Clinical trial NCT02958982
Conditions: Healthy Volunteers Asthma
Keywords: RP3128 Phase 1 Healthy volunteers
Sponsor: Rhizen Pharmaceuticals SA
Start date: 2016-11-03; Completion date: 2018-02-01
Enrollment: 57 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
RP3128 is a calcium release activated calcium (CRAC) channel modulator. The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of single and multiple ascending dose(s) of RP3128 in healthy volunteers and to evaluate the effect on late phase asthmatic response to allergen challenge in patients with mild asthma.

Detailed description:
The study consists of three parts; Part 1: single ascending dose (SAD), Part 2: multiple ascending dose (MAD) in healthy volunteers and Part 3: proof of concept (POC) study in mild asthmatics. There will be 5 cohorts in SAD and 3 cohorts in MAD, the doses used in the MAD will be based on emerging safety, tolerability and pharmacokinetics (PK) from Part 1 (SAD). POC is a randomized, placebo- controlled, double blind, two period cross-over, proof of concept study in male and female of non child bearing potential with history of mild asthma. the highest identified dose of RP3128 in Part 2 (MAD) will be considered for POC

Arms: arm 1: RP3128, A CRAC channel modulator arm 2: Placebo
Interventions: intervention 1: RP3128 intervention 2: Placebo
Intervention descriptions: intervention 1: Participants will receive single oral dose of RP3128 in SAD, multiple dose in MAD AND POC intervention 2: Participants will receive single oral dose of RP3128 in SAD, multiple dose in MAD AND POC

Protocol documents:
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SAP_001.pdf: 
  
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
An integrated Phase I/IIa, randomized, double-blind, placebo controlled study to evaluate 
the safety, tolerability and pharmacokinetics of single and multiple ascending dose(s) of 
oral RP3128 (CRAC channel modulators) in healthy volunteers and to evaluate the effect 
on Late Phase Asthmatic Response(LAR) to allergen challenge in patients with mild 
asthma 
 
Protocol Number: 
Inflamax Protocol Number: 15-MR-001 
Final Version 2 – 22 March 2017 
Clinical Research Organization: 
Inflamax Research Limited 
1310 Fewster Drive 
Mississauga, ON L4W 1A4 Canada 
Sponsor: 
Rhizen Pharmaceuticals SA 
Fritz-Courvoisier 40,  
Ch-2300 La Chaux-de-Fonds, 
Switzerland 
 
22June2017 
Final Version 1.0 
 
 
 
 
 
 




 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 3 of 95 
 
Revision History 
VERSI
DATE 
DESCRIPTION OF REVISIONS 
REVISED BY 
Draft 0.1 
02FEB2017 
Draft 0.1 
 
Draft 0.2 
02JUN2017 
Revised per internal and external comments 
Tian Fang 
Draft 0.3 
16JUN2017 
Revised per internal and external comments 
David Yu, Tian 
Fang 
Final 1.0 
22JUN2017   
Final 1.0 
 
 
   
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 4 of 95 
 
TABLE OF CONTENTS 
1 
GLOSSARY OF ABBREVIATIONS ........................................................................ 9 
2 
INTRODUCTION .................................................................................................... 11 
3 
TUDY OBJECTIVES .............................................................................................. 12 
3.1 
Primary Objective ............................................................................................................................... 12 
3.2 
Secondary Objective ............................................................................................................................ 12 
3.3 
Brief Description ................................................................................................................................. 12 
3.4 
Subject Selection ................................................................................................................................. 13 
3.5 
Determination of Sample Size .............................................................................................................. 13 
3.6 
Treatment Assignment ........................................................................................................................ 13 
3.7 
Administration of Study Medication .................................................................................................... 14 
4 
ENDPOINTS .......................................................................................................... 15 
4.1 
Primary Endpoints .............................................................................................................................. 15 
4.2 
Secondary Endpoints ........................................................................................................................... 15 
5 
ANALYSIS POPULATION .................................................................................... 17 
5.1 
Randomized Population ...................................................................................................................... 17 
5.2 
Safety Population ................................................................................................................................ 17 
5.3 
Pharmacokinetic (PK) Population ....................................................................................................... 17 
5.4 
Protocol Deviations ............................................................................................................................. 17 
6 
GENERAL ASPECTS FOR STATISTICAL ANALYSIS ........................................ 18 
6.1 
Summary Statistics .............................................................................................................................. 18 
6.1.1 
Summary Statistics Reporting Precision ......................................................................................... 18 
6.2 
Key Definitions .................................................................................................................................... 19 
6.3 
Attribution of Treatment-Emergent AE for Imcompleted AE date/time .............................................. 19 


 
 
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Study: Study 15-MR-001 
Statistical Analysis Plan  
 
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7 
DEMOGRAPHIC, OTHER BASELINE CHARACTERISTICS AND 
MEDICATION ............................................................................................................... 21 
7.1 
Subject Disposition and Withdrawals .................................................................................................. 21 
7.2 
Baseline Characteristics ...................................................................................................................... 21 
7.3 
Treatment Compliance ........................................................................................................................ 22 
8 
ANALYSIS OF PHARMACOKINETICS ................................................................ 23 
8.1 
Measurements ..................................................................................................................................... 23 
8.2 
Collection Schedule ............................................................................................................................. 23 
8.3 
Derived Data and Handling of Missing or below LLOQ data ............................................................... 23 
8.3.1 
Derivation of PK Parameters ......................................................................................................... 23 
8.3.2 
Handling of Missing Plasma Concentration Data or below LOQ ...................................................... 24 
8.4 
Data Summarization ........................................................................................................................... 25 
8.5 
Data Presentation ................................................................................................................................ 25 
9 
SAFETY ................................................................................................................. 27 
9.1 
Adverse Events .................................................................................................................................... 27 
9.2 
Laboratory Evaluations ....................................................................................................................... 28 
9.2.1 
Collection Schedule ...................................................................................................................... 28 
9.2.2 
Derived and Imputed Data............................................................................................................. 30 
9.2.3 
Data Summarization and Presentation ............................................................................................ 30 
9.3 
Vital Signs ........................................................................................................................................... 30 
9.3.1 
Measurements .............................................................................................................................. 30 
9.3.2 
Collection Schedule ...................................................................................................................... 31 
9.3.3 
Derived and Imputed Data............................................................................................................. 32 
9.3.4 
Data Summarization and Presentation ............................................................................................ 32 
9.4 
ECG .................................................................................................................................................... 32 
9.5 
Physical Examination .......................................................................................................................... 33 
9.6 
Cognitive Test ..................................................................................................................................... 34 
10 
EXPLORATORY ANALYSES ............................................................................ 35 
11 
INTERIM ANALYSES ........................................................................................ 36 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 6 of 95 
 
12 
CHANGES TO PLANNED ANALYSES ............................................................. 37 
13 
APPENDIX: ........................................................................................................ 38 
APPENDIX A 
 LIST OF CLINICAL LABORATORY TESTS (PART 1-3) .......................................... 38 
APPENDIX B :  PART 1 (SAD) – Schedule of Events .................................................................................. 39 
APPENDIX C: PART 2 (MAD) — Schedule of Events ................................................................................. 41 
14 
TABLE AND LISTING ........................................................................................ 44 
Table 14.1.1.S/M Disposition of Subjects (SAD/MAD) Randomized Population ............................................ 45 
Table 14.1.2.S/M Summary of Demographics (SAD/MAD) Safety Population .............................................. 46 
Table 14.2.1.1.X.S RP3128 Plasma Concentrations (ng/mL) by Time Point (SAD) Safety Population <Dose 
Level> .......................................................................................................................................................... 48 
Table 14.2.1.1.1.X.M RP3128 Plasma Concentrations (ng/mL) by Time Point (MAD) – Day 1 Safety 
Population <Dose Level> .............................................................................................................................. 49 
Table 14.2.1.1.2.X.M RP3128 Plasma Concentrations (ng/mL) by Time Point (MAD) – Day 7 Safety 
Population <Dose Level> .............................................................................................................................. 50 
Table 14.2.1.2.X.S RP3128 – Summary of PK Parameters (SAD) PK Population <Dose Level> .................... 51 
Table 14.2.1.2.1.X.M RP3128 – Summary of PK parameters (MAD) – Day 1 PK Population <Dose Level> .. 52 
Table 14.2.1.2.2.X.M RP3128 – Summary of Ctrough (MAD)  PK Population <Dose Level> ........................... 53 
Table 14.2.1.2.3.X.M RP3128 – Summary of PK parameters (MAD) – Day 7 PK Population <Dose Level> .. 54 
Table 14.2.2.X.1.M Summary of Cytokines <expression value>: Change from Baseline (MAD) .................... 55 
Table 14.2.2.X.2.M ANCOVA Results of Cytokine <expression value> Change from Baseline to Day 7 (Pre-
dose/Post-dose)/ Difference between Pre-dose and Post-dose on Day 7 (MAD) .............................................. 56 
Table 14.3.1.1.S/M Treatment-Emergent Adverse Events – Overall Summary (SAD/MAD) Safety 
Population.................................................................................................................................................... 57 
Table 14.3.1.2.S/M Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
(SAD/MAD) Safety Population ..................................................................................................................... 58 
Table 14.3.1.3.S/M Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and 
Maximum Intensity (SAD/MAD) Safety Population ..................................................................................... 59 
Table 14.3.1.4.S/M Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and 
Maximum Relationship (SAD/MAD) Safety Population ............................................................................... 60 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 7 of 95 
 
Table 14.3.3.1.X.S/M Summary of <laboratory Panel> (SAD/MAD) ............................................................. 61 
Table 14.3.3.2.X.S/M <Laboratory Panel>: Shift Table from Baseline to End of Treatment Results 
(SAD/MAD) Safety Population ..................................................................................................................... 63 
Table 14.3.4.X.S/M Summary of Vital Signs Data by Treatment, Visit and Time Point (SAD/MAD) Safety 
Population.................................................................................................................................................... 64 
Table 14.3.4.6.S/M Summary of Weight Data by Treatment and Time Point (SAD/MAD) Safety Population 65 
Table 14.3.5.1.S/M Summary of Overall ECG Interpretation (SAD/MAD) Safety Population ...................... 66 
Table 14.3.5.X.S/M Summary of ECG Continuous Data (SAD/MAD)  Safety Population ............................. 67 
Table 14.3.6.1.S/M Summary of Mini-Mental State Examination (SAD/MAD) Safety Population ................. 68 
Listing 16.1.7.S/M Randomization Scheme and Code (SAD/MAD) Randomized Population ......................... 69 
Listing 16.2.1.S/M Subject Disposition and Completion/Discontinuation (SAD/MAD) Randomized 
Population.................................................................................................................................................... 70 
Listing 16.2.2.S/M Protocol Deviations (SAD/MAD) Safety Population ........................................................ 71 
Listing 16.2.3.S/M Exclusions from Analysis Populations (SAD/MAD) Randomized Population ................... 72 
Listing 16.2.4.S/M Demographics and Informed Consent at Screening (SAD/MAD) Safety Population ........ 73 
Listing 16.2.5.1.S/M Study Drug Administration and Compliance (SAD/MAD) Safety Population ............... 74 
Listing 16.2.5.2.S/M Pharmacokinetic Sample Collection Data (SAD/MAD) Safety Population .................... 75 
Listing 16.2.5.3.S Pharmacokinetic Parameters (SAD) PK Population .......................................................... 76 
Listing 16.2.5.4.S/M Reasons Why Pharmacokinetic Parameters Could Not be Determined (SAD/MAD) ..... 77 
Listing 16.2.6.1: Cytokine assessment ........................................................................................................... 78 
Listing 16.2.7.1.S/M Adverse Events (SAD/MAD) Safety Population ............................................................ 79 
Listing 16.2.7.2.S/M Deaths, Other Serious and Significant Adverse Events Safety Population (SAD/MAD). 80 
Listing 16.2.8.X.S/M <Laboratory Panel> (SAD/MAD) Safety Population .................................................... 81 
Listing 16.2.8.X.S/M <Laboratory Panel>: Abnormal Results (SAD/MAD) Safety Population ..................... 81 
Listing 16.2.8.7.S/M Viral Screen and TB Test at Screening (SAD/MAD) Safety Population ........................ 83 
Listing 16.2.8.8.S/M Drug and Alcohol Screen (SAD/MAD) Safety Population ............................................. 84 
Listing 16.2.9.1.S/M Vital Signs (SAD/MAD) Safety Population ................................................................... 85 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 8 of 95 
 
Listing 16.2.10.1.S/M Electrocardiogram (ECG) (SAD/MAD) Safety Population .......................................... 86 
Listing 16.2.10.2.S/M ECG: Abnormal Results – Listing (SAD/MAD) Safety Population .............................. 87 
Listing 16.2.11.S/M Mini-Mental State Examination (SAD/MAD) Safety Population .................................... 88 
Listing 16.2.12.S/M Medical History (SAD/MAD) Safety Population ............................................................ 89 
Listing 16.2.13.S/M Clinical Events (SAD/MAD) Safety Population ............................................................. 90 
Listing 16.2.14.S/M Prior and Concomitant Medications (SAD/MAD) Safety Population ............................. 91 
Listing 16.2.15.M Electroencephalogram at Screening (MAD) Safety Population ......................................... 92 
Figure 14.4.1.S/M – Mean Plasma RP3128 Concentrations – Linear Scale (SAD/MAD) ............................... 93 
Figure 14.4.2.S/M – Mean Plasma RP3128 Concentrations – Semi-logarithmic Scale (SAD/MAD) ............... 94 
Figure 14.4.3.X.S/M–Individual Plasma RP3128 Concentrations – Linear Scale (SAD/MAD) ...................... 95 
Figure 14.4.4.X.S/M–Individual Plasma RP3128 Concentrations – Semi-logarithmic Scale (SAD/MAD) ...... 95 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 9 of 95 
 
1 GLOSSARY OF ABBREVIATIONS 
Abbreviation 
Description 
ADaM 
Analysis Data Model 
AE 
 Adverse Event 
ALP 
Alkaline Phosphatase 
ALT (SGOT) 
Alanine Aminotransferase 
ANC 
Absolute Neutrophil Count 
ANCOVA 
Analysis of Covariance 
AST (SGPT) 
Aspartate Aminotransferase 
AUC 
Area Under the Curve 
AUC0-t 
Area Under the Plasma-Concentration Time Curve from Zero Up to 
the Last Measurable time point 
AUC0-inf 
Area Under the Curve from Zero extrapolated to infinite time 
BUN 
Blood Urea Nitrogen 
bpm 
Beats per minute 
CFB 
Change from Baseline 
CK 
Creatinine kinase 
CM 
Concomitant Medication 
Cav 
Average concentration during the dosing interval 
Cmax 
Peak Drug Concentration 
Cmin 
Lowest observed plasma concentration in the dosing interval 
Ctrough 
Plasma concentration at the end of the dosing interval 
CRAC 
Calcium Release Activated Calcium Channel 
CRF 
Case Report Form 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
FSH 
Follicular Stimulating Hormone 
GGT 
Gamma Glutamyl Transpeptidase 
HCV 
Hepatitis C Virus 
HIV 
Human Immune Deficiency Virus 
Hr 
Hour 
HV 
Healthy Volunteers 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 10 of 95 
 
Abbreviation 
Description 
ICH 
International Conference on Harmonization 
IMP 
Investigational Medicinal Product 
LAR 
Late Phase Asthmatic Response 
LPS 
Lipopolysaccharide 
Kel 
Apparent terminal elimination rate constant 
MAD 
Multiple ascending dose 
MCH 
Mean Corpuscular Hemoglobin 
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
mmHg 
Millimeters of mercury 
MMSE 
Mini Mental State Examination 
MTD 
Maximum Tolerated Dose 
PCP 
Phencyclidine 
PFT 
Pulmonary Function Test 
PI 
Principal Investigator 
PK 
Pharmacokinetic 
PR 
P wave, R wave interval 
PT 
Preferred Term 
QRS 
Q wave, R wave, and S wave complex 
QTcB 
QT wave complex corrected for heart rate using Bazette’s formula 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SDTM 
Study Data Tabulations Model 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SRC 
Safety Review Committee 
t1/2 
Half life 
TEAE 
Treatment Emergent AE 
Tmax 
Time of Cmax 
Kel 
Terminal Rate Constant 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 11 of 95 
 
2 INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to provide a thorough description of 
statistical methods and presentation of the study data to be used for the analysis of data generated 
from the Single Ascending Dose (SAD) part and the Multiple Ascending Dose (MAD) part of 
the clinical trial described in protocol: “An integrated Phase I/IIa, randomized, double-blind, 
placebo controlled study to evaluate the safety, tolerability and pharmacokinetics of single and 
multiple ascending dose(s) of oral RP3128 (CRAC channel modulators) in healthy volunteers 
and to evaluate the effect on Late Phase Asthmatic Response(LAR) to allergen challenge in 
patients with mild asthma.”  
 
