xx (xx.x%)    
 Yes                                  n (%)      xx (xx.x%)    
 Not applicable                       n (%)      xx (xx.x%)    
 
Type of pregnancy test (#)  
 Urine dipstick                       n (%)      xx (xx.x%)    
 Serum                                n (%)      xx (xx.x%)    
 Unknown                              n (%)      xx (xx.x%)    
 
Pregnancy test result (#) 
 Negative                             n (%)      xx (xx.x%)    
 Positive                             n (%)      xx (xx.x%)    
 Unknown                              n (%)      xx (xx.x%)    
_________________________________________________________________________ 
Percentages are calculated on the number of patients (N) in the SAF analysis set. 
# Percentages are based on the number of female patients performing pregnancy test. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.7.1. 
 


Catalyst Pharmaceuticals, Inc. 
Page 38 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.1.8.  SMA History and SMN gene analysis / SAF  
 
 
Statistic 
Amifampridine 
(N=xx) 
 
 
 
Time from onset of SMA symptoms (years)* 
 
 
 
n 
xx 
 
Mean (SD) 
xx.x (xx.xx) 
 
Median 
xx.x 
 
Min, Max 
xx, xx 
 
 
 
Was the patient previously treated for SMA other 
than amifampridine phosphate? 
 
 
No 
n (%) 
xx (xx.x) 
Yes 
n (%) 
xx (xx.x) 
Unknown 
n (%) 
xx (xx.x) 
 
 
 
SMN gene analysis result 
 
 
Negative 
n (%) 
xx (xx.x) 
Positive (mutated) 
n (%) 
xx (xx.x) 
Not examined 
n (%) 
xx (xx.x) 
Unknown 
n (%) 
xx (xx.x) 
 
 
 
Percentages are calculated on the number of patients (N) in the SAF analysis set. 
* Time from onset of SMA symptoms was calculated as the difference in years from the year of the date of the informed consent  
and the year of onset of SMA symptoms reported in CRF. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.4.2.1 
 


Catalyst Pharmaceuticals, Inc. 
Page 39 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.1.9.  Medical History / SAF 
 
Body System 
Statistic 
Amifampridine 
(N=xx) 
 
 
 
Cardiovascular 
n (%) 
xx (xx.x) 
Respiratory 
n (%) 
xx (xx.x) 
Muscle-Skeletal 
n (%) 
xx (xx.x) 
Ears, nose, eyes and throat 
n (%) 
xx (xx.x) 
Hepatobiliary 
n (%) 
xx (xx.x) 
Endocrine & Metabolic 
n (%) 
xx (xx.x) 
Haemapoietic 
n (%) 
xx (xx.x) 
Central nervous 
n (%) 
xx (xx.x) 
Dermatologic 
n (%) 
xx (xx.x) 
Genitourinary 
n (%) 
xx (xx.x) 
Gastrointestinal 
n (%) 
xx (xx.x) 
Psychiatric Diseases 
n (%) 
xx (xx.x) 
Allergies 
n (%) 
xx (xx.x) 
 
 
 
The counts are the number of patients with at least one “Yes” response for the body 
system. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.4.2.2 
 
Programming Note: “Other Body System” is also recorded, but is not included in the above table; it is listed only.  
 
 


Catalyst Pharmaceuticals, Inc. 
Page 40 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.1.10.  Previous Diseases from Medical History by SOC and PT / SAF  
 
_________________________________________________________________________________________________________ 
 
  System Organ Class                                 Statistic                 Amifampridine            
     Preferred Term                                                              (N=xx)        
_________________________________________________________________________________________________________ 
 
 No. of patients with at least one previous disease   n (%)       
 
 xx (xx.x%)                     
 
  System Organ Class 1                                n (%)       
 
 xx (xx.x%)                   
     Preferred Term 1                                 n (%)       
 
 xx (xx.x%)       
     Preferred Term 2                                 n (%)        
 
 xx (xx.x%)       
     Preferred Term x                                 n (%)        
 
 xx (xx.x%)       
 
  System Organ Class 2                                n (%)        
 
 xx (xx.x%)                   
     Preferred Term 1                                 n (%)        
 
 xx (xx.x%)       
     Preferred Term 2                                 n (%)        
 
 xx (xx.x%)       
     Preferred Term x                                 n (%)        
 
 xx (xx.x%)       
 
  System Organ Class x                                n (%)        
 
 xx (xx.x%)                   
     Preferred Term 1                                 n (%)       
 
 xx (xx.x%)       
     Preferred Term 2                                 n (%)       
 
 xx (xx.x%)       
     Preferred Term x                                 n (%)       
 
 xx (xx.x%)    
_________________________________________________________________________________________________________ 
Previous diseases are those reported in the “Medical History” form of the eCRF with item “Present at study start?” flagged as “No”.  
Abnormalities were coded using the MedDRA dictionary version 23. Primary System Organ Class and Preferred Term are presented. 
Patients are only counted once per SOC and PT.   
Patients can have more than one previous disease. 
Percentages are calculated on the number of patients (N) in the SAF analysis set. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.4.2.2 
 


Catalyst Pharmaceuticals, Inc. 
Page 41 of 117  
Protocol SMA-002 
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Version Date: 29JUN2020  
 
Table 14.1.11.  Concomitant Diseases from Medical History by SOC and PT / SAF  
 
_________________________________________________________________________________________________________ 
 
  System Organ Class                                 Statistic                 Amifampridine            
     Preferred Term                                                              (N=xx)        
_________________________________________________________________________________________________________ 
 
 No. of patients with at least one concomitant 
 disease                                              n (%)       
 
 xx (xx.x%)                     
 
  System Organ Class 1                                n (%)       
 
 xx (xx.x%)                   
     Preferred Term 1                                 n (%)       
 
 xx (xx.x%)       
     Preferred Term 2                                 n (%)        
 
 xx (xx.x%)       
     Preferred Term x                                 n (%)        
 
 xx (xx.x%)       
 
  System Organ Class 2                                n (%)        
 
 xx (xx.x%)                   
     Preferred Term 1                                 n (%)        
 
 xx (xx.x%)       
     Preferred Term 2                                 n (%)        
 
 xx (xx.x%)       
     Preferred Term x                                 n (%)        
 
 xx (xx.x%)       
 
  System Organ Class x                                n (%)        
 
 xx (xx.x%)                   
     Preferred Term 1                                 n (%)       
 
 xx (xx.x%)       
     Preferred Term 2                                 n (%)       
 
 xx (xx.x%)       
     Preferred Term x                                 n (%)       
 
 xx (xx.x%)    
_________________________________________________________________________________________________________ 
Concomitant diseases are those reported in the “Medical History” form of the eCRF with item “Present at study start?” flagged as “Yes” or missing.  
Abnormalities were coded using the MedDRA dictionary version 23. Primary System Organ Class and Preferred Term are presented. 
Patients are only counted once per SOC and PT.   
Patients can have more than one concomitant disease. 
Percentages are calculated on the number of patients (N) in the SAF analysis set. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.4.2.2 
 


Catalyst Pharmaceuticals, Inc. 
Page 42 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.1.12.  Physical Examination / SAF  
 
 
System 
Statistic 
Amifampridine 
(N=xx) 
 
 
 
 
Screening 
Head & Neck 
n (%) 
xx (xx.x) 
 
Eyes 
n (%) 
xx (xx.x) 
 
Ears 
n (%) 
xx (xx.x) 
 
Nose 
n (%) 
xx (xx.x) 
 
Throat 
n (%) 
xx (xx.x) 
 
Cardiovascular 
n (%) 
xx (xx.x) 
 
Dermatologic 
n (%) 
xx (xx.x) 
 
Lymphatic 
n (%) 
xx (xx.x) 
 
Respiratory 
n (%) 
xx (xx.x) 
 
Gastrointestinal 
n (%) 
xx (xx.x) 
 
Musculoskeletal 
n (%) 
xx (xx.x) 
 
 
 
 
Month 3  
Head & Neck 
n (%) 
xx (xx.x) 
 
Eyes 
n (%) 
xx (xx.x) 
 
Ears 
n (%) 
xx (xx.x) 
 
Nose 
n (%) 
xx (xx.x) 
 
Throat 
n (%) 
xx (xx.x) 
 
Cardiovascular 
n (%) 
xx (xx.x) 
 
Dermatologic 
n (%) 
xx (xx.x) 
 
Lymphatic 
n (%) 
xx (xx.x) 
 
Respiratory 
n (%) 
xx (xx.x) 
 
Gastrointestinal 
n (%) 
xx (xx.x) 
 
Musculoskeletal 
n (%) 
xx (xx.x) 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
EOS  
Head & Neck 
n (%) 
xx (xx.x) 
 
Eyes 
n (%) 
xx (xx.x) 
 
Ears 
n (%) 
xx (xx.x) 
 
Nose 
n (%) 
xx (xx.x) 
 
Throat 
n (%) 
xx (xx.x) 
 
Cardiovascular 
n (%) 
xx (xx.x) 
 
Dermatologic 
n (%) 
xx (xx.x) 
 
Lymphatic 
n (%) 
xx (xx.x) 
 
Respiratory 
n (%) 
xx (xx.x) 
 
Gastrointestinal 
n (%) 
xx (xx.x) 
 
Musculoskeletal 
n (%) 
xx (xx.x) 
 
 
 
 
The counts are the number of patients with at least one “Yes” response for the body system. 
Percentages are calculated using the number of patients with “Yes” or “No” recorded for the Body System as the denominator. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.7.4. 
Programming Note: “Other Body System” is also recorded, but is not included in the above table; it is listed only.  
 
 


Catalyst Pharmaceuticals, Inc. 
Page 43 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.1.13.  Physical Examination Abnormalities by SOC and PT / SAF  
 
________________________________________________________________________________ 
 
  System Organ Class                                 Statistic     Amifampridine                                           
     Preferred Term                                                   (N=xx)      
________________________________________________________________________________ 
 
 No. of patients with at least one abnormality        n (%)           xx (xx.x%)                    
 
  System Organ Class 1                                n (%)           xx (xx.x%)                  
     Preferred Term 1                                 n (%)           xx (xx.x%)      
     Preferred Term 2                                 n (%)           xx (xx.x%)      
     Preferred Term x                                 n (%)           xx (xx.x%)      
 
  System Organ Class 2                                n (%)           xx (xx.x%)                  
     Preferred Term 1                                 n (%)           xx (xx.x%)      
     Preferred Term 2                                 n (%)           xx (xx.x%)      
     Preferred Term x                                 n (%)           xx (xx.x%)      
 
  System Organ Class x                                n (%)           xx (xx.x%)                  
     Preferred Term 1                                 n (%)           xx (xx.x%)      
     Preferred Term 2                                 n (%)           xx (xx.x%)      
     Preferred Term x                                 n (%)           xx (xx.x%) 
________________________________________________________________________________ 
Abnormalities are those reported in the “Physical Examination” form of the eCRF.  
Abnormalities were coded using the MedDRA dictionary version 23. Primary System Organ Class and Preferred Term are presented. 
Patients are only counted once per SOC and PT.   
Patients can have more than one abnormality. 
Percentages are calculated on the number of patients (N) in the SAF analysis set. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.7.4. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 44 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.2.1.  Duration of Treatment / SAF  
 
 
Amifampridine 
(N=xx) 
 
 
Duration of treatment (days) 
 
n 
xx 
Mean (SD) 
xx.x (xx.xx) 
Median 
xx.x 
Min, Max 
xx, xx 
 
 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.5.2.1. 
 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 45 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.2.3.  Amifampridine Dosage by Visit / SAF  
 
Visit: Screening 
 
Statistic 
Amifampridine 
(N=xx) 
 
 
 
Dose frequency 
 
 
3 times per day 
n (%) 
xx (xx.x) 
4 times per day 
n (%) 
xx (xx.x) 
 
 
 
Amifampridine total daily dose (mg) 
 
 
 
n 
xx 
 
Mean (SD) 
xx.x (xx.xx) 
 
Median 
xx.x 
 
Min, Max 
xx, xx 
 
 
 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.5.1.2. 
 
 
Programming Note: This table will be repeated for all visits (Screening, End of study month 3, End of study month 6, End of study 
month 9, End of study month 12, End of study month 15, End of study month 21, End of study month 27, EoS, Extra visit).  
 
 


Catalyst Pharmaceuticals, Inc. 
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Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.2.4.  Treatment Compliance / SAF  
 
 
Statistic 
Amifampridine 
(N=xx) 
 
 
 
Compliance (%) 
n 
xx 
 
Mean (SD) 
xx.xx (xx.xxx) 
 
Median 
xx.xx 
 
Min, Max 
xx.x, xx.x 
 
 
 
Compliance is 100%*(Number consumed)/(Number prescribed). 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.5.2.1. 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 47 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.3.1.  Summary of Treatment Emergent Adverse Events (TEAEs) / SAF 
 
 
Statistic 
Amifampridine 
(N=XX) 
 
 
 
No. of patients in SAF Population                         
n 
xx 
No. of TEAEs 
n 
xx 
No. of related TEAEs 
n 
xx 
No. of serious TEAEs 
n 
xx 
No. of serious related TEAEs 
n 
xx 
No. of TEAEs leading to premature discontinuation 
n 
xx 
No. of TEAEs leading to hospitalization 
n 
xx 
No. of life-threatening TEAEs 
n 
xx 
No. of patients with at least one TEAE                         
n (%) 
xx (xx.x%) 
No. of patients with at least one related TEAE     
n (%) 
xx (xx.x%) 
No. of patients with at least one TESAE     
n (%) 
xx (xx.x%) 
No. of patients with at least one related TESAE     
n (%) 
xx (xx.x%) 
No. of patients with at least one TEAE leading to premature discontinuation 
n (%) 
xx (xx.x%) 
No. of patients hospitalized due to a TEAE 
n (%) 
xx (xx.x%) 
No. of patients with at least one life-threatening 
n (%) 
xx (xx.x%) 
No. of patients dead 
n (%) 
xx (xx.x%) 
 
TEAE = any AE started at or after the first dose of study drug for the current Long-Term Study. 
TESAE = Treatment Emergent Serious Adverse Events. 
Treatment Emergent Adverse Events (TEAE) were defined as “Related” if the relationship to study drug was assessed as “Possible” or “Probable”.  
Missing relationship category was considered as related to the study drug. 
Percentages are calculated relative to the number of patients in SAF population. 
N = number of patients, % = percentage of patients.  
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.5.1. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 48 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.3.2.  Summary of TEAEs by SOC and PT / SAF 
 
 
Statistic 
Amifampridine 
(N=XX) 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
 TEAE = any AE started at or after the first dose of study drug for the current Long-Term Study. 
 The denominator for the calculation of the percentage is the total number of patients who received the treatment 
 and the numerator is the number of patients who received the treatment with at least one TEAE in the given System Organ Class (SOC) 
 n = number of patients, % = percentage of patients, E = number of events. 
 Each patient is counted at most once within each SOC and PT. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.5.1. 
 


Catalyst Pharmaceuticals, Inc. 
Page 49 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.3.3.  Summary of Related TEAEs by SOC and PT / SAF 
 
 
Statistic 
Amifampridine 
(N=XX) 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
TEAE = any AE started at or after the first dose of study drug for the current Long-Term Study. 
 TEAEs were defined as “Related” if the relationship to study drug was assessed as “Possible” or “Probable”.  
 Missing relationship category was considered as related to the study drug. 
 The denominator for the calculation of the percentage is the total number of patients who received the treatment 
 and the numerator is the number of patients who received the treatment with at least one TEAE in the given System Organ Class (SOC) 
 n = number of patients, % = percentage of patients, E = number of events. 
 Each patient is counted at most once within each SOC and PT. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.5.3. 
 


Catalyst Pharmaceuticals, Inc. 
Page 50 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.3.4.  Summary of TESAEs by SOC and PT / SAF 
 
 
Statistic 
Amifampridine 
(N=XX) 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
TEAE = any AE started at or after the first dose of study drug for the current Long-Term Study. 
 The denominator for the calculation of the percentage is the total number of patients who received the treatment 
 and the numerator is the number of patients who received the treatment with at least one TEAE in the given System Organ Class (SOC) 
 n = number of patients, % = percentage of patients, E = number of events. 
 Each patient is counted at most once within each SOC and PT. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.5.2. 
 


Catalyst Pharmaceuticals, Inc. 
Page 51 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.3.5.  Summary of Related TESAEs by SOC and PT / SAF 
 
 
Statistic 
Amifampridine 
(N=XX) 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
TEAE = any AE started at or after the first dose of study drug for the current Long-Term Study. 
 TESAEs were defined as “Related” if the relationship to study drug was assessed as “Possible” or “Probable”.  
 Missing relationship category was considered as related to the study drug. 
 The denominator for the calculation of the percentage is the total number of patients who received the treatment 
 and the numerator is the number of patients who received the treatment with at least one TEAE in the given System Organ Class (SOC) 
 n = number of patients, % = percentage of patients, E = number of events. 
 Each patient is counted at most once within each SOC, PT. 
 
  Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.5.4. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 52 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.3.6.  Summary of TEAEs Leading to Hospitalization by SOC and PT / SAF 
 
 
Statistic 
Amifampridine 
(N=XX) 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
TEAE = any AE started at or after the first dose of study drug for the current Long-Term Study. 
 The denominator for the calculation of the percentage is the total number of patients who received the treatment 
 and the numerator is the number of patients who received the treatment with at least one TEAE in the given System Organ Class (SOC) 
 n = number of patients, % = percentage of patients, E = number of events. 
 Each patient is counted at most once within each SOC and PT. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.5.5. 
 


Catalyst Pharmaceuticals, Inc. 
Page 53 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.3.7.  Summary of Life-Threatening TEAEs by SOC and PT / SAF 
 
 
Statistic 
Amifampridine 
(N=XX) 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
TEAE = any AE started at or after the first dose of study drug for the current Long-Term Study. 
 The denominator for the calculation of the percentage is the total number of patients who received the treatment 
 and the numerator is the number of patients who received the treatment with at least one TEAE in the given System Organ Class (SOC) 
 n = number of patients, % = percentage of patients, E = number of events. 
 Each patient is counted at most once within each SOC and PT. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.5.6. 
 


Catalyst Pharmaceuticals, Inc. 
Page 54 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.3.8.  Summary of TEAEs Leading to Premature Discontinuation by SOC and PT / SAF 
 
 
Statistic 
Amifampridine 
(N=XX) 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
<Primary SOC> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
<PT> 
n (%) E 
xx (xx.x%) xx 
 
 
 
TEAE = any AE started at or after the first dose of study drug for the current Long-Term Study. 
 The denominator for the calculation of the percentage is the total number of patients who received the treatment 
 and the numerator is the number of patients who received the treatment with at least one TEAE in the given System Organ Class (SOC) 
 n = number of patients, % = percentage of patients, E = number of events. 
 Each patient is counted at most once within each SOC and PT. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.5.7. 
 


Catalyst Pharmaceuticals, Inc. 
Page 55 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.3.9.  Summary of TEAEs by SOC and PT and Maximum Severity / SAF 
 
_______________________________________________________________________________________________________ 
                                                                                   
                                  ____________________________  Amifampridine ________________________     
   
                        Statistic   Grade 1       Grade 2       Grade 3  
 Grade 4        Grade 5    
_______________________________________________________________________________________________________ 
 
<Primary SOC> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx    xx(xx.x%)xx   xx(xx.x%)xx  
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx    xx(xx.x%)xx   xx(xx.x%)xx   
 
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx    xx(xx.x%)xx   xx(xx.x%)xx   
 
 
<Primary SOC> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx    xx(xx.x%)xx   xx(xx.x%)xx  
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx    xx(xx.x%)xx   xx(xx.x%)xx   
 
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx    xx(xx.x%)xx   xx(xx.x%)xx   
 
 
<Primary SOC> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx    xx(xx.x%)xx   xx(xx.x%)xx  
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx    xx(xx.x%)xx   xx(xx.x%)xx   
 
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx    xx(xx.x%)xx   xx(xx.x%)xx   
 
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx    xx(xx.x%)xx   xx(xx.x%)xx   
 
_______________________________________________________________________________________________________ 
TEAE = any AE started at or after the first dose of study drug for the current Long-Term Study. 
The denominator for the calculation of the percentage is the total number of patients who received the treatment 
and the numerator is the number of patients who received the treatment with at least one TEAE in the given System Organ Class (SOC) 
n = number of patients, % = percentage of patients, E = number of events. 
Each patient is counted at most once within each SOC and PT. 
If a patient experienced more than one TEAE with the same PT or primary SOC, the TEAE with the maximum severity was counted.  
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.5.1. 
 


Catalyst Pharmaceuticals, Inc. 
Page 56 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.3.10.  Summary of TEAEs by SOC and PT and Relationship to Treatment / SAF 
 
___________________________________________________________________________ 
                                                                         
                                  __________  Amifampridine ______________     
   
                        Statistic  Not related   Possibly      Probably  
  
___________________________________________________________________________ 
 
<Primary SOC> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx     
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx     
 
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx     
 
 
<Primary SOC> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx     
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx     
 
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx     
 
 
<Primary SOC> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx     
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx     
 
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx     
 
<PT> 
 
n (%) E  xx(xx.x%)xx   xx(xx.x%)xx   xx(xx.x%)xx     
 
___________________________________________________________________________ 
TEAE = any AE started at or after the first dose of study drug for the current Long-Term Study. 
The denominator for the calculation of the percentage is the total number of patients who received the treatment 
and the numerator is the number of patients who received the treatment with at least one TEAE in the given System Organ Class (SOC) 
n = number of patients, % = percentage of patients, E = number of events. 
Each patient is counted at most once within each SOC and PT. 
If a patient experienced more than one TEAE with the same PT or primary SOC, the TEAE with the worst relationship was counted.  
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.5.1. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 57 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.4.1.  Summary of Clinical Laboratory Tests: Haematology / SAF  
 ____________________________________________________________________________________________ 
 
                _________ Actual Values ___________      _______ Change from Screening ______              
 Visit          n   Mean   SD    Min   Median  Max       n   Mean   SD    Min   Median  Max   
 ____________________________________________________________________________________________ 
 
 Screening      xx  xx.x   xx.x  xx.x  xx.x    xx.x       
 Month 3        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x    
 Month 6        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x    
 Month 9        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 12       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 15       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 21       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 27       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 EOS            xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
_____________________________________________________________________________________________ 
 Change from Screening includes only those patients with both a Screening value and a value for summarized time period. 
 n represents number of patients contributing to summary statistics. 
 Source: xxx.sas, Run on ddmmmyyyy 
 Reference Listings: 16.2.6.2. 
 
