Conditions: Healthy Volunteers Chronic Kidney Disease
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 18
Healthy volunteers: yes

Brief summary:
This is a Phase 1b, single center, dose-escalating study evaluating the safety, tolerability, and pharmacodynamic effect of RBT-3 in healthy volunteers and in subjects with stage 3-4 chronic kidney disease.

Detailed description:

Arms:
arm 1: None arm 2: None arm 3: None

Interventions: intervention 1: RBT-3
Intervention descriptions: intervention 1: intravenous administration

Protocol document:
Prot_004.pdf: 

































































SAP_005.pdf: 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
A Phase 1b dose-escalating study with Iron Sucrose (FeS), in healthy 
volunteers and subjects with chronic kidney disease stage 3-4 
 
 
Protocol No.: IND 138109 
Protocol Date/Version: 10 October 2018  
IND No.: 138109  
Study Phase: 1b 
Study Drug: Iron Sucrose (FeS) 
Statistical Analysis Plan 
Date/Version 
25 April 2019 
Version 1.0 
Prepared by: Alfred Mbah, PhD 
Sponsor: Renibus Therapeutics, Inc.Renibus Therapeutics 
950 E State Highway 114, Suite 160 
Southlake, TX 76092 
Tel: (480) 220-7084 
 
 
 
 
 
 
Confidentiality Statement 
The information contained in this document is confidential and the property of Renibus Therapeutics, Inc.  
It should not be reproduced, revealed, or sent to third parties other than Institutional Review 
Boards/Independent Ethics Committees and the Investigator’s research support staff participating in the 
conduct of the study without the prior written authorization of Renibus Therapeutics, Inc. 


26 April 2019


Renibus Therapeutics, Inc. 
Protocol: REN-002 
Product: Iron Sucrose (FeS) 
Statistical Analysis Plan 
 
CONFIDENTIAL 
Page 3 of 27 
25 April 2019 
Table of Contents 
1. 
INTRODUCTION 
5 
2. 
STUDY OBJECTIVES 
5 
3. 
STUDY OVERVIEW 
5 
4. 
EFFICACY AND SAFETY VARIABLES 
6 
5. 
DEFINITIONS 
7 
6. 
ANALYSIS POPULATIONS 
7 
7. 
STATISTICAL METHODS OF ANALYSIS 
7 
7.1. 
General Principles 
7 
7.1.1. 
Handling Missing Values 
7 
7.1.1.1. 
Study Drug Administration Date or Time 
8 
7.1.1.2. 
Adverse Event or Concomitant Medications Dates or Times 
8 
7.1.2. 
Multiplicity Adjustments 
8 
7.1.3. 
By-Center Analyses 
8 
7.2. 
Subject Disposition 
8 
7.3. 
Description of Demographics and Baseline Characteristics 
9 
7.3.1. 
Demographics 
9 
7.3.2. 
Baseline Characteristics 
9 
7.4. 
Prior and Concomitant Medications 
9 
7.5. 
Measurements of Treatment Compliance 
10 
7.6. 
Efficacy Analysis 
10 
7.6.1. 
Percent Chamge in Response Biomarkers 
10 
7.6.2. 
Absolute Chamge 
11 
7.7. 
Safety Analyses 
11 
7.7.1. 
Adverse Events 
11 
7.7.2. 
Laboratory Test 
11 
7.7.3. 
Vital Signs 
11 
7.7.4. 
ECG 
12 
7.8. 
Interim Analysis 
12 
8. 
SAMPLE SIZE CALCULATIONS 
12 
9. 
REFERENCES 
12 
10. 
TIME AND EVENTS SCHEDULE OF STUDY PROCEDURES 
13 
11. 
CONVENTIONS FOR THE PRESENTATIONS OF TABLES, LISTINGS, AND FIGURES14 
12. 
LIST OF TABLES 
15 
13. 
LIST OF FIGURES 
26 
14. 
LIST OF LISTINGS 
27 


Renibus Therapeutics, Inc. 
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Statistical Analysis Plan 
 
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List of ACRONYMS/Abbreviations 
 
Abbreviation 
Definition 
AE 
Adverse event 
AKI 
acute kidney injury 
ALT 
alanine aminotransferase 
ARB 
angiotensin-receptor blockers 
AST 
aspartate aminotransferase 
BUN 
blood urea nitrogen 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CKD 
chronic kidney disease 
Cr 
creatinine 
CRO 
contract research organization 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
FDA 
Food and Drug Administration 
FeS 
Iron sucrose 
GCP 
Good Clinical Practice 
GFR 
glomerular filtration rate 
GLP 
Good Laboratory Practice 
HO-1 
Heme oxygenase 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
ICSR 
Individual Case Safety Report 
IEC 
Independent Ethics Committee 
IND 
investigational new drug 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
MITT 
Modified Intent-to-Treat 
NOAEL 
no-observed-adverse-effect level 
POC 
Proof of Concept 
PP 
Per Protocol 
SAS 
Statistical Analysis System 
TEAE 
treatment emergent adverse event 
 
 
 


Renibus Therapeutics, Inc. 
Protocol: REN-002 
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Statistical Analysis Plan 
 
CONFIDENTIAL 
Page 5 of 27 
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1. 
INTRODUCTION 
This is a Phase 1b single-center, dose-escalating study to evaluate the pharmacodynamic effect of 
FeS in healthy volunteers and in subjects with stage 3-4 chronic kidney disease (CKD). The 
following biomarkers will be used as surrogate measures of protective activity: Haptoglobin, 
Ferritin, Hemopexin, IL-10, and Heme Oxygenase-1.  
The purpose of this statistical analysis plan (SAP) is to specifying the statistical approaches for the 
data analysis prior to database lock. This SAP covers the planned analyses of all data collected on 
the electronic case report forms (eCRFs). This SAP supersedes the statistical methods described in 
the clinical protocol. Deviations/changes from the planned analyses described in this SAP will be 
identified, with justification, in the appropriate section of the clinical study report. This SAP is 
developed based on the clinical study protocol REN-002, version 1.0, dated 10 October 2018.  
The reader of this SAP is encouraged to also read the clinical protocol and other related documents 
for details on the planned conduct of this study.  Operational aspects related to the collection and 
timing of planned clinical assessments are not repeated in this SAP unless relevant to the planned 
analyses. 
 