This SAP is based on protocol RP3128-1601 Final Version 2 dated 22March2017. This 
document provides the detail statistical analysis plan for the SAD part and the MAD part of the 
protocol.  
 
The SAP includes details of data handling procedures and statistical methodology. The SAP also 
provides the shells for the Tables, Listings, and Graphs (TLGs) to be delivered to Rhizen 
Pharmaceuticals SA, Inc.  
 
The final statistical analysis will proceed in accordance with this SAP as approved by both 
Rhizen Pharmaceuticals SA and Inflamax Research Limited. Any deviation from this SAP will 
be documented in the final Clinical Study Report (CSR).  
 
For this study, the Study Data Tabulation Model (SDTM) as well as the Analysis Data Model 
(ADaM) specifications will be prepared by Inflamax Research and provided to the Sponsor.  
SDTM Model 1.4 and SDTM Implementation Guide (SDTM IG) version 3.2 will be used  
ADaM Model 2.1 and ADaM Implementation Guide (ADaM IG) version 1.0 will be used. 
SDTM/ADaM datasets will be provided separately for SAD and MAD parts. 
 
The following documents were also reviewed in preparation of this SAP: 
 Electronic Case Report Form (eCRF) SAD Final Version 1.0 dated 31OCT2016 
 Electronic Case Report Form (eCRF) MAD Final Version 1.0 dated 31OCT2016 
 eCRF Completion Guidelines SAD&MAD Final v1.0 dated 31OCT2016 
 Data Management Plan Final v1.0 dated  
 Codelist Details dated 28OCT2016 
 Safety Monitoring Committee charter, version 2.0, dated 21DEC2016 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 12 of 95 
 
3 TUDY OBJECTIVES 
The study objectives related to the SAD and MAD portion of the trial are described below. 
3.1 
PRIMARY OBJECTIVE 
 Part 1 (SAD) - to investigate the safety and tolerability of single ascending oral 
doses of RP3128 in Healthy Volunteers (HV). 
 Part 2 (MAD) - to investigate the safety and tolerability of once a day multiple 
ascending oral doses of RP3128 at three dose levels (highest safe doses 
identified in SAD) in HV. 
 
3.2 
SECONDARY OBJECTIVE 
 Part 1 (SAD) - To characterize the pharmacokinetic (PK) profile of single 
ascending oral doses of RP3128 in HV. 
 Part 2 (MAD) - To characterize the multiple dose PK profile of oral RP3128 at 
steady state when administered once day, at three dose levels in HV. 
 Part 2 (MAD) - To evaluate ex-vivo effect of RP3128 on various biomarkers 
(Th1, Th2 and Th17 cytokines) following Lipopolysaccharide (LPS) or 
CD3/CD28 stimulation. 
 
3.3 
BRIEF DESCRIPTION 
This is a phase I, single-center, double-blind, randomized, placebo-controlled study to evaluate 
the safety, tolerability, and PK of single or multiple ascending dose (SAD or MAD) of RP3128 
in healthy volunteers. 
There were 5 cohorts in SAD and 3 cohorts in MAD. In the first part of the study (Part 1, SAD), 
single dose of RP3128/placebo was administered on Day 1. In the second part (Part 2, MAD), 
multiple doses of RP3128/placebo were administered once a day from Day 1 to Day 7. In both 
SAD and MAD, the cohorts were dosed sequentially so that a minimum of 8 days was allowed 
between dose of previous cohort and the initiation of next cohort. Progression to the next higher 
dose occurred only after confirming safety, tolerability and PK of existing dose. In case of safety 
concern, additional subjects may be added to cohort for safety assessment as per the decision of 
Safety Review Committee (SRC).  
In addition, sentinel design was applied. Within each cohort, 2 sentinel subjects was dosed first 
for safety assessment. Safety and tolerability data up to 24 hours was reviewed along with any 
observation up to 36 hours by the investigator prior to dosing the remaining subjects at that dose 
level. The remainder of the cohort was dosed sequentially at least 48 hours after confirming 
safety and tolerability of sentinel cohort. 
 


 
 
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Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 13 of 95 
 
3.4 
SUBJECT SELECTION 
Healthy male subjects and female subjects of non-childbearing between the ages of 18 and 45 
years were randomized at the study site. 
All subjects must give written informed consent to be enrolled into the study  Subjects were 
considered eligible to participate in this study if all inclusion criteria was satisfied and no 
exclusion criteria was met at screening. Please refer to the Protocol for detailed 
inclusion/exclusion criteria. 
 
3.5 
DETERMINATION OF SAMPLE SIZE 
The sample size has been selected without performing a power calculation to provide descriptive 
information on the safety, tolerability, and PK following administration of RP3128. This trial 
enrolled up to 56 HV (32 in SAD and 24 in MAD). Number of subjects enrolled in this study is 
in line with standard phase I studies and is considered sufficient to provide descriptive 
information on the pharmacokinetics, safety and tolerability of RP3128 while minimizing 
exposure to humans. The actual number of dose cohorts will depend upon the emerging safety 
data.  
 
3.6 
TREATMENT ASSIGNMENT  
Subjects who entered the treatment phase was assigned a unique 4-digit randomization number 
in the format of XYZZ to identify study part (X), cohort number (Y) and subject identifier (ZZ). 
The first 2 randomization numbers XY01 and XY02 in each cohort represents the sentinel 
subjects in Part number X and cohort number Y. For SAD and MAD parts, X is 1 and 2 
respectively. For the SAD part, number Y is denoted by 1 to 5 for 5 cohorts, whereas for MAD 
part the number Y is denoted by 1 to 3 for 3 cohorts. Once any subject or randomization number 
is assigned, it cannot be reassigned to any other subject.  
Allocation to treatment was based on a predetermined random order. Randomization to RP3128 
or placebo took place for each cohort separately. The randomization lists were generated by an 
unblinded staff at Inflamax Research using the computer program Statistical Analysis System 
(SAS®) and managed according to the site’s standard operating procedures (SOPs). Separate 
randomization ratios were used for study SAD Part and MAD Part as indicated in the tables 
below. 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 14 of 95 
 
Dose escalation cohorts for Part 1 (SAD) 
Cohort 
Dose level 
n 
Sentinel cohort 
RP3128: Placebo 
Remaining cohort 
RP3128: Placebo 
Total cohort 
RP3128: Placebo 
S1 
25 mg 
4 
1:1 
2:0* 
3:1 
S2 
50 mg 
6 
1:1 
3:1 
4:2 
S3 
100 mg 
6 
1:1 
3:1 
4:2 
S4 
200 mg 
8 
1:1 
5:1 
6:2 
S5 
400 mg 
8 
1:1 
5:1 
6:2 
*Single blind (subject) 
 
Dose escalation cohorts for Part 2 (MAD) 
Cohort 
Dose level 
N 
Sentinel cohort 
RP3128: Placebo 
Remaining cohort 
RP3128: Placebo 
Total cohort 
RP3128: Placebo 
M1 
25 mg 
8 
1:1 
5:1 
6:2 
M2 
100 mg 
8 
1:1 
5:1 
6:2 
M3 
400 mg 
8 
1:1 
5:1 
6:2 
 
3.7 
ADMINISTRATION OF STUDY MEDICATION 
Depending on the cohort, specific dose/doses of RP3128/placebo was dispensed by pharmacy 
staff during the study. RP3128/placebo capsules was administered orally in the morning with 
approximately 240 mL (8 fluid ounces) of water at room temperature by the subject. For SAD 
part, the doses in 5 planned cohorts were 25 mg, 50 mg, 100 mg, 200 mg and 400 mg. For MAD 
part, the doses in 3 planned cohorts were determined to be 25mg, 100mg, and 400mg considering 
the safety and PK profile of RP3128 in SAD. 
 


 
 
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4 ENDPOINTS 
4.1 
PRIMARY ENDPOINTS 
The primary endpoints for both SAD and MAD parts are as follows: 
 Incidence of AEs 
 Changes in vital signs (blood pressure, pulse rate, respiratory rate, oral temperature) and 
weight 
 Changes in 12-lead ECG parameters 
 Changes in clinical laboratory assessments (hematology, chemistry, urinalysis) 
 
4.2 
SECONDARY ENDPOINTS 
The secondary endpoints include PK parameters and biomarker assessments 
SAD-PK Endpoints: 
 Maximum observed plasma concentration (Cmax) 
 Time to maximum observed plasma concentration (Tmax) 
 Area under the plasma concentration-time curve from time zero until the last time point 
with measurable concentration (AUC0-t) 
 Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) 
 Apparent termination elimination rate constant (Kel) 
 Apparent terminal elimination half-life (t1/2) 
MAD-PK Endpoints: 
 Maximum observed plasma concentration in the dosing interval (Cmax) (Day 1, Day 7) 
 Lowest observed plasma concentration in the dosing interval (Cmin) (Day 7) 
 Plasma concentration at the end of the dosing interval (Ctrough) (Day 3, Day 5, Day 7) 
 Average concentration during the dosing interval (Cav) (Day 7) 
 Time to maximum plasma concentration (Tmax) (Day 1, Day 7) 
 Area under the plasma concentration-time curve from time zero until the last time point 
with measurable concentration (AUC0-24) (Day 1, Day 7)  
 Degree of fluctuation [(Cmax-Cmin)/Cav] (Day 7) 
 Swing [(Cmax-Cmin)/Cmin] (Day 7)  
 Terminal half-life (t1/2) (Day 1, 7) 


 
 
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MAD-Biomarker Endpoints: 
 Levels of various biomarkers (Th1, Th2 and Th17 cytokines) following LPS or 
CD3/CD28 stimulation 
 


 
 
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5 ANALYSIS POPULATION 
5.1 
RANDOMIZED POPULATION 
The randomized population consists of all eligible subjects who are randomized to receive a 
treatment regardless whether they are actually treated.  These subjects are grouped by their 
randomized treatment group. The randomized population will be used to summarize subject 
disposition from randomization through termination. 
5.2 
SAFETY POPULATION 
The Safety population will include randomized subjects who receive at least one dose of study 
drug (RP3128 or placebo) during treatment phase. Subjects will be analyzed as treated, if any 
subjects received the study drug different from the drug they were randomized to receive. There 
will be separate safety populations each for SAD and MAD parts. The Safety population will be 
used for all analyses of safety endpoints, biomarker endpoints, as well as demographics and 
baseline characteristics. 
5.3 
PHARMACOKINETIC (PK) POPULATION 
The PK population will include all safety subjects with sufficient concentration-time data to 
determine PK parameters and no major protocol deviations. The PK population will be used for 
all analyses of PK endpoints.  
5.4 
PROTOCOL DEVIATIONS 
All protocol deviations related to study inclusion or exclusion criteria, conduct of the trial, 
subject management or subject assessment will be listed. The list of protocol deviations will be 
reviewed by the Sponsor, the PI, the study statistician and the study scientist before unblinding 
the study. 


 
 
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6 GENERAL ASPECTS FOR STATISTICAL ANALYSIS 
6.1 
SUMMARY STATISTICS 
The standard summary statistics that will be calculated for quantitative and qualitative variables 
are: 
 Quantitative:  
 Standard Statistics for both Safety/PK: Number of subjects, mean, median, 
standard deviation (SD), minimum and maximum of the raw data 
 Additional Statistics for PK: coefficient of variance (PK concentration and PK 
parameters), geometric mean, and geometric CV (%) ( PK parameters AUC and 
Cmax in SAD part and AUC0-24, Cmax, Cmin, Ctrough in MAD part) 
 Qualitative: number of subjects (n), number of missing observations (nmiss), absolute 
and relative frequencies (%) per category. 
Demographics and disposition will be summarized by treatment group and overall.  
Data collected pre- and post-dose during the treatment period (e.g., vital signs, ECG, and clinical 
laboratory) will be summarized by treatment group (dose level), visit and/or time point. For 
quantitative variables (ECG measurements, vital signs, hematology, etc.), change from baseline 
will be calculated and summarized by treatment, visit and/or time point together with baseline 
and post-dose value. For qualitative variables (e.g., ECG interpretation, urinalysis), standard 
summary of frequencies will be calculated by treatment, visit and/or time points. For safety lab 
data only, shift table will be produced to present the change of reference range indicator from 
baseline to post-dose. PK parameters will be summarized by treatment group, and visit (if 
applicable). All subjects assigned and treated with Placebo in different cohorts will be pooled 
together and summarized as a single group. 
6.1.1 Summary Statistics Reporting Precision 
Summary statistics will be presented to the following degree of precision: 
Table 1. Reporting Precision 
Statistics 
Degree of Precision 
Mean (of all kinds), Median 
One more decimal place than the raw data 
Standard deviation, Standard error 
Two more decimal places than the raw data 


 
 
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Minimum, Maximum 
The same number of decimal places as the 
raw data 
Percent, Coefficient of Variance 
Two decimal places for PK parameters, and 
one decimal place for all other parameters 
PK Concentration, AUC, Cmax 
The same number of decimal places as LLOQ 
 
All fractional numeric values will be presented with a zero to the left of the decimal point (for 
example, 0.12, - 0.30, not .12, - .30). 
6.2 
KEY DEFINITIONS 
The day of administration of the first dose of study drug during the treatment period is defined as 
Study Day 1. Study Day -1 is the day before dosing, all assessments prior to Study Day 1, 
including the Screening and Check-in Visits, will have negative study days. 
The baseline observation will be the last non-missing value prior to the first dose of study drug. 
Nominal Time is the scheduled measurement time relative to time 0. Time 0 is precisely defined 
for each analysis below. 
For AEs, onset time from dosing will be calculated as the difference between the event and 
dosing start date/time. Onset time from dosing will be expressed in days, hours and minutes. If 
time is missing, onset time from dosing will be calculated as the difference between the start date 
and dosing date plus 1 and expressed in days when the event date is on or after the dosing date; 
otherwise, onset time from dosing will be calculated only as difference between the start date and 
dosing date and expressed in negative numbers.  
Duration will be calculated for AEs that resolve as the difference between the AE resolution 
date/time and onset date/time and will be expressed in days, hours and minutes. If time is 
missing, duration will be calculated as the difference between the resolution date and onset date 
plus 1 and expressed in days. AE onset time from dosing and duration of AE will only be derived 
when both start and end dates are complete. 
6.3 
ATTRIBUTION OF TREATMENT-EMERGENT AE FOR 
IMCOMPLETED AE DATE/TIME  
AEs with incomplete start dates and times will be attributed to treatment according to the 
following algorithm: 
1. Only the year is reported: If the year is after the year of the dose, the event will be 
considered as treatment-emergent. If the year is the same as the day of the dose, the event 
will not be considered as treatment-emergent.  