 Programming Notes: Continue for the following haematology parameters: 
a) Haemoglobin  
b) Haematocrit  
c) WBC count 
d) RBC count 
e) Platelet count 
f) Differential cell count  
Values must be presented in SI unit. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 58 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.4.2.  Summary of Clinical Laboratory Tests: Blood Chemistry / SAF  
_____________________________________________________________________________________________ 
 
                _________ Actual Values ___________      _______ Change from Screening ______              
 Visit          n   Mean   SD    Min   Median  Max       n   Mean   SD    Min   Median  Max   
 ____________________________________________________________________________________________ 
 
 Screening      xx  xx.x   xx.x  xx.x  xx.x    xx.x       
 Month 3        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x    
 Month 6        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x    
 Month 9        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 12       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 15       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 21       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 27       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 EOS            xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
_____________________________________________________________________________________________ 
 Change from Screening includes only those patients with both a Screening value and a value for summarized time period. 
 n represents number of patients contributing to summary statistics. 
  
 Source: xxx.sas, Run on ddmmmyyyy 
 Reference Listings: 16.2.6.1. 
 
 Programming Notes: Continue for the following blood chemistry parameters: 
g) Albumin  
h) Alkaline phosphatase  
i) ALT (SGPT) 
j) AST (SGOT) 
k) Direct bilirubin 
l) Total bilirubin 
m) BUN 
n) Calcium 
o) Chloride 
p) Total cholesterol 
q) Bicarbonate 
r) Creatine phosphokinase 
s) Creatinine 
t) Glucose 
u) GGT 
v) LDH 
w) Phosphorus 
x) Potassium 
y) Total protein  
z) Sodium  
aa) Uric Acid 
Values must be presented in SI unit. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 59 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.4.3.  Summary of Haematology Shift Result Relative to the Normal Range / SAF  
 
 
Parameter (Units) 
 
Visit 
 
  
_________________ Screening ____________________ 
       Low              Normal             High 
 
 
 
 
 
 
Haemoglobin (g/L) 
Month 3 
n 
xx 
xx 
xx 
 
 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
… 
n 
xx 
xx 
xx 
 
 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
EOS 
n 
xx 
xx 
xx 
 
 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.6.2. 
 
Programming Notes: Continue for all Haematology parameters.  
 
 


Catalyst Pharmaceuticals, Inc. 
Page 60 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.4.4.  Summary of Blood Chemistry Shift Result Relative to the Normal Range / SAF  
 
 
Parameter (Units) 
 
Visit 
 
  
_________________ Screening ____________________ 
       Low              Normal             High 
 
 
 
 
 
 
AST (U/L) 
Month 3 
n 
xx 
xx 
xx 
 
 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
… 
n 
xx 
xx 
xx 
 
 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
EOS 
n 
xx 
xx 
xx 
 
 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.6.1. 
 
Programming Notes: Continue for all Blood Chemistry parameters.  
 
 


Catalyst Pharmaceuticals, Inc. 
Page 61 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.5.1.  Summary of Vital Signs: Systolic Blood Pressure / SAF  
_____________________________________________________________________________________________ 
 
                _________ Actual Values ___________      _______ Change from Screening ______              
 Visit          n   Mean   SD    Min   Median  Max       n   Mean   SD    Min   Median  Max   
 ____________________________________________________________________________________________ 
 
 Screening      xx  xx.x   xx.x  xx.x  xx.x    xx.x       
 Month 3        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x    
 Month 6        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x    
 Month 9        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 12       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 15       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 21       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 27       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 EOS            xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
_____________________________________________________________________________________________ 
 Change from Baseline includes only those patients with both a Baseline value and a value for summarized time period. 
 n represents number of patients contributing to summary statistics. 
 
 Source: xxx.sas, Run on ddmmmyyyy 
 Reference Listings: 16.2.7.2. 
 
 Programming Notes: Continue for the following parameters: 
a) Diastolic Blood Pressure (mmHg) 
b) Heart Rate (beats/min) 
c) Respiration Rate (breaths/min) 
d) Body Temperature (°C) 
e) Body weight (Kg) 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 62 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.5.2.  12-Lead ECG / SAF  
 
 
 
Statistic 
Amifampridine 
(N=XX) 
 
 
 
Screening 
 
xx (x.x) 
Normal tracing  
 n (%) 
xx (x.x) 
Abnormal tracing, NCS 
 n (%) 
xx (x.x) 
Abnormal tracing, CS 
 n (%) 
xx (x.x) 
Unknown 
 n (%) 
xx (x.x) 
 
 
 
Month 3 
 
xx (x.x) 
Normal tracing  
 n (%) 
xx (x.x) 
Abnormal tracing, NCS 
 n (%) 
xx (x.x) 
Abnormal tracing, CS 
 n (%) 
xx (x.x) 
Unknown 
 n (%) 
xx (x.x) 
 
 
 
… 
 
 
 
 
 
EOS 
 
xx (x.x) 
Normal tracing  
 n (%) 
xx (x.x) 
Abnormal tracing, NCS 
 n (%) 
xx (x.x) 
Abnormal tracing, CS 
 n (%) 
xx (x.x) 
Unknown 
 n (%) 
xx (x.x) 
CS: Clinically Significant. 
NCS: Not Clinically Significant. 
 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.7.3. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 63 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.5.3.  Childbearing Potential and Pregnancy Test / SAF 
_________________________________________________________________________________ 
                                                               Amifampridine 
Visit                                                 Statistic    (N=xx)         
_________________________________________________________________________________ 
 
Screening         Childbearing potential  
 Patient male                         n (%)      xx (xx.x%)     
 Menopause                            n (%)      xx (xx.x%)    
 Sterilized                           n (%)      xx (xx.x%)    
 Total hysterectomy                   n (%)      xx (xx.x%)    
 No contraception protection          n (%)      xx (xx.x%)    
 Contraception protection             n (%)      xx (xx.x%)    
 Child                                n (%)      xx (xx.x%)    
 Unknown                              n (%)      xx (xx.x%)    
 
Pregnancy test performed? 
 No                                   n (%)      xx (xx.x%)    
 Yes                                  n (%)      xx (xx.x%)    
 Not applicable                       n (%)      xx (xx.x%)    
 
Type of pregnancy test (#)  
 Urine dipstick                       n (%)      xx (xx.x%)    
 Serum                                n (%)      xx (xx.x%)    
 Unknown                              n (%)      xx (xx.x%)    
 
Pregnancy test result (#) 
 Negative                             n (%)      xx (xx.x%)    
 Positive                             n (%)      xx (xx.x%)    
 Unknown                              n (%)      xx (xx.x%)    
_________________________________________________________________________________ 
Percentages are calculated on the number of patients (N) in the SAF analysis set. 
# Percentages are based on the number of female patients performing pregnancy test. 
Source: xxx.sas, Run on ddmmmyyyy 
Reference Listings: 16.2.7.1. 
 
Programming Notes: To be repeated for Month 3, Month 6, Month 9, Month 12, Month 15, Month 21, Month 27 and EOS visits.  
 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 64 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
  Table 14.6.1.  Summary of INQoL: Weakness / ITTQOL  
_____________________________________________________________________________________________ 
 
                _________ Actual Values ___________      _______ Change from Screening ______              
 Visit          n   Mean   SD    Min   Median  Max       n   Mean   SD    Min   Median  Max   
 ____________________________________________________________________________________________ 
 
 Screening      xx  xx.x   xx.x  xx.x  xx.x    xx.x       
 Month 3        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x    
 Month 6        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 9        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 12       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 15       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 21       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 27       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 EOS            xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
_____________________________________________________________________________________________ 
 Change from Baseline includes only those patients with both a Baseline value and a value for summarized time period. 
 n represents number of patients contributing to summary statistics. 
 
 Source: xxx.sas, Run on ddmmmyyyy 
 Reference Listings: 16.2.7.4.1., 16.2.7.4.2., 16.2.7.4.3., 16.2.7.4.4., 16.2.7.4.5., 16.2.7.4.6. 
 
 Programming Notes: Continue for all INQoL domains: 
a) Symptoms (section 1): Muscle “locking”, Pain, Fatigue, Droopy eyelids, Double vision, and Swallowing difficulties. 
b) Life domains (section 2): Activities, Independence, Social relationship, Emotions, and Body image. 
c) Life domains (section 3): Perceived treatment effects and Expected treatment effects. 
d) Quality of Life.  
e) Provide graphs of means and SD values over the study as follows: 
 
Plot Means with Standard Deviations Bars
Time (months)
0
3
6
9
12
15
21
27
30
Score
0
10
20
30
40
50
60
 


Catalyst Pharmaceuticals, Inc. 
Page 65 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Table 14.6.2.  Summary of PEDSQL: About my Neuromuscular Disease / ITTQOL 
_____________________________________________________________________________________________ 
 
                _________ Actual Values ___________      _______ Change from Screening ______              
 Visit          n   Mean   SD    Min   Median  Max       n   Mean   SD    Min   Median  Max   
 ____________________________________________________________________________________________ 
 
 Screening      xx  xx.x   xx.x  xx.x  xx.x    xx.x       
 Month 3        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x    
 Month 6        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 9        xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 12       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 15       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 21       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 Month 27       xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
 EOS            xx  xx.x   xx.x  xx.x  xx.x    xx.x      xx  xx.x   xx.x  xx.x  xx.x    xx.x 
_____________________________________________________________________________________________ 
 Change from Baseline includes only those patients with both a Baseline value and a value for summarized time period. 
 n represents number of patients contributing to summary statistics. 
 
 Source: xxx.sas, Run on ddmmmyyyy 
 Reference Listings: 16.2.7.1.1., 16.2.7.1.2., 16.2.7.2.1., 16.2.7.2.2., 16.2.7.3.1., 16.2.7.3.2. 
 
 Programming Notes: Continue for all PEDSQL domains: 
a) Communication 
b) About our family resources 
c) Total score 
d) Provide graphs of means and SD values over the study as follows: 
 
 
Plot Means with Standard Deviations Bars
Time (months)
0
3
6
9
12
15
21
27
30
Score
0
10
20
30
40
50
60
 


Catalyst Pharmaceuticals, Inc. 
Page 66 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
 
 
Listing 16.2.1.  Completed and Discontinued Patients with Primary Reason for Discontinuation 
 
Site 
Patient 
SAF 
population 
ITTQOL 
population 
Complete the 
treatment? 
(1) 
If No, primary reason for 
discontinuation 
If reason is AE, Major 
Protocol Deviation, or 
Other Reason, specify 
If reason is Consent 
Withdrawal, specify 
the date 
xxx 
xxx 
Yes 
Yes 
Yes 
 
 
 
xxx 
xxx 
Yes 
Yes 
Yes 
 
 
 
xxx 
xxx 
No 
No 
No 
Consent Withdrawal 
 
DDMMMYYYY 
xxx 
xxx 
Yes 
Yes 
No 
Adverse event 
Xxxxxxxxxx 
 
xxx 
xxx 
Yes 
Yes 
No 
xxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
SAF=Safety Population 
ITTQOL=Efficacy Population 
 
(1) Did the patient complete the full course of treatment?  
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Note: Sort by site and patient number. 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 67 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.2.1  Inclusion Criteria 
 
 
Individuals eligible to participate in this study must meet all the following inclusion criteria:  
1 Participated in the SMA-001 study 
2 Willing and able to provide written informed consent after the nature of the study has been explained and before the start of any 
research-related procedures. 
3 Female patients of childbearing potential defined according to the Clinical Trial Facilitation Group - CTFG guidelines# must have a 
negative pregnancy test (urine human chorionic gonadotropin [HCG] at the end of SMA-001 study); and must practice an effective, reliable 
contraceptive regimen during the study and for up to 30 days following discontinuation of treatment 
4 Ability to participate in the study based on overall health of the patient and disease prognosis, as applicable, in the opinion of the 
Investigator; and able to comply with all requirements of the protocol, including completion of study questionnaires. 
 
 
 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 68 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.2.1.  Inclusion Criteria 
 
 
 
 
 
 
Criterion (1) 
Site 
Patient 
Date of visit 
Consent date 
Study Subject ID 
in SMA-001 study 
 
1. 
2. 
3. 
4. 
xxx 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
  See first page for criteria. 
  (1) Response for each criterion: Yes, No, Not Applicable 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Note: Sort by site and patient number. Place the criteria on the first page. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 69 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.2.2.  Exclusion Criteria 
 
 
Individuals who meet any of the following exclusion criteria are not eligible to participate in the study:  
[According to Study Protocol version 2.0] 
1 Epilepsy and currently on medication. 
2 Uncontrolled asthma. 
3 Concomitant use with sultopride. 
4 Concomitant use with medicinal products with a narrow therapeutic window. 
5 Concomitant use with medicinal products with a known to cause QTc prolongation. 
6 Clinically significant abnormalities in 12 lead ECG, in the opinion of the Investigator. 
7 Subjects with congenital QT syndromes. 
8 Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study. 
9 Intolerable amifampridine-related side effects   
10 Treatment with an investigational drug (other than amifampridine) or device while participating in this study. 
11 Any medical condition that, in the opinion of the Investigator, might interfere with the patient’s participation in the study, poses an added risk for the patient, 
or confound the assessment of the patient. 
12 History of drug allergy to any pyridine-containing substances or any amifampridine excipient(s). 
[According to Study Protocol version 3.0] 
1 Epilepsy and currently on medication. 
2 Uncontrolled asthma. 
3 Concomitant use with sultopride. 
4 Concomitant use with medicinal products with a narrow therapeutic window. 
5 Clinically significant abnormalities in 12 lead ECG, in the opinion of the Investigator. 
6 Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study. 
7 Intolerable amifampridine-related side effects   
8 Treatment with an investigational drug (other than amifampridine) or device while participating in this study. 
9 Any medical condition that, in the opinion of the Investigator, might interfere with the patient’s participation in the study, poses an added risk for the patient, 
or confound the assessment of the patient. 
10 History of drug allergy to any pyridine-containing substances or any amifampridine excipient(s). 
 
 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 70 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.2.2.  Exclusion Criteria 
 
 
 
 
 
 
 
Criterion (1) 
Site 
Patient 
Date of visit 
Consent date 
Protocol version 
1. 
2. 
3. 
4. 
5. 
6. 
7. 
8. 
9. 
10. 
11. 
12
xxx 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xx
xxx 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xx
xxx 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xx
xxx 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xx
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  See first page for criteria. 
  (1) Response for each criterion: Yes, No, Not Applicable 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Note: Sort by site and patient number. Place the criteria on the first page. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 71 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.3.1.  Protocol Deviations 
 
Site 
Patient 
 
PD number 
Deviation 
date 
Date 
identified 
Deviation 
identified 
by 
 
Deviation 
description 
 
Follow-up/ 
Resolution 
Type of 
deviation 
xxx 
xxx 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
Xxxxxxxxxx 
Xxxxxxxxxx 
Major 
xxx 
xxx 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
Xxxxxxxxxx 
Xxxxxxxxxx 
Minor 
xxx 
xxx 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
Xxxxxxxxxx 
Xxxxxxxxxx 
xxxxxxxxxx 
 
 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
Xxxxxxxxxx 
Xxxxxxxxxx 
xxxxxxxxxx 
 
 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
Xxxxxxxxxx 
Xxxxxxxxxx 
xxxxxxxxxx 
xxx 
xxx 
xxx 
DDMMMYYYY 
DDMMMYYYY 
xxx 
Xxxxxxxxxx 
Xxxxxxxxxx 
xxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Note: Sort by site and patient number and deviation date. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 72 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.3.2.  Patients Excluded from the Analysis Populations 
 
Site 
Patient 
Set from which patient 
is excluded (1) 
Reason for exclusion 
xxx 
xxx 
xxxxxxx 
Xxxxxxx 
xxx 
xxx 
xxxxxxx 
Xxxxxxx 
xxx 
xxx 
xxxxxxx 
Xxxxxxx 
xxx 
xxx 
xxxxxxx 
Xxxxxxx 
 
 
 
 
(1) SAF=Safety Population, ITTQOL=Efficacy Population 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Note: Sort by site and patient number. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 73 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.4.  Demographic Characteristics 
 
Site 
Patient 
Age 
(years) 
Date of birth 
Race 
If Other, 
specify 
Gender 
Height 
(cm) 
Weight 
(kg) 
BMI 
(kg/cm^2) 
xxx 
xxx 
xx 
DDMMMYYYY 
xxxxx 
 
xxxxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xx 
DDMMMYYYY 
xxxxx 
 
xxxxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xx 
DDMMMYYYY 
xxxxx 
 
xxxxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xx 
DDMMMYYYY 
Other 
Xxxxx 
xxxxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Note: Sort by site and patient number. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 74 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.4.2.1.  Medical History: SMA Characteristics 
 
Site 
Patient 
Year of onset of 
SMA symptoms 
Was the patient 
previously treated 
for SMA other than 
amifampridine 
phosphate? 
If YES, 
treatment 
specify 
Date of SMN 
gene analysis 
SMN gene analysis 
result 
xxx 
xxx 
xx 
xxx 
xxx 
DDMMMYYYY 
xxxxx 
xxx 
xxx 
xx 
xxx 
xxx 
DDMMMYYYY 
xxxxx 
xxx 
xxx 
xx 
xxx 
xxx 
DDMMMYYYY 
xxxxx 
xxx 
xxx 
xx 
xxx 
xxx 
DDMMMYYYY 
xxxxx 
 
 
 
 
 
 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Note: Sort by site and patient number. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 75 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.4.2.2.  Medical History: Previous and Concomitant Diseases 
 
Site 
Patient 
Body system 
Involved 
(1) 
If Yes, 
specify 
diagnosis 
System Organ 
Class 
Preferred 
Term 
Onset date 
Present at 
study start? 
(2) 
xxx 
xxx 
Cardiovascular 
Yes 
xxxxxxxxx 
xxxxxxxxx 
xxxxxxxxx 
DDMMMYYYY 
xxx 
 
 
Respiratory 
No 
 
 
 
 
 
 
 
Muscle-Skeletal 
No 
 
 
 
 
 
 
 
Ears, nose, eyes and throat 
Yes 
xxxxxxxxx 
xxxxxxxxx 
xxxxxxxxx 
DDMMMYYYY 
xxx 
 
 
. 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
Cardiovascular 
Yes 
xxxxxxxxx 
xxxxxxxxx 
xxxxxxxxx 
DDMMMYYYY 
xxx 
 
 
Respiratory 
Yes 
xxxxxxxxx 
xxxxxxxxx 
xxxxxxxxx 
DDMMMYYYY 
xxx 
 
 
Muscle-Skeletal 
Yes 
xxxxxxxxx 
xxxxxxxxx 
xxxxxxxxx 
DDMMMYYYY 
xxx 
 
 
Ears, nose, eyes and throat 
Yes 
xxxxxxxxx 
xxxxxxxxx 
xxxxxxxxx 
DDMMMYYYY 
xxx 
 
 
. 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(1) Involved: No, Yes, Not Examined 
(2) Present at study start: No, Yes, UNK 
Source: [program name].sas, Run on ddmmmyyyy. 
 
Programming Notes: Continue for Other Body systems (“Hepatobiliary”, “Endocrine & Metabolic”, 
“Haemapoietic”, “Central Nervous”, “Dermatologic”, “Genitourinary”, “Gastrointestinal”, “Psychiatric 
Diseases”, “Allergies” and “Other Body System”). There may be multiple entries for “Other”.  
Sort by site and patient number. 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 76 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.5.1.1.  Amifampridine Treatment at Screening 
 
Site 
Patient 
Screening 
failure? 
Are all 
inclusion and 
exclusion 
criteria 
satisfied? 
Inclusion/
Exclusion 
criteria 
number(s) 
not met 
First 
dose 
(mg) 
Timing 
of first 
dose 
(hh:mm) 
Second 
dose 
(mg) 
Timing of 
second 
dose 
(hh:mm) 
Third 
dose 
(mg) 
Timing of 
third 
dose 
(hh:mm) 
Fourth 
dose 
prescr
ibed? 
Fourth 
dose 
(mg) 
Timing of 
fourth 
dose 
(hh:mm) 
Total 
daily 
dose 
(mg) 
Date of 
adminsitr
ation of 
the first
dose 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xx:xx 
xxx 
xx:xx 
xxx 
xx:xx 
xxx 
xxx 
xx:xx 
xxx 
DDMMMYYYY
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xx:xx 
xxx 
xx:xx 
xxx 
xx:xx 
xxx 
xxx 
xx:xx 
xxx 
DDMMMYYYY
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xx:xx 
xxx 
xx:xx 
xxx 
xx:xx 
xxx 
xxx 
xx:xx 
xxx 
DDMMMYYYY
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xx:xx 
 
 
 
 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Note: Sort by site and patient number. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 77 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.5.1.2.  Amifampridine Treatment Over the Study 
 
Site 
Patient 
First 
dose 
(mg) 
Timing 
of first 
dose 
(hh:mm) 
Second 
dose 
(mg) 
Timing of 
second 
dose 
(hh:mm) 
Third 
dose 
(mg) 
Timing of 
third 
dose 
(hh:mm) 
Fourth 
dose 
prescr
ibed? 
Fourth 
dose 
(mg) 
Timing of 
fourth 
dose 
(hh:mm) 
Total 
daily 
dose 
(mg) 
xxx 
xxx 
xxx 
xx:xx 
xxx 
xx:xx 
xxx 
xx:xx 
xxx 
xxx 
xx:xx 
xxx 
xxx 
xxx 
xxx 
xx:xx 
xxx 
xx:xx 
xxx 
xx:xx 
xxx 
xxx 
xx:xx 
xxx 
xxx 
xxx 
xxx 
xx:xx 
xxx 
xx:xx 
xxx 
xx:xx 
xxx 
xxx 
xx:xx 
xxx 
xxx 
xxx 
xxx 
xx:xx 
 
 
 
 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Note: Sort by site and patient number. 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 78 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.5.2.1  Duration and Compliance over the Study 
 
Site 
Patient 
Number of 
tablets 
dispensed  
Number of 
tablets 
used 
 
Treatment 
duration 
(days) 
 
Compliance 
(%) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx.x 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx.x 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx.x 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx.x 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx.x 
 
 
 
 
 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
Programming Notes: Sort by site and patient number. Number of Tablets Dispensed, Number of Tablets Used, 
and Treatment Duration are totals from next listing. Compliance is determined from these totals. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 79 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.5.2.2  Study Drug Accountability  
 
Site 
Patient 
Date of IP 
dispensing 
 
 
Visit 
 (1) 
 