2. 
STUDY OBJECTIVES 
The primary objectives of the study are to evaluate: 
1. The effect of Iron Sucrose (FeS) on biomarkers which are potential surrogates for 
cytoprotective activity in healthy volunteers and in subjects with stage 3-4 CKD.  
2. To establish the biomarkers response to different doses of FeS.  
3. Evaluate safety of FeS in comparison to levels of cytoprotective biomarkers.  
 
3. 
STUDY OVERVIEW 
This is a Phase 1b, single-center, dose-escalating study to evaluate the pharmacodynamic effect of 
FeS in healthy volunteers and in subjects with stage 3-4 CKD. The following biomarkers will be 
used as surrogate measures of protective activity: Haptoglobin, Ferritin, Hemopexin, IL-10, and 
Heme Oxygenase-1.  Additionally, the P21 biomarker will be monitored at various points of the 
study. 
Subjects who meet all inclusion criteria and none of the exclusion criteria are eligible to be enrolled 
into the study.   
The study is designed as follows: 
• A screening period with baseline evaluations for study eligibility. 
• If subjects meet eligibility criteria, they will receive FeS IV on study day1.  
• Subjects will stay in the clinic for the initial 24 hours after administration of FeS and will be 
discharged at the end of Day 2 if no safety issues appear. 
• The study will be dose-escalating in 3 groups of 6 subjects consisting of 3 healthy volunteers 
and 3 subjects with CKD, evaluating doses of 120 mg FeS, 240 mg FeS and 360 mg FeS.  


Renibus Therapeutics, Inc. 
Protocol: REN-002 
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Statistical Analysis Plan 
 
CONFIDENTIAL 
Page 6 of 27 
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• Subjects will be followed for 8 days after the dose of FeS. Response biomarkers will be 
assessed at baseline and 2, 4, 8, 12, 18, 24, 48, 72, 96 and 168 hours after study drug 
administration.  
• Total study duration will be 8 days for each subject, in addition to a screening period of up 
to 14 days. 
Up to a total of 18 subjects consisting of 9 healthy volunteers and 9 chronic kidney disease subjects 
will receive single escalating doses of FeS. Six subjects consisting of 3 healthy volunteers and 3 
subjects with CKD will be enrolled in one of three dose levels, starting at the lowest dose of 120 mg 
FeS. 
For a complete list of assessments performed throughout the study, see the Time and Events 
Schedule (Section 13). 
 
4. 
EFFICACY AND SAFETY VARIABLES 
Efficacy Variables 
• Percent change from baseline in biomarkers at each postbaseline time point 
• Change from baseline in biomarkers at each postbaseline time point 
The biomarkers include the following pharmacodynamic variables 
• Haptoglobin (Hp) 
• Ferritin 
• Hemopexin 
• IL-10 
• Heme Oxygenase 1 (HO-1) 
• P21 
Safety Variables 
• Treatment-emergent adverse events 
• Infusion-related reactions 
• Clinical laboratory tests 
• ECG 
• Vital signs 
• Physical exams 
• Concomitant medications 
 


Renibus Therapeutics, Inc. 
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Statistical Analysis Plan 
 
CONFIDENTIAL 
Page 7 of 27 
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5. 
DEFINITIONS 
Terminology 
Definitions 
Enrolled 
Subjects who signed the informed consent, and are randomized to the study 
Completer 
Subjects who complete the End of Study (EOS) visit 
Study Day 
Day 1 is defined as the date subject took the study medication. Study Day for event 
post Day 1 is calculated as Event Date – Day 1 Date +1.  Study Day for event prior to 
Day 1 is calculated as Event Date – Day 1 Date. 
Baseline 
Baseline is defined as the non-missing value collected most recent to and before the 
study of the study medication infusion 
Prior Medication 
Medication started and ended prior to the study drug infusion 
Concomitant 
Medication 
Medication taken on/after the study drug infusion. Concomitant medication may start 
prior to study drug infusion 
Treatment-
emergent 
Adverse event with onset date/time on or after the start of study drug infusion 
 
6. 
ANALYSIS POPULATIONS 
The Safety Analysis Population will include all subjects who received study medication. This 
population will be used for all demographics, baseline characteristics, and safety summaries.  
 
7. 
STATISTICAL METHODS OF ANALYSIS 
7.1. 
General Principles 
The statistical analyses will be reported using summary tables, listings, and figures (TLFs).  All 
analyses and tabulations will be performed using SAS Version 9.4 or later.  Continuous variables 
will be summarized using descriptive statistics (sample size [n], mean, standard deviation [SD], 
minimum, median, and maximum).  Categorical variables will be tabulated with number and 
percentage of subjects.  Unless otherwise noted, percentages will be based on the number of 
subjects from the population, as appropriate. 
All individual subject data will be provided in listings.  All listings will be sorted by dose group, 
CKD status (CKD patients versus healthy volunteer subjects), and collection date and time, where 
applicable. 
Unless otherwise noted, tabulations of categorical data will present only those categories appearing 
in the data.  
7.1.1. Handling Missing Values 