 
 
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2. Only the month and year are reported: If the month is after the month of the first dose, 
event will be considered as treatment-emergent. If the month is the same as the month of 
the first dose, the event will not be considered as treatment-emergent.  
3. Only the time is missing: If the event occurred on or after the day of the first dose in the 
treatment period, then the event will be considered as treatment-emergent. Otherwise, the 
event will not be considered as treatment-emergent. 


 
 
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7 DEMOGRAPHIC, OTHER BASELINE CHARACTERISTICS AND 
MEDICATION 
7.1 
SUBJECT DISPOSITION AND WITHDRAWALS 
For subject disposition, the following frequencies (number and percent) will be displayed by 
treatment group and overall for the randomized population: 
 Subjects in the Randomized Population (number only) 
 Subjects in the Safety Population (number only) 
 Subjects in PK population  
 Subjects who completed the study 
 Subjects who discontinued early, as well as reasons for subject discontinuation 
The denominators for the percent calculations will be the number of safety subjects per treatment 
group or overall. 
A listing of randomization scheme will include the subject’s identification, cohort, date of 
randomization, and treatment assignment. 
Subjects’ completion/discontinuation status will be listed by cohort/treatment and will include 
date of completion/early discontinuation, date of dosing and, for those who discontinued early, 
the specific reason(s) for discontinuation. 
All deviations captured in eCRF will be listed. The list of protocol deviations will be reviewed 
by the Sponsor, the PI, the lead statistician and the study scientist and finalized before unblinding 
the treatment. 
A listing of subjects excluded from the analysis populations will also be produced. 
7.2 
BASELINE CHARACTERISTICS 
Demographics (age, sex, race, ethnicity), informed consent date, weight, height and BMI at 
screening will be listed and summarized using descriptive statistics (number of subjects, mean, 
standard deviation, minimum, median and maximum for quantitative variables and the 
proportion of subjects for qualitative variables) by treatment group and overall for the safety 
population. No formal statistical comparison between groups will be performed. 
Concomitant medication/medical history data, including clinical events, will be listed for all 
safety subjects. 


 
 
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7.3 
TREATMENT COMPLIANCE 
Subject must take study drug at the study site. Failure of treatment compliance will lead to 
termination of study. The necessary measures will be employed to ensure treatment compliance. 
The study drug will be dispensed or administered according to applicable standard operating 
procedures (SOPs). Study drug administration will be listed and ordered by cohort, treatment, 
subject and visit/day. 
 


 
 
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8 ANALYSIS OF PHARMACOKINETICS 
The PK population will be used for all PK analysis and listings. 
8.1 
MEASUREMENTS 
A 4 ml of blood sample were collected at each planned time point for measurement of drug 
concentration in plasma. The time and date of collection of each sample was recorded in CRF.  
8.2 
COLLECTION SCHEDULE 
For SAD part, blood samples will be collected for plasma levels of RP3128 on Day 1 (Pre-dose, 
0.25, 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0, 24.0 and 48 hr), Day 5, Day 8 and Day 15. For MAD part, 
blood samples will be collected for plasma levels of RP3128 on Day 1 (Pre-dose, 0.25, 0.5, 1.0, 
2.0, 4.0, 6.0, 8.0, 12.0 and 24.0 hr), Day 3, Day 5, Day 7 (Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0, 
8.0, 12.0 and 24.0 hr), Day 9 (48 hr), Day 10 (72 hr), Day 11 (96 hr), Day 12 (120 hr), Day 13 
(144 hr) and Day 15 (192 hr). 
8.3 
DERIVED DATA AND HANDLING OF MISSING OR BELOW LLOQ 
DATA 
8.3.1 Derivation of PK Parameters  
PK parameters for RP3128 will be derived with validated SAS programs for all RP3128 dose 
levels by non-compartmental analysis of the plasma concentration data using actual sampling 
times. 
The following pharmacokinetic variables will be derived: 
SAD: 
 Maximum observed plasma concentration (Cmax) 
 Time to maximum plasma concentration (Tmax) 
 Terminal half-life (t1/2) 
 Area under the plasma concentration-time curve from time zero until the last measurable 
time point (AUC0-t) 
 Area under the plasma concentration-time curve from time zero to infinity time (AUC0-
inf) 
 Elimination rate constant (Kel) 
MAD: 
 Maximum observed plasma concentration in the dosing interval (Cmax) (Day 1, Day 7) 


 
 
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 Lowest observed plasma concentration in the dosing interval (Cmin) (Day 7) 
 Plasma concentration at the end of the dosing interval (Ctrough) (Day 3, Day 5, Day 7) 
 Average concentration during the dosing interval (Cav) (Day 7) 
 Time to maximum plasma concentration (Tmax) (Day 1, Day 7) 
 Area under the plasma concentration-time curve from time zero until the last time point 
with measurable concentration (AUC0-24) (Day 1, Day 7)  
 Degree of fluctuation [(Cmax-Cmin)/Cav] (Day 7) 
 Swing [(Cmax-Cmin)/Cmin] (Day 7) 
The PK parameters will be estimated as follows: 
 The Cmax and the corresponding Tmax, Cmin and Ctrough will be read directly from the 
concentration-time plot (observed data, not predicted data by the program). 
 AUCs will be calculated using the linear trapezoidal rule. 
 The terminal elimination rate constant (Kel) will be determined by log linear regression 
obtained on at least the 3 last quantifiable concentrations and will not include Cmax. The 
adjusted square of the correlation coefficient (R-square adjusted) for the goodness of fit 
of the regression line through the data points must be at least 0.80 for the Kel value to be 
considered reliable.  If fewer than 3 quantifiable concentrations are available after Cmax 
or if R-square is less than 0.80, the Kel will be left uncalculated. 
 t1/2 is calculated by the program as ln2/ Kel. If Kel is not calculable, then t1/2 will also 
remain missing. 
 The AUC from 0 to infinity is calculated by the program as: 
 
AUC0-inf = AUC0-t + AUCt-inf where t is the sampling time point of the last measurable 
concentration. AUCt-inf is calculated by the program as: Ct/ Kel, where Ct is the observed 
concentration at time t and Kel is the elimination rate constant during the apparent 
terminal elimination phase.  If Kel is not calculable, AUC0-inf will be set to missing. 
 The AUC extrapolation to infinity (AUCt-inf) must be ≤20% of the total area for AUC0-inf 
to be considered reliable. 
8.3.2 Handling of Missing Plasma Concentration Data or below LOQ 
Plasma concentrations can only be missing if the sample was not collected.  These missing 
concentrations will be considered as non-informative missing and will not be imputed. 
However, if a plasma sample was collected, but the resulting assay failed to detect a quantifiable 
concentration, these will be imputed in the following way: 
 
Concentration values below the assay’s lower limit of quantification (<lower limit of 
quantification (LLOQ) or below the limit of quantification (BLQ)) in pre-dose samples and 


 
 
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in samples taken before the time of the first quantifiable concentration will be treated as 
zero. 
 
All sample collected prior to dosing will be treated as zero. 
 
Post-dose BLQ values after the first quantifiable time point that are flanked and followed by 
quantifiable concentrations will be set to LLOQ. 
 
Post-dose BLQ values after the first quantifiable time point that are not followed by 
quantifiable concentrations will be set to LLOQ. 
 
For PK profiles with no values reported above the LLOQ, these BLQ values will be set to 
LLOQ. 
 
8.4 
DATA SUMMARIZATION 
PK parameters and plasma concentration data will be summarized by treatment using the 
following descriptive statistics (Table 2): 
Table 2. PK Summary Statistics 
Variable 
Summarized with: 
Plasma concentration at each 
time point 
n, arithmetic mean, SD, CV%, minimum, median and 
maximum 
AUCs, Cmax, Cmin, Ctrough, Cav  
n, arithmetic mean, SD, CV% (calculated as 
100%*SD/mean), minimum, median, maximum, geometric 
mean and geometric CV% (calculated as 
, where z2 is the variance of ln(PK 
parameter) 
t1/2, Kel, Tmax ,degree of 
fluctuation, swing 
n, arithmetic mean, SD, CV%, minimum, median, 
maximum 
Samples taken outside the sampling windows may be excluded from by-time point summary 
statistics; this will be determined prior to unblinding. 
8.5 
DATA PRESENTATION 
The actual sampling time of PK blood sample collection will be listed for each cohort and will 
include the deviation in time from the protocol scheduled time, if applicable. 
Individual subject plasma concentration data will be listed by subject, time point and treatment 
and will be summarized at each time point by treatment group for the Safety population. 
Individual subject PK parameters will be listed in a table by subject and will be summarized by 
treatment group for the PK population. 
1
%
100
2 


ze
CV


 
 
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PK parameters of secondary interest, namely R-square adjusted, the number of data points used 
for estimating Kel, the upper and lower time point used for estimation of Kel, and the % AUC 
extrapolation from tlast (last time point of blood draw) to infinity will be listed by subject and 
dose level/cohort to enable verification of the exclusions, if any, of data from the summary 
statistics of the PK parameters of primary interest. 
 


 
 
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9 SAFETY 
The analysis population used for safety analyses will be the Safety population. Safety will be 
assessed on the basis of AE, clinical laboratory data, vital signs, ECG parameters, MMSE and 
physical examinations. 
9.1 
ADVERSE EVENTS 
All subjects in the Safety population will be included in the adverse event analysis. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding 
dictionary (Version 19.1 or higher)  
An AE is defined as any untoward medical occurrence in a subject administered a medicinal 
product and which does not necessarily have to have a causal relationship with this treatment. An 
adverse event can therefore be any unfavorable and unintended sign symptom (for example, an 
abnormal laboratory finding), or disease temporally associated with the use of a medicinal 
product, whether or not considered related to this medicinal product. In clinical studies, an AE 
can include an undesirable medical condition occurring at any time, including baseline or 
washout periods, even if no study treatment has been administered. 
In this study, all AEs that occur after any subject has been screened through the post-treatment 
follow-up period, whether or not they are related to the study, must be recorded on the eCRF, 
and must include the following:  date and time of onset, date and time of resolution, severity, 
seriousness, causality (relationship to study medication), actions required, and outcome. 
Clinically significant and severe AEs must be examined to determine whether they meet criteria 
of a dose-limiting toxicity. 
A treatment-emergent AE (TEAE) is any that is new in onset or was aggravated in severity or 
frequency following the first dose of study drug, up to and including the last visit of the study. 
Treatment emergence will be determined by comparing the AE start date/time with the actual 
date/time of first dose. In the case that the AE start date/time are incomplete, treatment 
emergence will be imputed according to the algorithm in SAP Section 6.5. 
Adverse events will be listed chronologically by cohort/treatment, subject and AE start date/time. 
This listing will include all data collected in the eCRF, along with the derived variables: onset 
time since first dose, duration of AE and the coded variables system organ class (SOC) and 
preferred term (PT). Time since dose and duration will be calculated as described in SAP Section 
6.3. In addition, serious AEs (SAEs) will be listed separately, if any occurs. 
The summary of AEs will be limited to TEAEs only. In cases where severity is missing for a 
TEAE, the TEAE will be considered to be the highest degree of severity: Severe. In cases where 
relationship information is missing for a TEAE, the TEAE will be considered to be reasonably 
related. Displays of TEAEs will include: 


 
 
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 Overall Summary of TEAEs 
This table will include the number of events, number and percent of subjects who 
experienced TEAEs, serious TEAEs, severe TEAEs, related TEAEs and TEAEs leading 
to study discontinuation, summarized by treatment group. 
 Summary of TEAEs by SOC, PT and Treatment Group 
A summary of the number of events, number and percent of subjects who experienced at 
least one TEAE, as well as the number of events, number and percent of subjects who 
experienced each specific SOC, and PT will be presented by treatment group (including 
pooled placebo and pooled RP3128). If a subject has more than one occurrence of the 
same PT then the PT will be counted only once for that subject under the SOC at which it 
was experienced. 
 Summary of TEAEs by SOC, PT, Treatment Group and Maximum Severity 
A summary of the number and percent of subjects who experienced at least one TEAE by 
maximum severity as well as the number and percent of subjects who experienced each 
specific SOC and PT by maximum severity will be presented by treatment group. For this 
analysis, if a subject has more than one occurrence of the same PT, then the PT will be 
counted only once for that subject under the maximum severity at which it was 
experienced. 
 Summary of TEAEs by SOC, PT, Treatment Group and Maximum Relationship 
A summary of the number and percent of subjects who experienced at least one TEAE by 
maximum relationship as well as the number and percent of subjects who experienced 
each specific SOC and PT by maximum relationship will be presented by treatment 
group. For this analysis, if a subject has more than one occurrence of the same PT, then 
the PT will be counted only once for that subject under the maximum relationship at 
which it was experienced. 
9.2 
LABORATORY EVALUATIONS 
All subjects in the Safety population will be included in the safety laboratory analysis. 
9.2.1 Collection Schedule 
At screening, Serology, Tuberculin test / QuantiFeron- TB®-Gold test, Alcohol and urine drug 
screening will be done to assess eligibility for the study. Drug screening includes opiates, 
methadone, cocaine, amphetamine, cannabinoids, barbiturates, and benzodiazepines.  Alcohol 
will be screened using alcohol breath test. If the subject has a positive result, the subject will be 
considered a screen failure and must be excluded from the study. The result will be listed by 
cohort/treatment, subject and visit. 
Female subjects will undergo a serum pregnancy test (quantitative β-HCG) test at screening.  