 
Box kit 
number 
No. of 
tablets 
dispensed 
Start date of 
period covered 
with this box  
End date of 
period covered 
with this box 
No. of 
tablets 
returned  
No. of 
tablets 
used 
No. of 
tablets 
lost 
Total tablets 
used, returned 
and lost  
(calculated) 
Divided in 
the 
following 
frequency 
(2) 
Total 
daily 
dose 
(mg) 
(3) 
xxx 
xxx 
DDMMMYYYY 
xx 
xx 
xx 
DDMMMYYYY 
DDMMMYYYY 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
DDMMMYYYY 
xx 
xx 
xx 
DDMMMYYYY 
DDMMMYYYY 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
DDMMMYYYY 
xx 
xx 
xx 
DDMMMYYYY 
DDMMMYYYY 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
DDMMMYYYY 
xx 
xx 
xx 
DDMMMYYYY 
DDMMMYYYY 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
DDMMMYYYY 
xx 
xx 
xx 
DDMMMYYYY 
DDMMMYYYY 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
DDMMMYYYY 
xx 
xx 
xx 
DDMMMYYYY 
DDMMMYYYY 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(1) Visit: Screening, End of study month 3, End of study month 6, End of study month 9, End of study month 12, End of study month 15, End of study month 
21, End of study month 27, EoS, Extra visit  
(2) Divided in the following frequency: 3 times per day, 4 times per day 
(3) Total Daily Dose (mg): 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
Programming Note: Sort by site and patient number and date of IP dispensing. 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 80 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.6.1.  Quality of Life (QoL): Type of Questionnaire 
 
Site 
Patient 
Visit 
QoL 
questionnaire 
performed? 
If No, 
specify 
reason 
Date of 
test 
performed 
Time of test 
performed 
(hh:mm) 
Type of 
questionnaire 
(1) 
xxx 
xxx 
Screening 
xxx 
 
DDMMMYYYY 
xx:xx 
xxxxxxxxx 
 
 
Month 3 
xxx 
 
DDMMMYYYY 
xx:xx 
xxxxxxxxx 
 
 
Month 6 
xxx 
 
DDMMMYYYY 
xx:xx 
xxxxxxxxx 
 
 
Month 9 
No 
xxxxxxxxx 
 
 
 
 
 
… 
xxx 
 
DDMMMYYYY 
xx:xx 
xxxxxxxxx 
 
 
EOS 
xxx 
 
DDMMMYYYY 
xx:xx 
xxxxxxxxx 
 
 
 
 
 
 
 
 
xxx 
xxx 
Screening 
xxx 
 
DDMMMYYYY 
xx:xx 
xxxxxxxxx 
 
 
Month 3 
xxx 
 
DDMMMYYYY 
xx:xx 
xxxxxxxxx 
 
 
Month 6 
xxx 
 
DDMMMYYYY 
xx:xx 
xxxxxxxxx 
 
 
Month 9 
xxx 
 
DDMMMYYYY 
xx:xx 
xxxxxxxxx 
 
 
… 
xxx 
 
DDMMMYYYY 
xx:xx 
xxxxxxxxx 
 
 
EOS 
xxx 
 
DDMMMYYYY 
xx:xx 
xxxxxxxxx 
 
 
 
 
 
 
 
 
(1) Type of questionnaire: PEDSQL Parent Report for Young Child (ages 5-7), PEDSQL Parent Report for Child (ages 8-12), PEDSQL teen (ages 13-18), INQOL 
(ages > 18) 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and visit. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 81 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.1.1  PEDSQL Parent Report for Young Child (5-7 years): About My Child’s Neuromuscular Disease (Items from 1 to 17) 
 
 
 
 
Items Section About My Child’s Neuromuscular Disease (1) 
Site 
Patient 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
xxx 
xxx 
Screening 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Month 3 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Month 6 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Month 9 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
… 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
EOS 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Statements are given after the next listing. 
(1) Each item response: 1=Never, 2=Almost never, 3=Sometimes, 4=Often, 5=Almost always, -1=UNK 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and visit. 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 82 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.1.2.  PEDSQL Parent Report for Young Child (5-7 years): Communication (Items from 1 to 3), About our Family Resources (Items from 1 to 5) 
and Questionnaire Scores 
 
 
 
 
Items Section 
Communication (1) 
Items Section About our Family 
Resources (1)             
Score 
Site 
Patient 
Visit 
1 
2 
3 
 
1 
2 
3 
4 
5 
  
Score section 1 Score section 2 Score section 3 
Total score 
xxx 
xxx 
Screening 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
Month 3 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
Month 6 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
Month 9 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
… 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
EOS 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
 
 
 
 
   
 
 
 
 
  
 
 
 
 
Items follow this listing. 
(1) Each item response: 1=Never, 2=Almost never, 3=Sometimes, 4=Often, 5=Almost always, -1=UNK 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and visit. 
 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 83 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
PEDSQL Parent Report for Young Child (5-7 years) Items 
About My Child’s neuromuscular disease 
1 
It’s hard for my child to breathe 
2 
My child gets sick easily 
3 
My child gets sores and/or rashes 
4 
My child's leg hurt 
5 
My child feels tired 
6 
My child's back feels stiff 
7 
My child wakes up tired 
8 
My child's hands are weak 
9 
It is hard for my child to use the bathroom 
10 
It's hard for my child to gain/lose weight when he/she wants to 
11 
It’s hard for my child to use his/her hands 
12 
It’s hard for my child to swallow food 
13 
It takes my child a long time to bathe/shower 
14 
My child gets hurt accidentally 
15 
My child takes a long time to eat 
16 
It’s hard for my child to turn him/herself during the night 
17 
It’s hard for my child to go places with his/her equipment 
 
Communication 
1 
It’s hard for my child to tell the doctors/nurses how he/she feels 
2 
It’s hard for my child to ask the doctors/nurses questions 
3 
It’s hard for my child to explain his/her illness to other people 
 
About our Family Resources 
1 
It’s hard for our family to plan activities like vacations 
2 
It’s hard for our family to get enough rest 
3 
I think money is a problem in our family 
4 
I think our family has a lot of problems 
5 
My child does not have the equipment he/she needs 
 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 84 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.2.1.  PEDSQL Parent Report for Child (8-12 years): About My Child’s Neuromuscular Disease (Items from 1 to 17) 
 
 
 
 
Items Section About My Child’s Neuromuscular Disease (1) 
Site 
Patient 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
xxx 
xxx 
Screening 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Month 3 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Month 6 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Month 9 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
… 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
EOS 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Statements are given after the next listing. 
(1) Each item response: 1=Never, 2=Almost never, 3=Sometimes, 4=Often, 5=Almost always, -1=UNK 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and visit. 
 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 85 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.2.2.  PEDSQL parent Report for Child (8-12 years): Communication (Items from 1 to 3), About our Family Resources (Items from 1 to 5) and 
Questionnaire Scores 
 
 
 
 
Items Section 
Communication (1) 
Items Section About our Family 
Resources (1)             
Score 
Site 
Patient 
Visit 
1 
2 
3 
 
1 
2 
3 
4 
5 
  
Score section 1 Score section 2 Score section 3 
Total score 
xxx 
xxx 
Screening 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
Month 3 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
Month 6 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
Month 9 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
… 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
EOS 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
 
 
 
 
   
 
 
 
 
  
 
 
 
 
Items follow this listing. 
(1) Each item response: 1=Never, 2=Almost never, 3=Sometimes, 4=Often, 5=Almost always, -1=UNK 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and visit. 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 86 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
PEDSQL parent Report for Child (8-12 years) Items 
About My Child’s neuromuscular disease 
1 
It’s hard for my child to breathe 
2 
My child gets sick easily 
3 
My child gets sores and/or rashes 
4 
My child's leg hurt 
5 
My child feels tired 
6 
My child's back feels stiff 
7 
My child wakes up tired 
8 
My child's hands are weak 
9 
It is hard for my child to use the bathroom 
10 
It's hard for my child to gain/lose weight when he/she wants to 
11 
It’s hard for my child to use his/her hands 
12 
It’s hard for my child to swallow food 
13 
It takes my child a long time to bathe/shower 
14 
My child gets hurt accidentally 
15 
My child takes a long time to eat 
16 
It’s hard for my child to turn him/herself during the night 
17 
It’s hard for my child to go places with his/her equipment 
 
Communication 
1 
It’s hard for my child to tell the doctors/nurses how he/she feels 
2 
It’s hard for my child to ask the doctors/nurses questions 
3 
It’s hard for my child to explain his/her illness to other people 
 
About our Family Resources 
1 
It’s hard for our family to plan activities like vacations 
2 
It’s hard for our family to get enough rest 
3 
I think money is a problem in our family 
4 
I think our family has a lot of problems 
5 
My child does not have the equipment he/she needs 
 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 87 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.3.1. PEDSQL Teen Report (13-18 years): About My Neuromuscular Disease (Items from 1 to 17) 
 
 
 
 
Items section About My Neuromuscular Disease (1) 
Site 
Patient 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
xxx 
xxx 
Screening 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Month 3 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Month 6 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Month 9 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
… 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
EOS 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Statements are given after the next listing. 
(1) Each item response: 1=Never, 2=Almost never, 3=Sometimes, 4=Often, 5=Almost always, -1=UNK 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and visit. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 88 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.3.2.  PEDSQL Teen Report (13-18 years): Communication (Items from 1 to 3), About our Family Resources (Items from 1 to 5) and Questionnaire 
Scores 
 
 
 
 
Items Section 
Communication (1) 
Items Section About our Family 
Resources (1)             
Score 
Site 
Patient 
Visit 
1 
2 
3 
 
1 
2 
3 
4 
5 
  
Score section 1 Score section 2 Score section 3 
Total score 
xxx 
xxx 
Screening 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
Month 3 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
Month 6 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
Month 9 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
… 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
EOS 
xx 
xx 
xx 
  xx 
xx 
xx 
xx 
xx 
  
xx 
xx 
xx 
xx 
 
 
 
 
 
 
   
 
 
 
 
  
 
 
 
 
Items follow this listing. 
(1) Each item response: 1=Never, 2=Almost never, 3=Sometimes, 4=Often, 5=Almost always, -1=UNK 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and visit. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 89 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
PEDSQL Teen Report (13-18 years) Items 
About My Neuromuscular Disease 
1 
It's hard to breathe 
2 
I get sick easily 
3 
I get sores and/or rashes 
4 
My legs hurt 
5 
I feel tired 
6 
My back feels stiff 
7 
I wake up tired 
8 
My hands are weak 
9 
It's hard to use the bathroom 
10 
It's hard to gain or lose weight when I want to 
11 
It's hard to use my hands 
12 
It's hard to swallow food 
13 
It takes me a long time to bathe or shower 
14 
I get hurt accidentally 
15 
I take a long time to eat 
16 
It's hard to turn myself during the night 
17 
It's hard for me to go places with my equipment 
 
Communication 
1 
It's hard for me to tell the doctors and nurses how I feel 
2 
It's hard for me to ask the doctors and nurses questions 
3 
It's hard for me to explain my illness to other people 
 
About our Family Resources 
1 
It's hard for my family to plan activities like vacations 
2 
It's hard for my family to get enough rest 
3 
I think money is a problem in our family 
4 
I think my family has a lot of problems 
5 
I do not have the equipment I need 
 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 90 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.4.1.  INQOL: Items from Section 1-1 to Section 1-5C 
 
 
 
 
Items section 1 
Site 
Patient 
Visit 
1 
1A 
1B 
1C 
2 
2A 
2B 
2C 
3 
3A 
3B 
3C 
4 
4A 
4B 
4C 
5 
5A 
5B 
5C 
xxx 
xxx 
Screening 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Month 3 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Month 6 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Month 9 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
… 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
EOS 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Statements are given after the next listings. 
Items 1/2/3/4/5 response: 1=Yes, 0=No, -1=UNK 
Items 1A/2A/3A/4A/5A response: 1=Very little, 2=Some, 3=A fair amount, 4=A moderate amount, 5=A considerable amount, 6=A lot, 7=An extreme amount, 
 -1=UNK 
Items 1B/2B/3B/4B/5B response: 0=Not at all, 1=Some, 2=A fair amount, 3=A moderate amount, 4=A considerable amount, 5=Very many, 6=An extreme amount, 
-1=UNK 
Items 1C/2C/3C/4C/5C response: 0=Not at all important, 1=Slightly important, 2=Reasonably important, 3=Moderately important, 4=Considerably important,  
                               5=Very important, 6=Extremely important, -1=UNK 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and visit. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 91 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.4.2.  INQOL: Items from Section 1-6 to Section 2-Question 1.B2 
 
 
 
 
Items section 1 
Items section 2 
Site 
Patient 
Visit 
6 
6A 
6B 
6C 
7 
7A 
7B 
7C 
 
1.A1 1.A2 1.A3 
1.A3  
specify 1 
1.A3 
specify 2 
1.B1 1.B2 
1.B2 
specify 
xxx 
xxx 
Screening 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
xx 
xxxx 
xxxx 
xx 
xx 
xxxx 
 
 
Month 3 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
xx 
xxxx 
xxxx 
xx 
xx 
xxxx 
 
 
Month 6 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
xx 
xxxx 
xxxx 
xx 
xx 
xxxx 
 
 
Month 9 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
xx 
xxxx 
xxxx 
xx 
xx 
xxxx 
 
 
… 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
xx 
xxxx 
xxxx 
xx 
xx 
xxxx 
 
 
EOS 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
xx 
xxxx 
xxxx 
xx 
xx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
Statements are given after the next listings. 
Items 6/7 response: 1=Yes, 0=No, -1=UNK 
Items 6A/7A response: 1=Very little, 2=Some, 3=A fair amount, 4=A moderate amount, 5=A considerable amount, 6=A lot, 7=An extreme amount, -1=UNK 
Items 6B/7B response: 0=None at all, 1=Some, 2=A fair amount, 3=A moderate amount, 4=A considerable amount, 5=Very many, 6=An extreme amount, -1=UNK 
Items 6C/7C/1.B2 response: 0=Not at all important, 1=Slightly important, 2=Reasonably important, 3=Moderately important, 4=Considerably important,  
                           5=Very important, 6=Extremely important, -1=UNK 
Items 1.A1/1.A2/1.A3 response: 0=Not at all, 1=Slightly, 2=A fair amount, 3=Moderately, 4=Considerably, 5=Very much, 6=Extremely, -1=UNK 
Items 1.B1 response: 0= Exactly as I would like it to be, 1=Good but not quite how I would like it to be, 2=OK but not how I would like it to be, 
                     3=Neither good nor bad, 4=Quite bad but it could be much worse, 5=Bad but it could be worse, 6=The worst it could possibly be, -
1=UNK 
 
 Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and visit. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 92 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.4.3.  INQOL: Items from Section 2-Question 2.A to Section 2-Question 3.B6 
 
 
 
 
 
Items section 2 
Site 
Patient 
Visit 
2.A 
2.B1 2.B2 
2.B2  
Specify 3.A1 
3.A1  
specify 3.A2 3.A3 3.A4 3.B1 3.B2 
3.B2  
specify 3.B3 3.B4 
3.B4 
specify 3.B5 3.B6 
3.B6 
specify
xxx 
xxx 
Screening 
xx 
xx 
xx 
xxxx 
xx 
xxxx 
xx 
xx 
xx 
xx 
xx 
xxxx 
xx 
xx 
xxxx 
xx 
xx 
xxxx 
 
 
Month 3 
xx 
xx 
xx 
xxxx 
xx 
xxxx 
xx 
xx 
xx 
xx 
xx 
xxxx 
xx 
xx 
xxxx 
xx 
xx 
xxxx 
 
 
Month 6 
xx 
xx 
xx 
xxxx 
xx 
xxxx 
xx 
xx 
xx 
xx 
xx 
xxxx 
xx 
xx 
xxxx 
xx 
xx 
xxxx 
 
 
Month 9 
xx 
xx 
xx 
xxxx 
xx 
xxxx 
xx 
xx 
xx 
xx 
xx 
xxxx 
xx 
xx 
xxxx 
xx 
xx 
xxxx 
 
 
… 
xx 
xx 
xx 
xxxx 
xx 
xxxx 
xx 
xx 
xx 
xx 
xx 
xxxx 
xx 
xx 
xxxx 
xx 
xx 
xxxx 
 
 
EOS 
xx 
xx 
xx 
xxxx 
xx 
xxxx 
xx 
xx 
xx 
xx 
xx 
xxxx 
xx 
xx 
xxxx 
xx 
xx 
xxxx 
 
 
 
 
 
 
Statements are given after the next listings. 
Items 2.A/3.A1/3.A2/3.A3/3.A4 response: 0=None at all, 1=Some, 2=A fair amount, 3=A moderate amount, 4=A considerable amount, 5=Very many, 6=An 
extreme amount, -1=UNK 
Items 2.B2/3.B2/3.B4/3.B6 response: 0=Not at all important, 1=Slightly important, 2=Reasonably important, 3=Moderately important, 4=Considerably 
important, 5=Very important, 6=Extremely important, -1=UNK 
Items 2.B1/3.B1/3.B3/3.B5 response: 0= Exactly as I would like it to be, 1=Good but not quite how I would like it to be, 2=OK but not how I would like 
it to be, 3=Neither good nor bad, 4=Quite bad but it could be much worse, 5=Bad but it could be worse, 6=The worst it could possibly be, -1=UNK 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and visit. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 93 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.4.4.  INQOL: Items from Section 2-Question 4.A1 to Section 3-Question 1.A3 
 
 
 
 
Items section 2 
Items section 3 
Site 
Patient 
Visit 
4.A1 4.A2 4.A3 4.A4 4.B1 4.B2 
4.B2  
specify 5.A 
5.B1 5.B2 
5.B2 
specify  1.A 
1.A1 
1.A1  
specify 1 
1.A1 
specify 2 1.A2 
1.A2  
specify 1.A3 
xxx 
xxx 
Screening 
xx 
xx 
xx 
xx 
xx 
xx 
xxxx 
xx 
xx 
xx 
xxxx 
 xx 
xx 
xxxx 
xxxx 
xx 
xxxx 
xx 
 
 
Month 3 
xx 
xx 
xx 
xx 
xx 
xx 
xxxx 
xx 
xx 
xx 
xxxx 
 xx 
xx 
xxxx 
xxxx 
xx 
xxxx 
xx 
 
 
Month 6 
xx 
xx 
xx 
xx 
xx 
xx 
xxxx 
xx 
xx 
xx 
xxxx 
 xx 
xx 
xxxx 
xxxx 
xx 
xxxx 
xx 
 
 
Month 9 
xx 
xx 
xx 
xx 
xx 
xx 
xxxx 
xx 
xx 
xx 
xxxx 
 xx 
xx 
xxxx 
xxxx 
xx 
xxxx 
xx 
 
 
… 
xx 
xx 
xx 
xx 
xx 
xx 
xxxx 
xx 
xx 
xx 
xxxx 
 xx 
xx 
xxxx 
xxxx 
xx 
xxxx 
xx 
 
 
EOS 
xx 
xx 
xx 
xx 
xx 
xx 
xxxx 
xx 
xx 
xx 
xxxx 
 xx 
xx 
xxxx 
xxxx 
xx 
xxxx 
xx 
 
 
 
 
 
 
 
Statements are given after the next listings. 
Items 4.A1/4.A2/4.A3/4.A4 response: 0=Not at all, 1=Slightly, 2=A fair bit, 3=Moderately, 4=Considerably, 5=Very much, 6=Extremely, -1=UNK 
Item 5.A response: 0=Not at all, 1=Slightly, 2=A fair amount, 3=A moderate amount, 4=A considerable amount, 5=Very much, 6=An extreme amount, -1=UNK 
Items 4.B2/5.B2/1.A3 response: 0=Not at all important, 1=Slightly important, 2=Reasonably important, 3=Moderately important, 4=Considerably important,  
                               5=Very important, 6=Extremely important, -1=UNK 
Items 4.B1/5.B1 response: 0= Exactly as I would like to be, 1=Good but not quite how I would like to be, 2=OK but not how I would like to be, 
                          3=Neither good nor bad, 4=Quite bad but I could be much worse, 5=Bad but I could be worse, 6=The worst I could possibly be, 
   -1=UNK 
Item 1.A response: 0=No, 1=Yes, -1=UNK 
Items 1.A1/1.A2 response: 0=None at all, 1=Some, 2=A fair amount, 3=A moderate amount, 4=A considerable amount, 5=Very many, 6=An extreme amount, -
1=UNK 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and visit. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 94 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.4.5.  INQOL: Items from Section 3-Question 1.B1 to Section 3-Question 1.B3 and Comments 
 
 
 
 
Items section 3 
 
Site 
Patient 
Visit 
1.B1 
1.B1  
specify 1 
1.B1  
specify 2 
1.B2 
1.B2  
specify 1.B3 
Comments 
xxx 
xxx 
Screening 
xx 
xxxx 
xxxx 
xx 
xxxx 
xx 
xxxxxxxxxxxxxx 
 
 
Month 3 
xx 
xxxx 
xxxx 
xx 
xxxx 
xx 
xxxxxxxxxxxxxx 
 
 
Month 6 
xx 
xxxx 
xxxx 
xx 
xxxx 
xx 
xxxxxxxxxxxxxx 
 
 
Month 9 
xx 
xxxx 
xxxx 
xx 
xxxx 
xx 
xxxxxxxxxxxxxx 
 
 
… 
xx 
xxxx 
xxxx 
xx 
xxxx 
xx 
xxxxxxxxxxxxxx 
 
 
EOS 
xx 
xxxx 
xxxx 
xx 
xxxx 
xx 
xxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
Statements are given after the next listing. 
Items 1.B1/1.B2 response: 0=Not at all, 1=Some, 2=A fair amount, 3=A moderate amount, 4=A considerable amount, 5=Very many, 6=An extreme amount, -
1=UNK 
Items 1.B3 response: 0=Not at all important, 1=Slightly important, 2=Reasonably important, 3=Moderately important, 4=Considerably important,  
                               5=Very important, 6=Extremely important, -1=UNK 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and visit. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 95 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.4.6.  INQOL: Questionnaire Scores 
 
 
 
 
Score section 1 
Score section 2 
 Score section 3 
Site 
Patient 
Visit 
1.1 
1.2 
1.3 
1.4 
1.5 
1.6 
1.7 
 
2.1 
2.2 
2.3 
2.4 
2.5 
2.6 
 3.1 
3.2 
xxx 
xxx 
Screening 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
 
 
Month 3 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
 
 
Month 6 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
 
 
Month 9 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
 
 
… 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
 
 
EOS 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
xx 
xx 
xx 
xx 
xx 
xx 
 xx 
xx 
 
 
 
 
 
 
 
Scores follow the listing. 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and visit. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 96 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
INQOL Items 
 
Section 1 
1 
Do you have any muscle weakness due to your muscle condition? 
1a 
How much weakness would you say you have in the muscles affected by your condition? 
1b 
Does your muscle weakness cause difficulties in your life at the moment? 
1c 
How important to you are any difficulties caused by your muscle weakness? 
2 
Do you have any pain as a result of your muscle condition? 
2a 
How much pain would you say you have at the moment? 
2b 
Does your pain cause difficulties in your life at the moment? 
2c 
How important to you are any difficulties caused by your pain? 
3 
Do you feel tired/fatigued as a result of your muscle condition? 
3a 
How much tiredness/fatigue would you say you have at the moment? 
3b 
Does your tiredness/fatigue cause difficulties in your life at the moment? 
3c 
How important to you are any difficulties caused by your tiredness/fatigue? 
4 
Do you have any "locking" (seizing up) of your muscles as a result of your muscle condition? By locking we mean a specific muscle 
symptom of myotonia which refers to difficulty relaxing the muscles after voluntary muscle contraction. Your particular muscle disease 
may not be associated with myotonia in which case tick NO and go on the next question. 
4a 
How much muscle "locking" would you say you have at the moment? 
4b 
Does the "locking" of your muscles cause difficulties in your life at the moment? 
4c 
How important to you are any difficulties caused by the "locking" of your muscles? 
5 
Do you have any drooping of the eyelids as a result of your muscle condition? 
5a 
How much drooping of the eyelids cause difficulties in your life at the moment? 
5b 
Does the drooping of the eyelids cause difficulties in your life at the moment? 
5c 
How important to you are any difficulties caused by the drooping of the eyelids? 
6 
Do you have any double vision as a result of your muscle condition? 
6a 
How much double vision would you say you have at the moment? 
6b 
Does the double vision cause difficulties in your life at the moment? 
6c 
How important to you are any difficulties caused by the double vision? 
7 
Do you have any swallowing difficulty as a result of your muscle condition? 
7a 
How much swallowing difficulty would you say you have at the moment? 
7b 
Does the swallowing difficulty cause difficulties in your life at the moment? 
7c 
How important to you are any difficulties caused by the swallowing difficulty? 
 