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Statistical Analysis Plan 
 
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7.1.1.1. 
Study Drug Administration Date or Time 
It is expected that all necessary information on study drug administration (start and stop date and 
time) will be complete.  Any such information that is missing and cannot be obtained through query 
resolution may be imputed, on a case-by-case basis, in a conservative manner that minimizes bias. 
7.1.1.2. 
Adverse Event or Concomitant Medications Dates or Times 
For AEs or concomitant medications with missing or partially missing start/stop date/time, the 
following imputation rules will be used when determining treatment-emergent or prior/concomitant 
status: 
For partial start date/time: 
• If the year is unknown, then the date will be assigned as the date and time of first dose of 
study treatment. 
• If the month is unknown, then: 
i) 
If the year matches the year of study drug administration, then the month and day 
will be imputed to be the first month and day. 
ii) 
Otherwise, ‘January’ will be assigned. 
• If the day is unknown, then: 
i) 
If the month and year match the month and year of the dose of the study drug 
administration date, then the day of the dose of earliest study drug administration 
date with matching month and year will be imputed. 
ii) 
Otherwise, ‘01’ will be assigned. 
• If the time is unknown, then: 
i) 
If the date (day, month, and year) matches the date of an administration of study drug, 
then the time of dose of study drug time from that date will be imputed. 
ii) 
Otherwise, ’00:00’ will be assigned. 
For partial stop date/time: 
• If the year is unknown, then the date will be assigned as the date subject discontinued from 
study, and the time will be set to the last time of the day (‘23:59’). 
• If the month is unknown, then the month subject discontinued from study will be assigned. 
• If the day is unknown, then the last day of the month will be assigned. 
• If the time is unknown, then the last time of the day will be assigned (‘23:59’). 
7.1.2. Multiplicity Adjustments 
Not applicable.  This is an early phase exploratory study. 
7.1.3. By-Center Analyses 
Not applicable.  This is a single-center study. 
 
7.2. 
Subject Disposition 


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Statistical Analysis Plan 
 
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Subject disposition will be tabulated by dose group and overall and will present the number and, 
when appropriate, percentage of subjects who were: 
• Enroled 
o Not treated 
o Treated 
• Completed the study as planned 
• Discontinued from the study, and 
• Reasons for discontinuation from the study 
Percentages for all rows will use the number of subjects treated as the denominator.   
Data will be summarized for the pool of CKD patients and healthy volunteers. 
 
7.3. 
Description of Demographics and Baseline Characteristics  
7.3.1. Demographics  
The summary of demographic data will present: 
• Age (years) – descriptive statistics 
• Sex – n (%) 
• Ethnicity – n (%) 
• Race – n (%) 
 
Age is calculated from the date the subject signed the informed consent form (ICF) and birth.  It is 
presented as the number of years, rounding down to the nearest integer year.  For partial birthdates, 
impute the first of the month for missing day and January for missing month to calculate age.  It is 
presumed that birth year is known. 
The demographic summary will present the data for each dose group and overall as well as by CKD 
status.  
7.3.2. Baseline Characteristics 
The summary of baseline characteristic data will present: 
• Physical examination and weight 
• Electrocardiogram 
Descriptive statistics (n, mean, SD, median, minimum and maximum) will be provided by dose 
group for the Safety Analysis Set.  
 
7.4. 
Prior and Concomitant Medications 
Prior medications are defined as medications with a stop date and time prior to the start of study 
drug administration.   
Concomitant medications are defined as medications taken after the start of study drug 
administration (i.e., started prior to the start of study drug administration and continued after or 
started after the start of study drug administration).   


Renibus Therapeutics, Inc. 
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Statistical Analysis Plan 
 
CONFIDENTIAL 
Page 10 of 27 
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Prior and concomitant medications will be listed for each subject with pertinent variables.   
 
7.5. 
Measurements of Treatment Compliance 
Study treatment is administered by the site personnel other than the subject him/herself, therefore 
compliance is assured.   
 
7.6. 
Efficacy Analysis 
7.6.1. Percent Chamge in Response Biomarkers  
The efficacy endpoint is the percent change (PCHT) in each response biomarker relative to the 
Baseline period.  
PCHT will be calculated as 100 x (T – B)/B, where T and B are Response biomarker at 2, 4, 8, 12, 
18, 24, 48, 72, 96 and 168 hours post dose (T) and baseline period (B).  
PCHT will be analyzed using a Mixed-Effect Model for Repeated Measure (MMRM) as follows: 
• A 2-way MMRM pooling CKD patients and healthy subjects together  
• A 2-way MMRM for CKD patients 
• A 2-way MMRM for Healthy subjects 
The model will include dose level, visit (Day 1 2, 4, 8, 12, 18, and 24 hours, Day 2, Day 3, Day 4, 
Day 5, and Day 8), and dose-by-visit interaction as factors and baseline response biomarker as 
covariate.  The model parameters will be estimated using the restricted maximum likelihood method 
with the toeplitz variance-covariance matrix and Kenward-Roger estimate for the denominator 
degrees of freedom. Least squares mean (LSM) and the associated 95% confidence interval (CI) for 
each dose level will be presented at each time point.  Percent change from baseline will be analyzed 
by the t-test from the model for statisticial significance. The between dose comparison will be 
performed using constrast in the main effect and the simple contrast at each time point. The 
difference in LSM between doses, the 95% CI and the t-test for the difference will also be 
presented. Results will be presented for the pooled population, as well as for the CKD and healthy 
populations separately.  
As a sensitivity analysis, percent change from baseline at each time point and between dose 
difference in percent change from baseline will be analyzed respectively by the Wilcoxon signed-
rank test and the Wilcoxon rank-sum test. 
Additionally, LSM for each dose group will be plotted over time for the CKD patients and healthy 
volunteers pooled population as well as for each population separately. Dose response relationship 
will be examined graphically and may be analyzed where appropriate. 