 
 
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UPT (Urine pregnancy tests) will be performed at later time points in case of suspected 
pregnancy. The result will be listed by cohort/treatment, subject and visit. 
Follicular Stimulating Hormone (FSH) will be evaluated at screening to confirm post-
menopausal status for the females who reported having no menses less than 12 months. 
For SAD part, the clinical laboratory evaluations, including Clinical chemistry, hematology, 
serum electrolyte, coagulation and urinalysis, will be performed at screening, Day -1, Day 2, Day 
3, Day 8 and Day 15. For MAD part, the clinical laboratory evaluations, including Clinical 
chemistry, hematology, serum electrolyte, coagulation and urinalysis, will be performed at 
screening, Day -1, Day 2, Day 5, Day 7, Day 8 and Day 15. If blood, nitrites or leukocytes are 
abnormal, automatically microscopic urinalysis will be performed. Additional investigations will 
be performed if clinically indicated.  
Laboratory assessment times are shown below in Table 3. 
Table 3. Laboratory Parameters Assessment Times 
Visit/Day 
Clinical 
Laboratory 
 
 
Serology 
 
FSH 
Drug 
and 
alcohol 
screen 
Pregnancy 
testing 
Screening 
 
 
 
 
 
Day -1 
(Check-in) 
 
 
 
 
 
Day 2 
 
 
 
 
 
Day 3 
(SAD) 
 
 
 
 
Day 5 
(MAD) 
 
 
 
 
Day 7 
(MAD) 
 
 
 
 
Day 8 
 
 
 
 
 
Day 15  
 
 
 
 
 
 


 
 
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9.2.2 Derived and Imputed Data 
Some numeric lab values may be reported as ‘>n.n’ or <n.n; these will be analyzed in the 
summary statistics as n.n. For example, potassium recorded as >9.0 mmol/L would be 
summarized as 9.0 mmol/L. 
Baseline is defined as the last non-missing observation prior to first dosing on Day 1. 
9.2.3 Data Summarization and Presentation 
Laboratory sample data and values from laboratory assessments will be listed chronologically by 
cohort/treatment, subject, and visit. Abnormal findings in laboratory data will be listed with a 
flag for clinical significance based on investigator judgment. Abnormal laboratory findings will 
also be provided in a separate listing. 
For quantitative data, change-from-baseline (CFB) will be calculated as the difference between 
the post-dose visit and baseline. For the SAD part, CFB will be calculated for Day 2, Day 3 (at 
discharge), Day 8, and Day 15. For the MAD part, CFB will be calculated for Day 2, Day 5, Day 
7, Day 8 (at discharge), and Day 15.  
The laboratory will assign a reference range indicator to all test results by comparing the actual 
test value to the reference range. The quantitative results will have indicator values of Low, 
High, and Normal, while the qualitative results will have indicator values of Normal and 
Abnormal. . The investigator or designee will review non-normal results to judge their clinical 
significance. 
Quantitative results will be summarized for baseline, post-dose visits and CFB values by 
treatment group using standard summary statistics (n, mean, SD, minimum, median and 
maximum). Qualitative results (e.g., some tests in urinalysis) will be summarized by treatment 
group using frequency and percentage. The reference range indicator data will also be tabulated 
using frequency and percentage for both quantitative and qualitative results. No inferential tests 
will be conducted on lab data. 
In addition, 3 by 3 shift tables will be produced to compare the change in reference range 
indicator from baseline to Day 3 for the SAD / Day 8 for the MAD part for each laboratory test. 
For parameters where only two possible values are available (i.e., Normal and Abnormal), the 
Abnormal values will be counted as High (H) in the 3 by 3 table. 
9.3 
  VITAL SIGNS 
All subjects in the Safety population will be included in the vital signs analysis. 
9.3.1 Measurements 
Vital signs will consist of blood pressure (systolic and diastolic blood pressure, mmHg), heart 
rate (beats per minute (bpm)), respiratory rate (breaths/min), temperature (°C) and weight. At 


 
 
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screening, vital signs will be assessed in the supine position after the subject has rested for at 
least 3 minutes. Blood pressure and pulse will be assessed again after three minutes in the 
standing position. At other time points, vitals will be measured after 3 minutes supine rest. Vitals 
should be completed within +/- 30 minute of schedule timing to avoid overlapping. 
Height and weight (without shoes) will be collected at Screening and BMI will be calculated.  
Height, weight and BMI will be collected and calculated at other time points (check-in, follow-
up and ET visit).  
9.3.2 Collection Schedule 
For SAD, vital signs on screening, Day -1 (at the time of admission), Day 1 (pre-dose, 30 min, 1, 
2, 4, 6, 8, 12 and 24 hrs post dose), Day2, Day 3, Day 5, Day 8 and Day 15. For MAD, vital 
signs on screening, Day -1 (at the time of admission), Day 1 & Day 2 (pre-dose, 30 min, 1, 2, 4, 
6, 8, 12 and 24 hrs post dose), Day 3, Day 4, Day 5, Day 6, Day 7 (pre-dose, 30 min, 1, 2, 4, 6, 
12 hrs post dose), Day 8, Day 9, Day 11 and Day 15. Assessment times for vital sign parameters 
are presented below in Table 4 & 5.  
Table 4. Vital Sign Assessment Times (SAD) 
Visit/Day 
Vital Sign Assessment Times 
Screening 
 
Check-in Day -1 
 
Day 1 (Treatment) 
pre-dose, 30 min, 1, 2, 4, 6, 8, 12 and 24 hrs post dose  
Day 3 (Discharge) 
 
Day 5 
 
Day 8 
 
Day 15  
 
 
Table 5. Vital Sign Assessment Times (MAD) 
Visit/Day 
Vital Sign Assessment Times 
Screening 
 
Check-in Day -1 
 


 
 
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Day 1 (Treatment) 
Pre-dose, 30 min, 1, 2, 4, 6, 8, 12 and 24 hrs post dose 
Day 3 (Treatment) 
 
Day 4 (Treatment) 
 
Day 5 (Treatment) 
 
Day 6 (Treatment) 
 
Day 7 (Treatment) 
Pre-dose, 30 min, 1, 2, 4, 6, 8, 12 and 24 hrs post dose 
Day 8 (Discharge) 
 
Day 9  
 
Day 11 
 
Day 15  
 
9.3.3 Derived and Imputed Data 
Baseline will be defined as the last non-missing observation prior to the dosing on Day 1. 
9.3.4 Data Summarization and Presentation 
Vital signs data will be listed chronologically by cohort/treatment, subject, visit/day, and time 
point when applicable.  
Baseline values, absolute values and change from baseline for each post-dose time point will be 
summarized by treatment group using standard descriptive statistics. Off-treatment vital signs 
(e.g., Screening, Day -1, Unscheduled visit) will be listed but not otherwise analyzed. No 
inferential tests will be conducted. 
Weight (without shoes) is measured at screening, check-in, follow-up and ET visit, the screening 
observation is used to summarize demographics, and the last non-missing observation prior to 
dosing on Day 1 (mostly likely the check-in observation) is defined as baseline to calculate 
weight change at post-doing visits.  
 
9.4 
ECG 
All subjects in the Safety population will be included in the ECG analysis. 
For SAD, a standard 12-lead ECG will be performed with the subject in a supine position at 


 
 
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Screening, Day -1 (at the time of admission), Day 1 (pre-dose, 15, 30, 45 min, 1, 2, 4, 6, 8, 12 
and 24 hrs post dose), Day 3, Day 5, Day 8 and Day 15 or Early Termination. For MAD, a 
standard 12-lead ECG will be performed with the subject in a supine position at Screening, Day -
1 (at the time of admission), Day 1 (pre-dose, 15, 30, 45 min, 1, 2, 4, 6, 8, 12 and 24 hrs post 
dose), Day 5, Day 7 (pre-dose, 15, 30, 45 min, 1, 2, 4, 6, 8, 12 and 24 hrs post dose), Day 8 and 
Day 15 or Early Termination. Triplicate ECG will be taken 1 minute apart on screening, Day 1 
(pre-dose) and for confirmation of abnormality detected in the single ECG measurement based 
on Investigator judgement.  
For each assessment, the ECG will be reviewed by the qualified physician and the interpretation 
will be recorded in the eCRF as normal, abnormal but not clinically significant, abnormal and 
clinically significant.  In addition, the standard ECG parameters including ventricular rate (VR), 
and intervals for PR, QRS, QT, and QTcB (Bazette’s corrections for heart rate) will be recorded. 
Baseline will be defined as the last non-missing observation prior to dosing on Day 1. 
All ECG data will be listed chronologically by cohort/treatment, subject, visit/day, and time 
point. Abnormal ECG results will be provided in a separate listing. 
Overall interpretation of ECG measurements will be summarized by treatment at each time point 
using frequencies. Baseline values, absolute values, and CFB will be summarized by treatment 
group using standard descriptive statistics for VR, PR interval, QRS duration, and QT interval. 
Off-treatment ECG data (e.g., Screening, Day -1, and Unscheduled visits) will be listed but not 
otherwise analyzed. No inferential tests will be conducted on ECG data. 
9.5 
PHYSICAL EXAMINATION 
For SAD, a complete physical examination will be performed at screening, Day -1, Day 3, Day 8 
and Day 15, or if necessary at the Early Termination visit. For MAD, a complete physical 
examination will be performed at screening, Day -1, Day 4, Day 8 and Day 15, or if necessary at 
the Early Termination visit.  This exam will include general appearance, skin, neck (including 
thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, extremities, 
vascular, and neurological.  If indicated based on medical history and/or symptoms, rectal, 
external genitalia, breast, and/or pelvic exams may be performed. Information for all physical 
examinations must be included in the source documentation at the study site and will not be 
recorded the CRF. Significant findings that are present prior to informed consent are included in 
the Relevant Medical History CRF. Significant findings observed after informed consent 
signature which meet the definition of an Adverse Event must be appropriately recorded on the 
Adverse Event CRF. No listings and summary tables will be produced separately. 
 


 
 
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9.6 
COGNITIVE TEST 
A cognitive test (e.g. Mini-Mental State Examination (MMSE)) will be performed at Screening 
and Day 3 (SAD)/ Day 8 (MAD) to assess the effect of drug on cognitive function.  
MMSE data will be listed chronologically by cohort/treatment, subject, and visit/day. The 
classification of MMSE results as normal/abnormal follows the rules in Table 6. Such 
information will also be included in the listing.  
Baseline will be defined as the observation collected at screening. Baseline values, absolute 
values, and CFB will be summarized by treatment group using standard descriptive statistics. No 
inferential tests will be conducted on MMSE data.  
Table 6. Classification of Normal/Abnormal MMSE Results 
Classification 
Description 
Rules 
Normal 
No cognitive impairment 
Score 24-30 (inclusive) 
Abnormal 
Cognitive impairment 
Score <24 
 
 


 
 
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10 EXPLORATORY ANALYSES 
Exploratory assessments will be conducted on blood biomarkers (Th1, Th2 and Th 17 cytokines) 
in MAD part only. Blood samples will be collected at baseline (Day1, pre-dose), and Day 7 (pre-
dose and 4 hrs post dose). See laboratory manual for biomarker processing instructions.  
In the descriptive analysis, two types of baselines are considered to calculated CFB values. First, 
set Day 1 pre-dose value as baseline and calculate CFB for all collection time points after the 
first dosing on Day 1. Second, set Day 7 pre-dose value as baseline and calculate CFB for the 4-
hour post-dose time point on Day 7. Descriptive statistics (number of observations, mean, 
standard deviation, median, minimum and maximum) will be provided for baseline (Day 1, pre-
dose), Day 7 (Pre-dose), change from Baseline to Day 7 (Pre-dose), Day 7 (4 hrs Post-dose), 
change from Baseline to Day 7 (4 hrs Post-dose), and change from Day 7 (Pre-dose) to Day (4 
hrs Post-dose) by treatment.  
Paired t-test will be applied on CFB values 1) between Day 1 pre-dose and Day 7 (pre-dose) and 
2) between Day 7 pre-dose and Day 7 4 hrs post-dose to determine whether the change within 
placebo and RP3128 is significant or not.  
The CFB values in cytokine expression levels will be compared between placebo and RP3128 
using an ANCOVA with the CFB values as the dependent variable, treatment as a fixed effect 
and corresponding baseline as a covariate. Three different types of CFB will be used: 1) CFB 
from Day 1 (Pre-dose) to Day 7 (Pre-dose), 2) CFB from Day 1 (Pre-dose) to Day 7 (4 hrs Post-
dose), and 3) CFB from Day 7 (Pre-dose) to Day 7 (4 hrs Post-dose). The LSMeans, Standard 
Errors for each treatment and treatment difference will be presented together with the 
corresponding 95%-confidence interval and p-value.  
 


 
 
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11 INTERIM ANALYSES 
There is no interim analysis planned in this study. Please note that the results of SAD and MAD 
will be produced separately. As stated in the protocol, the escalation to next dose level was 
decided based on the review of blinded safety data from each cohort. Also the dose levels for 
MAD part was determined based on full blinded safety review of all SAD cohorts. Therefore, the 
results of the SAD portion of the trial shall have no effect on the MAD), unless there are safety 
considerations recommended by the Safety Monitoring Committee.   


 
 
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12 CHANGES TO PLANNED ANALYSES 
Due to the nature of the study design of multiple-ascending dose, a few additional endpoints of 
PK parameters were added to the MAD part. 


 
 
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13 APPENDIX:  
 APPENDIX A 
 LIST OF CLINICAL LABORATORY TESTS (PART 1-3) 
Hematology  
 Hemoglobin, Hematocrit, Red blood Cell count, White blood cell count (WBC) with 
differentials, mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), 
Mean corpuscular hemoglobin concentration (MCHC), platelet count 
 
Coagulation parameters  
 Prothrombin time, Activated partial prothrombin time (APTT)  
 
Clinical Chemistry  
 Liver function test: Total bilirubin, Bilirubin (Conjugated and unconjugated), Alkaline 
Phosphatase, Gamma-GT (GGT), Aspartate aminotransferase (AST), Alanine 
aminotransferase (ALT),  
 Lactate dehydrogenase, Creatinine kinase (CK) 
 Kidney function test:  Creatinine, Blood Urea nitrogen (BUN), Uric acid 
 Lipid profile: Cholesterol, Triglyceride, HDL-Cholesterol, LDL- Cholesterol. 
 Total protein, albumin, Glucose  
 Electrolytes: Sodium, potassium, calcium, bicarbonates and phosphates  
 
Serology (Screening only)  
 HBsAg, Anti-HCV, Anti-HIV 1, 2 
 
Hormones (Post-menopausal female only) (Screening only) 
 FSH 
 
Tuberculin test / QuantiFeron- TB®-Gold test (Screening only) 
 
Pregnancy test (female only)  
 Serum B-HCG 
 Urine pregnancy test (UPT) will be performed at later time points in case of suspected 
pregnancy. 
 