 
 
Section 2 
1.A I 
Daily activities 
1.A II 
Leisure activities 
1.A III 
Work activities 
1.A III specify 1 
If you have no paid employment (ex. unemployed or retired or do house-work) please tick here 
1.A III specify 2 
If you are not working due to your condition, please tick here 
1.B I 
In the face of my condition, my ability to do all the things I want to do is: 


Catalyst Pharmaceuticals, Inc. 
Page 97 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
1.B II 
How important to you is the effect of your muscle condition on your ability to do all the things you want to do? 
1.B II specify 
OR, If your ability is "exactly as you would like", please tick here 
2.A 
At the moment, how much help do you need from other people in carrying out your activities? 
2.B I 
In the face of my condition, my level of independence is: 
2.B II 
How important to you is the effect of your muscle condition on your level of independence? 
2.B II specify 
OR, if your independence is "exactly as you would like" please tick here 
3.A I 
Partner / Spouse 
3.A I specify 
If you are not married or in a relationship at the moment OR if you are widowed please tick here 
3.A II 
Other family members 
3.A III 
Friends 
3.A IV 
Other people 
3.B I 
In the face of my condition, my close family relationships are: 
3.B II 
How important to you is the effect of your muscle condition on your close family relationships? 
3.B II specify 
OR, if your close family relationships are "exactly as you would like", please tick here 
3.B III 
In the face of my condition, my close friendships are: 
3.B IV 
How important to you is the effect of your muscle condition on your close friendships? 
3.B IV specify 
OR, If your close friendships are "exactly as you would like" please tick here 
3.B V 
In the face of my condition, my relationships with other people (acquaintances, strangers, and colleagues) are: 
3.B VI 
How important to you is the effect of your muscle condition on your relationships with these other people? 
3.B VI specify 
OR, If your relationships with others are "exactly as you would like" please tick here 
4.A I 
Anxious / Worried 
4.A II 
Depressed 
4.A III 
Frustrated 
4.A IV 
Low in confidence / self-esteem 
4.B I 
In the face of my condition, the way I feel emotionally is: 
4.B II 
How important to you is the effect of your muscle condition upon the way you feel emotionally? 
4.B II specify 
OR, If the way you feel emotionally is "exactly as you would like" please tick here 
5.A 
At the moment, does your muscle condition affect the way you look? 
5.B I 
In the face of my condition, the way I look is: 
5.B II 
How important to you is the effect of your muscle condition upon the way you look? 
5.B II specify 
OR, If the way you look is "exactly as you would like", please tick here 
 
 
 
Section 3 
A 
Do you receive, or are you about to start receiving treatment for your muscle condition? (Fr example surgery, tablets, injections or 
physiotherapy) 
1.A I 
Do you feel the treatment you receive for your muscle condition has had beneficial effects? 
1.A I specify 1 
If you are not receiving treatment, please tick here 
1.A I specify 2 
If you are unsure, please tick here 
1.A II 
Do you feel the treatment you receive for your muscle condition will have beneficial effects in the future? 
1.A II specify 
If you are unsure, or if you have not thought about it please tick here 


Catalyst Pharmaceuticals, Inc. 
Page 98 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
1.A III 
How important to you are the beneficial effects of treatment? 
1.B I 
Do you feel the treatment you receive for your muscle condition has had harmful side effects? 
1.B I specify 1 
If you are not yet receiving treatment, please tick here 
1.B I specify 2 
If you are unsure, please tick here 
1.B II 
Do you think the treatment you receive for your muscle condition will have side effects in the future? 
1.B II specify 
If you are unsure, or if you have not thought about it please tick here 
1.B III 
How important to you are the side effects of the treatment? 
Comments 
If you have any comments you would like to make about your condition and the way it affects you, please use the apace below 
 
 
 
Scores 
1.1 
Weakness  
1.2 
Pain  
1.3 
Fatigue  
1.4 
Locking  
1.5 
Eyelids  
1.6 
Double vision 
1.7 
Swallowing  
2.1 
Activities  
2.2 
Independence 
2.3 
Social relationship 
2.4 
Emotions 
2.5 
Body imagine 
2.6 
QoL  
3.1 
Perceived treatment 
3.2 
Expected treatment 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 99 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.5.1.  Treatment Emergent Adverse Events 
 
Site 
Patient 
System Organ 
Class 
Preferred 
Term 
Verbatim 
Term 
SAE
(1) 
Was AE 
started in 
SMA-001 
study? 
Start date End date 
Ongoing 
(2) 
Duration 
(3) 
Severity 
(4) 
Relations
hip (5) 
Action taken 
(6) 
Outcome 
(7) 
Date of 
death 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx No 
DDMMMYYYY 
DDMMMYYYY 
No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx No 
DDMMMYYYY 
DDMMMYYYY 
No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
Death 
DDMMMYYYY
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx Yes 
DDMMMYYYY 
DDMMMYYYY 
No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx No 
DDMMMYYYY 
DDMMMYYYY 
No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx No 
DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   (1) SAE: No, Yes, UNK 
   (2) Ongoing: No, Yes, UNK 
   (3) Duration= End Date – Start Date + 1; Duration =Date of Last Dose – Start Date + 1 if AE is ongoing 
   (4) Severity: 1= Mild, 2= Moderate, 3= Severe, 4= Life-threatening, 5= Death, UNK 
   (5) Relationship: Not related, Possibly, Probably, UNK 
   (6) Action Taken: None, Treatment required, Study drug dose reduction, Study drug dose discontinued & restarted, Study drug permanently discontinued, 
UNK 
   (7) Outcome: Resolved, Resolved w/sequelae, Not resolved, Death, UNK 
   (8) Seriousness: Fatal, Life threatening, Hospitalization, Persistent disability, Congenital anomaly, Important medical Event, UNK 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and start date. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 100 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.5.2.  Treatment Emergent Serious Adverse Events 
 
Site 
Patient 
SOC 
PT 
Verbatim 
Term 
SAE
(1) Start date End date 
Ongoing 
(2) 
Duration 
(3) 
Severity 
(4) 
Relations
hip (5) 
Action taken 
(6) 
Outcome 
(7) 
Date of 
death 
Seriou
sness
(8) 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
DDMMMYYYY xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   (1) SAE: No, Yes, UNK 
   (2) Ongoing: No, Yes, UNK 
   (3) Duration= End Date – Start Date + 1; Duration =Date of Last Dose – Start Date + 1 if AE is ongoing 
   (4) Severity: 1= Mild, 2= Moderate, 3= Severe, 4= Life-threatening, 5= Death, UNK 
   (5) Relationship: Not related, Possibly, Probably, UNK 
   (6) Action Taken: None, Treatment required, Study drug dose reduction, Study drug dose discontinued & restarted, Study drug permanently discontinued, 
UNK 
   (7) Outcome: Resolved, Resolved w/sequelae, Not resolved, Death, UNK 
   (8) Seriousness: Fatal, Life threatening, Hospitalization, Persistent disability, Congenital anomaly, Important medical Event, UNK 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and start date. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 101 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.5.3.  IMP Related Treatment Emergent Adverse Events 
 
Site 
Patient 
SOC 
PT 
Verbatim 
Term 
SAE
(1) Start date End date 
Ongoing 
(2) 
Duration 
(3) 
Severity 
(4) 
Relations
hip (5) 
Action taken 
(6) 
Outcome 
(7) 
Date of 
death 
Seriou
sness
(8) 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
DDMMMYYYY xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   (1) SAE: No, Yes, UNK 
   (2) Ongoing: No, Yes, UNK 
   (3) Duration= End Date – Start Date + 1; Duration =Date of Last Dose – Start Date + 1 if AE is ongoing 
   (4) Severity: 1= Mild, 2= Moderate, 3= Severe, 4= Life-threatening, 5= Death, UNK 
   (5) Relationship: Not related, Possibly, Probably, UNK 
   (6) Action Taken: None, Treatment required, Study drug dose reduction, Study drug dose discontinued & restarted, Study drug permanently discontinued, 
UNK 
   (7) Outcome: Resolved, Resolved w/sequelae, Not resolved, Death, UNK 
   (8) Seriousness: Fatal, Life threatening, Hospitalization, Persistent disability, Congenital anomaly, Important medical Event, UNK 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and start date. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 102 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.5.4.  IMP Related Treatment Emergent Serious Adverse Events  
 
Site 
Patient 
SOC 
PT 
Verbatim 
Term 
SAE
(1) Start date End date 
Ongoing 
(2) 
Duration 
(3) 
Severity 
(4) 
Relations
hip (5) 
Action taken 
(6) 
Outcome 
(7) 
Date of 
death 
Seriou
sness
(8) 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
DDMMMYYYY xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   (1) SAE: No, Yes, UNK 
   (2) Ongoing: No, Yes, UNK 
   (3) Duration= End Date – Start Date + 1; Duration =Date of Last Dose – Start Date + 1 if AE is ongoing 
   (4) Severity: 1= Mild, 2= Moderate, 3= Severe, 4= Life-threatening, 5= Death, UNK 
   (5) Relationship: Not related, Possibly, Probably, UNK 
   (6) Action Taken: None, Treatment required, Study drug dose reduction, Study drug dose discontinued & restarted, Study drug permanently discontinued, 
UNK 
   (7) Outcome: Resolved, Resolved w/sequelae, Not resolved, Death, UNK 
   (8) Seriousness: Fatal, Life threatening, Hospitalization, Persistent disability, Congenital anomaly, Important medical Event, UNK 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and start date. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 103 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.5.5.  Treatment Emergent Adverse Events Leading to Hospitalization  
 
Site 
Patient 
SOC 
PT 
Verbatim 
Term 
SAE
(1) Start date End date 
Ongoing 
(2) 
Duration 
(3) 
Severity 
(4) 
Relations
hip (5) 
Action taken 
(6) 
Outcome 
(7) 
Date of 
death 
Seriou
sness
(8) 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
DDMMMYYYY xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   (1) SAE: No, Yes, UNK 
   (2) Ongoing: No, Yes, UNK 
   (3) Duration= End Date – Start Date + 1; Duration =Date of Last Dose – Start Date + 1 if AE is ongoing 
   (4) Severity: 1= Mild, 2= Moderate, 3= Severe, 4= Life-threatening, 5= Death, UNK 
   (5) Relationship: Not related, Possibly, Probably, UNK 
   (6) Action Taken: None, Treatment required, Study drug dose reduction, Study drug dose discontinued & restarted, Study drug permanently discontinued, 
UNK 
   (7) Outcome: Resolved, Resolved w/sequelae, Not resolved, Death, UNK 
   (8) Seriousness: Fatal, Life threatening, Hospitalization, Persistent disability, Congenital anomaly, Important medical Event, UNK 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and start date. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 104 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.5.6.  Life-Threatening Treatment Emergent Adverse Events 
 
Site 
Patient 
SOC 
PT 
Verbatim 
Term 
SAE
(1) Start date End date 
Ongoing 
(2) 
Duration 
(3) 
Severity 
(4) 
Relations
hip (5) 
Action taken 
(6) 
Outcome 
(7) 
Date of 
death 
Seriou
sness
(8) 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
DDMMMYYYY xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   (1) SAE: No, Yes, UNK 
   (2) Ongoing: No, Yes, UNK 
   (3) Duration= End Date – Start Date + 1; Duration =Date of Last Dose – Start Date + 1 if AE is ongoing 
   (4) Severity: 1= Mild, 2= Moderate, 3= Severe, 4= Life-threatening, 5= Death, UNK 
   (5) Relationship: Not related, Possibly, Probably, UNK 
   (6) Action Taken: None, Treatment required, Study drug dose reduction, Study drug dose discontinued & restarted, Study drug permanently discontinued, 
UNK 
   (7) Outcome: Resolved, Resolved w/sequelae, Not resolved, Death, UNK 
   (8) Seriousness: Fatal, Life threatening, Hospitalization, Persistent disability, Congenital anomaly, Important medical Event, UNK 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and start date. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 105 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.5.7.  Treatment Emergent Adverse Events Leading to Premature Discontinuation 
 
Site 
Patient 
SOC 
PT 
Verbatim 
Term 
SAE
(1) Start date End date 
Ongoing 
(2) 
Duration 
(3) 
Severity 
(4) 
Relations
hip (5) 
Action taken 
(6) 
Outcome 
(7) 
Date of 
death 
Seriou
sness
(8) 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
DDMMMYYYY xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   (1) SAE: No, Yes, UNK 
   (2) Ongoing: No, Yes, UNK 
   (3) Duration= End Date – Start Date + 1; Duration =Date of Last Dose – Start Date + 1 if AE is ongoing 
   (4) Severity: 1= Mild, 2= Moderate, 3= Severe, 4= Life-threatening, 5= Death, UNK 
   (5) Relationship: Not related, Possibly, Probably, UNK 
   (6) Action Taken: None, Treatment required, Study drug dose reduction, Study drug dose discontinued & restarted, Study drug permanently discontinued, 
UNK 
   (7) Outcome: Resolved, Resolved w/sequelae, Not resolved, Death, UNK 
   (8) Seriousness: Fatal, Life threatening, Hospitalization, Persistent disability, Congenital anomaly, Important medical Event, UNK 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and start date. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 106 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.5.8.  Treatment Emergent Adverse Events Leading to Death 
 
Site 
Patient 
SOC 
PT 
Verbatim 
Term 
SAE
(1) Start date End date 
Ongoing 
(2) 
Duration 
(3) 
Severity 
(4) 
Relations
hip (5) 
Action taken 
(6) 
Outcome 
(7) 
Date of 
death 
Seriou
sness
(8) 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
DDMMMYYYY xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
DDMMMYYYY No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   (1) SAE: No, Yes, UNK 
   (2) Ongoing: No, Yes, UNK 
   (3) Duration= End Date – Start Date + 1; Duration =Date of Last Dose – Start Date + 1 if AE is ongoing 
   (4) Severity: 1= Mild, 2= Moderate, 3= Severe, 4= Life-threatening, 5= Death, UNK 
   (5) Relationship: Not related, Possibly, Probably, UNK 
   (6) Action Taken: None, Treatment required, Study drug dose reduction, Study drug dose discontinued & restarted, Study drug permanently discontinued, 
UNK 
   (7) Outcome: Resolved, Resolved w/sequelae, Not resolved, Death, UNK 
   (8) Seriousness: Fatal, Life threatening, Hospitalization, Persistent disability, Congenital anomaly, Important medical Event, UNK 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and start date. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 107 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.5.9.  Adverse Events Started Before the First Dose of Study Drug for the Current Long-Term Study 
 
Site 
Patient 
SOC 
PT 
Verbatim 
Term 
SAE
(1) 
Was AE 
started in 
SMA-001 
study? 
Start date End date 
Ongoing
(2) 
Duration 
(3) 
Severity 
(4) 
Relations
hip (5) 
Action 
taken 
(6) 
Outcome 
(7) 
Date of 
death 
Seriou
sness
(8) 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx No 
DDMMMYYYY 
DDMMMYYYY 
No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx No 
DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
DDMMMYYYY xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx Yes 
DDMMMYYYY 
DDMMMYYYY 
No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
xxxxxx 
xxxxxx 
xxxxxx 
xxx No 
DDMMMYYYY 
DDMMMYYYY 
No 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
xxxxxx 
xxxxxx 
xxxxxx 
xxx No 
DDMMMYYYY 
 
Yes 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
xxxxx 
 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   (1) SAE: No, Yes, UNK 
   (2) Ongoing: No, Yes, UNK 
   (3) Duration= End Date – Start Date + 1; Duration =Date of Last Dose – Start Date + 1 if AE is ongoing 
   (4) Severity: 1= Mild, 2= Moderate, 3= Severe, 4= Life-threatening, 5= Death, UNK 
   (5) Relationship: Not related, Possibly, Probably, UNK 
   (6) Action Taken: None, Treatment required, Study drug dose reduction, Study drug dose discontinued & restarted, Study drug permanently discontinued, 
UNK 
   (7) Outcome: Resolved, Resolved w/sequelae, Not resolved, Death, UNK 
   (8) Seriousness: Fatal, Life threatening, Hospitalization, Persistent disability, Congenital anomaly, Important medical Event, UNK 
 
 Source: [program name].sas, Run on ddmmmyyyy. 
 
  Programming Notes: Sort by site, patient number and start date. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 108 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.6.1.  Clinical Laboratory Evaluations: Blood Chemistry 
 
 
 
 
 
 
 
Original Unit 
Standard Unit (SI) 
Site 
Patient 
Visit 
Blood 
sample 
taken? 
Sample 
date 
Laboratory 
parameter 
Values 
Unit 
(1) 
NRLL 
 
 
 
NRUL 
Clinical 
assessment 
(2) 
Assessment 
respect to 
Normal 
Ranges 
(3) 
Value 
Unit 
CFB 
xxx 
xxx 
Screening 
xxx 
DDMMMYYYY 
Albumin 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
Alkaline 
Phosphatase 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
ALT 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
AST 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Month 3 
No 
 
Albumin 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alkaline 
Phosphatase 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ALT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AST 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
xxx 
DDMMMYYYY 
Albumin 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
Alkaline 
Phosphatase 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
ALT 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
AST 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EOS 
xxx 
DDMMMYYYY 
Albumin 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
Alkaline 
Phosphatase 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
ALT 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
AST 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   CFB=Change from Baseline. 
 
    
   NRLL: Normal Range Lower Limit; NRUL: Normal Range Upper Limit. 
   (1) Unit: mg/dL, µmol/L, g/dL, g/L, mmol/L, IU/L, meq/L, sec, 10^3/µL, 10^6/µL, 10^9/L, 10^12/L, 10^3/mm^3, 10^6/mm^3, %, Other, UNK, NA 
   (2) Clinical Assessment: Within normal range, Out of range (not clinically significant), Out of range (clinically significant), UNK 
    (3) Assessment respect to normal ranges: Below normal range, Within normal range, Above normal range, UNK 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
Programming Notes: Continue for other blood chemistry parameters: direct bilirubin, total bilirubin, BUN, 
calcium, chloride, total cholesterol, bicarbonate, creatine phosphokinase, creatinine, glucose, GGT, LDH, 
phosphorus, potassium, total protein, sodium and uric acid.  
Sort by site, patient number and visit.  


Catalyst Pharmaceuticals, Inc. 
Page 109 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.6.2.  Clinical Laboratory Evaluations: Hematology 
 
 
 
 
 
 
 
Original Unit 
Standard Unit (SI) 
Site 
Patient 
Visit 
Blood 
sample 
taken? 
Sample 
date 
Laboratory 
parameter 
Values 
Unit 
(1) 
NRLL 
 
 
 
NRUL 
Clinical 
assessment 
(2) 
Assessment 
respect to 
Normal 
Ranges 
(3) 
Value 
Unit 
CFB 
xxx 
xxx 
Screening 
xxx 
DDMMMYYYY 
Hemoglobin 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
Hematocrit 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
WBC count 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
RBC count 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Month 3 
No 
 
Hemoglobin 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematocrit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WBC count 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RBC count 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
xxx 
DDMMMYYYY 
Hemoglobin 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
Hematocrit 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
WBC count 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
RBC count 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EOS 
xxx 
DDMMMYYYY 
Hemoglobin 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
Hematocrit 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
WBC count 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
RBC count 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   CFB=Change from Baseline. 
 
    
   NRLL: Normal Range Lower Limit; NRUL: Normal Range Upper Limit. 
   (1) Unit: mg/dL, µmol/L, g/dL, g/L, mmol/L, IU/L, meq/L, sec, 10^3/µL, 10^6/µL, 10^9/L, 10^12/L, 10^3/mm^3, 10^6/mm^3, %, Other, UNK, NA 
   (2) Clinical Assessment: Within normal range, Out of range (not clinically significant), Out of range (clinically significant), UNK 
    (3) Assessment respect to normal ranges: Below normal range, Within normal range, Above normal range, UNK 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
Programming Notes: Continue for other hematology parameters: platelets count, neutrophils, lymphocytes, 
monocytes, eosinophils and basophils.  
Sort by site, patient number and visit.  
 