Renibus Therapeutics, Inc. 
Protocol: REN-002 
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Statistical Analysis Plan 
 
CONFIDENTIAL 
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A sample SAS code is provided as follows. The code assumes that “visit” has 10 values (2, 4, 8, 12, 
18, 24, 48, 72, 96 and 168 hours), “dose” is coded as 1 = 120 mg FeS, 2 = 240 mg FeS, and 3 = 360 
mg FeS, “ckd” is coded as 2=CKD patients and healthy volunteers pooled, 1 = patients with CKD, 0 
= healthy colunteers, and “resp” = PCHT, the % change from baselin being analyzed.  
ODS OUTPUT LSMEANS=lsm DIFFS=diff ESTIMATE=estm; 
PROC MIXED DATA=XXXX METHOD=REML; 
BY ckd; 
CLASS dose usubjid visit; 
MODEL resp = base visit dose dose*visit / DDF=KR2;  
REPEATED visit / SUBJECT=usubjid(dose) TYPE=CS; 
LSMEANS dose / DIFF CL; 
LSMEANS dose*visit / PDIFF CL; 
RUN; 
ODS OUTPUT CLOSE; 
Note: Depending on the convergence status in the computation, Toeplitz (toep), 1st order 
autoregressive AR(1), and compound symmetry (CV) variance-covariance matrix will be applied 
sequentially.  The final analysis will be based on the first matrix leading to the convergence in the 
computation. 
7.6.2. Absolute Chamge 
In addition to the percent changes from baseline, absolute change from baseline will also be 
analyzed using MMRM. The method of analysis will be identical after replacing variable “resp” 
with “T-B”in Section 10.6.1. 
 
7.7. 
 Safety Analyses 
No inferential statistics are planned for any safety assessment.  
7.7.1. Adverse Events 
Safety assessments will be based mainly on the nature, frequency, relationship, and severity of adverse 
events (AEs).  All AEs will be listed with onset/stop day, relationship to study drug, severity, action 
taken, and outcome. Pertinent subject information including dose group and demographics will also be 
included. Separate listings will be provided for TEAEs leading to study discontinuation, treatment-
emergent serious AEs (TESAEs), and infusion-related TEAEs. 
7.7.2. Laboratory Test 
Hematology, biochemistry, and urinalysis (pH and specific gravity) test results and their change 
from baseline will be summarized by dose group and visit using descriptive statistics.   
A complete lab data listing, including hematology, biochemistry, and urinalysis will be provided for 
all subjects.  Abnormal results will be flagged. 
7.7.3. Vital Signs 
Vitals signs are resting heart rate (bpm), pulse (beats per minute), oral body temperature (oC), 
systolic blood pressure (mmHg), and diastolic blood pressure (mmHg).  Vital signs will be 


Renibus Therapeutics, Inc. 
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Statistical Analysis Plan 
 
CONFIDENTIAL 
Page 12 of 27 
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summarized by dose group at each scheduled timepoint.  Summaries will present both actual and 
change-from-baseline results.   
7.7.4. ECG 
The investigator evaluation for the overall ECG findings by normal, abnormal not clinically 
significant (NCS), and abnormal clinically significant (CS) will be tabulated with number and % of 
subjects at each time point.  
 
7.8. 
Interim Analysis 
No interim analyses are planned for this study. 
 
8. 
SAMPLE SIZE CALCULATIONS 
No formal sample size calculation has been performed for the study. However, it is believed that 6 
subjects per dose group will be adequate to establish differences in biomarker response between 
groups.  
 
9. 
REFERENCES 
 
 


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Statistical Analysis Plan 
 
CONFIDENTIAL 
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10. 
TIME AND EVENTS SCHEDULE OF STUDY PROCEDURES  
Study Day 
Screening 
 
1 
2,3,4,5,8(EOS)1 
Parameter 
Within 14 days 
prior to first 
dose 
 
 
Written informed consent 
X 
 
 
Eligibility criteria 
X 
 
 
Demographics 
X 
 
 
Medical history 
X 
 
 
Physical examination and weight 
X 
X2 
 
Electrocardiogram 
X 
X1,2 
 
Vital signs 
X 
X2 
X 
Serum chemistry7,8 
X 
X2 
X 
Hematology7,8 
X 
X2 
X 
Response biomarkers7, 10 
 
X2,3 
X 
 
 
 
 
Urinalysis including sediment8 
X 
X2 
X 
Urine pregnancy test9 
X 
X 
X at Day 8 (EOS) 
Urine drug/alcohol/cotinine screen 
X 
 
 
Confinement in clinical testing unit4 
 
X4 
 
FeS IV 
 
X5 
 
Discharge from clinical testing unit 
 
 
X6 
Prior/Concomitant medications 
X 
X 
X 
Adverse events 
 
X 
X 
Investigational product reconciliation 
 
 
X 
 
1 
Day 8 (EOS) visit will occur (± 1) days after administration of FeS. 
2 
Baseline parameters performed prior to dosing on Study Day 1. 
3 
Additional biomarker samples collected at 2, 4, 8, 12, 18 hours (±15 minutes) after completion of IV dose 
4 
Subjects will be confined in the clinical testing unit a minimum of 24 hours from the morning of Study Day 1 until after 
collection of the 24-hour post-dose sample on Study Day 2. 
5 
FeS will be administered as an IV dose after Baseline ECG, vital signs and blood and urine samples are collected.  
6 
Discharge from unit following evaluations and sample collection required on Study Day 2 
7 
Measured fasting (nothing by mouth except water, coffee or tea, with or without milk and/or sugar, and essential medications 
only for a minimum of 8 hours prior to sample collection at the clinic).  
8 
Parameters to be measured are detailed in Protocol Appendix 1.  
9 
For women of childbearing potential using kits supplied by the laboratory 
10 Haptoglobin, Ferritin, Hemopexin, IL-10, P21 and HO-1. 
 