Alcohol and urine drug screen  
 Opiates, methadone, 
cocaine, amphetamine, cannabinoids, 
barbiturates 
and 
benzodiazepines.   
 Alcohol (breath test) 
 
Urinalysis  
 pH, hemoglobin, urobilinogen, ketones, glucose, protein, blood, leukocytes and nitrites  


 
 
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APPENDIX B :  PART 1 (SAD) – SCHEDULE OF EVENTS 
 
 
Assessment period  
Visits  
Screening 
CPU confinement  
Ambulatory/ follow up visit 
Study Day 
-28 to -1 
-1 
Admission  
1 
2 
3 
(Discharge) 
5 
8 (±1) 
15 (±1) 
EOS14 
Confinement1  
 
X 
X 
X 
- 
- 
- 
- 
Ambulatory visits2  
 
- 
- 
- 
- 
X 
X 
X 
Informed consent3  
X 
 
- 
- 
- 
- 
- 
- 
Medical history4  
X 
X 
- 
- 
- 
X 
X 
X 
Demographics5  
X 
- 
- 
- 
- 
- 
- 
- 
Physical examination6  
X 
X 
- 
- 
X 
- 
X 
X 
Vital signs7  
X 
X 
X 
X 
X 
X 
X 
X 
Eligibility assessment 
X 
X 
- 
- 
- 
- 
- 
- 
12-lead ECG8 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical laboratory9 
X 
X 
- 
X 
X 
- 
X 
X 
Drug and alcohol screen10  
X 
X 
- 
- 
- 
- 
- 
- 
HBsAg, HCV, HIV 
X 
- 
- 
- 
- 
- 
- 
- 
Tuberculin test / QuantiFeron- 
TB ®-Gold test 
X 
 
 
 
 
 
 
 
Randomization  
- 
- 
X 
- 
- 
- 
- 
- 
Pregnancy test (female) 11 
X 
X 
- 
- 
- 
- 
- 
- 
Cognitive test (e.g. MMSE) 
X 
- 
- 
- 
X 
- 
- 
- 
Study drug administration  
- 
- 
X 
- 
- 
- 
- 
- 
PK sampling blood12 
- 
- 
X 
X 
X 
X 
X 
X 
Adverse events13  
X 
X 
X 
X 
X 
X 
X 
X 


 
 
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Concomitant medication  
X 
X 
X 
X 
X 
X 
X 
X 
Foot notes:     
1. CPU confinement: subjects will enter the CPU on Day -1 (afternoon) and will be discharged on Day 3 (morning) after safety assessment. 
2. Ambulatory visit: Day 5, Day 8 and Day 15. 
3. Informed Consent must be obtained ≤28 days prior to the initiation of trial treatment.    
4. Detailed history will be taken at screening this include present history, past history, allergy, family history, concomitant medication and 
prior medication (in last 6 weeks); and other medical history. Abbreviated history will be taken at all subsequent visits.  
5. Demographic will age, sex and race. 
6. Physical examination includes local and systemic examination and measuring height and weight. Detailed examination will be performed 
at screening, Day -1, Day 3, Day 8 and Day 15. At other time point, examination will be done as clinically indicated. 
7. Vitals (temperature, systolic and diastolic blood pressure, respiratory rate and pulse rate) on screening, Day -1 (at the time of admission), 
Day 1 & Day 2 (pre-dose, 30 min, 1, 2, 4, 6, 8, 12 and 24 hrs post dose), Day 3, Day 5, Day 8 and Day 15. At screening, vital signs will be 
assessed in the supine position after the subject has rested for at least 3 minutes. Blood pressure and pulse will be assessed again after three 
minutes in the standing position. At other time points, vitals will be measured after 3 minutes supine rest. Vitals should be completed within 
+/- 30 minute of schedule timing to avoid overlapping; however, in case of adverse events, safety evaluations including vitals and ECGs to 
be prioritized.  
8. ECG (single measurement unless stated otherwise): on screening, Day -1 (at the time of admission), Day 1 & Day 2 (pre-dose, 15, 30, 45 
min, 1, 2, 4, 6, 8, 12 and 24 hrs post dose), Day 3, Day 5, Day 8 and Day 15. Triplicate ECG will be taken 1 minute apart on screening, Day 
1 (pre-dose) and for confirmation of abnormality detected in the single ECG measurement based on Investigator judgement.   
9. Laboratory assessment: Clinical chemistry, hematology, serum electrolyte, coagulation and urinalysis will be performed. Additionally, FSH 
will be evaluated at screening to confirm post-menopausal status. Lab investigations will be performed on screening, Day -1, Day 2, Day 3, 
Day 8 and Day 15. If blood, nitrites or leukocytes are abnormal, automatically microscopic urinalysis will be perform. Additional 
investigations will be performed if clinically indicated. 
10. Drug and alcohol screen: This will include screening for opiates, methadone, cocaine, amphetamine, cannabinoids, barbiturates, and 
benzodiazepines. Alcohol will be screened using alcohol breath test.  
11. Pregnancy test: β-HCG will be conducted in serum at screening. UPT will be performed at later time points in case of suspected pregnancy. 
12. PK time points: Day 1 (Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0, 24.0 and 48 hrs) and at Day 5, Day 8 and Day 15. Window period 
for sample collection will be outlined in pharmacokinetic manual 
13. In case of drug related SAE/AE or treatment discontinuation due to adverse event, the subjects will be followed till the 
resolution/stabilization of the AE or 30 days after the last study dose whichever is the earlier. 
14. In all subjects, telephone assessments for adverse events and concomitant medications are performed 3 days prior to the EOS visit and as 
required by physician. 


 
 
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APPENDIX C: PART 2 (MAD) — SCHEDULE OF EVENTS 
Study Day 
Screen
ing 
Assessment period 
 
 
Admission 
CPU Confinement 
Discha
rge 
Ambulatory visits 
Study Day 
-60 to -1 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11  
12 
13 
15 (±1) 
EOS18 
Confinement1 
- 
X 
X 
X 
X 
X 
X 
X 
X 
- 
- 
 
- 
 
 
- 
Ambulatory visits2 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
X 
X 
X 
X 
X 
X 
Informed consent3 
X 
 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Medical history4 
X 
X 
- 
- 
- 
- 
- 
- 
- 
- 
X 
- 
X 
- 
- 
X 
Demographics5 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Physical 
examination6 
X 
X 
- 
- 
- 
X 
- 
- 
- 
X 
- 
- 
- 
- 
- 
X 
Vital signs7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 
X 
- 
- 
X 
Eligibility 
assessment 
X 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
12-lead ECG8 
X 
X 
X 
X 
- 
- 
X 
- 
X 
X 
- 
- 
- 
- 
- 
X 
Clinical laboratory9 
X 
X 
- 
X 
 
- 
X 
- 
X 
X 
- 
- 
- 
- 
- 
X 
Drug and alcohol 
screen10 
X 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
HbsAg, HCV, HIV 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Tuberculin test / 
QuantiFeron- TB 
®-Gold test 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
EEG11 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Randomization 
- 
- 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Pregnancy test 
(female) 12 
X 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 


 
 
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Cognitive test (e.g. 
MMSE) 
X 
- 
- 
- 
- 
- 
- 
- 
- 
X 
- 
- 
- 
- 
- 
- 
Study drug 
dispensing13 
- 
- 
X 
X 
X 
X 
X 
X 
X 
- 
- 
- 
- 
- 
- 
- 
Study drug 
administration14 
- 
- 
X 
X 
X 
X 
X 
X 
X 
- 
- 
- 
- 
- 
- 
- 
PK sampling 
blood15 
- 
- 
X 
X 
X 
- 
X 
- 
X 
X 
X 
X 
X 
X 
X 
X 
Biomarkers16 
- 
- 
X 
- 
- 
- 
- 
- 
X 
- 
- 
- 
- 
- 
- 
- 
Adverse events17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Foot notes: 
1. CPU confinement: Subjects will enter the CPU on Day -1 (afternoon) and will be discharged on day 8 after safety assessment. 
2. Ambulatory visit: Day 9, Day 10, Day 11, Day 12, Day 13 and Day 15. 
3. The screening assessments will be performed ≤ 60 days prior to initiation of treatment and informed consent will be obtained prior to 
initiating any study procedures.   
4. Detailed history will be taken at screening this include present history, past history, allergy, family history, concomitant medication and 
prior medication (in last 8 weeks); and other medical history. Abbreviated history will be taken at all subsequent visits.  
5. Demographic will age, sex and race. 
6. Physical examination includes local and systemic examination and measuring height and weight. Detailed examination will be performed 
at screening, Day -1, Day 4, Day 8 and Day 15. At other time point, examination will be done as clinically indicated. Height will only be 
measured at screening. 
7. Vitals (temperature, systolic and diastolic blood pressure, respiratory rate and pulse rate) on screening, Day -1 (at the time of admission), 
Day 1 (pre-dose, 30 min, 1, 2, 4, 6, 12 and 24 hrs post dose), Day 3, Day 4, Day 5, Day 6, Day 7 (pre-dose, 30 min, 1, 2, 4, 6, 12 hrs post 
dose), Day 8, Day 9, Day 11 and Day 15. At screening, vital signs will be assessed in the supine position after the subject has rested for at 
least 3 minutes. Blood pressure and pulse will be assessed again after three minutes in the standing position. At other time points, vitals will 
be measured after 3 minutes supine rest. Vitals should be completed within +/- 30 minute of schedule timing to avoid overlapping; however, 
in case of adverse events, safety evaluations including vitals and ECGs to be prioritized.  
8. ECG (single measurement unless stated otherwise): on screening, Day -1 (at the time of admission), Day 1 (pre-dose, 30 min, 1, 2, 4, 6, and 
8 hrs post dose), Day 2, Day 5, Day 7 (pre-dose, 30 min, 1, 2, 4, 6, and 8 hrs post dose), Day 8 and Day 15. Triplicate ECG will be taken 
approximately 1 minute apart on screening and Day 1 (pre-dose). Duplicate repeats will be performed for confirmation of abnormality 
detected in the single ECG measurement based on Investigator judgement. 


 
 
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9. Laboratory assessment: Screening, Day -1 (at the time of admission), Day 2 (pre-dose), Day 5 (pre-dose), Day 7 (pre-dose), Day 8 (at 
discharge) and Day 15. Clinical chemistry, hematology, serum electrolyte, coagulation and urinalysis will be performed. Additionally, FSH 
will be evaluated at screening to confirm post-menopausal status.  If blood, nitrites or leukocytes are abnormal, automatically microscopic 
urinalysis will be perform. Additional investigations will be performed if clinically indicated.  
10. Drug and alcohol screen: This will include screening for opiates, methadone, cocaine, amphetamine, cannabinoids, barbiturates, and 
benzodiazepines. Alcohol will be screened using alcohol breath test.  
11. EEG will be performed if clinically indicated in case of any symptom. 
12. Pregnancy test: β-HCG will be conducted in serum at screening. UPT will be performed at later time points in case of suspected pregnancy.  
13. Study drug (RP3128/placebo) will be dispensed on Day 1 to Day 7.  
14. Study drug (RP3128/placebo) will be administered once a day from Day 1 to Day 7 at CPU.  
15. PK time points: Day 1 (Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0 and 24.0 hr), Day 3, Day 5, Day 7 (Pre-dose, 0.25, 0.5, 1.0, 2.0, 4.0, 
6.0, 8.0, 12.0 and 24.0 hrs), Day 9 (48 hrs), Day 10 (72 hrs), Day 11 (96 hrs), Day 12 (120 hrs), Day 13 (144 hrs) and Day 15 (192 hrs). 
Blood will be collected for PK. Window period for sample collection will be outlined in pharmacokinetic manual.  
16. Biomarkers: The blood sample will be collected at baseline (Day 1), Day 7 (pre-dose and 4 h post dosing). Measurement of biomarkers 
(Th1, Th2, and Th17 cytokines) following LPS or CD3/CD28 challenge. 
17. In case of drug related SAE/AE or treatment discontinuation due to adverse event, the subjects will be followed till the resolution/stabilization 
of   the AE or 30 days after the last study dose whichever is the earlier. 
18.  Window for study assessments: ECG: +/- 15 minutes of the scheduled time; Pre-dose procedures: within 2 hours of dosing.  
 
 


 
 
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14 TABLE AND LISTING 
The following TL shells are provided as a framework for the display of data from this study. The shells may change due to unforeseen 
circumstances. These shells may not be reflective of every aspect of this study but are intended to show the general layout of the Tables 
and Listings that will be included in the final report. Tables and Listings are numbered following the International Conference on 
Harmonization (ICH) structure.  Table headers, variables names and footnotes will be modified as needed following a review of the 
blinded data and also following data analyses. Please note that all summary tables and listings will be generated using SAS® Version 9.2 
or higher.  
 
 


 
 
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Table 14.1.1.S/M Disposition of Subjects (SAD/MAD) 
Randomized Population 
 
Pooled 
Placebo 
RP3128 
25 mg 
RP3128 
50 mg 
RP3128 
100 mg 
RP3128 
200 mg 
RP3128 
400 mg 
Total 
n (%) 
Number of Subjects Randomized (N) 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Number of Subjects in Safety Population (N) 
xx  
xx  
xx  
xx  
xx  
xx  
xx  
Number of Subjects in PK Population [n (%)] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Number of Subjects who Completed the Study [n (%)] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
Number of Subjects who Discontinued Early [n (%)] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Adverse Event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Allergic Reaction / Anaphylaxis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Concomitant Medication Interfering W/ PK 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Emesis Within 10 hrs Post Dose 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Lost to Follow-up 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Physician Decision 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Serious Adverse Event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Study Terminated by Sponsor 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Withdrawal by Subject 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Note: Percentages are calculated based on the number of subjects in the Safety population per treatment group and overall. 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 46 of 95 
 
Table 14.1.2.S/M Summary of Demographics (SAD/MAD) 
Safety Population 
 
Pooled 
Placebo 
(N=xx) 
RP3128 
25 mg 
(N=xx) 
RP3128 
50 mg 
(N=xx) 
RP3128 
100 mg 
(N=xx) 
RP3128 
200 mg 
(N=xx) 
RP3128 
400 mg 
(N=xx) 
All Subjects 
(N=xx) 
Age (years)* 
 
 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Sex, n (%) 
 
 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Male 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Female 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
 
*Age at Informed Consent 
Note: Percentages are calculated based on the number of subjects in the Safety population per treatment group and overall. 
Programming Note: Table will also include race, ethnicity, height (cm), weight (kg), and BMI (kg/m2). 
 