Catalyst Pharmaceuticals, Inc. 
Page 110 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.6.3.  Clinical Laboratory Evaluations: Urinalysis 
 
Site 
Patient 
Visit 
Urine 
sample 
taken? 
Appearance 
Color 
Sample date 
Laboratory parameter 
Values 
Unit 
(1) 
Other unit 
Clinical 
assessment 
(2) 
CFB 
xxx 
xxx 
Screening 
xxx 
xxxxx 
xxxxx 
DDMMMYYYY 
pH 
xxx 
 
 
xxx 
xxx 
 
 
 
 
 
 
 
Specific gravity 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
Ketones 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
Protein 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Month 3 
No 
 
 
 
pH 
 
 
 
 
xxx 
 
 
 
 
 
 
 
Specific gravity 
 
 
 
 
xxx 
 
 
 
 
 
 
 
Ketones 
 
 
 
 
xxx 
 
 
 
 
 
 
 
Protein 
 
 
 
 
xxx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
xxx 
xxxxx 
xxxxx 
DDMMMYYYY 
pH 
xxx 
 
 
xxx 
xxx 
 
 
 
 
 
 
 
Specific gravity 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
Ketones 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
Protein 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EOS 
xxx 
xxxxx 
xxxxx 
DDMMMYYYY 
pH 
xxx 
 
 
xxx 
xxx 
 
 
 
 
 
 
 
Specific gravity 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
Ketones 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
Protein 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   CFB=Change from Baseline. 
   (1) Unit: mg/dL, µmol/L, g/dL, g/L, mmol/L, IU/L, meq/L, sec, 10^3/µL, 10^6/µL, 10^9/L, 10^12/L, 10^3/mm^3, 10^6/mm^3, %, Other, UNK, NA 
       Specific gravity Unit: g/L, Kg/L, Other, UNK, NA 
(2) Clinical Assessment: Within normal range, Out of range (not clinically significant), Out of range (clinically significant), UNK 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
Programming Notes: Continue for other urine parameters: glucose, bilirubin, nitrite, urobilinogen and 
hemoglobin.  
Sort by site, patient number and visit.  
 
 


Catalyst Pharmaceuticals, Inc. 
Page 111 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.1.  Pregnancy Test 
 
Site 
Patient 
Visit 
Childbearing 
potential 
Test 
performed? 
Type of 
pregnancy test 
Date of test 
 
Result 
xxx 
xxx 
Screening 
xxxxxxxx 
xxx 
Urine 
DDMMMYYYY 
xxxxxxxx 
 
 
Month 3 
xxxxxxxx 
No 
 
 
 
 
 
Month 6 
xxxxxxxx 
xxx 
Urine 
DDMMMYYYY 
xxxxxxxx 
 
 
… 
xxxxxxxx 
xxx 
Serum 
DDMMMYYYY 
xxxxxxxx 
 
 
EOS 
xxxxxxxx 
xxx 
xxx 
DDMMMYYYY 
xxxxxxxx 
 
 
 
 
 
 
 
 
xxx 
xxx 
Screening 
xxxxxxxx 
xxx 
xxx 
DDMMMYYYY 
xxxxxxxx 
 
 
Month 3 
xxxxxxxx 
xxx 
xxx 
DDMMMYYYY 
xxxxxxxx 
 
 
Month 6 
xxxxxxxx 
xxx 
xxx 
DDMMMYYYY 
xxxxxxxx 
 
 
… 
xxxxxxxx 
xxx 
xxx 
DDMMMYYYY 
xxxxxxxx 
 
 
EOS 
xxxxxxxx 
xxx 
xxx 
DDMMMYYYY 
xxxxxxxx 
 
 
 
 
 
 
 
 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
Programming Note: Sort by site, patient number and visit. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 112 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.2.  Vital Signs 
 
Site 
Patient 
Visit 
Were vital 
signs 
collected?  
Date of 
examination 
Sitting SBP 
(mmHg) 
Sitting DBP 
(mmHg) 
Sitting heart 
rate  
(bpm) 
Respiration 
rate 
(breaths/min) 
Body 
temperature 
(°C) 
Body weight 
(kg) 
 
 
 
 
 
Value 
CFB 
Value 
CFB 
Value 
CFB 
Value 
CFB 
Value 
CFB 
Value 
CFB 
xxx 
xxx 
Screening 
xxx 
DDMMMYYYY 
xxx 
 
xxx 
 
xxx 
 
xxx 
 
xxx 
 
xxx 
 
 
 
Month 3 
xxx 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
Month 6 
xxx 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
Month 9 
xxx 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
Month 12 
xxx 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
… 
xxx 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
EOS 
xxx 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
Screening 
xxx 
DDMMMYYYY 
xxx 
 
xxx 
 
xxx 
 
xxx 
 
xxx 
 
xxx 
 
 
 
Month 3 
xxx 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
Month 6 
xxx 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
Month 9 
xxx 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
Month 12 
xxx 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
… 
xxx 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
EOS 
xxx 
DDMMMYYYY 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   CFB=Change from Baseline. 
Source: [program name].sas, Run on ddmmmyyyy. 
 
Programming Notes: Sort by site, patient number and visit. Height is recorded with Demography at Screening 
only. 
 
 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 113 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.3.  ECG 
 
Site 
Patient 
Visit 
Was an ECG 
performed?  
Date 
performed 
Tracing 
(1) 
If Abnormal,  
please specify 
System Organ 
Class 
Preferred 
Term 
xxx 
xxx 
Screening 
xxx 
DDMMMYYYY 
xxxxxxxxxxx 
 
 
 
 
 
Month 3 
xxx 
DDMMMYYYY 
Abnormal 
Xxxxxxxxx 
xxxxxxxxxxx 
xxxxxxxxxxx 
 
 
… 
No 
 
 
 
 
 
 
 
EOS 
xxx 
DDMMMYYYY 
xxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
Screening 
xxx 
DDMMMYYYY 
xxxxxxxxxxx 
 
 
 
 
 
Month 3 
xxx 
DDMMMYYYY 
Abnormal 
Xxxxxxxxx 
xxxxxxxxxxx 
xxxxxxxxxxx 
 
 
… 
xxx 
DDMMMYYYY 
xxxxxxxxxxx 
 
 
 
 
 
EOS 
xxx 
DDMMMYYYY 
xxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
(1) Tracing Assessment: Normal tracing, Abnormal tracing (not clinically significant), Abnormal tracing (clinically significant), UNK. 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Note: Sort by site, patient number and visit. 
 
 


Catalyst Pharmaceuticals, Inc. 
Page 114 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.7.4.  Physical Examination 
 
Site 
Patient 
Visit 
Physical examination 
performed?  
(1) 
If not 
performed, 
reason 
Body system 
Result 
(2) 
If Abnormal findings, 
specify 
System Organ 
Class 
Preferred 
Term 
xxx 
xxx 
Screening 
xxx 
 
Head/Neck 
xxxxx 
 
 
 
 
 
 
 
 
Eyes 
Abnormal 
Xxxxxxxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
 
 
 
 
 
Ears 
Abnormal 
Xxxxxxxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
 
 
 
 
 
Nose 
xxxxx 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Month 3 
No 
Xxxxxxxx 
Head/Neck 
 
 
 
 
 
 
 
 
 
Eyes 
 
 
 
 
 
 
 
 
 
Ears 
 
 
 
 
 
 
 
 
 
Nose 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
xxx 
 
Head/Neck 
xxxxx 
 
 
 
 
 
 
 
 
Eyes 
xxxxx 
 
 
 
 
 
 
 
 
Ears 
Abnormal 
Xxxxxxxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
 
 
 
 
 
Nose 
xxxxx 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EOS 
xxx 
 
Head/Neck 
Abnormal 
Xxxxxxxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
 
 
 
 
 
Eyes 
xxxxx 
 
 
 
 
 
 
 
 
Ears 
xxxxx 
 
 
 
 
 
 
 
 
Nose 
xxxxx 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(1) Was a complete physical examination performed? 
(2) Result: Normal, Abnormal, Not examined 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
Programming Notes: Continue for other body system: throat, cardiovascular, dermatologic, lymphatic, 
respiratory, gastrointestinal, musculoskeletal and other. Sort by site, patient number and visit.  
 
 


Catalyst Pharmaceuticals, Inc. 
Page 115 of 117  
Protocol SMA-002 
Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.8.  Concomitant Medications 
 
Site 
Patient 
Patient receive 
medication? 
(1) 
# 
Generic name 
Total 
daily 
dose 
Units 
Route 
(2) 
If Other 
Route, 
specify 
Start 
date 
End date 
Ongoing at 
end of 
study? 
Reason for 
administration
(3) 
Indication 
for use 
xxx 
xxx 
xxx 
x 
xxxxxxxxx 
xxxx 
xxxxx 
xxxx 
xxxxxx 
DDMMMYYYY 
DDMMMYYYY 
No 
xxxxxxxxx 
xxxxxxxxx 
 
 
 
x 
xxxxxxxxx 
xxxx 
xxxxx 
xxxx 
xxxxxx 
DDMMMYYYY 
 
Yes 
xxxxxxxxx 
xxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
xxx 
x 
xxxxxxxxx 
xxxx 
xxxxx 
xxxx 
xxxxxx 
DDMMMYYYY 
DDMMMYYYY 
No 
xxxxxxxxx 
xxxxxxxxx 
 
 
 
x 
xxxxxxxxx 
xxxx 
xxxxx 
xxxx 
xxxxxx 
DDMMMYYYY 
DDMMMYYYY 
No 
xxxxxxxxx 
xxxxxxxxx 
 
 
 
x 
xxxxxxxxx 
xxxx 
xxxxx 
xxxx 
xxxxxx 
DDMMMYYYY 
DDMMMYYYY 
No 
xxxxxxxxx 
xxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxx 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(1) Did the patient receive Previous and/or Concomitant medications? 
(2) Route: PO, IM, IV, SC, Rectal, Topical, Nasal, Inhaled, Other, UNK 
(3) Reason for administration?: Therapeutic, Prophylaxis, Other, AE treatment, UNK 
 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Notes: Sort by site, patient number and start date. 
 
 


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Statistical Analysis Plan ver 1.0 
Version Date: 29JUN2020  
 
Listing 16.2.9.  End of Study 
 
Site 
Patient 
End of 
study 
assessment 
date 
Did the patient 
take at least one 
dose of study 
medication? 
Date of last 
study drug dose 
intake 
Complete the 
treatment? 
(1) 
If No, report the 
primary reason for 
discontinuation 
If reason is AE, 
Major Protocol 
Deviation, or Other 
Reason, specify 
If reason is Consent 
Withdrawal, specify 
the date 
xxx 
xxx 
DDMMMYYYY 
xxx 
DDMMMYYYY 
Yes 
 
 
 
xxx 
xxx 
DDMMMYYYY 
xxx 
DDMMMYYYY 
Yes 
 
 
 
xxx 
xxx 
DDMMMYYYY 
No 
 
No 
Consent Withdrawal 
 
DDMMMYYYY 
xxx 
xxx 
DDMMMYYYY 
xxx 
DDMMMYYYY 
No 
Adverse event 
Xxxxxxxxxx 
 
xxx 
xxx 
DDMMMYYYY 
xxx 
DDMMMYYYY 
No 
xxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
  (1) Did the patient complete the full course of treatment?  
  
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Note: Sort by site and patient number. 
 
 
 
 
 


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Listing 16.2.10.  Comments 
 
Site 
Patient 
Presence 
of 
comments? 
Visit (1) 
Form (2) 
Comment 
xxx 
xxx 
xxx 
xxx 
xxx 
Xxxxxxxxxxxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Xxxxxxxxxxxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Xxxxxxxxxxxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Xxxxxxxxxxxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Xxxxxxxxxxxx 
 
 
 
 
 
 
(1) Visit:  Screening, End of study month 3, End of study month 6, End of study month 9, End of study month 12,  
End of study month 15, End of study month 21, End of study month 27, EoS, Extra visit 
(2) Form: Inclusion Criteria, Exclusion Criteria, Demographics characteristics, Medical History, Physical Examination, 
Vital signs, ECG, Pregnancy Test, Blood Chemistry, Hematology, Urinalysis, Amifampridine Treatment, QoL, 
IP Treatment Dispensing & Accountability, End of Study, Adverse Events, Previous and Concomitant Medications, 
Investigator’s Declaration, Other 
Source: [program name].sas, Run on ddmmmyyyy. 
 
 Programming Note: Sort by site and patient number. 
 

Prot_001.pdf: 


 
 
SMA-002 
Page 1 
 
Proprietary and Confidential 
 
Version 3.0 12 April 2019 
CLINICAL STUDY PROTOCOL 
Study Title: 
Long Term Safety Study of Amifampridine Phosphate in 
Ambulatory Patients with Spinal Muscular Atrophy (SMA) 
Type 3 
Protocol Number: 
SMA-002 
Investigational Product: Amifampridine phosphate (3,4-diaminopyridine phosphate) 
IND/EUDRACT 
Number: 
142044 / 2018-000160-28 
Indication: 
Spinal Muscular Atrophy Type 3 
External Support: 
Catalyst Pharmaceuticals, Inc. 
Development Phase: 
Phase 2 
Medical Officer: 
Gary Ingenito, MD, PhD 
Study Design: 
Open Label  
Dose: 
15-80 mg total daily dose   
Patient Population: 
Ambulatory patients with SMA Type 3 
Version and Date of 
Protocol: 
Version 2.0 dated 24 July 2018  
Version 3.0 dated 12 April 2019 (amendment) 
 
Property of Catalyst Pharmaceuticals, Inc. 
CONFIDENTIAL 
May not be divulged, published, or otherwise disclosed to others without prior written 
approval from Catalyst Pharmaceuticals, Inc. 
 
This study will be conducted according to the principles of Good Clinical Practice as 
described in the U.S. Code of Regulations and the International Conference on 
Harmonisation Guidelines, including the archiving of essential documents. 
 
 
 
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2 
PROCEDURES IN CASE OF AN EMERGENCY 
Emergency Contact Information 
 
 
Role in Study 
Name 
Contact Information 
Medical Monitor 
Stanley Iyadurai, MD, PhD 
Vice President, Clinical 
Affairs 
Catalyst Pharmaceuticals, Inc. 
355 Alhambra Circle, Suite 1250 
Coral Gables, FL 33134 
Tel: 305-420-3200, ext. 139 
Email: 
siyadurai@catalystpharma.com 
Contract Research 
Organization 
High Research s.r.l. for 
Italy 
 
 
 
Easthorn Clinical Services 
for countries outside Italy 
Vaile Abruzzi 13/A 
20131 Milan, Italy 
Tel: +39 02 66712580 
Email: l.cottini@highresearch.it 
 
Obilicev venac 15 
11000 Belgrade, Serbia 
Tel: +381 11 3286 305 
Email: ivana.mucic@easthorn.eu 
Safety Reporting 
 
PhAST Consulting s.r.l.  
 
 
 
 
 
Jonathan Rubine, MD 
Associate Medical Director 
Via Roma 74 - 20060  
Cassina de’ Pecchi (MI) Italy 
Tel. +39.039.9416900 
Fax +39.039.3305126 
Email: ClinicalTrial@phast.it 
 
Catalyst Pharmaceuticals, Inc. 
Tel: 305-420-3233 
Email: 
jrubine@catalystpharma.com 
 
 
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3 
SYNOPSIS 
TITLE OF STUDY: 
Long Term Safety Study of Amifampridine Phosphate in Ambulatory Patients with Spinal 
Muscular Atrophy (SMA) Type 3 
PROTOCOL NUMBER: 
SMA-002 
STUDY SITES:  
Up to 3 sites 
PHASE OF DEVELOPMENT: 
Phase 2a 
STUDY RATIONALE: 
The purpose of this study is to evaluate the long-term safety and tolerability of amifampridine 
phosphate in ambulatory patients with SMA Type 3 who completed Protocol SMA-001 or. who 
benefit from the medication but were not meet the criteria enter the double-blind portion of SMA-
001. 
OBJECTIVES: 
Primary 
• 
To characterize the long-term safety and tolerability of amifampridine phosphate in 
patients SMA Type 3 
Secondary 
• 
To assess the clinical efficacy of amifampridine phosphate over time in patients with SMA 
Type 3 based on changes in quality of life (QoL)  
STUDY DESIGN AND PLAN:  
This is a long-term extension study for patients who participated in Protocol SMA-001 where the 
efficacy and safety of amifampridine was evaluated, in ambulatory patients with SMA Type 3. The 
planned duration of participation for each patient is approximately 2 years (i.e. until amifampridine 
is approved by Regulatory Agencies for the treatment of SMA Type 3 or the development program 
is discontinued for this indication). 
All patients who have completed study SMA-001 and sign an informed consent may enroll in the 
long-term study.  Those patients who demonstrated benefit after completing the dose titration 
period but failed to meet the randomization criteria on Day 0 (end of the Run-in period for SMA-
001 may also be eligible for this study.  The evaluations at the end of participation in Study SMA-
001 will as baseline for the Long-Term study. 
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The optimal dose and schedule for amifampridine from the end of the Run-in Period from Study 
SMA-001 will initially be used for each patient. The Investigator may adjust the dose of 
amifampridine during the course of this trial, in order to optimize neuromuscular benefit for the 
patient. Clinic visits for safety assessment and for evaluation of QoL will be made at Months 3, 6, 
9, 12, 15, 21 and 27.  Additional visits may occur at the discretion of the Investigator.   
NUMBER OF PATIENTS PLANNED:  
About 12 SMA Type 3 ambulatory patients will be studied. 
CRITERIA FOR INCLUSION AND EXCLUSION:  
Individuals eligible to participate in this study must meet all the following inclusion criteria: 
1. Participated in the SMA-001 study 
2. Willing and able to provide written informed consent after the nature of the study has been 
explained and before the start of any research-related procedures. 
3. Female patients of childbearing potential must have a negative pregnancy test (urine 
human chorionic gonadotropin [HCG] at the end of SMA-001 study); and must practice an 
effective, reliable contraceptive regimen during the study and for up to 30 days following 
discontinuation of treatment. 
4. Ability to participate in the study based on overall health of the patient and disease 
prognosis, as applicable, in the opinion of the Investigator; and able to comply with all 
requirements of the protocol, including completion of study questionnaires. 
 
Individuals who met any of the exclusion criteria in the original protocol or those listed below are 
not eligible to participate in the study: 
1. Epilepsy and currently on medication. 
2. Uncontrolled asthma. 
3. Concomitant use with sultopride. 
4. Concomitant use with medicinal products with a narrow therapeutic window. 
5. Clinically significant abnormalities in 12 lead ECG, in the opinion of the Investigator. 
6.  Breastfeeding or pregnant at Screening or planning to become pregnant at any time during 
the study. 
7. Intolerable amifampridine-related side effects   
8. Treatment with an investigational drug (other than amifampridine) or device while 
participating in this study. 
9. Any medical condition that, in the opinion of the Investigator, might interfere with the 
patient’s participation in the study, poses an added risk for the patient, or confound the 
assessment of the patient. 
10. History of drug allergy to any pyridine-containing substances or any amifampridine 
excipient(s). 
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INVESTIGATIONAL PRODUCT(S), DOSE, ROUTE, AND REGIMEN:  
The investigational product (IP) is amifampridine tablets 10 mg, and it will be provided in round, 
white-scored tablets, containing amifampridine phosphate formulated to be the equivalent of 10 mg 
amifampridine base per tablet. Dosing is up to 80 mg/day in 3 or 4 divided doses. 
 
The investigational product will be provided by Catalyst Pharmaceuticals, Inc., 355 Alhambra 
Circle, Suite 1250, Coral Gables, Florida, 33134, United States. 
REFERENCE THERAPY, DOSE, ROUTE, AND REGIMEN:  
None 
DURATION OF TREATMENT: 
Amifampridine will be continued for a period of up to 2 years or until the drug is approved by 
Regulatory Agencies or until the development of the drug is discontinued for this indication.  
CRITERIA FOR EVALUATION: 
Safety (primary endpoint): 
Safety will be assessed by the incidence of treatment-emergent adverse events (TEAEs), including 
serious adverse events (SAEs). Vital signs, 12-lead ECGs, clinical laboratory tests, physical 
examination findings, and concomitant medications will also be evaluated.  
Efficacy (secondary endpoint):  
Efficacy will be assessed by changes in QoL over time. 
STATISTICAL METHODS: 
Sample Size Determination 
The study is not powered with respect to any endpoint, but is a study to assess long term safety and 
lack of tolerance to the effects of amifampridine on QoL.    
Safety Analysis 
Safety analyses will be conducted on the safety population (i.e. all patients who receive at least 1 
dose of amifampridine. The safety analysis will be descriptive and will be presented on observed 
data only. 
All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). The 
incidence of TEAEs will be summarized by system organ class, preferred term, relationship to 
treatment, and severity.  
All other safety measures including ECGs, vital signs, laboratory tests, physical examination and 
concomitant medications data will also be summarized. 
 