 
 


Renibus Therapeutics, Inc. 
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Statistical Analysis Plan 
 
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11. 
CONVENTIONS FOR THE PRESENTATIONS OF TABLES, 
LISTINGS, AND FIGURES  
• 
Report output will be provided as MS Word Rich Text Format (RTF) and 
Portable Document Format (PDF) generated using SAS. 
• 
Font – Times New Roman font with minimum of 9 point font size for tables 
and 7 point for listings. 
• 
Margins – Minimum of 1.2” bound edge margin (top margin for landscape) and 
0.5” other margins on 8.5”x11” paper as per the FDA guidance for e-
submission. 
• 
Continuous data will be summarized using n (number of subjects with non-
missing observations), mean, median, standard deviation (SD), minimum 
value, and maximum value.  
• 
Categorical data will be summarized using the frequency count and 
percentage (n, %) of subjects in each category.  
• 
Number of subjects with non-missing values or number of subjects with 
missing values (eg, Not Done) will be presented, where appropriate.  
Subjects with missing values will not contribute to the denominator of 
percentage calculations.  
• 
Counts of zero in any category will be presented without percentage. 
• 
Precision of summary statistics: 
o 
Sample size (n, N) and number of missing responses (if displayed) – 
Integer. 
o 
Mean, confidence interval – One additional decimal place than 
reported/collected. 
o 
Standard 
deviation 
– 
Two 
additional 
decimal 
places 
than 
reported/collected. 
o 
Median other percentile – One additional decimal place than 
reported/collected. 
o 
Minimum, 
maximum 
– 
Same 
number 
of 
decimal 
places 
as 
reported/collected. 
o 
Ratios – two decimal places. 
o 
Percentages – one decimal place generally, or two decimal places for 
<0.1%. 
• 
P-values will be reported to 4 decimal places. Values that are less than 
<0.0001 will be presented as “<0.0001”.  Similarly, large p-values will be 
presented as “>0.9999”. 
• 
Data listings will be sorted in the order of dose group, subject ID, 
assessment date/time and assessment name. 
• 
Dates will be presented in the ISO-8601 format YYYY-MM-DD.  Times will be 
displayed in 24-hour clock format. 
• 
Numbering for tables, figures and listings will follow ICH E3 Guidelines. 
• 
The shell provides a general guidance for how the data will be presented.  
The actual presentation may be modified to accommodate the page size 
restriction.   
• 
For TFLs with multiple pages, page numbers will be included.  
• 
All TFLs will have SAS program names and folder names in the footnote for 
tracking purpose. 
 
 


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12. 
LIST OF TABLES  
Note, all tables will be repeated for CKD Patients Population and Healthy Subjects Population with 
Table numbers changed to Table 14.x-x.x.2 and 14.x-x.x.3 from 14.x-x.x1, respectively. 
 
TABLE 14.1-1.1: TABULATION OF SUBJECT DISPOSITION – CKD AND HEALTHY SUBJECTS 
POOLED 
17 
TABLE 14.1-2.1: SUMMARY OF SUBJECT DEMOGRAPHICS - CKD PATIENTS AND HEALTHY 
SUBJECTS POOLED 
18 
TABLE 14.1-3.1: SUMMARY OF SUBJECT CHARACTERISTICS AT BASELINE – 
19 
TABLE 14.2-1.1.1: MMRM ANALYSIS OF PERCENT CHANGE FROM BASELINE IN FERRITIN (FE) 
– CKD PATIENTS AND HEALTHY VOLUNTEERS POOLED, MITT POPULATION 20 
TABLE 14.2-1.2.1: MMRM ANALYSIS OF CHANGE FROM BASELINE IN FERRITIN – CKD 
PATIENTS AND HEALTHY SUBJECTS POOLED 
21 
TABLE 14.2-2.1.1: MMRM ANALYSIS OF PERCENT CHANGE FROM BASELINE IN HAPTOGLOBIN 
(HP) – CKD PATIENTS AND HEALTHY SUBJECTS POOLED 
21 
TABLE 14.2-2.2.1: MMRM ANALYSIS OF CHANGE FROM BASELINE IN HAPTOGLOBIN (HP) – 
CKD PATIENTS AND HEALTHY SUBJECTS POOLED 
21 
TABLE 14.2-3.1.1: MMRM ANALYSIS OF PERCENT CHANGE FROM BASELINE IN HEMOPEXIN – 
CKD PATIENTS AND HEALTHY SUBJECTS POOLED 
21 
TABLE 14.2-3.2.1: MMRM ANALYSIS OF CHANGE FROM BASELINE IN HEMOPEXIN – CKD 
PATIENTS AND HEALTHY SUBJECTS POOLED 
21 
TABLE 14.2-4.1.1: MMRM ANALYSIS OF PERCENT CHANGE FROM BASELINE IN 
21 
TABLE 14.2-4.2.1: MMRM ANALYSIS OF CHANGE FROM BASELINE IN 
21 
TABLE 14.2-5.1.1: MMRM ANALYSIS OF PERCENT CHANGE FROM BASELINE IN HEME 
OXYGENASE 1 (HO-1) – CKD PATIENTS AND HEALTHY SUBJECTS POOLED 
21 
TABLE 14.2-5.2.1: MMRM ANALYSIS OF CHANGE FROM BASELINE IN HEME OXYGENASE 1 
(HO-1) 
21 
TABLE 14.2-6.1.1: MMRM ANALYSIS OF PERCENT CHANGE FROM BASELINE IN P21 – CKD 
PATIENTS AND HEALTHY SUBJECTS POOLED 
21 
TABLE 14.2-6.2.1: MMRM ANALYSIS OF CHANGE FROM BASELINE IN P21 – CKD PATIENTS 
AND HEALTHY SUBJECTS POOLED 
21 
TABLE 14.2-7.1.1: MMRM ANALYSIS OF PERCENT CHANGE FROM BASELINE IN SERUM 
CREATININE – CKD PATIENTS AND HEALTHY SUBJECTS POOLED 
21 
TABLE 14.2-7.2.1: MMRM ANALYSIS OF CHANGE FROM BASELINE IN SERUM CREATININE – 
CKD PATIENTS AND HEALTHY SUBJECTS POOLED 
21 
TABLE 14.3-1.1.1: SUMMARY OF HEMATOLOGY OVER TIME – CKD PATIENTS AND HEALTHY 
SUBJECTS POOLED 
22 
TABLE 14.3-1.2.1: BLOOD CHEMISTRY: CHANGE FROM BASELINE CLASSIFICATION BY TIME 
POINT - CKD PATIENTS AND HEALTHY SUBJECTS POOLED 
23 
TABLE 14.3-1.3.1: URINALYSIS: CHANGE FROM BASELINE CLASSIFICATION BY TIME POINT - 
CKD PATIENTS AND HEALTHY SUBJECTS POOLED 
23 
TABLE 14.3-2.1: SUMMARY OF VITAL SIGNS OVER TIME – CKD PATIENTS AND HEALTHY 
SUBJECTS POOLED 
24 