 


 
 
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Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 47 of 95 
 
Table 14.1.3.M Summary of Drug Administration (MAD) 
Safety Population 
 
 
Pooled 
Placebo 
(N=xx) 
RP3128 
25 mg 
(N=xx) 
RP3128 
100 mg 
(N=xx) 
RP3128 
400 mg 
(N=xx) 
Number (%) of subjects who received all doses 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Number of Days on Treatment 
 
 
 
 
    n 
xx 
xx 
xx 
xx 
    Mean 
xx.x 
xx.x 
xx.x 
xx.x 
    SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
    Minimum 
xx 
xx 
xx 
xx 
    Median 
xx.x 
xx.x 
xx.x 
xx.x 
    Maximum 
xx 
xx 
xx 
xx 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 48 of 95 
 
Table 14.2.1.1.X.S RP3128 Plasma Concentrations (ng/mL) by Time Point (SAD) 
Safety Population 
<Dose Level> 
 
 
 
Time Point 
 
Cohort 
/Subject 
0h 
0.25h 
0.5h  
1h 
2h 
4h 
6h 
8h 
12h 
24h  
48h  
96h  
168h 
336h 
 
xxxx 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
 
….. 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Statistics 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N 
 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Mean1 
 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
SD 
 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
CV (%) 
 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Minimum 
 
xxx 
xxx 
xxx 
Xxx 
Xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Median 
 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Maximum 
 
xxx 
xxx 
xxx 
Xxx 
Xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
N= Number of subject for which plasma sample was collected at each time point. 
1Mean calculated based on number of subjects (N). 
Programming Note: X will be assigned as 1, 2, 3…. as per each RP3128 dose level. Time point may vary depending on the actual number of sample collection. 
<Dose Level> = RP3128 25 mg, 50 mg, 100 mg, 200 mg, 400 mg in SAD  
 
 


 
 
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Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 49 of 95 
 
Table 14.2.1.1.1.X.M RP3128 Plasma Concentrations (ng/mL) by Time Point (MAD) – Day 1 
Safety Population 
<Dose Level> 
 
 
 
Time Point 
 
Cohort 
/Subject 
0h 
0.25h 
0.5h  
1h 
2h 
4h 
6h 
8h 
12h 
24h  
 
xxxx 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
 
….. 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Statistics 
 
 
 
 
 
 
 
 
 
 
 
N 
 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Mean1 
 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
SD 
 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
CV (%) 
 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Minimum 
 
xxx 
xxx 
xxx 
Xxx 
Xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Median 
 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Maximum 
 
xxx 
xxx 
xxx 
Xxx 
Xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
N= Number of subject for which plasma sample was collected at each time point. 
1Mean calculated based on number of subjects (N). 
Programming Note: X will be assigned as 1, 2, 3…. as per each RP3128 dose level. Time point may vary depending the actual data. 
<Dose Level> = RP3128 25mg, 100mg, 400mg in MAD 
 
 


 
 
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Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 50 of 95 
 
Table 14.2.1.1.2.X.M RP3128 Plasma Concentrations (ng/mL) by Time Point (MAD) – Day 7 
Safety Population 
<Dose Level> 
 
 
 
Time Point 
 
Cohort 
/Subject 
0h 
0.25h 
0.5h  
1h 
2h 
4h 
6h 
8h 
12h 
24h  
48h  
72h  
96h  
120h 
144h 
192h 
 
xxxx 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
 
….. 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Statistics 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N 
 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Mean1 
 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
SD 
 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
CV (%) 
 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Minimum 
 
xxx 
xxx 
xxx 
Xxx 
Xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Median 
 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Maximum 
 
xxx 
xxx 
xxx 
Xxx 
Xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
N= Number of subject for which plasma sample was collected at each time point. 
1Mean calculated based on number of subjects (N). 
Programming Note: X will be assigned as 1, 2, 3…. as per each RP3128 dose level. Time point may vary depending the actual data. 
<Dose Level> = RP3128 25mg, 100mg, 400mg in MAD 
 
 


 
 
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Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 51 of 95 
 
Table 14.2.1.2.X.S RP3128 – Summary of PK Parameters (SAD) 
PK Population 
<Dose Level> 
Cohort/Subject 
AUC0-t 
(h*ng/mL) 
AUC0-inf 
(h*ng/mL) 
Cmax 
(ng/mL) 
Tmax 
(h) 
Kel 
(1/h) 
T1/2 
(h) 
xxxx 
xxx 
Xxx 
xxx 
xxx 
xxx 
xxx 
xxxx 
xxx 
Xxx 
xxx 
xxx 
xxx 
xxx 
….. 
xxx 
Xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
Statistics 
 
 
 
 
 
 
N 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
SD 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
CV (%) 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Minimum 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Median 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
Maximum 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Geo Mean1 
xxx.x 
xxx.x 
xxx.x 
NA 
NA 
NA 
Geometric CV% 
xx.x 
xx.x 
xx.x 
NA 
NA 
NA 
 
 
 
 
 
 
 
N=Number of subjects with derivable PK parameter. 
<Dose Level> = RP3128 25 mg, 50 mg, 100 mg, 200 mg, 400 mg 
Programming Notes: Geometric mean shall be calculated for all PK parameters except Tmax, t1/2 and Kel. Tmax will only have n, median, min, max provided. 
                                  X will be assigned as 1, 2, 3…. as per each RP3128 dose level. 
 
 
 


 
 
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Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 52 of 95 
 
Table 14.2.1.2.1.X.M RP3128 – Summary of PK parameters (MAD) – Day 1 
PK Population 
<Dose Level> 
Cohort/Subject 
Cmax 
(ng/mL) 
AUC0-24 
(ng·h/mL) 
Tmax 
(h) 
T1/2 
(h) 
xxxx 
xxx 
xxx 
xxx 
xxx 
xxxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
Statistics 
 
 
 
 
N 
xx 
xx 
xx 
xx 
Mean 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
SD 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
CV (%) 
xx.x 
xx.x 
xx.x 
xx.x 
Minimum 
xxx 
x.x 
x.x 
x.x 
Median 
xxx.x 
xx.x 
xx.x 
xx.x 
Maximum 
xxx 
x.x 
x.x 
x.x 
Geo Mean1 
xxx.x 
xxx.x 
NA 
NA 
Geometric CV% 
xx.x 
xx.x 
NA 
NA 
N=Number of subjects with derivable PK parameter. 
1: Geo Mean: Geometric means are based on the arithmetic means of ln-transformed values 
Programming Note: <Dose Level> = RP3128 25mg, 100mg, and 400mg.                                 
                                 X will be assigned as 1, 2, and 3 as per each RP3128 dose level. 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 53 of 95 
 
Table 14.2.1.2.2.X.M RP3128 – Summary of Ctrough (MAD)  
PK Population 
<Dose Level> 
Cohort/Subject 
Ctrough (ng/mL) 
Day 3 
Day 5 
Day 7 
xxxx 
xxx 
xxx 
xxx 
xxxx 
xxx 
xxx 
xxx 
 
 
 
 
Statistics 
 
 
 
N 
xx 
xx 
xx 
Mean 
xxx.x 
xxx.x 
xxx.x 
SD 
xxx.xx 
xxx.xx 
xxx.xx 
CV (%) 
xx.x 
xx.x 
xx.x 
Minimum 
xxx 
xxx 
x.x 
Median 
xxx.x 
xxx.x 
xx.x 
Maximum 
xxx 
xxx 
x.x 
Geo Mean1 
xxx.x 
xxx.x 
xxx.x 
Geometric CV% 
xx.x 
xx.x 
xx.x 
N=Number of subjects with derivable PK parameter. 
1: Geo Mean: Geometric means are based on the arithmetic means of ln-transformed values 
Programming Note: <Dose Level> = RP3128 25mg, 100mg, and 400mg.                                 
                                 X will be assigned as 1, 2, and 3 as per each RP3128 dose level. 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 54 of 95 
 
Table 14.2.1.2.3.X.M RP3128 – Summary of PK parameters (MAD) – Day 7 
PK Population 
<Dose Level> 
Cohort/Subject 
Cmax 
(ng/mL) 
Cmin 
(ng/mL) 
AUC0-24 
(ng·h/mL) 
Cav 
(ng/mL) 
Degree of 
Fluctuation 
Swing 
Tmax 
(h) 
T1/2 
(h) 
xxxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
Statistics 
 
 
 
 
 
 
 
 
N 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
SD 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
xxx.xx 
CV (%) 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Minimum 
xxx 
xxx 
x.x 
xxx 
xxx 
x.x 
x.x 
x.x 
Median 
xxx.x 
xxx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Maximum 
xxx 
xxx 
x.x 
x.x 
x.x 
x.x 
x.x 
x.x 
Geo Mean1 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
NA 
NA 
NA 
NA 
Geometric CV% 
xx.x 
xx.x 
xx.x 
xx.x 
NA 
NA 
NA 
NA 
N=Number of subjects with derivable PK parameter. 
1: Geo Mean: Geometric means are based on the arithmetic means of ln-transformed values 
Programming Note: <Dose Level> = RP3128 25mg, 100mg, and 400mg 
                                 X will be assigned as 1, 2, and 3 as per each RP3128 dose level. 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 55 of 95 
 
Table 14.2.2.X.1.M Summary of Cytokines <expression value>: Change from Baseline (MAD) 
Safety Population 
 
Treatment  
 
Visit and Time Point 
Statistic 
Placebo 
(N=xx) 
RP3128 
(N=xx) 
Baseline (Day 1, Pre-dose)  
 
n 
Xx 
Xx 
Mean ± SD 
xx.x ± x.xx 
xx.x ± x.xx 
Median 
xx.x 
xx.x 
Min, Max 
xx , xx 
xx , xx 
 
 
Day 7 (Pre-dose)  
 
n 
xx 
Xx 
Mean ± SD 
xx.x ± x.xx 
xx.x ± x.xx 
Median 
xx.x 
xx.x 
Min, Max 
xx , xx 
xx , xx 
 
 
Change from Baseline 1 
n 
xx 
Xx 
Mean ± SD 
xx.x ± x.xx 
xx.x ± x.xx 
Median 
xx.x 
xx.x 
Min, Max 
xx , xx 
xx , xx 
 
 
Paired t-test 
x.xx 
x.xx 
Day 7 (4 hr Post-dose) 
Change from Baseline 1 
 
 
Change from Baseline 2  
 
 
 
 
 
Note: 1 Baseline set at Day 1 pre-dose;  
          2 baseline set at Day 7 pre-dose 
Data source: Listings 16.2.6.1 
Programming note: Replace <expression value> with Th1, Th2, and Th17 and X will be assigned as 1, 2, and 3 for expression Th1, Th2 and Th17 respectively 
 


 
 
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Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 56 of 95 
 
Table 14.2.2.X.2.M ANCOVA Results of Cytokine <expression value> Change from Baseline to Day 7 (Pre-dose/Post-dose)/ Difference between Pre-dose and 
Post-dose on Day 7 (MAD) 
Safety Population 
 
Difference between RP3128 to Placebo 
Item 
Treatment 
 
n 
LSMeans Std Err 
LSMeans 
Std Err 
95%-confidence 
Interval 
P-value 
Treatment 
P-value 
Baseline 
CFB Day 7 (Pre-dose) 
Overall 
xxx 
x.xxxx 
x.xxxx 
 
Placebo 
xxx 
x.xxx 
x.xxx 
RP3128  
xxx 
x.xxx 
x.xxx 
x.xxx 
x.xxx 
x.xxx, x.xxx 
x.xxxx 
CFB1 Day 7 (4 hr Post-dose) 
Overall 
xxx 
x.xxxx 
x.xxxx 
 
Placebo 
xxx 
x.xxx 
x.xxx 
 
RP3128  
xxx 
x.xxx 
x.xxx 
x.xxx 
x.xxx 
x.xxx, x.xxx 
x.xxxx 
CFB2 Day 7(4 hr Post dose) 
… 
 
 
Note: 1 Baseline set at Day 1 pre-dose 
          2 Baseline set at Day 7 pre-dose 
          LSMeans: Least square means; Std Err: Standard error  
          LSMeans, Std Err, 95% confidence intervals and p-values are based on an ANCOVA with change from baseline as dependent variable, visit and treatment as 
fixed effect and baseline as covariate. P-values are from two-sided test at 5%-level. 
       
Data source: Listings 16.2.6.1 
Programming note: Replace <expression value> with Th1, Th2, and Th17 and X will be assigned as 1, 2, and 3 for expression Th1, Th2 and Th17 respectively 
 
 


 
 
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Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 57 of 95 
 
Table 14.3.1.1.S/M Treatment-Emergent Adverse Events – Overall Summary (SAD/MAD) 
Safety Population 
 
 
Treatment at Onset of Adverse Event 
 
Pooled  
Placebo 
(N=xx) 
RP3128 
25 mg 
(N=xx) 
RP3128 
50 mg 
(N=xx) 
RP3128 
100 mg 
(N=xx) 
RP3128 
200 mg 
(N=xx) 
RP3128 
400 mg 
(N=xx) 
RP3128 
Overall 
(N=xx) 
Number (%) of Subjects 
with TEAE 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
Number (%) of Subjects 
with Serious TEAE 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
Number (%) of Subjects 
with Severe TEAE 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
Number (%) of Subjects 
with Related TEAE 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
Number (%) of Subjects 
with Study Discontinued 
due to TEAE 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
Notes: A treatment-emergent adverse event (TEAE) is an AE, which starts or worsens after treatment with the study drug. 
            An AE is considered to be related if it is reasonably related to study treatment. 
            Summaries are presented as: number of subjects (percentage of subjects) [number of events] 
 
 


 
 
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Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 58 of 95 
 
Table 14.3.1.2.S/M Treatment-Emergent Adverse Events by System Organ Class and Preferred Term (SAD/MAD) 
Safety Population 
 
Treatment at Onset of Adverse Event 
 
 
System Organ Class/ 
Preferred Term 
Pooled  
Placebo 
(N=xx) 
RP3128 
25 mg 
(N=xx) 
RP3128 
50 mg 
(N=xx) 
RP3128 
100 mg 
(N=xx) 
RP3128 
200 mg 
(N=xx) 
RP3128 
400 mg 
(N=xx) 
RP3128 
Overall 
(N=xx) 
Any System Organ Class 
 
 
 
 
 
 
 
Any Event 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
Cardiac Disorders 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
Any Event 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
Bradycardia 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
xx (xx.x%) [xx] 
… 
 
 
 
 
 
 
 
Notes: A treatment-emergent adverse event (TEAE) is an AE, which starts or worsens after treatment with the study drug. 
           For each row category, a subject with two or more adverse events in that category is counted only once. 
           Summaries are presented as: number of subjects (percentage of subjects) [number of events] 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 59 of 95 
 
Table 14.3.1.3.S/M Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Maximum Intensity (SAD/MAD) 
Safety Population 
 
 
Treatment at Onset of Adverse Event 
 
 
System Organ Class/ 
Preferred Term 
Maximum 
Intensity 
Pooled 
Placebo 
(N=xx) 
RP3128 
25 mg 
(N=xx) 
RP3128 
50 mg 
(N=xx) 
RP3128 
100 mg 
(N=xx) 
RP3128 
200 mg 
(N=xx) 
RP3128 
400 mg 
(N=xx) 
RP3128 
Overall 
(N=xx) 
Any System Organ 
Class 
 
 
 
 
 
 
 
 
Any Event 
Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Cardiac Disorders 
 
 
 
 
 
 
 
 
Any Event 
Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
 
 
Notes: A treatment-emergent adverse event (TEAE) is an AE which starts or worsens after treatment with the study drug. 
           For each row category, a subject with two or more adverse events in that category is counted only once at the maximum severity level. 
           Summaries are presented as: number of subjects (percentage of subjects) 
 
 


 
 
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Table 14.3.1.4.S/M Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Maximum Relationship (SAD/MAD) 
Safety Population 
 
 
Treatment at Onset of Adverse Event 
 
 
System Organ Class/ 
Preferred Term 
Maximum Relationship 
Pooled 
Placebo 
(N=xx) 
RP3128 
25 mg 
(N=xx) 
RP3128 
50 mg 
(N=xx) 
RP3128 
100 mg 
(N=xx) 
RP3128 
200 mg 
(N=xx) 
RP3128 
400 mg 
(N=xx) 
RP3128 
Overall 
(N=xx) 
Any System Organ 
Class 
 
 
 
 
 
 
 
 
Any Event 
No Reasonable Possibility 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Reasonable Possibility 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Cardiac Disorders 
 
 
 
 
 
 
 
 
Any Event 
No Reasonable Possibility 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Reasonable Possibility 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
 
 
Notes: A treatment-emergent adverse event (TEAE) is an AE which starts or worsens after treatment with the study drug. 
           For each row category, a subject with two or more adverse events in that category is counted only once at the maximum relationship level. 
           Summaries are presented as: number of subjects (percentage of subjects) 
 
 
 
 


 
 
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Table 14.3.3.1.X.S/M Summary of <laboratory Panel> (SAD/MAD) 
Safety Population 
Example of quantitative data: 
Parameter 
(unit) 
 
Statistic 
Pooled 
Placebo 
(N=xx) 
RP3128 
25 mg 
(N=xx) 
RP3128 
50 mg 
(N=xx) 
RP3128 
100 mg 
(N=xx) 
RP3128 
200 mg 
(N=xx) 
RP3128 
400 mg 
(N=xx) 
Albumin (g/L) 
Baseline* 
 
 
 
 
 
 
 
 
 
Summary Statistics 
 
 
 
 
 
 
 
 
       n 
xx 
xx 
xx 
xx 
xx 
Xx 
 
 
       Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
       SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
       Minimum 
xx 
xx 
xx 
xx 
xx 
Xx 
 
 
       Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
       Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Relation to Reference Range, n (%) 
 
 
 
 
 
 
 
 
       n 
n 
n 
n 
n 
n 
n 
 
 
       Missing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
       Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
       Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
       High 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day X 
 
… 
 
 
 
 
 
 
CFB on Day X 
 
… 
 
 
 
 
 
….. 
 