Efficacy Analysis 
Efficacy analysis will be conducted on all patients who receive at least 1 dose of amifampridine 
and have at least one post-treatment efficacy assessment. The efficacy analysis will be descriptive 
and will be presented on observed data only. 
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4 TABLE OF CONTENTS 
1 TITLE PAGE .......................................................................................................................1 
2 PROCEDURES IN CASE OF AN EMERGENCY ............................................................2 
3 SYNOPSIS ...........................................................................................................................3 
4 TABLE OF CONTENTS .....................................................................................................6 
5 LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ....................................10 
6 ETHICS..............................................................................................................................11 
6.1 Independent Ethics Committee / Institutional Review Board ...................................11 
6.2 Ethical Conduct of Study ..........................................................................................12 
6.3 Patient Information and Informed Consent ...............................................................12 
7 INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ........................13 
8 INTRODUCTION .............................................................................................................13 
8.1 Effectiveness in SMA and Other Indications ............................................................14 
8.2 Safety of Amifampridine and Amifampridine Phosphate .........................................15 
8.3 Overall Risks and Benefits ........................................................................................16 
8.4 Study Rationale .........................................................................................................17 
9 STUDY OBJECTIVES ......................................................................................................17 
9.1 Primary Objective .....................................................................................................17 
9.2 Secondary Objective .................................................................................................17 
10 INVESTIGATIONAL PLAN ............................................................................................18 
10.1 Overall Study Design and Plan .................................................................................18 
10.2 Selection of Study Population ...................................................................................20 
10.2.1 Inclusion Criteria .........................................................................................20 
10.2.2 Exclusion Criteria ........................................................................................20 
10.2.3 Removal of Patients from Treatment or Assessment ..................................21 
10.2.4 Patient Identification ...................................................................................22 
10.3 Treatments .................................................................................................................22 
10.3.1 Treatments Administered ............................................................................22 
10.3.2 Identity of Investigational Product ..............................................................22 
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10.3.2.1 
Product Characteristics and Labeling ..........................................23 
10.3.2.2 
Storage .........................................................................................23 
10.3.3 Directions for Administration .....................................................................23 
10.3.4 Method of Assigning Patients to Treatment Groups ...................................24 
10.3.5 Selection of Doses Used in the Study .........................................................24 
10.3.6 Blinding .......................................................................................................24 
10.3.7 Treatment Compliance ................................................................................24 
10.3.8 Investigational Product Accountability .......................................................24 
10.3.9 Return and Disposition of Clinical Supplies ...............................................24 
10.4 Prior and Concomitant Medications .........................................................................25 
10.5 Dietary or Other Protocol Restrictions......................................................................26 
10.5.1 Dietary Restrictions .....................................................................................26 
10.5.2 Contraception ..............................................................................................26 
10.6 Safety Variables ........................................................................................................26 
10.6.1 Adverse Events ............................................................................................26 
10.6.2 Vital Signs ...................................................................................................26 
10.6.3 Clinical Laboratory Assessments ................................................................27 
10.6.4 Pregnancy Testing .......................................................................................28 
10.6.5 Electrocardiogram (ECG) ............................................................................28 
10.6.6 Physical Examination ..................................................................................29 
10.7 Efficacy Variables .....................................................................................................29 
10.7.1 Quality of life assessment ............................................................................29 
11 REPORTING ADVERSE EVENTS .................................................................................30 
11.1 Adverse Events .........................................................................................................30 
11.2 Serious Adverse Events ............................................................................................32 
11.3 Safety Blood Collection ............................................................................................34 
11.4 Pregnancy ..................................................................................................................34 
11.5 Urgent Safety Measures ............................................................................................34 
11.6 Medical Monitor Contact Information ......................................................................35 
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12 APPROPRIATENESS OF MEASUREMENTS ...............................................................35 
13 STUDY PROCEDURES ...................................................................................................35 
13.1 Start of Long Term Study .........................................................................................35 
13.2 End of Months 3, 6, 9, 12, 15, 21 and 27 in Long Term Study ................................36 
13.2.1 End of Study Visit .......................................................................................37 
14 DATA QUALITY ASSURANCE .....................................................................................37 
15 STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE ..................38 
15.1 Statistical and Analytical Plans .................................................................................38 
15.1.1 Interim Analyses ..........................................................................................38 
15.2 Analysis Populations .................................................................................................38 
15.3 Primary Endpoint ......................................................................................................38 
15.4 Secondary Endpoint ..................................................................................................38 
15.5 Safety Analysis .........................................................................................................38 
15.6 Determination of Sample Size ..................................................................................39 
15.7 Changes in the Conduct of the Study or Planned Analyses ......................................39 
16 COMPENSATION, INSURANCE, AND INDEMNITY .................................................39 
17 CASE REPORT FORMS AND SOURCE DOCUMENTS ..............................................40 
18 STUDY MONITORING AND AUDITING .....................................................................41 
19 RETENTION OF RECORDS ...........................................................................................41 
20 USE OF INFORMATION AND PUBLICATION ...........................................................42 
21 REFERENCES ..................................................................................................................43 
22 INVESTIGATOR RESPONSIBILITIES ..........................................................................45 
22.1 Conduct of Study and Protection of Human Patients ...............................................45 
23 SIGNATURE PAGE .........................................................................................................46 
 
 
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 List of Appendices 
APPENDIX  1  PROTOCOL VERSION  3.0 .........................................................................47 
 
 
List of In-text Tables 
Table 1 Schedule of Events......................................................................................................19 
Table 2 Clinical Laboratory Tests ............................................................................................28 
Table 3 Categories of Severity of Adverse Events ..................................................................31 
Table 4 Description of Relationship to Adverse Event Categories .........................................32 
 
List of In-text Figure 
Figure 1 Chemical Structure of Amifampridine Phosphate .....................................................23 
 
 
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5 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviations 
Abs 
Antibodies 
Ach 
Acetylcholine 
AChR 
Acetylcholine receptor 
ADL 
Activities of Daily Living 
AE(s) 
adverse event(s) 
ALT 
alanine aminotransferase  
AST 
aspartate aminotransferase 
ATU 
Autorisations Temporaires d'Utilisation Normative 
CMS 
congenital myasthenia syndromes 
CRA(s) 
clinical research associate(s) 
CRF 
CRO 
case report form 
contract research organization 
CTFG 
Clinical Trial Facilitation Group 
DBP 
diastolic blood pressure 
ECG(s) 
electrocardiogram(s) 
eCRF 
electronic case report form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HCG 
human chorionic gonadotropin 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
ICH E6 
ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice E6 
IEC 
independent ethics committee 
IP 
investigational product 
IRB 
institutional review board 
K+ 
potassium ion 
kg 
kilogram 
LEMS 
Lambert-Eaton myasthenic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
MG 
Myasthenia Gravis 
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MI 
myocardial infarction 
mmHg 
millimeters of mercury 
MS 
multiple sclerosis 
MuSK 
muscle-specific receptor tyrosine kinase 
MuSK-MG 
muscle-specific receptor tyrosine Kinase-Myasthenia Gravis 
PI 
Principal Investigator 
PK 
pharmacokinetic 
QoL 
Quality of life 
REB 
research ethics board 
SAE(s) 
serious adverse event(s) 
SAP 
statistical analysis plan 
SBP 
systolic blood pressure 
SMA 
spinal muscular atrophy 
 
Definition of Terms:  
Investigational Product (IP): 
“A pharmaceutical form of an active ingredient or placebo being tested or used as a reference 
in a clinical trial, including a product with a marketing authorization when used or assembled 
(formulated or packaged) in a way different from the approved form, or when used for an 
unapproved indication, or when used to gain further information about an approved use” 
(from International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use ICH Harmonised Tripartite Guideline: 
Guideline for Good Clinical Practice E6 [ICH E6]). The terms “IP” and “study drug” may be 
used interchangeably in the protocol. 
6 
ETHICS 
6.1 
Independent Ethics Committee / Institutional Review Board 
The Investigator will provide the Independent Ethics Committee (IEC) with all appropriate 
material, including the protocol, Investigator Brochure or Package Insert, the Informed 
Consent Form (ICF) including compensation procedures, and any other written information 
provided to the patients. The study will not be initiated and Investigational Product (IP) 
supplies will not be shipped to the site until appropriate documents from the IEC confirming 
unconditional approval of the protocol, the ICF, and all patient recruitment materials are 
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obtained in writing by the Investigator, and copies are received at Catalyst or its designee. 
The approval document should refer to the study by protocol title and Catalyst protocol 
number (if possible), identify the documents reviewed, and include the date of the review and 
approval. The Investigator is responsible to ensure that the appropriate reports on the 
progress of the study are made to the IEC in accordance with applicable guidance documents 
and governmental regulations. 
6.2 
Ethical Conduct of Study 
This study will be conducted in accordance with the following: 
• ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice E6 
(ICH E6); and 
• The ethical principles established by the Declaration of Helsinki. 
Specifically, this study is based on adequately performed laboratory and animal 
experimentation. The study will be conducted under a protocol reviewed and approved by an 
IEC and will be conducted by scientifically and medically qualified persons. The benefits of 
the study are in proportion to the risks. The rights and welfare of the patients will be 
respected and the Investigators conducting the study do not find the hazards to outweigh the 
potential benefits. Each patient will provide written, informed consent prior to any 
study-related tests or evaluations being performed. 
6.3 
Patient Information and Informed Consent 
A properly written and executed ICF, in accordance with the Declaration of Helsinki, ICH E6 
(Section 4.8), and other applicable local regulations, will be obtained for each patient before 
entering the patient into the study. The Investigator will prepare the ICF and provide the 
documents to Catalyst, or designee, for review. The IEC must approve the documents before 
their implementation. A copy of the approved ICF and a copy of the approved patient 
information sheet must also be received by Catalyst, or designee, prior to any study-specific 
procedures being performed. 
The Investigator will provide copies of the signed ICF to each patient and will maintain the 
original in the record file of the patient. 
 
 
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7 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE 
Before beginning the study, the Investigator must provide to Catalyst or designee, a fully 
executed and signed US Food and Drug Administration (FDA) Form FDA 1572 and a 
Financial Disclosure Form.  All sub-investigators must be listed on Form FDA 1572 and 
provide a Financial Disclosure Form. 
Clinical research associates (CRAs) or trained designees will monitor the site on a periodic 
basis, both remotely and with onsite visits, and perform verification of source documentation 
for a representative sample of patients as well as other required review processes. Principal 
Investigator (PI) will be responsible for the timely reporting of serious adverse events (SAEs) 
to Catalyst, or designee, and the IEC. Catalyst Medical Department (or designee) will be 
responsible for the timely reporting of SAEs to appropriate regulatory authorities, as 
required. 
Laboratory evaluations will be performed at the local laboratory associated with the study 
site.  
8 
INTRODUCTION 
Information on disease background, amifampridine, previously completed nonclinical and 
clinical studies of amifampridine, is described in the Introduction of SMA-001 and in the 
Investigator Brochure supplied by Catalyst (March 2019). Investigators are to review this 
document before initiating this study.  
Amifampridine is a non-specific voltage-dependent potassium (K+) channel blocker. 
Blockade of K+ channels causes depolarization of the presynaptic membrane and slows down 
or inhibits repolarization. Prolonged depolarization results in opening of slow voltage-
dependent calcium (Ca2+) channels and allows a subsequent influx of Ca2+. The increased 
concentration of intracellular Ca2+ induces exocytosis of the synaptic vesicles containing 
acetylcholine (ACh), thus releasing an increased level of ACh into the synaptic cleft 
(Maddison, 1998a; Maddison, 1998b). The influx of ACh into the presynaptic cleft enhances 
neuromuscular transmission, providing improved muscle function. 
Mori et al. (2012) found that amifampridine improved neuromuscular transmission by 
predominantly increasing ACh release in the neuromuscular junction of in mice with MG 
induced by antibodies against muscle-specific kinase (MuSK).  Furthermore, a mouse model 
of MuSK-myasthenia gravis (MG), amifampridine significantly enhanced neuromuscular 
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transmission after 1 week of treatment without exacerbating loss of endplate AChRs 
(Morsch et al. 2013).  
Multiple studies were conducted to evaluate the cardiac safety, pharmacokinetics and 
toxicity profile in rats and dogs. Reproductive and developmental toxicity studies with 
amifampridine were also conducted in rats and rabbit as well a variety of in vitro and in vivo 
genotoxicity studies, and in vitro metabolism/transporter studies. The main nonclinical 
findings related to amifampridine were central and autonomic nervous system effects, the 
development of Schwannomas, and histologic changes in muscle tissues. Below is an 
abbreviated summary of the effectiveness of amifampridine in MuSK-MG and overall safety 
in other patient populations. 
8.1 
Effectiveness in SMA and Other Indications 
Recent studies in SMA animal models and SMA patients have shown that the NMJ displays 
significant structural and functional defects that precede overt disease symptoms, suggesting 
that impaired NMJ function may contribute to SMA pathogenesis and symptoms. Defects in 
the NMJ appear to precede degeneration of motor neurons suggesting that abnormal 
formation and/or maintenance of this structure may be a key event in disease pathogenesis. 
These defects have been observed at both the pre- and postsynaptic components of the NMJ, 
which likely contribute to the failure to maintain the NMJ and muscle innervation in mouse 
models of SMA. Finally, NMJ dysfunction has been also demonstrated in SMA patients, 
mainly in Type 3 subgroup, contributing to the symptoms associated with the disease. 
Small studies have demonstrated the beneficial effects of amifampridine in patients with 
muscle-specific receptor tyrosine kinase-myasthenia gravis (MuSK-MG) in 2 children, who 
achieved some benefit (Skjei, 2013) and 1 adult (Evoli, 2016).  Following 4 months of 
treatment, the authors report the adult patient had obvious improvement of ptosis, decreased 
neck weakness and arm fatigability. In an Investigator-Sponsored MuSK-MG randomized, 
double-blind, placebo-controlled, cross-over study conducted in Italy, 7 MuSK-MG patients 
demonstrated statistically significantly higher functional performance in all validated 
assessment scales when they were administered amifampridine compared to placebo. 
Tolerability to amifampridine was excellent (unpublished data). 
A review of the literature documents that amifampridine is a safe and effective treatment in 
multiple neurologic disorders and is recommended by the EFNS for first-line symptomatic 
treatment of patients with LEMS (Skeie, 2006; Skeie, 2010; Lindquist, 2011).  
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8.2 
Safety of Amifampridine and Amifampridine Phosphate 
Safety data collected from 1,454 patients or healthy volunteers in controlled study LMS-002 
[(Lambert-Eaton myasthenic syndrome LEMS)], controlled and uncontrolled published 
studies of LEMS or other neurologic conditions, a 3-year safety surveillance study (ATU), 
and pharmacokinetic (PK) studies demonstrate amifampridine is well tolerated up to and 
including 80 mg/day (Firdapse Investigator Brochure, March 2019). The most common 
adverse events observed from the clinical safety data were perioral and peripheral 
paresthesias and gastrointestinal disorders (abdominal pain, nausea, diarrhea, epigastralgia).  
These events were typically mild or moderate in severity, and transient, seldom requiring 
dose reduction or withdrawal from treatment. In the pharmacogenomic study in healthy 
subjects (classified as either slow acetylators or fast acetylators), slow acetylators 
experienced >80% more drug-related AEs compared with fast acetylators (FIR-001). 
Clinically significant or serious adverse events were infrequent in all studies for all 
indications. A total of 12 deaths were reported in the 1,454 patients or healthy subjects. Six 
of 12 deaths were associated with accompanying malignancy (1 of 6 with pulmonary 
embolus as terminal event), 1 due to tracheobronchitis, and 2 due to myocardial infarction 
(MI). Attribution to amifampridine for 2 of 3 deaths from the ATU study was specified as 
unrelated; causality for the third death was not reported. No attribution was specified in the 
academic series, but the author singled out the fatal MI as the only serious incident during 
amifampridine therapy, implying that the 2 deaths due to malignancy, the 1 due to 
malignancy and pulmonary embolus and the 1 due to tracheobronchitis were not related in 
his opinion. The author further states that no pathological findings related to amifampridine 
were found in the patient who died of tracheobronchitis. For 1 of the fatal MIs, the author 
speculates that a “sudden increase of physical activity” with amifampridine may have been a 
contributor (Lundh, 1984; Lundh, 1993); no causality was reported for the other fatal MI 
(Bertorini, 2011). Three deaths occurred in children with congenital myasthenia syndromes 
(CMS), including 2 with fast-channel CMS (Beeson, 2005). Although no causal relationship 
was established with amifampridine, the authors advise its use cautiously in children and in 
fast-channel patients. The other CMS death was not thought to be related to amifampridine 
(Palace, 1991). Overall 7 of 12 deaths were not considered related to amifampridine; neither 
cause nor causality is known for 4 deaths; and amifampridine may have contributed 
indirectly to 1 of the MI-related deaths.   
The most frequent clinically significant or serious event was seizure. A total of 10 (0.69%) 
patients out of 1,454 patients or healthy subjects experienced seizures or convulsions after 
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treatment with amifampridine. Electroencephalogram findings, reported for 3 of the 10 
patients, did not show epileptiform activity. Three of 10 seizures occurred in patients with 
LEMS (3/209; 1.44%), 4 occurred in patients with MS (4/774; 0.5%), 1 occurred in a patient 
with CMS (1/88; 1.14%) (Harper, 2000) and 2 seizures were reported in a literature-based 
study where both MG and LEMS patients were enrolled, but the paper did not state the 
indication (Sanders, 1993; Sanders, 2000; Flet, 2010; McEvoy, 1989; Boerma, 1995; Bever, 
1996).  
Three patients (LEMS or MG) experienced seizures on a daily dose of ≥90 mg/day. No other 
cause was apparent in 2 cases; 1 patient had concurrent toxic serum levels of theophylline 
(McEvoy, 1989; Sanders, 1993). A fourth patient with LEMS had multiple seizures 
following accidental ingestion of 360 mg/day amifampridine for 7 days (prescribed dose 
60 mg/day) (Boerma, 1995). There were potentially contributing conditions in 6 patients, 
specifically, concurrent treatment with theophylline (n=1; LEMS or MG), or coexistent brain 
metastases (n=1; LEMS), epilepsy and multiple sclerosis (MS) (n=1); and MS (n=4). In cases 
where follow-up was reported, most seizures did not recur with amifampridine dose 
reduction or treatment withdrawal. In the one accidental overdose case, seizures were 
controlled with intravenous clonazepam and the patient made a full recovery (Boerma, 1995). 
It is noteworthy that a seizure rate of 4% can be expected in the natural course of patients 
with MS (Engelsen, 1997; Moreau, 1998; Kinnunen, 1987). Among the 774 MS patients 
treated with amifampridine included in the safety assessment of this report, 4 (0.5%) 
experienced seizures. 
Other clinically significant or SAEs reported in more than 1 patient were palpitations 
(8/1,454; 0.56%), abnormal liver enzymes (6/1,454; 0.41%), QTc prolongation (2/1,454; 
0.14%), and premature ventricular contraction/increased ventricular extrasystoles (2/1,454; 
0.14%). Each of the following serious or clinically significant events was reported in a single 
patient: chorea, paresthesias, paroxysmal supraventricular tachycardia, cardiac arrest, drug-
induced hepatitis, gastroesophageal reflux, increased lipase and amylase, aspiration 
pneumonia with confusion, and urinary tract infection with confusion. 
8.3 
Overall Risks and Benefits 
Data on amifampridine treatment in 1,454 patients or healthy volunteers support the 
favorable safety profile of amifampridine (both base and phosphate formulations) at doses up 
to 80 mg per day. To date, current data demonstrate that amifampridine phosphate has an 
acceptable tolerability profile with a positive risk-benefit in patients treated with 
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amifampridine for patients with LEMS and CMS, but longer-term studies are needed in 
patients with SMA. Amifampridine phosphate has also been approved for LEMS in the EU 
since 2009, so there is a well established safety history.  
Patients with SMA Type 3 would already have been treated with amifampridine for several 
weeks as they come from the SMA-001 protocol before entering SMA-002 study.  Therefore, 
the tolerability of amifampridine phosphate and clinical benefit would already be established, 
minimizing risk. 
8.4 
Study Rationale 
A considerable amount of clinical experience is available with amifampridine and, in 
December 2009, amifampridine tablets 10 mg, as amifampridine phosphate, received 
marketing approval by the European Commission as Firdapse® for the symptomatic 
treatment of patients with LEMS. Case reports, animal data suggest that amifampridine may 
also have clinical utility in patients with SMA Type 3, providing symptomatic relief through 
its action on the impaired NMJ transmission. The present long-term extension study will 
evaluate safety and tolerability of amifampridine on clinical laboratory test variables, ECGs, 
AEs, vital signs, physical examinations and the effects on quality of life (QoL) score over 
several months in patients with SMA Type 3. This information is needed to demonstrate that 
the product is safe and provides continued benefit to patients with SMA Type 3.   
9 
STUDY OBJECTIVES 
9.1 
Primary Objective 
The primary objective of the study is: 
• 
To evaluate the long-term safety and tolerability of amifampridine in patients with SMA 
Type 3. 
9.2 
Secondary Objective 
The secondary objective of the study is: 
• 
To assess the clinical efficacy of amifampridine phosphate over time in patients with SMA 
Type 3 based on changes in QoL.  
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10 
INVESTIGATIONAL PLAN 
10.1 
Overall Study Design and Plan 
This open label outpatient extension study is designed to evaluate the long-term safety, 
tolerability of amifampridine in patients diagnosed with SMA Type 3. In addition, evaluation 
of the effects of amifampridine on the QoL will be made. The study will enroll those patients 
who have completed the SMA-001 study and after all final evaluations for that study have 
been completed, or those who demonstrated benefit after completing the dose titration period 
but failed to meet the randomization criteria on Day 0 of SMA-001.  
The duration of participation for each patient is expected to be at least 12 months as patients 
may continue in the study until amifampridine is approved by Regulatory Agencies or the 
clinical development of amifampridine is terminated for this indication. In addition to 
amifampridine, patients will continue to receive previous concomitant medications, as 
needed.  
After a new informed consent is signed and inclusion / exclusion criteria for the current 
protocol are satisfied, eligible patients will be given the optimal dose and dosing schedule 
that was identified in the Run-in Period from Protocol SMA-001.   
The findings from the physical exam (including vital signs, weight); 12-lead ECG; clinical 
laboratory test results (including pregnancy testing) and any ongoing adverse events will be 
used as the baseline for the Long-Term safety evaluation.   
The efficacy measurement is QoL which will be completed every 3 or 6 months. Safety and 
tolerability assessments will be made every 3 or 6 months or more frequently at the 
discretion of the Investigator. The study will continue until amifampridine is approved by 
Regulatory Agencies or until development of the product for this indication is halted. The 
Investigator may alter the dose and dosing frequency during the Long-Term Study as well as 
schedule additional clinic visits for any reason.   
Patients will be seen in the clinic at the end of Months 3, 6, 9, 12, 15, 21 and 27 as detailed in 
the Schedule of Assessments in Table 1 and Section 13. In between the 3-or 6-month visits, 
patients may also have telephone/video contact with the site, or unscheduled visits, if needed. 
Any unused medication must be returned to the clinic at each visit for drug accountability, 
and an additional supply will be dispensed. 
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The study will be completed when amifampridine is approved by Regulatory Agencies for 
Spinal Muscular Atrophy or the clinical development of amifampridine is terminated for this 
indication. 
Table 1 Schedule of Events 
Study Assessment  
or Event  
Screening 
and 
Enrollment* 
End of Study Month ± 1 week 
3 
6 
9 
12 
15 
21 
27 
EoSg 
Informed consent a 
x 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
x 
 
 
 
 
 
 
 
 
Complete physical exam b 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Vital signs  
x 
x 
x 
x 
x 
x 
x 
x 
x 
12-Lead ECG  
x 
x 
x 
x 
x 
x 
x 
x 
x 
Clinical laboratory tests c 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Pregnancy test d 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Amifampridine Treatment 
 
x 
x 
x 
x 
x 
x 
x 
 
QoL  
x 
x 
x 
x 
x 
x 
x 
x 
x 
Dispense IP e 
x 
x 
x 
x 
x 
x 
x 
 
 
IP accountability 
 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse events/SAEs f 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Concomitant medications 
x 
x 
x 
x 
x 
x 
x 
x 
x 
EoS= End of Study is the patients last visit to the site and discontinuation of study medication; 
IP=investigational product; QoL=quality of life; SAE=serious adverse event.  
a Informed consent must be obtained before any study procedures are performed. 
b Complete physical examination includes evaluation of all major body systems, including weight at 
all visits (Section 10.6.6). 
c Clinical laboratory tests include serum chemistry, hematology, and urinalysis. 
d Urine pregnancy tests will be obtained from female patients of childbearing potential. 
e Pharmacist will dispense sufficient amount of medication until the next clinic visit. All unused 
medication must be returned to the clinic for drug accountability. 
f SAE reporting commences after informed consent is signed. Non-serious adverse event reporting 
commences after the first dose of study drug for the current Long-Term Study. 
g EoS or early termination visit if the last visit does not coincide the scheduled 3- or 6-month visit. 
*These data may be obtained from Study SMA-001. If data not available, then the assessment should 
be repeated. 
 