Renibus Therapeutics, Inc. 
Protocol: REN-002 
Product: Iron Sucrose (FeS) 
Statistical Analysis Plan 
 
CONFIDENTIAL 
Page 16 of 27 
 25 April 2019 
 
TABLE 14.3-3.1: TABULATION OF INVESTIGATOR’S OVERALL EVALUATION OF ECG FINDINGS 
- CKD PATIENTS AND HEALTHY SUBJECTS POOLED, SAFETY POPULATION 
25 
 
 


Renibus Therapeutics, Inc. 
 
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Statistical Analysis Plan 
 
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Table 14.1-1.1: Tabulation of Subject Disposition – CKD and Healthy Subjects Pooled 
 
 
 
360 mg FeS 
[N=XX]  
n (%) 
240 mg FeS 
[N=XX]  
n (%) 
120 mg FeS 
[N=XX]  
n (%) 
Total 
[N=XX] 
n (%) 
 
 
 
 
 
Screened 
 
 
 
xx 
Enrolled 
xx 
xx 
xx 
xx 
  Not Treated 
xx 
xx 
xx 
xx 
  Treated 
xx (100) 
xx (100) 
xx (100) 
xx (100) 
 
 
 
 
 
Safety Population  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Modified Intent to Treat Population 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Pharmacokinetic Population  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Completed Study 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Discontinued from Study 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Reasons for discontinuation 
 
 
 
 
    Death 
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) 
    Lost to Follow-up 
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) 
    Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
Note to programmer: For reasons for discontinuation only those reasons that appear in the data will appear on the 
table.  All percentages are based on the number of enrolled and treated subjects.  
 
 
 
 


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Statistical Analysis Plan 
 
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Table 14.1-2.1: Summary of Subject Demographics - CKD Patients and Healthy Subjects Pooled  
 
 
 
Statistic 
360 mg FeS 
[N=XX]  
240 mg FeS 
[N=XX]  
120 mg FeS 
[N=XX]  
Total 
[N=XX] 
 
 
 
 
 
 
Age (yrs) 
n 
xx 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
 
SD 
x.xx 
x.xx 
x.xx 
x.xx 
 
Median  
xx 
xx 
xx 
xx 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Sex 
 
 
 
 
 
  Female 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Male 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Ethnicity 
 
 
 
 
 
  Hispanic or Latino 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Not Hispanic or Latino 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Race 
 
 
 
 
 
  American Indian/Alaska Native 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Asian 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Black/African American 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Native Hawaiian/Pacific Islander 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  White  
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Other 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 


Renibus Therapeutics, Inc. 
 
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Product: Iron Sucrose (FeS) 
 
Statistical Analysis Plan 
 
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Table 14.1-3.1: Summary of Subject Characteristics at Baseline – CKD Patients and Healthy Subjects Pooled 
 
 
 
360 mg FeS 
[N=xx] 
240 mg FeS 
[N=XX] 
120 mg FeS 
[N=xx] 
 
 
 
 
 
Weight (kg) 
n 
xx 
xx 
xx 
Mean 
xxx.x 
xxx.x 
xxx.x 
 
SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
Median 
xxx.x 
xxx.x 
xxx.x 
 
Min, Max 
xxx.x, xxx.x 
xxx.x, xxx.x 
xxx.x, xxx.x 
 
 
 
 
 
Height (cm) 
n 
xx 
xx 
xx 
Mean 
xxx.x 
xxx.x 
xxx.x 
 
SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
Median 
xxx.x 
xxx.x 
xxx.x 
 
Min, Max 
xxx.x, xxx.x 
xxx.x, xxx.x 
xxx.x, xxx.x 
 
 
 
 
 
BMI (kg/m2) 
n 
xx 
xx 
xx 
Mean 
xxx.x 
xxx.x 
xxx.x 
 
SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
Median 
xxx.x 
xxx.x 
xxx.x 
 
Min, Max 
xxx.x, xxx.x 
xxx.x, xxx.x 
xxx.x, xxx.x 
 
 
 
 
 
 
 
 
 
 


Renibus Therapeutics, Inc. 
 
Protocol: REN-002 
Product: Iron Sucrose (FeS) 
 
Statistical Analysis Plan 
 
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Table 14.2-1.1.1: MMRM Analysis of Percent Change from Baseline in Ferritin (Fe) – CKD Patients and Healthy Volunteers 
Pooled, MITT Population 
 
Time Point 
 
Statistic 
360 mg FeS 
[N=XX] 
240 mg FeS 
[N=XX] 
120 mg FeS 
[N=XX] 
 
 
 
 
 
 
 
Baseline 
n 
xx 
xx 
xx 
 
 
Mean 
xxx.x 
xxx.x 
xxx.x 
 
 
SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
 
Median 
xxx.x 
xxx.x 
xxx.x 
 
 
Min, Max 
xxx.x, xxx.x 
xxx.x, xxx.x 
xxx.x, xxx.x 
 
 
 
 
 
 
 
2 hours 
 
 
 
 
 
Actual 
n 
xx 
xx 
xx 
 
 
Mean 
xxx.x 
xxx.x 
xxx.x 
 
 
SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
 
Median 
xxx.x 
xxx.x 
xxx.x 
 
 
Min, Max 
xxx.x, xxx.x 
xxx.x, xxx.x 
xxx.x, xxx.x 
 
 
 
 
 
 
 
% change from 
Baseline 
n 
xx 
xx 
xx 
 
 
Mean 
xxx.x 
xxx.x 
xxx.x 
 
 
SD 
xxx.xx 
xxx.xx 
xxx.xx 
 
 
Median 
xxx.x 
xxx.x 
xxx.x 
 
 
Min, Max 
xxx.x, xxx.x 
xxx.x, xxx.x 
xxx.x, xxx.x 
 
 
 
 
 
 
 
 
LS Mean  
xxx.x 
xxx.x 
xxx.x 
 
 
95% CI of LS Mean  
(xx.x, xx.x) 
(xx.x, xx.x) 
(xx.x, xx.x) 
 
 
 
 
 
 
 
 
LSM Difference from 120mg FeS  
xxx.x 
xxx.x 
 
 
 
95% CI of Difference from 120mg FeS 
(xx.x, xx.x) 
(xx.x, xx.x) 
 
 
 
MMRM P-value for Difference from 120mg FeS 
0.xxxx 
0.xxxx 
 
 
 
CMH P-value for Difference from 120mg FeS 
0.xxxx 
0.xxxx 
 
 
 
 
 
 
 
 
 
LSM Difference from 240mg FeS  
xxx.x 
 
 
 
 
95% CI of Difference from 240mg FeS 
(xx.x, xx.x) 
 
 
 
 
MMRM P-value for Difference from 240mg FeS 
0.xxxx 
 
 
 
 
CMH P-value for Difference from 120mg FeS 
0.xxxx 
0.xxxx 
 
 
 
 
 
 
 
 
. . . 
 
 
 
 
 
 
 
 
 
 
 
168 hours 
. . . 
 
 
 
 
 
. . . 
 
 
 
 
 
 
 
 
 
 
Overall 
. . . 
 
 
 
 
 
. . . 
 
 
 
 
 
 
 
 
 
 


Renibus Therapeutics, Inc. 
 
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Statistical Analysis Plan 
 
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Note: MMRM model includes Dose, Time Point, and Dose-by-Time Point interaction as factor variables, Baseline as 
covariate, and Subject as repeated measure unit over Time Points. The between dose comparison at each time point is 
based on the simple contrast and the Overall betwee dose comparison is based on the contrast for the main effect.  
CMH test at each time point is stratified by baseline quintiles. The Overall CMH test is stratified by Time Point and 
baseline quintiles. Modified ridit scores are used in the computation. 
 
Note to programmer: Time points are: baseline, Day 1 2, 4, 8, 12, 18, and 24 hours, Day 2, Day 3, Day 4, Day 5, and Day 
8.   
 
Use 14.2-1.1.1 shell for 
 
Table 14.2-1.2.1: MMRM Analysis of Change from Baseline in Ferritin – CKD Patients and Healthy Subjects Pooled 
 
Table 14.2-2.1.1: MMRM Analysis of Percent Change from Baseline in Haptoglobin (Hp) – CKD Patients and Healthy Subjects 
Pooled 
 
Table 14.2-2.2.1: MMRM Analysis of Change from Baseline in Haptoglobin (Hp) – CKD Patients and Healthy Subjects Pooled 
 
Table 14.2-3.1.1: MMRM Analysis of Percent Change from Baseline in Hemopexin – CKD Patients and Healthy Subjects Pooled 
 
Table 14.2-3.2.1: MMRM Analysis of Change from Baseline in Hemopexin – CKD Patients and Healthy Subjects Pooled 
 
Table 14.2-4.1.1: MMRM Analysis of Percent Change from Baseline in IL-10 – CKD Patients and Healthy Subjects Pooled 
 
Table 14.2-4.2.1: MMRM Analysis of Change from Baseline in IL-10 – CKD Patients and Healthy Subjects Pooled 
 
Table 14.2-5.1.1: MMRM Analysis of Percent Change from Baseline in Heme Oxygenase 1 (HO-1) – CKD Patients and Healthy 
Subjects Pooled 
 
Table 14.2-5.2.1: MMRM Analysis of Change from Baseline in Heme Oxygenase 1 (HO-1) 
 
Table 14.2-6.1.1: MMRM Analysis of Percent Change from Baseline in P21 – CKD Patients and Healthy Subjects Pooled 
 
Table 14.2-6.2.1: MMRM Analysis of Change from Baseline in P21 – CKD Patients and Healthy Subjects Pooled 
 
Table 14.2-7.1.1: MMRM Analysis of Percent Change from Baseline in Serum Creatinine – CKD Patients and Healthy Subjects 
Pooled 
 
Table 14.2-7.2.1: MMRM Analysis of Change from Baseline in Serum Creatinine – CKD Patients and Healthy Subjects Pooled 
 
 
 


Renibus Therapeutics, Inc. 
 