 
 
 
 
 
 
 
Note: CFB = Change from Baseline  
          *Baseline is defined as the last observation prior to dosing on Day 1. 
<Laboratory Panel> = Hematology, Chemistry, Urinalysis 
Programming Note: X will be assigned as 1, 2, and 3 as per laboratory panels. Day X will depends on SAD or MAD;  
                                 Relation to Reference Range will be summarized for raw data only, not for change-from-baseline values 
 


 
 
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Example of qualitative data: 
Parameter (unit) 
Visit 
 
Pooled 
Placebo 
(N=xx) 
RP3128 
25 mg 
(N=xx) 
RP3128 
50 mg 
(N=xx) 
RP3128 
100 mg 
(N=xx) 
RP3128 
200 mg 
(N=xx) 
RP3128 
400 mg 
(N=xx) 
Urine Protein (G/L) 
Baseline* 
 
 
 
 
 
 
 
 
 
Frequency, n (%) 
 
 
 
 
 
 
 
 
      n 
n 
n 
n 
n 
n 
n 
 
 
     Category 1  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
     Category 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Relation to Reference Range, n (%) 
 
 
 
 
 
 
 
 
      n 
n 
n 
n 
n 
n 
n 
 
 
      Missing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
      Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
      Abnormal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day X 
 
… 
 
 
 
 
 
 
Follow-up or 
ET 
 
… 
 
 
 
 
 
…. 
 
 
 
 
 
 
 
 
*Baseline is defined as the last observation prior to dosing on Day 1. 
Notes: Percentages are calculated based on the number of subjects in the Safety population per treatment group. 
<Laboratory Panel> = Hematology, Chemistry, Urinalysis 
Programming Note: X will be assigned as 1, 2, 3 as per laboratory panels. 
 
 
 
 
 
 


 
 
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Table 14.3.3.2.X.S/M <Laboratory Panel>: Shift Table from Baseline to End of Treatment Results (SAD/MAD) 
Safety Population  
 
 
 
Baseline (n=xx)* 
Laboratory Parameter 
(unit) 
Study Day 
[Treatment] 
Parameter 
Low 
Normal 
High/Abnormal# 
Total 
 
Parameter 1 (unit) 
Day 3/8 [Placebo] 
Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
High 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Total 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Day 3/8 [RP3128 25 mg] 
…. 
… 
 
 
 
 
 
 
…. 
… 
 
 
 
 
…. 
 
 
 
 
 
 
 
Note: Doses are Total Daily Dose. 
Notes: *Baseline is defined as the last observation prior to dosing on Day 1. 
           # For categorical assays, abnormal results are counted under the “High/Abnormal” column (‘Low’ column is ‘N/A’) 
Note: Percentages are calculated based on the number of subjects in the Safety population per treatment group. 
Note: <Laboratory Panel> = Hematology, Chemistry, Urinalysis 
Programming Note: Table will continue for other lab parameters.  X will be assigned as 1, 2, 3 as per laboratory panels. For SAD, Day 3 will be used to compare with 
Baseline. For MAD, Day 8 will be used. 
 
 
 
 
 


 
 
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Table 14.3.4.X.S/M Summary of Vital Signs Data by Treatment, Visit and Time Point (SAD/MAD) 
Safety Population 
<Vital Signs Parameter (unit)> 
 
Time Point/  
Visit (Day) 
 
Statistic 
Pooled  
Placebo 
(N=xx) 
RP3128 
25 mg 
(N=xx) 
RP3128 
50 mg 
(N=xx) 
RP3128 
100 mg 
(N=xx) 
RP3128 
200 mg 
(N=xx) 
RP3128 
400 mg 
(N=xx) 
Baseline* 
 
 
 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
Xx 
 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx 
xx 
xx 
xx 
xx 
Xx 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx 
xx 
xx 
xx 
xx 
Xx 
0.5h Day 1 
 
 
 
 
 
 
 
0.5h Day 1 CFB 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Baseline is defined as the last observation prior to the dose on Day 1. 
Note: CFB = Change from Baseline 
<Vital Signs Parameter (unit)> = Systolic Blood Pressure (mmHg), Diastolic Blood Pressure (mmHg), Heart Rate (bpm), Respiratory Rate (breaths/min), Oral 
Temperature (°C) 
Programming Note: Table also includes all days and time points except screening and check-in.  
                                X will be assigned as 1, 2, 3, 4 and 5 as per vital sign parameters (unit). 
 
 
 
 


 
 
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Table 14.3.4.6.S/M Summary of Weight Data by Treatment and Time Point (SAD/MAD) 
Safety Population 
 
Time Point 
 
Statistic 
Pooled 
Placebo 
(N=xx) 
RP3128 
25 mg 
(N=xx) 
RP3128 
50 mg 
(N=xx) 
RP3128 
100 mg 
(N=xx) 
RP3128 
200 mg 
(N=xx) 
RP3128 
400 mg 
(N=xx) 
 Check-in  
(Baseline) 
 
 
 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
Day 3/4 
 
 
 
 
 
 
 
Day 3/4 CFB 
 
 
 
 
 
 
 
Day 8 
Day 8 CFB 
Day 15 
Day 15 CFB 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Baseline is defined as the last observation prior to the dose on Check-in. 
Note: CFB = Change from Baseline 
 
Programming Note: For SAD, Day 3 will be applied. For MAD, Day 4 will be applied. 
 


 
 
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Table 14.3.5.1.S/M Summary of Overall ECG Interpretation (SAD/MAD) 
Safety Population 
 
Pooled  
Placebo 
(N=xx) 
RP3128 
25 mg 
(N=xx) 
RP3128 
50 mg 
(N=xx) 
RP3128 
100 mg 
(N=xx) 
RP3128 
200 mg 
(N=xx) 
RP3128 
200 mg 
(N=xx) 
Baseline 
 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
Xx 
Normal, n (%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Not Clinically Significant, n (%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Clinically Significant, n (%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Missing, n (%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
Follow-up or ET 
 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
Xx 
Normal, n (%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Not Clinically Significant, n (%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal, Clinically Significant, n (%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Missing, n (%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Note: Percentages are calculated based on the number of subjects in the Safety population per treatment group. 
Programming Note: Table also includes time points and visits listed in the section 9.5 
 
 
 
 


 
 
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Table 14.3.5.X.S/M Summary of ECG Continuous Data (SAD/MAD)  
Safety Population 
<ECG Parameter (unit)> 
Time Point/ 
Statistic 
Pooled  
Placebo 
(N=xx) 
RP3128 
20 mg 
(N=xx) 
RP3128 
60 mg 
(N=xx) 
RP3128 
120 mg 
(N=xx) 
RP3128 
240 mg 
(N=xx) 
Baseline* 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
Xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Minimum 
xx 
xx 
xx 
xx 
Xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Maximum 
xx 
xx 
xx 
xx 
Xx 
5 min 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
… 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Maximum 
xx 
xx 
xx 
xx 
xx 
5 min CFB 
 
 
 
 
 
… 
 
 
 
 
 
CFB = Change from Baseline 
Note: *Baseline is defined as the last observation prior to the dose. 
<ECG Parameter (unit)> = Ventricular Rate (bpm), PR interval (msec), QRS duration (msec), QT Interval (msec), QTcB Interval (msec) 
Programming Note: Table also includes time points and visits listed in the section 9.5 
                                 X will be 2, 3, 4, 5 and 6 for VR, PR, QRS, QT and QTcB. 
 


 
 
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Table 14.3.6.1.S/M Summary of Mini-Mental State Examination (SAD/MAD) 
Safety Population 
Visit/Statistic 
Pooled  
Placebo 
(N=xx) 
RP3128 
25 mg 
(N=xx) 
RP3128 
50 mg 
(N=xx) 
RP3128 
100 mg 
(N=xx) 
RP3128 
200 mg 
(N=xx) 
RP3128 
400 mg 
(N=xx) 
Baseline* 
 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
Day 3/8 
 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
… 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
Day 3/8 CFB 
 
 
 
 
 
 
… 
 
 
 
 
 
 
CFB = Change from Baseline 
Note: *Baseline is defined as the observation from screening. 
Programming Note: Day 3 will be used for SAD and Day 8 will be used for MAD. 
 
 


 
 
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Listing 16.1.7.S/M Randomization Scheme and Code (SAD/MAD) 
Randomized Population 
Randomization 
Number 
Cohort/Treatment 
Age* 
(years) 
Date of Randomization 
Sex 
 
 
 
 
 
xxxx 
1/Placebo 
30 
DDMONYYYY 
F 
…. 
 
 
 
 
*Age at Informed Consent 
 
 


 
 
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Listing 16.2.1.S/M Subject Disposition and Completion/Discontinuation (SAD/MAD) 
Randomized Population 
Cohort/ 
Treatment 
Subject 
Completed 
Study 
Date of Study Completion 
or Early Discontinuation / 
Date of last Contact 
Date of dosing 
Reason for Study 
Discontinuation* 
1/Placebo 
xxxx 
Yes 
DDMONYYYY/ 
DDMONYYYY 
DDMONYYYY 
xxxxxxxxxxx 
… 
 
 
 
 
 
*A corresponding AE number will be displayed if Reason for Treatment Discontinuation or Reason for Study Discontinuation is “Adverse Event”. 
 
 


 
 
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Listing 16.2.2.S/M Protocol Deviations (SAD/MAD) 
Safety Population 
Cohort/ 
Treatment 
Subject 
Start Date of 
deviation 
Visit/Day 
Description of Protocol Deviation 
Classification 
Category 
1/Placebo 
xxxx 
DDMONYYYY 
xxxx 
Xxxxxxx 
Major/Minor 
Procedures/Assessments 
Outside Protocol Window 
…. 
 
 
 
 
 
 
 
 


 
 
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Listing 16.2.3.S/M Exclusions from Analysis Populations (SAD/MAD) 
Randomized Population 
 
Cohort/ 
Treatment 
Subject 
Excluded from 
Safety Population 
Reason for Exclusion from 
the Safety Population 
Excluded from 
PK Population 
Reason for Exclusion from 
the PK Population 
1/Placebo 
xxxx 
No 
Xxxxxxx 
Yes 
Xxxxxxx 
… 
 
 
 
 
 
 
 


 
 
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Listing 16.2.4.S/M Demographics and Informed Consent at Screening (SAD/MAD) 
Safety Population 
Cohort/ 
Treatment 
Subject 
Informed 
Consent Date 
Sex 
Date of Birth 
Age* 
(years) 
Race 
Ethnicity 
 
Height 
(cm) 
Weight 
(kg) 
BMI 
(kg/m2) 
1/Placebo 
xxxx 
DDMONYYYY 
x 
DDMONYYYY 
xx 
xxxxx 
xxxxx 
xxx 
xx 
xx 
… 
 
 
 
 
 
 
 
 
 
 
*Age at Informed Consent 
 
 


 
 
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Listing 16.2.5.1.S/M Study Drug Administration and Compliance (SAD/MAD) 
Safety Population 
Cohort/ 
Treatment 
Subject 
Visit/Day 
Study Drug 
Administered? 
Route of 
Administration 
Dose/Unit 
Start date 
Start time/End 
time 
Treatment 
Comment 
1/Placebo 
xxxx 
Day 1 
Yes 
Oral 
xx/mg 
DDMONYYYY 
HH:MM/HH:MM 
xxxxxxxxx 
… 
 
 
 
 
 
 
 
 
 
 


 
 
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Listing 16.2.5.2.S/M Pharmacokinetic Sample Collection Data (SAD/MAD) 
Safety Population 
Cohort/ 
Treatment 
Subject 
Dosing Date and 
Time 
Date of Sample 
Collection 
Scheduled 
Time Point (hr) 
Elapsed Time* 
(hr)* 
Actual Sample 
Collection Time 
(HH:MM) 
Time 
Deviation** 
(min) 
Plasma 
Concentration 
(ng/mL) 
 
 
 
 
 
 
 
 
 
1/RP3128 
20 mg 
xxxx 
DDMONYYYY 
HH:MM 
DDMONYYYY 
Pre-dose 
-1.4 
HH:MM 
xx 
xx 
 
 
 
 
0.083 
0.083 
HH:MM 
xx 
xx 
 
 
 
 
0.25 
0.25 
HH:MM 
xx 
xx 
 
 
 
 
0.5 
0.51 
HH:MM 
xx 
xx 
 
 
 
 
2  
2.1 
HH:MM 
xx 
xx 
 
 
 
 
6  
6 
HH:MM 
xx 
xx 
 
 
 
 
12  
12 
HH:MM 
xx 
xx 
 
 
…. 
…. 
 
 
 
 
 
…. 
 
 
 
 
 
 
 
 
*Difference between actual sample collection time and dosing time 
**Difference actual collection and scheduled collection time (post treatment time points only) 
Note: BLQ = Below the limit of quantification. 
 
Note: HH:MM = Hours: Minutes 
 
 
 
 
 
 
 


 
 
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Listing 16.2.5.3.S Pharmacokinetic Parameters (SAD) 
PK Population 
Cohort/Treatment 
Subject 
Lower 
Time*  
(h) 
Upper 
Time* 
(h) 
Number of points used in 
Kel estimation 
 
Adjusted 
R-Square 
Kel  
(1/h) 
t1/2 
(h) 
 
 
 
 
 
 
 
 
1/RP3128 25 mg 
xxxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
… 
 
 
 
 
 
 
*Lower time and upper time are the lower and upper limits on time, respectively, for values to be included in the estimation of Kel. 
Note: Minimum 3 points will be used to estimate Kel. 
 