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10.2 Selection of Study Population 
Patients who complete Protocol SMA-001 or who have demonstrated benefit after completing 
the dose titration period but failed to meet randomization criteria for SMA-001 and who meet 
the inclusion and exclusion criteria for participation in the current study will be eligible. 
10.2.1 Inclusion Criteria 
Individuals eligible to participate in this study must meet all the following inclusion criteria: 
1. Participated in the SMA-001 study 
2. Willing and able to provide written informed consent after the nature of the study has 
been explained and before the start of any research-related procedures. 
3. Female patients of childbearing potential defined according to the Clinical Trial 
Facilitation Group - CTFG guidelines* must have a negative pregnancy test (urine 
human chorionic gonadotropin [HCG] at the end of SMA-001 study); and must 
practice an effective, reliable contraceptive regimen during the study and for up to 30 
days following discontinuation of treatment. 
4. Ability to participate in the study based on overall health of the patient and disease 
prognosis, as applicable, in the opinion of the Investigator; and able to comply with 
all requirements of the protocol, including completion of study questionnaires. 
* According to CTFG guidelines a woman is considered of childbearing potential, i.e. fertile, 
following menarche and until becoming post-menopausal unless permanently sterile. 
Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral 
oophorectomy. A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause.  
10.2.2 Exclusion Criteria 
Individuals who met any of the exclusion criteria in the original protocol or those listed 
below are not eligible to participate in the study: 
1. Epilepsy and currently on medication. 
2. Uncontrolled asthma. 
3. Concomitant use with sultopride. 
4. Concomitant use with medicinal products with a narrow therapeutic window. 
5. Clinically significant abnormalities in 12 lead ECG, in the opinion of the Investigator. 
  
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6. Breastfeeding or pregnant at Screening or planning to become pregnant at any time 
during the study. 
7. Intolerable amifampridine-related side effects   
8. Treatment with an investigational drug (other than amifampridine) or device while 
participating in this study. 
9. Any medical condition that, in the opinion of the Investigator, might interfere with 
the patient’s participation in the study, poses an added risk for the patient, or 
confound the assessment of the patient. 
10. History of drug allergy to any pyridine-containing substances or any amifampridine 
excipient(s). 
10.2.3 Removal of Patients from Treatment or Assessment 
Patients may withdraw their consent to participate in the study or to receive treatment with IP 
at any time without prejudice. The Investigator must withdraw from the study or from 
treatment with IP any patient who requests to be withdrawn. A patient’s participation in the 
study or treatment with IP may be discontinued at any time at the discretion of the 
Investigator and in accordance with his or her clinical judgment.  
Catalyst must be notified of all patient withdrawals from the study or from treatment with IP 
as soon as possible. Catalyst also reserves the right to discontinue the study at any time for 
either clinical or administrative reasons and to discontinue participation by an individual 
Investigator or site for poor enrollment or noncompliance. 
Reasons for which the Investigator or Catalyst may withdraw a patient from the study 
treatment include, but are not limited to, the following: 
• Patient experiences a serious or intolerable AE; 
• Patient requires medication prohibited by the protocol;  
• Patient becomes pregnant (refer to Section 11.4 for details on the reporting 
procedures to follow in the event of pregnancy); 
• Patient does not adhere to study requirements specified in the protocol; 
• Patient was erroneously admitted into the study or does not meet inclusion criteria;  
• Patient is lost to follow-up. 
If a patient fails to return for scheduled visits, a documented effort must be made to 
determine the reason. If the patient cannot be reached by telephone, a certified letter should 
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be sent to the patient requesting contact with the Investigator. This information should be 
recorded in the study records. 
The Investigator or designee must explain to each patient, before enrollment into the study, 
that for evaluation of study results, the patient’s protected health information obtained during 
the study may be shared with Catalyst, regulatory agencies, and IRB/IEC/REB. It is the 
Investigator’s (or designee’s) responsibility to obtain written permission to use protected 
health information, per country-specific regulations, from each patient. If permission to use 
protected health information is withdrawn, it is the Investigator’s responsibility to obtain a 
written request, to ensure that no further data will be collected from the patient and the 
patient will be removed from the study. 
10.2.4 Patient Identification 
Each patient will be assigned a unique patient identifier (2 digit for the site and 2 digit for 
each patient enrolled). This unique identifier will be on all CRF pages.  
10.3 Treatments 
10.3.1 Treatments Administered 
Catalyst or its designee will provide the study site with a supply of Investigational product: 
amifampridine tablets 10 mg at various intervals sufficient for the completion of the study. 
Amifampridine will be provided in round, white-scored tablets and containing amifampridine 
phosphate formulated to be the equivalent of 10 mg amifampridine base per tablet. The 
product will be provided in bottles of bulk tablets to the Catalyst designee who will dispense 
to the site an amount for each portion of the study, in a patient-specific labeled bottle. 
10.3.2 Identity of Investigational Product 
The chemical name of amifampridine phosphate is: 
• 3,4-pyridinediamine, phosphate (1:1) diamino-3,4-pyridine, phosphate salt 
• 3,4-diaminopyridine phosphate 
The chemical structure is provided in Figure 1. 
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Figure 1. 
Chemical Structure of Amifampridine Phosphate 
 
10.3.2.1 Product Characteristics and Labeling 
Drug product is formulated as a phosphate salt of amifampridine. Tablets were developed to 
provide the equivalent of 10 mg of amifampridine base for oral administration. Each tablet 
contains amifampridine phosphate, microcrystalline cellulose, colloidal anhydrous silica, and 
calcium stearate. The bottles of tablets are labeled “Amifampridine Phosphate Tablets, 
10 mg.” 
The tablets are to be dispensed by the Catalyst designee into suitably sized pharmacy 
containers for patient use. Each bottle provided to patients will be labeled to include the 
compound name, site number, patient ID number, date dispensed, storage instructions, the 
statement ‘Caution – New Drug – Limited to investigational use’, trial number, manufacturer 
name and address, and area for instructions for use. Regional label requirements and 
translations should be used in accordance with local regulations. 
10.3.2.2 
Storage 
All IP must be stored under the conditions specified, 20-25○ Celsius (C) (excursions between 
15-30°may be permitted) and in a secure area accessible only to the pharmacist. All IP must 
be stored and inventoried, and the inventories must be carefully and accurately documented 
according to applicable national and local regulations, ICH GCP, and study procedures. 
10.3.3 Directions for Administration 
All doses of study drug will be taken as outpatients. Study drug should be taken every day at 
approximately the same time, on empty stomach or with small amount of food (crackers) 
since food significantly delays the absorption of the drug and will slow onset of action, at the 
dose and frequency instructed by Investigator. 
The dose of amifampridine will be based on optimal neuromuscular benefit determined from 
the Run-in Period from SMA-001 or may be modified as the discretion of the Investigator. 
H3PO4
N
NH2
NH2
4
1
2
3
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The maximum single dose is 20 mg.  The dose range for patients 6 to 16 years of age is 15 to 
60 mg and for those 17 years and older, the range is from 30 to 80 mg daily. The daily dose 
of amifampridine can be adjusted during this long-term at the discretion of the Investigator. 
10.3.4 Method of Assigning Patients to Treatment Groups 
All patients will receive open label amifampridine. Details on study drug preparation, 
dispensing medication will be included in the Pharmacy Manual.  
10.3.5 Selection of Doses Used in the Study 
Initially, the daily amifampridine dose will be the one that was determined at the end of the 
Run-in Period from SMA-001. The usual range is 20 to 80 mg total daily dose, given in 3 or 
4 divided doses, with no single dose >20 mg. Safety of a single maximum dose of 20 mg is 
based on completed animal and in vitro pharmacology, PK, and toxicology studies.  
10.3.6 Blinding 
This is an open label study.  
10.3.7 Treatment Compliance 
Patients will be instructed to take study medication as directed and bring all IP containers and 
remaining test medication at each study visit. Patient compliance with the dosing regimen 
will be assessed by reconciliation of the used and unused IP. The quantity dispensed, 
returned, used, lost, etc., must be recorded on the medication dispensing log provided for the 
study. 
10.3.8 Investigational Product Accountability 
The  Catalyst designee is responsible for maintaining accurate records (including dates and 
quantities) of IP received and sending IP to the site.  The clinical site is responsible for 
maintaining accurate records for IP dispensed, returned, and IP lost or destroyed. The 
Investigator, study site coordinator or designee must retain all unused or expired study 
supplies until the study monitor (on-site CRA) has confirmed the accountability data. 
10.3.9 Return and Disposition of Clinical Supplies 
Unused IP must be kept in a secure location for accountability and reconciliation by the study 
monitor. The Investigator or designee must provide an explanation for any destroyed or 
missing IP or study materials. 
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Unused IP may be destroyed on site, per the site’s standard operating procedures, but only 
after Catalyst has granted approval for drug destruction. The monitor must account for all IP 
in a formal reconciliation process prior to IP destruction. All IP destroyed on site must be 
documented. Documentation must be provided to Catalyst and retained in the Investigator 
study files. If the site is unable to destroy IP appropriately, the site can return unused IP to 
Catalyst upon request. The return of IP or IP materials must be accounted for on a Study 
Drug Return Form provided by Catalyst. 
All IP and related materials should be stored, inventoried, reconciled, and destroyed or 
returned according to applicable regulations and study procedures. 
10.4 
Prior and Concomitant Medications 
All prescription and over-the-counter medications and herbal and nutritional supplements 
taken during the Long-Term study will be recorded on the designated CRF.  All prior 
medications taken within 14 days of initiation of this study are to be recorded on the CRF 
which is also recorded in the appropriate CRF pages of Study SMA-001 as concomitant 
medication. 
The Investigator may prescribe additional medications during the study, if the prescribed 
medication is not prohibited by the protocol. In the event of an emergency, any needed 
medications may be prescribed without prior approval, but the medical monitor must be 
notified of the use of any contraindicated medications immediately thereafter. Any 
concomitant medications added or discontinued during the study should be recorded on the 
CRF. 
Medications that are contraindicated when combined with amifampridine phosphate are: 
• Medicinal products with narrow therapeutic window 
• Sultopride 
Amifampridine phosphate should be used with caution when combined with the following 
products: 
• Medicinal products known to lower the epileptic threshold 
• Medicinal products with atropinic effects 
• Medicinal products with cholinergic effects 
• Non depolarizing muscle relaxant acting medicinal products 
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• Depolarizing muscle relaxant acting medicinal products. 
10.5 Dietary or Other Protocol Restrictions 
10.5.1 Dietary Restrictions 
There are no dietary restrictions for patients during any part of this study. 
10.5.2 Contraception 
Sexually active males and females of childbearing potential and their partners must use 
effective forms of contraception, including: combined hormonal contraception associated 
with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal 
contraception associated with inhibition of ovulation (oral, injectable or implantable); 
intrauterine device; intrauterine hormone-releasing system; bilateral tual occlusion; 
vasectomised partner; sexual abstinence.   
According to CTFG guidelines a woman is considered of childbearing potential, i.e. fertile, 
following menarche and until becoming post-menopausal unless permanently sterile. 
Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral 
oophorectomy. 
A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause.  
10.6 Safety Variables 
Safety in this study will be determined from evaluation of AEs/SAEs, vital signs 
assessments, clinical laboratory assessments, ECGs, and physical examinations. Pregnancy 
testing is also required for females of childbearing potential. The timing of the required 
evaluations is described in the Schedule of Events in Table 1 and in Section 13. 
10.6.1 Adverse Events 
The determination, evaluation and reporting of AEs will be performed as outlined in 
Section 11.  
10.6.2 Vital Signs 
Specific visits for obtaining vital signs are provided in Table 1 and in Section 13. Vital signs 
will be measured while in a sitting position, after resting for 5 minutes, and include SBP and 
DBP measured in millimeters of mercury (mmHg), heart rate in beats per minute, respiration 
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rate in breaths per minute. Weight (kg) and temperature in degrees C will also be measured. 
Clinically significant changes from baseline will be recorded as AEs. 
10.6.3 Clinical Laboratory Assessments 
Specific visits for obtaining clinical laboratory assessment samples are provided in Table 1 
for the tests required by Protocol. The scheduled clinical laboratory tests are listed in Table 2. 
In brief, clinical laboratory evaluations are to be performed every 3 to 6 months. These tests 
can be performed more frequently at the discretion of the Investigator. 
All abnormal clinical laboratory result pages should be initialed and dated by an Investigator, 
along with a comment for each abnormal result indicating whether or not it is clinically 
significant. Any abnormal test results determined to be clinically significant by the 
Investigator should be repeated (at the Investigator’s discretion) until the cause of the 
abnormality is determined, the value returns to baseline or to within normal limits, or the 
Investigator determines that the abnormal value is no longer clinically significant. 
Each clinically significant laboratory result should be recorded as an AE. The diagnosis, if 
known, associated with abnormalities in clinical laboratory tests that are considered clinically 
significant by the Investigator will be recorded on the AE CRF. 
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Table 2 Clinical Laboratory Tests 
Blood Chemistry 
Hematology 
Urine Tests 
Other 
Albumin  
Hemoglobin  
Appearance 
Pregnancy test, if applicable 
Alkaline phosphatase  
Hematocrit  
Color 
ALT (SGPT) 
WBC count 
pH 
 
AST (SGOT) 
RBC count 
Specific gravity 
 
Direct bilirubin 
Platelet count 
Ketones 
 
Total bilirubin 
Differential cell count  
Protein  
 
BUN 
 
Glucose  
 
Calcium 
 
Bilirubin 
 
Chloride 
 
Nitrite 
Total cholesterol 
 
Urobilinogen 
 
CO2 or bicarbonate 
 
Blood in urine 
 
Creatine phosphokinase 
 
 
 
Creatinine 
 
 
 
Glucose 
 
 
 
GGT 
 
 
LDH 
 
 
Phosphorus 
 
 
 
Potassium 
 
 
Total protein  
 
 
 
Sodium  
 
 
 
Uric acid 
 
 
 
 
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CO2, carbon 
dioxide; GGT, gamma-glutamyl transferase; LDH, lactate dehydrogenase; RBC, red blood cell; SGOT, serum 
glutamic-oxaloacetic transaminase; SGPT, serum glutamic-pyruvic transaminase; WBC, white blood cell. 
 
10.6.4 Pregnancy Testing 
Female patients of childbearing potential will have a urine pregnancy test at the end of the 
double-blind period on Day 10 and at other time points specified in the Schedule of Events 
(Table l) and in Section 13. Female patients with a positive pregnancy test at end of the 
double-blind study are not eligible for enrollment. Additional pregnancy tests will be 
performed at any visit in which pregnancy status is in question. 
Refer to Section 11.4 for details on the reporting procedures to follow in the event of 
pregnancy. 
10.6.5 Electrocardiogram (ECG) 
A standard 12-lead safety ECG (single tracing) will be recorded with the patient resting 
comfortably in the supine position at the time points specified in the Schedule of Events 
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(Table 1) and in Section 13. Clinically significant changes from baseline will be recorded as 
AEs.  
10.6.6 Physical Examination 
A complete physical examination is to be performed at each clinic visit or, if applicable, at 
early discontinuation from the study. Complete physical examination will include 
assessments of general appearance as well as the following: 
• Head 
• Eyes 
• Ears 
• Nose 
• Throat 
• Cardiovascular 
• Dermatologic 
• Lymphatic 
• Respiratory 
• Gastrointestinal 
• Musculoskeletal 
Body weight will be measured with each physical examination throughout the study.  
Other body systems may be examined. Clinically significant changes from baseline will be 
recorded as AEs. 
10.7 
Efficacy Variables 
Every 3 or 6 months, each patient will be assessed with the QoL questionnaire.  
10.7.1 Quality of life assessment 
The Individualized Quality of Life for neuromuscular disease (INQoL) or the Pediatric 
Quality of Life (PEDSQLTM) will be assessed for adult or pediatric patients, respectively.  
For the purposes of this study, the same QoL assessment instrument must be used throughout 
the study even if he/she becomes an adult. Each QoL evaluation is available in the local 
language for the appropriate sites.  
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11 REPORTING ADVERSE EVENTS 
11.1 Adverse Events 
For this protocol, a reportable AE is any untoward medical occurrence (e.g. sign, symptom, 
illness, disease or injury) in a patient administered the IP or other protocol-imposed 
intervention, regardless of attribution. This includes: 
• AEs not previously observed in the patient, that emerge during the study. 
• Pre-existing medical conditions judged by the Investigator to have worsened in 
severity or frequency or changed in character during the study. 
• Complications that occur as a result of non-drug protocol-imposed interventions. 
An adverse drug reaction is any AE for which there is a reasonable possibility that the IP 
caused the AE. “Reasonable possibility” means there is evidence to suggest a causal 
relationship between the IP and the AE. 
Whenever possible, it is preferable to record a diagnosis as the AE term rather than a series 
of terms relating to a diagnosis. 
All ongoing non-serious AEs, even those which began under Protocol SMA-001, will be 
reported from the end of the double-blind study (SMA-001) or from Day 0 for those not 
randomized to double blind medication in SMA-001 through the termination visit or at the 
early termination visit and will be recorded on the AE page of the eCRF. All ongoing SAEs 
from SMA-001 will be reported. The criteria for determining, and the reporting of new SAEs 
is provided in Section 11.2. 
The Investigator should follow all unresolved AEs until the events are resolved or stabilized, 
the patient is lost to follow-up, or it has been determined that the study treatment or 
participation is not the cause of the AE. Resolution of AEs (with dates) should be 
documented on the appropriate CRF page(s) and in the patient’s medical record. 
The Investigator responsible for the care of the patient or qualified designee will assess AEs 
for severity, relationship to IP, and seriousness (refer to Section 11.2 for SAE definition). 
Severity (as in mild, moderate or severe headache) is not equivalent to seriousness, which 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.  
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The Investigator will determine the severity of each AE using grades defined in Table 3 
Categories of Severity of Adverse Events (the event will be recorded on the source 
documents and AE CRF). Events that are Grades 4 and 5 are serious events and require 
completion of both an SAE form and AE CRF.  
 
Table 3 Categories of Severity of Adverse Events 
Severity 
Description 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental ADL*. 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL**. 
Grade 4 
Life-threatening consequences; urgent 
intervention indicated. 
Note: Grade 4 and 5 
adverse events should 
always be reported as 
serious adverse events 
Grade 5 
Death related to AE. 
Activities of Daily Living (ADL) 
* Instrumental ADLs refer to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
** Self-care ADLs refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 
The Investigator will suggest the relationship of an AE to the IP and will record it on the 
source documents and AE CRF, using the relationship categories defined in Table 4  
Description of Relationship to Adverse Event Categories. 
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Table 4  Description of Relationship to Adverse Event Categories 
Relationship 
Category 
Description 
Not Related 
Exposure to the IP has not occurred 
OR 
The administration of the IP and the occurrence of the AE are not 
reasonably related in time  
OR 
The AE is considered likely to be related to an etiology other than the use 
of the IP; that is, there are no facts [evidence] or arguments to suggest a 
causal relationship to the IP. 
Possibly 
Related 
The administration of the IP and the occurrence of the AE are reasonably 
related in time 
AND 
The AE could be explained equally well by factors or causes other than 
exposure to the IP. 
Probably 
Related 
The administration of IP and the occurrence of the AE are reasonably 
related in time  
AND 
The AE is more likely explained by exposure to the IP than by other factors 
or causes. 
 
In order to classify AEs and diseases, preferred terms will be assigned by the sponsor to the 
original terms entered in the CRF, using Medical Dictionary for Regulatory Activities 
(MedDRA) terminology. 
11.2 
Serious Adverse Events 
A serious adverse event is any untoward medical occurrence that at any dose meets 1 or more 
of the following criteria: 
• Is fatal 
• Is life threatening 
• Note: Life-threatening refers to an event that places the patient at immediate risk 
of death. This definition does not include a reaction that, had it occurred in a more 
severe form, might have caused death 
• Requires or prolongs in-patient hospitalization 
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• Results in persistent or significant disability or incapacity 
• Is a congenital anomaly or birth defect, that is, an AE that occurs in the child or fetus 
of a patient exposed to IP prior to conception or during pregnancy 
• Is an important medical event or reaction.  
The reporting period for SAEs begins after informed consent is obtained for the current 
SMA-002 study and continues through 4 weeks after the last visit.  
Any SAE, whether or not considered related to study drug, must be reported within 24 hours 
of knowledge of the event by forwarding (fax, email) the study-specific SAE Report Form to 
Catalyst and its designee PhAST Consulting s.r.l.. The Investigator should not wait to collect 
information that fully documents the SAE before notifying Catalyst. As additional 
information becomes available, including but not limited to the outcome of the SAE and any 
medication or other therapeutic measures used to treat the event, it must be reported within 
24 hours in a follow-up report. 
The Investigator should follow all unresolved SAEs until the events are resolved or 
stabilized, the patient is lost to follow-up, or it has been determined that the study treatment 
or participation is not the cause of the AE. Resolution of AEs (with dates) should be 
documented in the CRF and in the patient’s medical record. 
For some SAEs, Catalyst or designee may follow up by telephone, fax, email, and/or a 
monitoring visit to obtain additional case details deemed necessary to appropriately evaluate 
the SAE report (e.g. hospital discharge summary, consultant report, autopsy report). 
At the last scheduled visit, the Investigator should instruct each patient to report any 
subsequent SAEs that the patient’s personal physician(s) believes might be related to prior 
study treatment. 
The Investigator should notify Catalyst and its designee PhAST Consulting s.r.l of any death 
or SAE occurring at any time after a patient has discontinued, or terminated study 
participation, if felt to be related to prior study treatment. Catalyst and its designee PhAST 
Consulting s.r.l should also be notified if the Investigator should become aware of the 
development of cancer, or of a congenital anomaly, in a subsequently conceived offspring of 
a patient that participated in this study.  
Reporting of SAEs to the IEC will be done in compliance with the standard operating 
procedures and policies of the IEC and with applicable regulatory requirements. Adequate 
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documentation must be provided showing that the IEC was properly and promptly notified as 
required. 
11.3 Safety Blood Collection 
Patients who experience a serious or severe AE should have, at the discretion of the 
Investigator, a blood sample drawn for safety labs as soon as possible after the AE has 
occurred. 
Additional blood sampling may be performed at any time during the study if warranted to 
monitor patient safety. 
11.4 Pregnancy 
Pregnancy in a patient or partner should be reported within 24 hours of the site becoming 
aware of the pregnancy by fax or email of the Pregnancy Reporting Form in the study 
reference materials to Catalyst and its designee PhAST Consulting s.r.l.  In addition, 
pregnancy in a patient is also reported on the End of Study CRF. The Investigator must make 
every effort to follow the patient through resolution of the pregnancy (delivery or 
termination) and to report the resolution on the follow-up form (Pregnancy Reporting Form: 
Additional Information) in the study reference materials. In the event of pregnancy in the 
partner of a study patient, the Investigator should make every reasonable attempt to obtain 
the woman’s consent for release of protected health information. 
11.5 Urgent Safety Measures 
The regulations governing clinical trials state that the sponsor and Investigator are required to 
take appropriate urgent safety measures to protect subjects against any immediate hazards 
that may affect the safety of subjects, and that the appropriate regulatory bodies should be 
notified according to their respective regulations. According to the European Union (EU) 
Clinical Trial Directive 2001/20/EC, “…in the light of the circumstances, notably the 
occurrence of any new event relating to the conduct of the trial or the development of the 
investigational medicinal product where that new event is likely to affect the safety of the 
subjects, the sponsor and the Investigator shall take appropriate urgent safety measures to 
protect the subjects against any immediate hazard. The sponsor shall forthwith inform the 
competent authorities of those new events and the measures taken and shall ensure that the 
IEC is notified at the same time.” The reporting period for urgent safety measures is the 
period from the time of signing of the ICF through the completion of the last study visit. 
Investigators are required to report any urgent safety measures with 24 hours. 
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Examples of situations that may require urgent safety measures include discovery of the 
following: 
• An immediate need to revise IP administration (i.e. modified dose amount or 
frequency not defined in protocol). 
• Lack of study scientific value, or detrimental study conduct or management. 
• Discovery that the quality or safety of IP does not meet established safety 
requirements. 
 