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Statistical Analysis Plan 
 
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Table 14.3-1.1.1: Summary of Hematology over Time – CKD Patients and Healthy Subjects Pooled 
 
Hemoglobin (Unit) 
 
 
360 mg FeS 
[N=XX]  
240 mg FeS 
[N=XX]  
120 mg FeS 
[N=XX]  
Timepoint 
Statistic 
Observed 
Value 
Change From 
Baseline 
 
Observed 
Value 
Change From 
Baseline 
 
Observed 
Value 
Change From 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline 
n 
xx 
 
 
xx 
 
 
xx 
 
 
Mean 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
 
SD 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
 
Median 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
 
Min, Max 
xx.x, xx.x 
 
 
xx.x, xx.x 
 
 
xx.x, xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 hours 
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 
 
 
Median 
xx.x 
xx.x 
 
xx.x 
xx.x 
 
xx.x 
xx.x 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
 
xx.x, xx.x 
xx.x, xx.x 
 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
4 hours 
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 
 
 
Median 
xx.x 
xx.x 
 
xx.x 
xx.x 
 
xx.x 
xx.x 
 
 
Min, Max 
xx.x, xx.x 
xx.x, xx.x 
 
xx.x, xx.x 
xx.x, xx.x 
 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note to programmer: Hematology parameters are Hemoglobin, Hematocrit, Erythrocyte count (red blood cells), Differential 
leukocytes, Total leukocytes (white blood cells), Platelets 
Time points, in order of appearance, for this table are: baseline, 2, 4, 8, 12, 18, 24, 48, 72, 96 and 168 hours.  Only 
included change from baseline for post-baseline assessments.   
 
 
 


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Statistical Analysis Plan 
 
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Use 14.3-1.1 for 
Table 14.3-1.2.1: Blood Chemistry: Change from Baseline Classification by Time Point - CKD Patients and Healthy 
Subjects Pooled 
 
Total protein, Albumin, Bicarbonate, Blood urea nitrogen (BUN), Creatinine, Total bilirubin, Alkaline phosphatase, 
Glucose, Sodium, Potassium, Inorganic phosphate, Calcium (total and ionized), Magnesium, Gamma-glutamyl transferase 
 
 
Table 14.3-1.3.1: Urinalysis: Change from Baseline Classification by Time Point - CKD Patients and Healthy Subjects 
Pooled 
 
pH, Specific Gravity  
 
 
 
 


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Use 14.3-1.1.1 shell for  
 
Table 14.3-2.1: Summary of Vital Signs over Time – CKD Patients and Healthy Subjects Pooled 
 
Note to programmer: Vital signs, in order of appearance, for this table are Systolic Blood Pressure (mmHg), Diastolic 
Blood Pressure (mmHg), Pulse (bpm), Oral Body Temperature (°C), Respiratory Rate (bpm).   
Time points, in order of appearance, for this table are: baseline at 2, 4, 8, 12, 18, 24, 48, 72, 96 and 168 hours.   
 
 


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Protocol: REN-002 
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Statistical Analysis Plan 
 
CONFIDENTIAL 
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Table 14.3-3.1: Tabulation of Investigator’s Overall Evaluation of ECG Findings - CKD Patients and Healthy Subjects 
Pooled, Safety Population 
 
Time Point 
Evaluation 
360 mg FeS 
[N=XX]  
n (%) 
240 mg FeS 
[N=XX]  
n (%) 
120 mg FeS 
[N=XX]  
n (%) 
Total 
[N=XX] 
n (%) 
 
 
 
 
 
 
Predose 
n 
xx 
xx 
xx 
xx 
 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal, Not Clinically Significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal, Not Clinically Significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
0.5 hour postdose 
n 
xx 
xx 
xx 
xx 
 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal, Not Clinically Significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal, Not Clinically Significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
1 hour postdose 
n 
xx 
xx 
xx 
xx 
 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal, Not Clinically Significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Abnormal, Not Clinically Significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
. . . 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Statistical Analysis Plan 
 
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13. 
 LIST OF FIGURES 
 
Figure 1.1: Plot of Least Square Means (95% CI) of Ferritin (unit) Over Time by 
Dose Group – CKD Patients and Healthy Subjects Pooled 
 
Figure 1.2: Plot of Least Square Means (95% CI) of Ferritin (unit) Over Time by 
Dose Group - CKD Patients, MITT Population 
 
Figure 1.3: Plot of Least Square Means (95% CI) of Ferritin (unit) Over Time by 
Dose Group – Healthy Subjects, MITT Population 
 
Figure 2.1: Plot of Mean (± SE) Haptoglobin (unit) Over Time by Dose Group – CKD 
Patients and Healthy Subjects Pooled, PK Population 
 
Figure 2.2: Plot of Mean (± SE) Haptoglobin (unit) Over Time by Dose Group – CKD 
Patients, PK Population 
 
Figure 2.3: Plot of Mean (± SE) Haptoglobin (unit) Over Time by Dose Group –
Healthy Subjects, PK Population 
 
Repeat for Hemopexin, IL-10, Heme Oxygenase 1, P21, and Serum Creatinine 
 
 
Programmer’s note: annotate the curve with ‘P=0.0xx” for the time points where 
the t-test for the change from baseline is significant 
 
 


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Statistical Analysis Plan 
 
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14. 
LIST OF LISTINGS 
1. 
Disposition 
2. 
Demographics and Body Characteristics 
3. 
Medical History 
4. 
Study Drug Administration 
5. 
Prior and Concomitant Medications 
6. 
Physical Examinations 
7. 
Efficacy Biomarkers over Time 
8. 
Adverse Events 
9. 
Hematology 
10. Serum Chemistry 
11. Urinalysis  
12. ECG Evaluation 
13. Vital Signs