 
 
 
 
 
 
 
 
 
 


 
 
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Listing 16.2.5.4.S/M Reasons Why Pharmacokinetic Parameters Could Not be Determined (SAD/MAD) 
 
Cohort/Treatment 
Subject 
Pharmacokinetic Parameter  
(Units) 
Original 
Value 
Reason 
 
 
 
 
 
1/RP3128 20 mg 
xxxx 
Kel (h) 
xxx 
Xxxxxxxxxx 
 
… 
 
 
 
…… 
 
 
 
 
 
 


 
 
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Listing 16.2.6.1: Cytokine assessment 
Cohort/Treatment 
 
Subject 
 
Visit 
Date 
Time 
Point 
Cytokine Test 
Th1 
Th2 
Th17 
1/Placebo 
1001 
Day 1 
DDMMMYYYY Pre-dose 
xx 
xx 
xx 
 
Day 7 
DDMMMYYYY Pre-dose 
xx 
xx 
xx 
 
Day 7 
DDMMMYYYY post-dose 
xx 
xx 
xx 
…… 
2/RP3128 25mg 
xxxx 
 
Programming Note: the list of cytokine here is just an example, the final listing will show all cytokines available in the eCRF. 
 
 
 
 
 
 
 
 
 
 


 
 
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Listing 16.2.7.1.S/M Adverse Events (SAD/MAD) 
Safety Population 
Cohort/ 
Treatment 
Subject 
Visit 
 
A
E 
# 
System Organ 
Class/ 
Preferred 
Term/ 
Verbatim Term 
TE
AE
? 
Ongo
-ing? 
Start Date and 
Time/ 
Stop Date and 
Time/ 
Time from 
Dosing/ 
Duration 
(DD:HH:MM)* 
Toxicity 
Grade ( if 
applicable) 
Severity/ 
Serious/  
Relationship to 
Study Drug/ 
Outcome 
Study Drug  
Action Taken/  
Non-Drug  
Action Taken 
Caused 
Study  
Disconti
nuation  
 
 
 
x 
Gastrointestina
l disorders/ 
Vomiting/ 
Vomiting 
Y 
    Y 
DDMONYYYY 
HH:MM 
DD:HH:MM/  
DD:HH:MM 
2 
Moderate/ No/ 
Related / 
Recovered/Res
olved 
Not Applicable/ 
None 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
*DD:HH:MM = Days:Hours:Minutes 
 
 
 
 
 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 80 of 95 
 
Listing 16.2.7.2.S/M Deaths, Other Serious and Significant Adverse Events Safety Population (SAD/MAD) 
Cohort/ 
Treatment 
Subject 
System Organ Class/ 
Preferred Term/ 
Verbatim Term 
Date and Time of Event/ 
Date and Time of 
Resolution 
Severity/ Serious/ 
Relationship to Study Drug/ 
Outcome 
Study Drug Action 
Taken/ Other Action 
Taken 
 
 
 
 
 
 
1/Placebo 
xxxx 
Nervous system disorders/ 
Migraine/ Migraine 
DDMONYYYY HH:MM/ 
DDMONYYYY HH:MM 
Mild/ No/ Possibly Related/ 
Recovered/Resolved 
Dose Not Changed/ 
ConMed Taken (CM # 
1) 
 
… 
 
 
 
 
 
Programming Note: this listing will only be produced when any SAE has occurred during the study. 
 
 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 81 of 95 
 
Listing 16.2.8.X.S/M <Laboratory Panel> (SAD/MAD) 
Safety Population 
Cohort/ 
Treatment 
Subject 
Visit/Day 
Date of Sample 
Collection 
Lab test (Unit) 
Value 
Reference 
Range 
Indicator 
Normal 
Range 
Completion 
Status 
1/Placebo 
xxxx 
Screening 
DDMONYYYY 
Xxxxxxxxxxxxxx 
(xxxx) 
xx 
  High 
xx - xxx 
Yes 
 
 
 
 
Xxxxxxxxxxxxxx 
(xxxx) 
xx 
Abnormal 
Negative 
Yes 
 
… 
 
 
 
 
 
 
 
<Laboratory Panel> = Hematology, Chemistry, Urinalysis 
Note to programmer: X will be assigned as 1, 2, and 3 as per each laboratory panels. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Listing 16.2.8.X.S/M <Laboratory Panel>: Abnormal Results (SAD/MAD) 
Safety Population  
Cohort/Treatment 
Subject 
Visit/Day 
Date/Time  
Lab test (Unit) 
Value  
Reference 
Normal 
Significance# 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 82 of 95 
 
Range 
Indicator 
Range 
1/Placebo 
xxxx 
Screening 
DDMONYY
YY HH:MM 
xxxxxxx  
x.x  
Abnormal 
     Negative 
NCS 
 
 
….. 
 
 
 
High 
xx-xxx 
CS 
… 
 
 
 
 
 
 
 
 
Note: #Significance: CS = Clinically Significant, NCS = Not Clinically Significant 
<Laboratory Panel> = Hematology, Chemistry, Urinalysis 
Note to programmer: X will be assigned as 4, 5, and 6 as per each laboratory panels. 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 83 of 95 
 
  
Listing 16.2.8.7.S/M Viral Screen and TB Test at Screening (SAD/MAD) 
Safety Population 
Cohort/Treatment 
Subject 
Date and Time 
Hepatitis B Surface 
Antigen 
Hepatitis C Virus 
Antibody 
HIV 1/2 Antibody 
Tuberculin test 
/QuantiFeron-TB - Gold test 
1/Placebo 
xxxx 
DDMONYYYY 
HH:MM 
Negative 
Negative 
Non-Reactive 
Negative 
 
… 
 
 
 
 
 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 84 of 95 
 
Listing 16.2.8.8.S/M Drug and Alcohol Screen (SAD/MAD) 
Safety Population 
Cohort/ 
Treatment 
Subject 
Visit 
Collection 
Date  
Opiates 
Methadone 
Cocaine 
Amphe
tamine 
Cannabinoids 
Barbiturate 
Benzodia
-zepine 
Alcohol Breath 
Test 
 
 
 
 
 
 
 
 
 
 
 
 
1/Placebo 
xxxx 
Screening 
DDMON 
YYYY  
Negative 
Negative 
Positive 
 
Negative 
Negative 
Negative 
Negative 
Negative 
 
 
Day -1 
…. 
 
 
 
 
 
 
 
 
 
    ….. 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 85 of 95 
 
Listing 16.2.9.1.S/M Vital Signs (SAD/MAD) 
Safety Population 
Cohort/Treat
ment 
Subject 
Visit 
Time 
Point 
Position  
Date 
Time 
SBP 
(mmH
g) 
DBP 
(mmH
g) 
HR 
(bpm) 
RR 
(bpm) 
Temp 
(ºC) 
Weight 
(kg) 
1/Placebo 
xxxx 
Screening 
 
Supine 
DDMONY
YYY 
HH:M
M 
xxx 
xx 
xx 
xx 
xx 
xx 
 
 
Check-in 
Day -1 
 
 
DDMONY
YYY 
HH:M
M 
xxx 
xx 
xx 
xx 
xx 
xx 
 
 
Day 1 
Pre-dose 
 
DDMONY
YYY 
HH:M
M 
xxx 
xx 
xx 
xx 
xx 
 
 
 
 
  30 min  
 
 
DDMONY
YYY 
HH:M
M 
xxx 
xx 
xx 
xx 
xx 
 
 
 
 
  1 hour  
 
 
DDMONY
YYY 
HH:M
M 
xxx 
xx 
xx 
xx 
xx 
 
 
 
Day 2 
 
 
 
 
 
 
 
 
 
 
 
 
Follow-
up or ET 
 
 
 
 
 
 
 
 
 
 
 
…. 
 
 
 
 
 
 
 
 
 
 
 
………. 
 
 
 
 
 
 
 
 
 
 
 
 
Note: SBP = Systolic Blood Pressure; DBP = Diastolic Blood Pressure; HR = Heart Rate; RR = Respiration Rate; Temp = Oral Temperature; bpm = Beats per 
Minute or Breaths per Minute 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 86 of 95 
 
Listing 16.2.10.1.S/M Electrocardiogram (ECG) (SAD/MAD) 
Safety Population 
Cohort/ 
Treatment 
Subject 
Visit 
Time 
Point 
Date and 
Time 
Was the 
ECG 
Performed
? 
ECG Overall 
Interpre- 
tation 
VR 
(bpm) 
PR 
(msec) 
QRS 
(msec) 
QT 
(msec) 
QTcB 
(msec)  
 
1/Placebo 
xxxx 
Screening 
 
DDMONYYYY 
HH:MM 
Yes 
Abnormal/NCS 
xx 
xxx 
xx 
xx 
xxx 
 
 
Day 1 
Pre-dose 
DDMONYYYY 
HH:MM 
No 
 
 
 
 
 
 
 
 
 
15 min 
DDMONYYYY 
HH:MM 
Yes 
Normal 
xx 
xxx 
xx 
xx 
xxx 
 
 
 
30 min 
DDMONYYYY 
HH:MM 
NU 
 
 
 
 
 
 
 
 
 
45 min 
DDMONYYYY 
HH:MM 
Yes 
Normal 
xx 
xxx 
xx 
xx 
xxx 
 
 
 
1 hour 
DDMONYYYY 
HH:MM 
Yes 
Normal 
xx 
xxx 
xx 
xx 
xxx 
 
 
 
…. 
 
 
 
 
 
 
 
 
 
 
Day 3 
 
DDMONYYYY 
HH:MM 
Yes 
Normal 
xx 
xxx 
xx 
xx 
xxx 
 
 
Follow-up 
or ET 
 
DDMONYYYY 
HH:MM 
Yes 
Normal 
xx 
xxx 
xx 
xx 
xxx/N 
 
…. 
 
 
 
 
 
 
 
 
 
 
…… 
 
 
 
 
 
 
 
 
 
 
 
Note: CFB: Change from baseline; NU: Not Useable;   CS = Abnormal, Clinically Significant; NCS = Abnormal, Not Clinically Significant; VR = Ventricular Rate; 
PR=Pulse Rate. 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 87 of 95 
 
Listing 16.2.10.2.S/M ECG: Abnormal Results – Listing (SAD/MAD) 
Safety Population 
Cohort/Treatment 
Subject 
Day 
Time Point 
Date and Time of 
ECG 
ECG Abnormality 
Clinically 
Significant 
1/Placebo 
xxxx 
Day 1 
Pre-dose 
DDMONYYYY 
HH:MM 
Sinus bradycardia otherwise normal 
ECG, physician comments 
transcribed as per monitor’s request 
No 
 
… 
 
 
 
 
 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 88 of 95 
 
Listing 16.2.11.S/M Mini-Mental State Examination (SAD/MAD) 
Safety Population 
 
Cohort/Treatment 
Subject 
Day 
Date and Time 
Score 
Results 
1/Placebo 
xxxx 
Screening 
DDMONYYYY HH:MM 
XX  
Normal 
 
… 
 
 
 
 
  Note: MMSE - Mini-Mental State Examination 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 89 of 95 
 
Listing 16.2.12.S/M Medical History (SAD/MAD) 
Safety Population 
Cohort/ 
Treatment 
Subject 
MH # 
Body System/ 
Preferred Term 
Condition 
Start Date 
End Date 
 
Ongoing 
1/Placebo 
xxxx 
x 
Xxxx/Xxxxx 
Xxxxxx 
DDMONYY
YY 
DDMONYYYY 
No 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 90 of 95 
 
Listing 16.2.13.S/M Clinical Events (SAD/MAD) 
Safety Population 
Cohort/ 
Treatment/ 
Subject 
Clinical Event  
Planned time point 
Start Date and Time 
End Date and Time 
Ongoing? 
 
 
 
 
 
 
 
1/Placebo 
xxxx 
XXXXXX 
Pre-dose 
DDMONYYYY  
 
DDMONYYYY  
 
No 
 
 
XXXXXX 
5 min 
DDMONYYYY 
 
 
Yes 
 
… 
 
 
 
 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 91 of 95 
 
Listing 16.2.14.S/M Prior and Concomitant Medications (SAD/MAD) 
Safety Population 
Cohort/ 
Treatment 
Subject 
Medication 
# 
Drug 
Class/ 
Preferred 
Term/ 
Verbatim 
Term 
Medication 
Information* 
Start Date/Stop 
Date 
Ongoing? 
Indication 
 
Administered 
for AE? 
Administered 
for MH? 
 
 
 
 
 
 
 
 
 
 
1/Placebo 
xxxx 
1 
xxxx 
xxx/ mg/ 
Once/ Oral 
DDMONYYYY/ 
DDMONYYYY 
No 
Headache  
 
Yes (AE # 4) 
No 
 
 
2 
xxxx 
xxx/ mg/ 
Once/ Oral 
DDMONYYYY 
Yes 
Xxxxx 
No 
Yes (MH #2) 
… 
 
 
 
 
 
 
 
 
 
*Dose/Unit/Frequency/Route 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 92 of 95 
 
Listing 16.2.15.M Electroencephalogram at Screening (MAD) 
Safety Population 
Cohort/ 
Treatment 
Subject 
EEG Test Date and Time 
Results 
Clinically Significant 
 
 
 
 
 
1/Placebo 
xxxx 
DDMONYYYY HH:MM 
 
Abnormal 
No 
 
… 
 
 
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 93 of 95 
 
Figure 14.4.1.S/M – Mean Plasma RP3128 Concentrations – Linear Scale (SAD/MAD) 
Safety Population 
 
 
Programming Notes: Replace XX with corresponding dose of indicated cohort.  
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 94 of 95 
 
Figure 14.4.2.S/M – Mean Plasma RP3128 Concentrations – Semi-logarithmic Scale (SAD/MAD) 
PK Population 
 
Programming Notes: Replace XX with corresponding dose of indicated cohort.  
 
 
 


 
 
Sponsor: Rhizen Pharmaceuticals SA 
Study: Study 15-MR-001 
Statistical Analysis Plan  
 
Page 95 of 95 
 
Figure 14.4.3.X.S/M–Individual Plasma RP3128 Concentrations – Linear Scale (SAD/MAD) 
 (ZZ mg) 
Safety Population 
 
Programming Notes: Similar to 14.4.1 except graphs will represent individual subject graphs within each cohort. Increase value of X by 1 
with each cohort. Replace ZZ with corresponding dose of indicated cohort. 
 
Figure 14.4.4.X.S/M–Individual Plasma RP3128 Concentrations – Semi-logarithmic Scale (SAD/MAD) 
 (ZZ mg) 
Safety Population 
 
Programming Notes: Similar to 14.4.2 except graphs will represent individual subject graphs within each cohort. Increase value of X by 1 
with each cohort. Replace ZZ with corresponding dose of indicated cohort.