11.6 Medical Monitor Contact Information 
Contact information and additional requirements will be provided in the SMA-002 Study 
Reference Manual. 
The Investigator is encouraged to discuss with the medical monitor any AEs for which the 
issue of seriousness is unclear or questioned. Contact information for the study Medical 
Monitor is listed below. 
Stanley Iyadurai, MD, PhD 
Vice President Clinical Affairs 
Catalyst Pharmaceuticals, Inc. 
Tel: +1 305-420-3239 
Email: siyadurai@catalystpharma.com 
 
12 APPROPRIATENESS OF MEASUREMENTS 
The measures of safety used in this study are routine clinical and laboratory procedures. 
The efficacy measure is based on the QoL assessment.  
13 REPORTING ADVERSE EVENTS STUDY PROCEDURES 
13.1 Start of Long Term Study 
An ICF for the Long-Term Study must be signed and dated by the patient and parents for 
patients with age < 18 years, the Investigator or designee, and witness (if required) before 
any study-related procedures are performed.  
The following procedures are to be performed as schedule for either the Day 0 (in the case 
where patient was not randomized) or the Day 28 visit for the SMA-001 protocol and can 
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serve as baseline for the Long-Term study. Any procedure not performed for SMA-001 
protocol needs to be completed before the patient can be enrolled in this trial. 
• Informed Consent for SMA-002; 
• Inclusion/Exclusion criteria for the current study must be verified; 
• Standard 12-lead ECG after 5 minutes in the supine position; 
• Complete physical examination including weight;  
• Vital signs (seated position), including SBP, DBP, heart rate, respiration, and body 
temperature;  
• Clinical laboratory tests including hematology, chemistry, and urinalysis; 
• Urine pregnancy test in females of childbearing potential only; 
• QoL (use data from Day 0 of SMA-001 for those patients not randomized in SMA-
001); 
• AEs;  
• Concomitant medications. 
13.2 
End of Months 3, 6, 9, 12, 15, 21 and 27 in Long Term Study  
The following assessments and procedures will be determined at the end of Months 3, 6, 9, 
12, 15, 21 and 27. Each month has a clinic visit window of ± 1 week. Additional visits are 
allowed as necessary. 
• Assessment of AEs/SAEs; 
• Complete physical exam with weight; 
• Vital signs (seated position), including SBP, DBP, heart rate, respiration, and body 
temperature; 
• Standard 12-lead ECG after 5 minutes in the supine position; 
• Clinical laboratory tests including hematology, chemistry, and urinalysis;  
• Urine pregnancy test in females of childbearing potential only; 
• Concomitant medications; 
• IP accountability of medication; 
• QoL  
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All IP should be collected from the patient at each visit, in order to perform drug 
accountability. The investigator or her/his designee will dispense sufficient amifampridine 
for daily outpatient administration for 90 days (or 180 days from Months 15 to 27).   
Patients may continue to receive amifampridine until the study is terminated, the patient 
decides to withdraw from the study, or the development program is discontinued for this 
indication.  
13.2.1 End of Study Visit  
Patients will report to the study site at the end of the study and have the assessments and 
procedures listed below completed.  This visit may be incorporated at the scheduled 3-or 6-
month visit. 
• Assessment of AEs/SAEs; 
• Complete physical exam with weight; 
• Vital signs (seated position), including SBP, DBP, heart rate, respiration, and body 
temperature; 
• 12-Lead ECG; 
• Clinical laboratory tests; 
• Urine pregnancy test in females of childbearing potential only; 
• Concomitant medications;  
• IP accountability; 
• 
QoL   
14 DATA QUALITY ASSURANCE 
Catalyst personnel or designees will visit or telephone the study site before initiation of the 
study to review with the site personnel information about the IP, protocol and other 
regulatory document requirements, source document requirements, CRFs, monitoring 
requirements, and procedures for reporting AEs/SAEs.  
At visits during and after the study, a CRA will monitor the site for compliance with 
regulatory documentation, with a focus on accurate and complete recording of data on CRFs 
from source documents, adherence to protocol, AE/SAE reporting, and drug accountability 
records. 
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15 STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
15.1 Statistical and Analytical Plans 
15.1.1 Interim Analyses 
No interim analyses are planned. 
15.2 Analysis Populations 
The analysis population in this study is the safety population and will consist of all patients 
who are enrolled in the Long-Term study and have received at least one dose of 
amifampridine.     
15.3 Primary Endpoint 
The primary endpoint of the study is safety and tolerability of amifampridine at Months 3, 6, 
9, 12, 15, 21 and 27.  For more details see Section 15.5 below. 
15.4 
Secondary Endpoint  
The secondary endpoint of the study is the QoL scores at Months 3, 6, 9, 12, 15, 21 and 27.  
15.5 Safety Analysis  
Prior to analysis, all AEs will be coded using the MedDRA coding dictionary. Based on these 
coded terms, TEAEs and SAEs will be summarized using system organ class and preferred 
terms, as well as by relationship to treatment. All AEs will be listed, regardless of whether 
they were study treatment related.   
Vital signs will be summarized using descriptive statistics (mean, standard deviation, median, 
minimum, maximum, and number of non-missing observations) by time point.  Changes 
from baseline will also be summarized by post-dose time point. 
Clinical laboratory parameters will be summarized using descriptive statistics (mean, 
standard deviation, median, minimum, maximum, and number of non-missing observations) 
by time point.  Changes from baseline will also be summarized by post-dose time point.  In 
addition, a shift table will be constructed to show the shifts in laboratory results by parameter 
relative to the normal ranges.  The number and percentage of subjects with the following 
shifts will be presented: normal/normal, normal/low, normal/high, low/low, low/normal, 
low/high, high/low, high/normal, and high/high. Similar shift tables will also be constructed 
for physical exam results. ECG results will be summarized in a shift table with the following 
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shifts presented: normal/normal, normal/abnormal, abnormal/normal and 
abnormal/abnormal. A table of descriptive statistics for QTc will be created. 
Additional safety analyses may be performed as described in the Statistical Analysis Plan 
(SAP) for the study. 
15.6 Determination of Sample Size 
The study is not powered with respect to any endpoint and no hypothesis is being tested.  
15.7 Changes in the Conduct of the Study or Planned Analyses 
Any change in study conduct considered necessary by the Investigator will be made only 
after consultation with Catalyst, who will then issue a formal protocol amendment to 
implement the change. The only exception is when an Investigator considers that a patient’s 
safety is compromised without immediate action.  
Protocol amendments that influence patient risk or the study objectives, or require revision of 
the ICF, must receive approval from the IEC prior to their implementation. 
When a protocol amendment substantially alters the study design or the potential risks or 
burden to patients, the ICF will be amended and approved by Catalyst and the IRB/IEC/REB, 
and all active patients must again provide informed consent. 
Note: If discrepancies exist between the text of the statistical analysis as planned in the 
protocol, and the final SAP, a protocol amendment will not be issued, and the SAP will 
prevail. 
16 COMPENSATION, INSURANCE, AND INDEMNITY 
There will be no charge to study patients to be in this study. Catalyst will pay all costs of 
tests, procedures, and treatments that are part of this study (as included in the site budget). In 
addition, after IEC approval, Catalyst may reimburse the cost of travel for study-related 
visits. Catalyst will not pay for any hospitalizations, tests, or treatments for medical problems 
of any sort, whether or not related to the study patient’s disease that are not part of this study. 
Costs associated with hospitalizations, tests, and treatments should be billed and collected in 
the way that such costs are usually billed and collected. 
The Investigator should contact Catalyst immediately upon notification that a study patient 
has been injured by the IP or by procedures performed as part of the study. Any patient who 
experiences a study-related injury should be instructed by the Investigator to seek medical 
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treatment at a pre-specified medical institution if possible, or at the closest medical treatment 
facility if necessary. The patient should be given the name of a person to contact to seek 
further information about, and assistance with, treatment for study-related injuries. If the 
patient has followed the Investigator’s instructions, Catalyst will pay for reasonable and 
necessary medical services to treat the injuries caused by the IP or study procedures, if these 
costs are not covered by health insurance or another third party that usually pays these costs. 
17 CASE REPORT FORMS AND SOURCE DOCUMENTS 
The CRO data management department or designee will perform all data management 
activities, including the writing of a data management plan outlining the systems and 
procedures to be used. 
Electronic case report forms (eCRFs) will be provided. The eCRF system, and procedures, 
and electronic signatures follow ICH requirements and applicable laws and local regulations. 
All system users will be trained on the eCRF before being granted system access. In the 
event of an entry error, or if new information becomes available, users will correct the value 
by deselecting the erroneous response and then selecting or entering the factual response. The 
documented audit trail will include the reason for the change, the original value, the new 
value, the time of the correction and the identity of the operator. 
In the application, study data on the eCRFs will be verified to the source data, which 
necessitates access to all original recordings, laboratory reports, and patient records. 
In addition, all source data should be attributable (signed and dated). The Investigator must 
therefore agree to allow direct access to all source data. Patients must also allow access to 
their medical records, and patients will be informed of this and will confirm their agreement 
when giving informed consent. The Investigator must review and electronically sign the 
completed eCRF casebook to verify its accuracy. A CRA designated by Catalyst will 
compare the eCRFs in the application with the original source documents at the study site 
and evaluate them for completeness and accuracy before designating them as “Source Data 
Verified” in the application. If an error is discovered at any time or a clarification is needed, 
the Data Manager, CRA, or designee, will create an electronic query on the associated field. 
Site personnel will then answer the query by either correcting the data or responding to the 
query. The Data Manager or CRA will then review the response and determine either to close 
the query or re–query the site if the response does not fully address the question. This process 
will be repeated until all open queries are answered and closed. 
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The Investigator will then electronically sign the casebook, specifying that the information 
on the eCRFs is accurate and complete. An electronic copy of the site’s casebooks will be 
sent to the site for retention with other study documents.  
18 STUDY MONITORING AND AUDITING 
Qualified individuals approved and/or designated by Catalyst will monitor all aspects of the 
study according to GCP and SOPs for compliance with applicable government regulations. 
The monitoring will take place on site as well as remotely as the monitors can view all 
clinical data electronically and can follow-up with any queries for more information. The 
Investigator agrees to allow these monitors direct access to the clinical supplies, dispensing, 
and storage areas and to the clinical files, including original medical records, of the study 
patients, and, if requested, agrees to assist the monitors. The Investigator and staff are 
responsible for being present or available for consultation during routinely scheduled site 
visits conducted by Catalyst or its designees.  
Members of Catalyst’s GCP Quality Department or designees may conduct an audit of the 
clinical site at any time before, during, or after completion of the study. The Investigator will 
be informed if an audit is to take place and advised as to the scope of the audit. 
Representatives of the FDA or other regulatory agencies may also conduct an audit of the 
study. If informed of such an inspection, the Investigator should notify Catalyst immediately. 
The Investigator will ensure that the auditors have access to the clinical supplies, study site 
facilities, original source documentation, and all study files. 
19 RETENTION OF RECORDS 
The Investigator must retain all study records required by Catalyst and by the applicable 
regulations in a secure and safe facility. The Investigator must consult a Catalyst 
representative before disposal of any study records and must notify Catalyst of any change in 
the location, disposition or custody of the study files. The Investigator/institution must take 
measures to prevent accidental or premature destruction of essential documents, that is, 
documents that individually and collectively permit evaluation of the conduct of a study and 
the quality of the data produced, including paper copies of study records (e.g. patient charts) 
as well as any original source documents that are electronic as required by applicable 
regulatory requirements.  
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All study records must be retained for at least 2 years after the last approval of a marketing 
application in an ICH region and until (1) there are no pending or contemplated marketing 
applications in an ICH region or (2) at least 2 years have elapsed since the formal 
discontinuation of clinical development of the IP. The Investigator/institution should retain 
patient identifiers and records for at least 15 years after the completion or discontinuation of 
the study. Patient files and other source data must be kept for the maximum period of time 
permitted by the hospital, institution or private practice. These documents should be retained 
for a longer period, however, if required by the applicable regulatory requirements or by a 
Catalyst agreement. Catalyst must be notified and will assist with retention should 
Investigator/institution be unable to continue maintenance of patient files. It is the 
responsibility of Catalyst to inform the Investigator /institution as to when these documents 
no longer need to be retained. 
20 USE OF INFORMATION AND PUBLICATION 
Catalyst recognizes the importance of communicating medical study data and therefore 
encourages their publication in reputable scientific journals and at seminars or conferences. 
The details of the processes of producing and reviewing reports, manuscripts, and 
presentations based on the data from this study will be described in the Clinical Trial 
Agreement between Catalyst and the institution of the Investigator. 
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Palace J, Wiles CM, Newsom-Davis J. 3,4-Diaminopyridine in the treatment of congenital 
(hereditary) myasthenia. J Neurol Neurosurg Psychiatry 54[12]: 1069-1072, 1991. 
 
Sanders DB, Massey JM, Sanders LL, Edwards LJ. A randomized trial of 3,4-
diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology 54[3], 603-607. 2000.  
 
Sanders DB, Howard JF Jr, Massey JM. 3,4-Diaminopyridine in Lambert-Eaton myasthenic 
syndrome and myasthenia gravis. Ann N Y Acad Sci 681, 588-590. 1993.  
 
Skjei KL, Lennon VA, Kuntz NL: Muscle specific kinase autoimmune myasthenia gravis in 
children: A case series. Neuromuscul Disorders 2013 Nov;23(11):874-882 
 
Skeie GO, Apostolski S, Evoli A, Gilhus NE, et al. Guidelines for the treatment of 
autoimmune neuromuscular transmission disorders. Eur J Neurol 17[7], 893-902. 2010. 
 
Skeie GO, Apostolski S, Evoli A, Gilhus NE, et al. Guidelines for the treatment of 
autoimmune neuromuscular transmission disorders. Eur J Neurol 13[7], 691-699. 2006.  
 
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22 INVESTIGATOR RESPONSIBILITIES 
22.1 Conduct of Study and Protection of Human Patients 
The Investigator will ensure that: 
• He or she will conduct the study in accordance with the relevant, current protocol and 
will only make changes in a protocol after notifying the sponsor, except when 
necessary to protect the safety, rights, or welfare of patients. 
• He or she will personally conduct or supervise the study. 
• He or she will inform any potential patients, or any persons used as controls, that the 
drugs are being used for investigational purposes and he or she will ensure that the 
requirements relating to obtaining informed consent in compliance with ICH E6 
(Section 4.8), and other applicable local regulations, are met.  
• He or she will report to the sponsor adverse experiences that occur during the 
investigation in compliance with the standard operating procedures and policies of the 
IRB/IEC/REB and with applicable regulatory requirements. 
• He or she has read and understands the information in the Investigator Brochure, 
including potential risks and side effects of the drug. 
• His or her staff and all persons who assist in the conduct of the study are informed 
about their obligations in meeting the above commitments. 
• He or she will ensure that adequate and accurate records are kept in accordance with 
ICH and GCP requirements and to ensure those records are available for inspection. 
• He or she will ensure that the IRB/IEC/REB complies with ICH and GCP 
requirements, and other applicable regulations, and conducts initial and ongoing 
reviews and approvals of the study. He or she will also ensure that any change in 
research activity and all problems involving risks to human patients or others are 
reported to the IRB/IEC/REB. Additionally, he or she will not make any changes in 
the research without IRB/IEC/REB approval, except where necessary to eliminate 
apparent immediate hazards to human patients. 
• He or she agrees to comply with all other requirements regarding the obligations of 
clinical Investigators and all other pertinent ICH and GCP requirements. 
• He or she agrees to comply with electronic signature requirements in accordance with 
ICH requirements and applicable laws and local regulations. 
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APPENDIX  1  PROTOCOL VERSION  3.0  
PURPOSE: The purpose of this version is as follows: 
To add an additional site, update medical monitor information, and update product 
information, based upon FDA approval. 
Risk: these administrative changes provide clarity, adding no additional risk to the patient. 
 
MODIFICATIONS TO PROTOCOL: 
Bold and underlined text: 
 
Changed Text 
Bold and strike through text: 
Deleted Text 
Bold and italicized text: 
 
Added Text 
 
CLINICAL STUDY PROTOCOL,  
IND Number was updated  106263 142044   
Version and Date of Protocol, added text to indicate this is protocol Version 3.0 
Version 3.0 dated 12 April 2019 (amendment) 
Footer was updated to reflect new version information 
 
Section numbers have been added to  
2 PROCEDURES IN CASE OF AN EMERGENCY  and  3 SYNOPSIS. 
Other section numbers in the remainder of the document have been adjusted accordingly. 
 
Section 2, PROCEDURES IN CASE OF AN EMERGENCY, under Medical Monitor, 
changed the Name and Contact Information. 
Gary Ingenito, Chief Medical Officer 
ext. 123 
gingenito@catalystpharma.com 
Stanley Iyadurai, MD, PhD 
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Vice President, Clinical Affairs 
ext. 139 
siyadurai@catalystpharma.com 
 
Section 2, PROCEDURES IN CASE OF AN EMERGENCY, Investigators Name and 
Contact Information section were removed.  
 
Section 2, PROCEDURES IN CASE OF AN EMERGENCY, under Contract Research 
Organization, for High Research s.r.l., the phrase  for Italy  was added. 
 
Section 2, PROCEDURES IN CASE OF AN EMERGENCY, under Contract Research 
Organization, additional CRO contact information was added as follows : 
 
Easthorn Clinical Services for countries outside Italy 
Obilicev venac 15 
11000 Belgrade, Serbia 
Tel: +381 11 3286 305 
Email: ivana.mucic@easthorn.eu 
 
Section 2, PROCEDURES IN CASE OF AN EMERGENCY, Safety Reporting, changed 
address for PhAST Consulting s.r.l. 
Via A. Gramsci 10 
20090 Monza, Italy 
 
Via Roma 74 - 20060  
Cassina de’ Pecchi (MI) Italy 
 
Section 3 SYNOPSIS, under Study Sites, changed reference to single site, to reflect added 
sites 
Single site in Italy 
Up to 3 sites 
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Section 3 SYNOPSIS, under Phase of Development, added ‘a’ to Phase 3a 
 
On Page 3 SYNOPSIS, Criteria for Inclusion and Exclusion, the following were removed: 
5.  Concomitant use of medicinal products with a known potential to cause QTc 
prolongation. 
7. Subjects with congenital QT syndromes. 
 
Section 4  TABLE OF CONTENTS, has been updated with the following: 
Sections 2 PROCEDURES IN CASE OF AN EMERGENCY and 3 SYNOPSIS have been 
included, other section numbers in the remainder of the document have been adjusted. 
 
Appendix 1 Quality of Life Assessments was removed, and APPENDIX 1  PROTOCOL 
VERSION 3.0  history has been added to Table of Contents. 
 
Section 8 INTRODUCTION, and Section 8.2, the Firdapse Investigator Brochure date was 
updated 
June 2017 March 2019 
 
Section 10.2.2 Exclusion Criteria, the following were removed: 
5.  Concomitant use of medicinal products with a known to cause QTc prolongation. 
8. Subjects with congenital QT syndromes. 
 
Section 10.3.2.2 Storage, the following was added: 
(excursions between 15-30° may be permitted) 
 
Section 10.4 Prior and Concomitant Medications, the following were removed: 
• Medicinal products known to prolong QTe interval 
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• Medicinal products with a narrow therapeutic window 
 
Table 2 Clinical Laboratory Tests, Blood Chemistry item has been updated: 
CO2 or bicarbonate 
 
Table 2 Clinical Laboratory Tests, under the column Urine Tests, text was changed: 
Hemoglobin   Blood in urine 
 
Section 10.7.1 Quality of life assessment, the following has been changed: 
A copy of the Quality of Life assessments is in Appendix 1.  
Each QoL evaluation is available in the local language for the appropriate sites. 
 
Section 11.6 Medical Monitor Contact Information, changed the Name and Contact 
Information. 
Gary Ingenito, Chief Medical Officer 
ext. 123 
gingenito@catalystpharma.com 
Stanley Iyadurai, MD, PhD 
Vice President Clinical Affairs 
Catalyst Pharmaceuticals, Inc. 
Tel: +1 305-420-3239 
Email: siyadurai@catalystpharma.com 
 
Section 13.1 Start of Long Term Study, protocol number was added: 
• QoL (use data from Day 0 of SMA-001 for those patients not randomized in SMA-
001); 
 
Section 23, Signature Page, information below the Medical Monitor Signature was updated.  
Gary Ingenito, MD, PhD 
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Chief Medical Officer 
 
Stanley Iyadurai, MD, PhD 
Vice President Clinical Affairs 
Catalyst Pharmaceuticals, Inc. 
 
Appendix 1 Quality of Life Assessments has been removed. 
Appendix 1 Protocol Version 3.0 has been added to record changes made to this protocol.  
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Prot_000.pdf: