Conditions: Idiopathic Parkinson's Disease
Keywords: Parkinson's disease Moderate to Severe Parkinson's Disease
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 239
Healthy volunteers: no

Brief summary:
This is a Phase 3, 52-week, open-label, flexible-dose, multinational, multicenter study to evaluate the safety and tolerability of istradefylline 20 or 40 mg/d in subjects with moderate to severe PD with motor fluctuations and dyskinesia on levodopa combination (levodopa/carbidopa or levodopa/benserazide) therapy plus at least one adjunctive PD medication. Subjects who completed 12 weeks of double-blind treatment and the 30-day follow-up period in Study No. 6002-014 will undergo Screening and Baseline evaluations for eligibility for the study. Eligible subjects will be treated with istradefylline at a starting dose of 20 mg/d with an option for a dose adjustment to 40 mg/d at Week 12 based on the Investigator's judgment of each subject's response and tolerability. If deemed necessary, one unscheduled dose adjustment visit between Week 2 to Week 12 is allowed in accordance with clinical judgment of the Investigator. Subjects who had a dose adjustment to 40 mg/d can have their dose decreased to 20 mg/d by the Investigator at a second unscheduled dose adjustment visit if there are tolerability issues. The istradefylline dose should remain fixed between Week 26 to Week 52. Consultation with the Sponsor's Medical Monitor is required prior to any unscheduled dose adjustment visits. A subject may discontinue from the study at any time.

Detailed description:

Arms:
arm 1: Treatment for 52 weeks

Interventions: intervention 1: Istradefylline 20 mg or 40 mg
Intervention descriptions: intervention 1: Istradefylline 20 or 40 mg

Protocol document:
Prot_000.pdf: 



















































































































SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
KYOWA Kirin Pharmaceutical Development, Inc 
6002-018
 
CONFIDENTIAL 
1 
 
 
Statistical Analysis Plan 
 
A Phase 3, Long-term, Open-label Study of Istradefylline in Subjects with 
Moderate to Severe Parkinson’s Disease 
 
Protocol Number: 6002-018 
 
US IND Number:  58,356 
EudraCT Number:  2015-003887-34 
 
Date: 21 June 2017 
 
 
 
Confidentiality Statement 
The information contained in this document is the property of or under the control of Kyowa Kirin 
Pharmaceutical Development, Inc. and its affiliated companies.  This information is provided to you in 
confidence as an investigator, potential investigator or consultant, for review by you, your staff and applicable 
Institutional Review Board/Ethics Committee.  You shall not disclose this information to others without prior 
written authorization from Kyowa Kirin Pharmaceutical Development, Inc., except to the extent necessary to 
obtain informed consent from those persons to whom the drug may be administered, and except as may be 
required by federal, state, or local laws or regulations. 


STATISTICAL ANALYSIS PLAN
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Statistical Analysis Plan Signature Page 
 
Manager, Biostatistics          Jed Henke 
 
  
 
 
 
________________________ 
Inventiv Health 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
________________________ 
 
 
 
 
 
 
 
Date 
 
VP Biometrics          June (Junfang) Li PhD 
 
 
 
Kyowa Kirin Pharmaceutical Development, Inc. 
________________________ 
 
212 Carnegie Center, Suite 101  
 
 
Signature 
 
Princeton, NJ  08540 
 
Phone: 609-580-5711  
                                                  
 
 
 
________________________ 
 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 


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Contents 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE ................................................... 2 
LIST OF ABBREVIATIONS ................................................................................................. 5 
1 
INTRODUCTION ......................................................................................................... 6 
2 
STUDY OBJECTIVES ................................................................................................. 7 
2.1 
Primary Objective ........................................................................................................ 7 
3 
STATISTICAL CONSIDERATIONS OF PROTOCOL .......................................... 8 
3.1 
General Statistical Consideration ................................................................................. 8 
3.2 
Overall Study Design and Plan .................................................................................... 8 
3.3 
Treatment Plan ............................................................................................................. 9 
3.4 
Determination of Sample Size ................................................................................... 10 
3.5 
Disposition of Subjects .............................................................................................. 10 
3.6 
Analysis Populations .................................................................................................. 10 
3.7 
Demographic and Other Baseline Characteristics ..................................................... 10 
3.7.1 
Medical History ...................................................................................................... 11 
3.8 
Prior/Concomitant Medications ................................................................................. 11 
3.9 
Duration of Therapy and Drug Compliance .............................................................. 11 
3.10 
Efficacy Analysis ....................................................................................................... 12 
3.11 
Safety Analysis .......................................................................................................... 12 
3.11.1 
Adverse Events ....................................................................................................... 13 
3.11.2 
Clinical Laboratory Evaluation .............................................................................. 13 
3.11.3 
Vital Signs, Height and Weight .............................................................................. 14 
3.11.4 
12-Lead Electrocardiogram .................................................................................... 14 
3.11.5 
Physical and Neurological Examinations ............................................................... 14 
4 
REFERENCES ............................................................................................................ 15 
5 
PROGRAMMING CONSIDERATIONS ................................................................. 16 
5.1 
Table, Listing, and Figure Format ............................................................................. 16 
5.1.1 
General ................................................................................................................... 16 
5.1.2 
Headers ................................................................................................................... 16 
5.1.3 
Display Titles ......................................................................................................... 16 
5.1.4 
Column Headers ..................................................................................................... 17 


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5.1.5 
Body of the Data Display ....................................................................................... 17 
5.1.6 
Footnotes ................................................................................................................ 18 
5.2 
Data-Handling Rules .................................................................................................. 19 
5.2.1 
Visits ....................................................................................................................... 19 
5.2.2 
Demographics and Baseline Characteristics .......................................................... 19 
5.2.3 
Prior and Concomitant Medications ....................................................................... 20 
5.2.4 
Change from Baseline ............................................................................................ 20 
5.2.5 
Safety ...................................................................................................................... 20 
6 
LIST OF TABLES, LISTINGS, AND FIGURES .................................................... 21 
 


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List of Abbreviations 
Abbreviations 
AE 
adverse event 
ATC 
anatomical therapeutic chemical  
BP 
blood pressure 
CS 
clinically significant 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
HR 
heart rate 
ICH 
International Conference on Harmonization 
MedDRA 
Medical Dictionary for Regulatory Activities 
PGI-I 
Patient Global Impression-Improvement 
PD 
Parkinson’s Disease 
PT 
preferred term  
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
TLFs 
tables, data listings, figures 
US 
United States 
WHO 
World Health Organization 
 


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1 
INTRODUCTION 
This Statistical Analysis Plan (SAP) has been developed after review of Kyowa Kirin 
Pharmaceutical Development Inc. Protocol 6002-018(final version dated 28 SEP 2015). 
This is a Phase 3, 52-week, open-label, flexible-dose, multinational, multicenter study to 
evaluate the safety and tolerability of istradefylline 20 to 40 mg/d in subjects with moderate 
to severe Parkinson’s Disease (PD) with motor fluctuations and dyskinesia on levodopa 
combination (levodopa/carbidopa or levodopa/benserazide) therapy plus at least one 
adjunctive PD medication. For subjects who completed 12 weeks of double-blind treatment 
and the 30-day follow-up period in Study No. 6002-014, the final study evaluations at Week 
12  will serve as the screening evaluations for eligibility for the study. Eligible subjects will 
initially be treated with istradefylline at a starting dose of 20 mg/d with an option for a dose 
adjustment to 40 mg/d at Week 12 based on the Investigator’s judgment of each subject’s 
response and tolerability. If deemed necessary, one unscheduled dose adjustment visit 
between Week 2 to Week 12 is allowed in accordance with clinical judgment of the 
Investigator. Subjects who had a dose adjustment to 40 mg/d can have their dose decreased to 
20 mg/d by the Investigator at a second unscheduled dose adjustment visit if there are 
tolerability issues. The istradefylline dose should remain fixed between Week 26 to Week 52.  
This SAP is being written with consideration of the recommendations outlined in the 
International Conference on Harmonisation (ICH) E9 Guideline entitled “Guidance for 
Industry: Statistical Principles for Clinical Trials” (ICH Harmonised Tripartite Guideline E9 
5FEB1998) and the most recent ICH E3 Guideline entitled, “Guidance for Industry: Structure 
and Content of Clinical Study Reports” (ICH Harmonised Tripartite Guideline E3 
30NOV1995).  


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2 
STUDY OBJECTIVES 
The objectives of this study are as follows:  
2.1 
Primary Objective 
The primary objective of the study is to evaluate the long-term safety and tolerability of oral 
istradefylline (20 to 40 mg/d) as treatment for subjects with moderate to severe PD.  
 


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3 
STATISTICAL CONSIDERATIONS OF PROTOCOL 
3.1 
General Statistical Consideration 
Descriptive statistics (number of subjects, mean, standard deviation [SD], median, minimum, 
and maximum) for continuous variables and frequency distributions and percentages for 
discrete (or any categorical) variables will be utilized. The mean and median values will be 
displayed to one decimal place greater than the original value and the measure of variability 
(i.e., SD) will be displayed to two decimal places greater than the original value. All 
summaries and analyses conducted will be by assigned therapy and/or combined total 
subjects. The last pre-administration observation will be used as the baseline value for 
calculating post-administration changes from baseline.   
All tabulations of summary statistics, graphical presentations, and statistical analyses will be 
performed using SAS® Version 9.4 or higher. 
3.2 
Overall Study Design and Plan 
This is a Phase III, 52-week, open-label, flexible-dose, multinational, multicenter study to 
evaluate the safety and tolerability of istradefylline 20 or 40 mg/d in subjects with moderate 
to severe PD with motor fluctuations and dyskinesia.  Evaluations will occur on levodopa 
combination (levodopa/carbidopa or levodopa/benserazide) therapy plus at least one 
adjunctive PD medication.  
Safety outcomes will be assessed by summary of Adverse Events (AEs) and clinical 
laboratory tests. Vital signs including blood pressure, heart rate, temperature, respiration, 
weight, and height will be assessed at Screening.  Concomitant medications and adverse 
events, Patient Global Impression-Improvement (PGI-I), will be assessed at every visit 
throughout the study.  Decrease in the dosages of levodopa combinations 
(levodopa/carbidopa or benserazide/levodopa) due to levodopa-related events will be 
permitted at the Investigator’s discretion and the extent of levodopa/carbidopa or 
benserazide/levodopa dose reduction will be captured.  
The scheduled study visits and procedures are shown in Table 3.2-1       
 
 


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 Table 3.2-1 
Schedule of Visits 
Procedure 
Screeninga 
Week -1 
(Day –1 
to 7) 
Baseline 
Day 1 
Open-Label Treatment 
Follow-up 
30 days 
following 
Week 
52/ET 
(± 7 days) 
Week 12 
(Day 85 
± 4 days) 
Week 26 
(Day 183 
± 4 days) 
Week 52 
or ET 
(Day 365 ± 
4 days) 
Written informed consent 
X 
 
 
 
 
 
Inclusion/Exclusion criteria  
X 
 
 
 
 
 
Medical history/Demographics  
X 
 
 
 
 
 
Physical examination  
X 
 
 
 
 
 
Weight  
X 
 
 
 
 
 
Height  
X 
 
 
 
 
 
Vital signsb  
X 
 
 
 
 
 
Clinical laboratory tests 
X 
 
 
X 
X 
 
Serum pregnancy testc  
X 
Xd 
Xd 
X
X 
 
Serum FSHe  
X 
 
 
 
 
 
12‐lead ECG  
X 
 
 
 
 
 
Concomitant medications  
X 
X 
X 
X 
X 
Xf 
Adverse Eventsg    
X 
X 
X 
X 
X 
Xf 
PGI‐I  
X 
Xh 
X 
X 
X 
 
Treatment compliance  
 
 
X 
X 
X 
 
Dispense study drug 
 
X 
X 
X 
 
 
Note: Visits should occur in the ON state. If possible, subjects should have each visit scheduled for approximately the same 
time of day from Baseline and onwards. 
a: For subjects who have completed 12 weeks of double-blind treatment and the 30-day follow-up period in Study No. 6002-
014 immediately prior to entering this study, the Screening Visit for those subjects will correspond to the Follow-up visit of 
Study No. 6002-014. 
b: Vital signs to be measured are blood pressure, heart rate, temperature, and respiration rate; all measurements are to be 
taken in the ON state. 
c: For women of childbearing potential. 
d: A urine dipstick pregnancy test will be conducted at Baseline and Week 12. 
e: For post-menopausal women only. 
f: Subjects will be contacted by telephone for a follow-up visit 30 days (± 7 days) after their last dose of istradefylline. 
g: If there are tolerability issues, subjects can be seen at an unscheduled visit in accordance with clinical judgment of the 
Investigator. At these visits, assessments will include concomitant medications, adverse events, and treatment compliance. 
h: Identification only the “key symptom” on the PGI-I for subjects. 
ECG=electrocardiogra m; ET=Early Termination; FSH=follicle stimulating hormone; PGI-I=Patient Global Impression -
Improvement Scale 
 
3.3 
Treatment Plan 
All subjects will be treated with istradefylline at a starting dose of 20 mg/d with an option for 
a dose adjustment to 40 mg/d at Week 12 based on the Investigator’s judgment of each 
subject’s response and tolerability. If deemed necessary, one unscheduled dose adjustment 
visit between Week 2 to Week 12 is allowed in accordance with clinical judgment of the 
Investigator. Subjects who had a dose adjustment to 40 mg/d can have their dose decreased to 


STATISTICAL ANALYSIS PLAN
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20 mg/d by the Investigator at a second unscheduled dose adjustment visit if there are 
tolerability issues. The istradefylline dose should remain fixed between Week 26 to Week 52. 
In general, summary tables will display one total column.  Subjects with dose adjustments 
will not be displayed separately except where specified. 
3.4 
Determination of Sample Size 
Approximately 300 subjects are anticipated to participate in this study. The sample size was 
estimated based on the number of subjects anticipated to complete 12 weeks of treatment in 
Study No. 6002-014 and, of these, the estimated proportion meeting the inclusion/exclusion 
of this study protocol and the estimated number of eligible subjects who agree to participate. 
3.5 
Disposition of Subjects 
Subject disposition will be based on all subjects who are eligible for this study. The number 
entered, completed, and number discontinuing at each visit will be presented. A summary of 
reasons for early discontinuation will be provided. Reasons for early discontinuation include 
AEs, lack of efficacy, protocol violation, or non-compliance with study drug, subject’s 
withdrawal of consent, or other (to be specified by the Investigator).  
3.6 
Analysis Populations 
The following analysis populations will be used in the study: 
 Intent-to-Treat Set (ITT): Includes all subjects with both a valid screening and 
at least one valid post-screening efficacy assessment. 
 Safety Analysis Set: Includes all subjects who received at least one dose of 
assigned study drug (even a partial dose).  
The number of subjects in each of the ITT and Safety Analysis sets will be presented.  
3.7 
Demographic and Other Baseline Characteristics 
Demographic and Baseline characteristics will be summarized descriptively for the ITT and 
Safety Analysis Sets for each treatment arm and in total.  These summaries will include 
demographics (including age, race, sex, height, weight, daily caffeine intake, smoking status, 
and body mass index (BMI), medical history, and physical examination results of note. 
Baseline will be defined as the last observation obtained prior to the first dose of study drug 
in this study.  
All demographic data and Baseline disease characteristics data will be listed by subject. 


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3.7.1 
 Medical History 
Medical history for those subjects reporting any past or present conditions at screening will 
be summarized by body system for the Safety Analysis Set for each treatment arm and in 
total. Medical history data will be listed by subject. 
3.8 
Prior/Concomitant Medications 
All prior and concomitant medications will be coded to preferred drug names and therapeutic 
drug class using the World Health Organization (WHO) Drug Dictionary.  Prior medications 
refer to medications taken within 30 days prior to the first dose of study medication (i.e. the 
duration when taken overlaps the time interval between first dose date minus 30 to first dose 
date minus 1 at any single time).  Concomitant medications are those with start date on or 
after the date of the first dose or that started prior to the date of the first dose but are indicated 
as continuing into the treatment period. Any medications with partial start and/or stop dates 
will be considered concomitant if the assignment is uncertain. 
The number and percentage of subjects taking concomitant medications during the treatment 
period will be summarized by anatomical therapeutic chemical (ATC) and preferred term 
(PT) for the Safety Analysis Set. If a subject took a coded medication more than once, the 
subject will be counted once for that coded medication total. If a subject had more than one 
coded medication in a therapeutic class, the subject will be counted only once in that 
therapeutic class total. 
All prior and concomitant medications will be listed by subject. 
3.9 
Duration of Therapy and Drug Compliance 
Duration of therapy will be summarized as the number of weeks [defined as (days from first 
dosing to last dosing)/7, with precision to one decimal place] receiving treatment from the 
first day of dosing until the last day of dosing. 
The percent compliance for taking study drug as prescribed will be calculated at Weeks 12, 
26, and 52 using the formula (with precision to one decimal place): 
Compliance = 
(Number of tablets dispensed – Number of tablets returned) 
× 100 
(Number of tablets expected to be taken) 
Compliance over the entire open-label treatment period will be similarly computed using the 
total number of tablets dispensed from Screening to Week 52 and the total number of tablets 
returned and the total number of tablets expected to be taken for this period. The number of 
tablets expected to be taken will be derived as follows: end of study/treatment date minus 


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first treatment date, plus one. If subjects are escalated to 40 mg per day, and are dispensed 20 
mg tablets, two tablets per day will be expected and the number of expected tablets for this 
time period will be derived as follows: end of treatment period date minus first treatment 
period date, plus one, multiplied by two.  Summary statistics for compliance will be 
presented for the Safety Analysis Set.  
Treatment adjustments will be summarized by time period, Baseline to Week 12, >Week 12 
to Week 26, and >Week 26 to Week 52.  The number of subjects who remained on 
Istradefylline 20 mg, the number for whom dose was escalated to Istradefylline 40 mg and 
remained at 40 mg, and the number for whom dose was escalated to Istradefylline 40 mg and 
later de-escalated to Istradefylline 20 mg will be displayed for each time period. 
3.10 Efficacy Analysis 
All efficacy data collected from the PGI-I scale used in this study will be summarized using 
descriptive statistics for the ITT population. Summaries will be performed overall and by 
treatment in 6002-014, Istradefylline versus placebo. The PGI-I scale will be summarized 
categorically, displaying the number and percentage of subjects in each category outlined 
below at weeks 12, 26, and 52.  PGI-I overall condition score and subscores will be reported 
(fatigue, sleep, motivated to get tasks done, key symptom).  
  1=Moderate improvement (or greater)  
  2=Mild improvement  
  3=No change from Baseline  
  4=Mild deterioration  
  5=Moderate deterioration (or greater) 
No statistical tests (i.e. p-values) will be performed. 
3.11 Safety Analysis 
All safety analyses will be based on the Safety Analysis Set. All continuous safety data 
collected in this study will be summarized using descriptive statistics at each assessment time 
based on actual values and change from Baseline values. Baseline is defined as the last non-
missing value obtained prior to first treatment. Continuous variables will be summarized 
using n, mean, SD, median, minimum, and maximum values. Categorical variables will be 
summarized using the number and percentage of subjects in each category. All out-of-
normal-range results and clinically significant changes in any safety variable will be flagged 
in the subject data listings.  


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3.11.1 
Adverse Events 
The Medical Dictionary for Regulatory Activities (MedDRA) will be used to classify all AEs 
reported during the study by system organ class (SOC) and PT. All summary tables will 
include counts of subjects with treatment-emergent adverse events (TEAEs), defined as those 
AEs that have a start date after the start of study drug. AEs with missing start dates, but with 
stop dates either overlapping into the treatment period or missing, will be considered TEAEs, 
taking the worst-case approach. All other AEs will be classified as non-TEAEs and identified 
in listings only. An overall summary table of TEAEs will be presented with the number and 
percentage of subjects having a TEAE, a serious TEAE, a TEAE leading to study 
discontinuation, a TEAE with an outcome of death, a TEAE related to study drug (‘possibly’, 
‘probably’, or ‘definitely’ related), or a severe TEAE. The overall incidence of TEAEs will 
be summarized by SOC and by SOC and PT using the number and percentage of subjects 
reporting an event and by the number of events reported. The incidence of TEAEs resulting 
in death, serious TEAEs, and TEAEs leading to study discontinuation will be summarized in 
a similar manner. TEAEs will also be summarized by maximum severity (mild, moderate, or 
severe), and closest relationship to study drug (related or not related) with the percentage of 
subjects in each category. A TEAE with missing severity or relationship will be considered 
severe or related, respectively. If more than one TEAE is recorded for a subject within any 
SOC or PT, the subject will only be counted once within that SOC or PT total. Serious 
TEAEs, TEAEs leading to study discontinuation, and TEAEs with an outcome of death will 
also be presented in separate listings. 
A summary of TEAEs and drug related TEAEs will be provided by dose at the first 
occurrence (Istradefyline 20 mg or 40 mg) and by SOC and PT. For subjects uptitrating from 
20 mg to 40 mg or down-titrating from 40 mg to 20 mg, treatment start and stop dates will be 
used to identify the dose level at the time of the event.  Subjects receiving both dose levels 
will be included in the denominator of both dose levels. 
3.11.2 
Clinical Laboratory Evaluation 
Actual values and change from Baseline values for continuous data from clinical laboratory 
tests will be summarized descriptively at all scheduled study. Categorical data from clinical 
laboratory tests will be similarly summarized for the actual values. Clinical laboratory tests 
categorized as in or out of normal range will be summarized using shift tables by visit. Shift 
tables will be the cross tabulation of the Baseline result category (high, normal, low) with 
post-Baseline result category (high, normal, low) for each visit during the treatment period. 
All out-of-normal range results will be flagged in the subject data listings. 


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3.11.3 
Vital Signs, Height and Weight 
Vital signs measurements, including heart rate (HR), systolic and diastolic blood pressure 
(BP), respiratory rate, temperature, height and body weight are collected at screening and 
will be listed by subject. 
3.11.4 
12-Lead Electrocardiogram  
Electrocardiogram (ECG) interpretations by the Investigator are collected at screening and at 
unscheduled visits based on clinical indication. All ECG overall interpretations will be listed 
by subject.  
3.11.5 
Physical and Neurological Examinations 
Physical and neurological examinations are performed at screening and at unscheduled visits 
as clinically indicated.  All examination findings, including general appearance, head (eyes, 
ears, nose, and throat), cardiovascular, respiratory, abdominal, musculoskeletal, extremities, 
lymph nodes, skin, and neurological examination results (cranial nerves, sensory, motor, 
stance/gait, reflexes, mental status), will be listed by subject. 


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4 
REFERENCES 
1. International Conference on Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline, Statistical 
Principles for Clinical Trials (E9), 5 February 1998. 
2. International Conference on Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline, Structure and 
Content of Clinical Study Reports (E3), 30 November 1995. 


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5 
PROGRAMMING CONSIDERATIONS 
All tables, data listings, figures (TLFs), and statistical analyses will be generated using SAS® 
Version 9.4. Generated outputs will adhere to the following specifications. 
5.1 
Table, Listing, and Figure Format 
5.1.1 
General 
1) All TLFs will be produced in landscape format. 
2) All TLFs will be produced using the Courier New font, size 10. 
3) The data displays for all TLFs will have a 1.5-inch binding margin on top of a 
landscape oriented page and a minimum 1-inch margin on the other 3 sides. 
4) Headers and footers for figures will be in Courier New font, size 8. 
5) Legends will be used for all figures with more than 1 variable, group, or item 
displayed. 
6) TLFs will be in black and white (no color). 
7) Specialized text styles, such as bolding, italics, borders, shading, and superscripted 
and subscripted text, will not be used in the TLFs. On some occasions, superscripts 1, 
2, or 3 may be used (see below). 
8) Only standard keyboard characters will be used in the TLFs. Special characters, such 
as non-printable control characters, printer-specific, or font-specific characters, will 
not be used. Hexadecimal-derived characters will be used, where possible, if they are 
appropriate to help display math symbols (e.g., μ). Certain superscripts (e.g., cm2) 
will be employed on a case-by-case basis. 
9) Mixed case will be used for all titles, footnotes, column headers, and programmer-
supplied formats. 
5.1.2 
Headers 
1) All output should have the following header at the top of the page: 
Kyowa Kirin Pharmaceutical Development, Inc.  
 
 
DDMMMYYYY  
Istradefylline: Protocol 6002-018                                                                      Page n of N 
All output should have page numbers. TLFs should be internally paginated in relation to the 
total length (i.e., the page number should appear sequentially as page n of N, where N is the 
total number of pages in the table). 
5.1.3 
Display Titles 
1) Each TLF should be identified by a numeral, and the designation (i.e., Table 1) 
should be centered above the title. A decimal system (14.x.y.z and 16.2.x.y) should be 


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used to identify TLFs with related contents. The title is centered in initial capital 
characters. The analysis set should be identified on the line immediately following the 
title. The title and table designation are single spaced. A solid line spanning the 
margins will separate the display titles from the column headers. There will be 1 
blank line between the last title and the solid line. 
Table 14.x.y.z 
First Line of Title 
Second Line of Title if Needed 
Analysis Set 
5.1.4 
Column Headers 
1) Column headings should be displayed immediately below the solid line described 
above in initial upper-case characters. 
2) For numeric variables, include “unit” in column or row heading when appropriate. 
3) Analysis set sizes will be presented for each treatment group in the column heading as 
(N=xx) (or in the row headings if applicable). This is distinct from the ‘n’ used for the 
descriptive statistics representing the number of subjects in the analysis set. 
4) The majority of the tables will be summarized using a “Total” column. For those 
tables displaying “by treatment”, the order of treatments will be: Istradefylline 
20 mg/day, Istradefylline 40 mg/day, and Total. 
5.1.5 
Body of the Data Display 
1) Listings will be sorted for presentation in order of treatment groups as above, subject 
identification, collection day, and collection time (as applicable). 
2) If the categories of a parameter are ordered, then all categories between the maximum 
and minimum category should be presented in the table, even if n=0 for all treatment 
groups in a given category that is between the minimum and maximum level for that 
parameter. For example, the frequency distribution for symptom severity would 
appear as: 
Severity Rating 
n 
severe 
0 
moderate 
8 
mild 
3 
Where percentages are presented in these tables, any counts of 0 will be presented as 
0 and not as 0 (0%). 
3) If the categories are not ordered (e.g., Medical History, Reasons for Discontinuation 
from the Study, etc.), then only those categories for which there is at least 1 subject 
represented in 1 or more groups should be included. Exception, if ‘other’ category is 
present with at least 1 subject, all pre-specified categories will be included. 
4) An Unknown or Missing category for categorical summarization should be added to 
any parameter for which information is not available for 1 or more subjects. 


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5) Unless otherwise specified, the estimated mean and median for a set of values should 
be printed out to 1 more significant digit than the original values, and standard 
deviations should be printed out to 2 more significant digits than the original values. 
The minimum and maximum should report the same significant digits as the original 
values. For example, for systolic BP: 
N 
   XX 
Mean 
XXX.X 
SD 
      X.XX 
Median 
XXX.X 
Range 
(XXX, XXX) 
 
 
6) Data in columns of a table should be formatted as follows: 
• 
alpha-numeric values are left-justified; 
• 
whole numbers (e.g., counts) are right-justified; and 
• 
numbers containing fractional portions are decimal aligned. 
8) Percentage values should be printed with 1 digit to the right of the decimal point in 
parentheses 1 space after the count (e.g., 7 (12.8%), 13 (5.4%)). Less-than-signs 
“<0.1%” should be printed when values are >0.0% and <0.1% (not 0.0%). Unless 
otherwise noted, for all percentages, the number of subjects in the analysis set for the 
treatment group who have an observation will be the denominator. 
9) Tabular display of data for prior / concomitant medications, and all tabular displays of 
adverse event data should be presented by the body system, drug class, or SOC with 
the highest occurrence in the active treatment group in decreasing order. Within the 
body system, drug class and SOC, medical history (by PT), drugs (by ATC1 code), 
and adverse events (by PT) should be displayed in decreasing order. If incidence for 
more than 1 term is identical, they should then be sorted alphabetically. 
10) Missing data should be represented on subject listings as either a hyphen (“-”) with a 
corresponding footnote (“ - = unknown or not evaluated”), or as “N/A”, with the 
footnote “N/A = not applicable”, whichever is appropriate. Missing descriptive 
statistics or p-values due to non-estimability should be reported as “-”. 
11) Dates should be printed in SAS® DATE9.format (“DDMMMYYYY”: 01JUL2000). 
Missing portions of dates should be represented on subject listings as dashes (--
JUL2000). Dates that are missing because they are not applicable for the subject are 
output as “N/A”, unless otherwise specified. 
12) All observed time values must be presented using a 24-hour clock HH:MM:SS format 
(e.g., 01:35:45, or 11:26). Time will only be reported if it was measured as part of the 
study. 
5.1.6 
Footnotes 
1) A solid line spanning the margins will separate the body of the data display from the 
footnotes.  


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2) All footnotes will be left justified with single-line spacing immediately below the 
solid line underneath the data display. 
3) Footnotes should always begin with “Note:” if an informational footnote, or asterisks 
and other non-numeric symbols if an annotated footnote. Each new footnote starts on 
a new line. 
4) Footnotes will be present on the page where they are first referenced and thereafter on 
each page of the table, unless the footnote is specific only to certain pages. Subject 
specific footnotes should be avoided. 
5) Footnotes will be used sparingly and must add value to the table, figure, or data 
listing. If more than 4 footnotes are planned, then a cover page may be used to display 
footnotes, and only those essential to comprehension of the data will be repeated on 
each page. Footnotes should not repeat definitions already provided in the SAP. 
6) The last line of the footnote section will be a standard source line that indicates the 
data source called in by the program, the name of the program used to produce the 
data display, and the listing source (i.e., ‘Data source: xyzabc.sas7bdat    Program 
source: myprogram.sas    Listing source: 16.x.y.z’). 
5.2 
Data-Handling Rules 
This section describes naming conventions and rules for calculations that would be common 
to all applicable tables. Some rules specific to a table can be found in the relevant mock-ups. 
5.2.1 
Visits 
1) Relative Study Day: The first day of treatment is Day 1. A minus (-) sign indicates 
days prior to the start of treatment (e.g., Day -5 represents 5 days before start of 
therapy. There is no Day 0.). The relative study day for a specific visit is calculated as 
(Visit Date - Date of First Dose +1). 
2) Baseline: Evaluation taken on Day 1 or the last available evaluation prior to the first 
dose of study drug if the former is missing. 
5.2.2 
Demographics and Baseline Characteristics 
• 
Age (if derived) = (Date of informed consent - Date of birth + 1) / 365.25 and 
truncated to complete years. 
• 
Conversion factors and calculations for height, weight, and BMI (with precision to 
one decimal place): 
• 
Height (in cm) = height (in inches) * 2.54 
• 
Weight (in kg) = weight (in lbs) * 0.4536 
• 
BMI (kg/m2) = Weight(kg)/[Height(m)2] 


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5.2.3 
Prior and Concomitant Medications 
1) Prior and concomitant medications will be coded and classified using the WHODRUG 
dictionary. The specific dictionary version will be provided in the actual tables/listings. 
Prior medications refer to medications taken within 30 days prior to the first dose of 
study medication (i.e. the duration when taken overlaps the time interval between first 
dose date minus 30 to first dose date minus 1 at any single time).  Concomitant 
medications are those with start date/time on or after the date/time of dosing or that 
started prior to the date/time of dosing but are indicated as continuing into the 
treatment period. Any medications with partial start and/or stop dates will be 
considered concomitant if the assignment is uncertain. 
2) Medications missing both start and stop dates, or having a start date prior to the last 
dose of study drug and missing the stop date, or having a stop date after the start of 
study drug and missing the start date, will be counted as concomitant. When partial 
dates are present in the data, both a partial start date and/or a partial stop date will be 
evaluated to determine whether it can be conclusively established that the medication 
either ended prior to the start of study drug or started after the end of study drug. If the 
above cannot be conclusively established based on the partial and/or present dates, 
then the medication will be counted as concomitant. 
5.2.4 
Change from Baseline 
Change from Baseline is defined as X-baseline for each X value at Weeks 12, 26, and 
52. 
5.2.5 
Safety 
1) If multiple results (e.g., laboratory test results) are reported at a study visit, then the 
first available result reported for that visit will be used in that visit summary. 
2) Adverse events will be coded and classified using MedDRA dictionary. The specific 
dictionary version will be provided in the actual tables/listings. 
3) Counting rules for TEAEs: Adverse event tables will include all recorded adverse 
signs and symptoms, except those with onset or stop dates prior to the first day of 
study drug. Adverse events with missing start dates, but with stop dates either 
overlapping into the treatment period or missing, will be counted as treatment-
emergent, taking the worst-case approach. Special care will be taken regarding partial 
dates with similar logic to that of the prior/concomitant medications applied. 
4) For purposes of flagging individual subject data, laboratory abnormalities are defined 
as values above or below the normal range. 
5) Conversion factor for body temperature: 
Temperature (in °C) = 5/9 * (Temperature [in °F]-32), with precision to one decimal place. 


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6 
LIST OF TABLES, LISTINGS, AND FIGURES 
Disposition and Demography Tables  
 
Efficacy Tables 
 
 
 
 
 
Table 14.1.1 
Subject Enrollment by Center  
Table 14.1.2 
Subject Disposition 
Table 14.1.3 
Demographic and Baseline Characteristics – Safety Analysis Set 
Table 14.1.4 
Parkinson’s Disease History – Safety Analysis Set 
Table 14.1.5.1 
Prior Medications (Excluding Antiparkinsonian Medications) – Safety Analysis Set 
Table 14.1.5.2 
Concomitant Medications (Excluding Antiparkinsonian Medications) – Safety Analysis 
Set 
Table 14.1.6.1 
Prior Antiparkinsonian Medications – Safety Analysis Set 
Table 14.1.6.2 
Concomitant Antiparkinsonian Medications – Safety Analysis Set 
Table 14.1.7.1 
Duration of Therapy (weeks) – Safety Analysis Set 
Table 14.1.7.2 
Compliance Rate – Safety Analysis Set 
Table 14.1.7.3 
Treatment Adjustments – Safety Analysis Set 
Table 14.2.1.1 
Patient Global Impression - Improvement by Study Visit – Overall Condition – ITT 
Analysis Set  
Table 14.2.1.2 
Patient Global Impression - Improvement by Study Visit – Fatigue – ITT Analysis Set  
Table 14.2.1.3 
Patient Global Impression - Improvement by Study Visit – Sleep – ITT Analysis Set  
Table 14.2.1.4 
Patient Global Impression - Improvement by Study Visit –Motivated to Get Things 
Done – ITT Analysis Set  
Table 14.2.1.5 
Patient Global Impression - Improvement by Study Visit – Key Symptom – ITT 
Analysis Set  


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Safety Tables 
Table 14.3.1.1 
Overall Summary of Treatment-Emergent Adverse Events – Safety Analysis Set 
Table 14.3.1.2 
Subjects with Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term – Safety Analysis Set 
Table 14.3.1.3 
Subjects with Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term, and Maximum Severity – Safety Analysis Set 
Table 14.3.1.4 
Subjects with Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term, and Relationship to Study Drug – Safety Analysis Set 
 
 
 
 
Table 14.3.2.1 
Subjects with Treatment-Emergent Adverse Events Leading to Deathby System Organ 
Class and Preferred Term – Safety Analysis Set 
Table 14.3.2.2 
Subjects with Serious Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term – Safety Analysis Set 
Table 14.3.2.3 
Subjects with Treatment-Emergent Adverse Events Leading to Discontinuation from the 
Study by System Organ Class and Preferred Term – Safety Analysis Set 
Table 14.3.4.1 
Summary Statistics by Laboratory Test: Hematology – Parameter (unit) –– Safety 
Analysis Set 
Table 14.3.4.2 
Summary Statistics by Laboratory Test: Blood Chemistry – Parameter (unit) –Safety 
Analysis Set 
Table 14.3.4.3 
Summary Statistics by Laboratory Test: Urinalysis – Parameter (unit) –Safety Analysis 
Set 
Table 14.3.4.4 
Shift Tables by Laboratory Test: Hematology –Safety Analysis Set 
Table 14.3.4.5 
Shift Tables by Laboratory Test: Blood Chemistry –Safety Analysis Set 
Table 14.3.4.6 
Shift Tables by Laboratory Test: Urinalysis – Continuous  Parameters Safety Analysis Set 
Table 14.3.4.7 
Shift Tables by Laboratory Test: Urinalysis – Categorical  Parameters Safety Analysis Set 


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Listings 
Listing 16.2.1.1 
Subject Completion/Discontinuation 
Listing 16.2.1.2 
Screen Failures 
Listing 16.2.2.1 
Protocol Deviations 
Listing 16.2.2.2 
Inclusion/Exclusion Criteria 
Listing 16.2.3 
Subjects Excluded from Analysis Sets 
Listing 16.2.4.1 
Demography 
Listing 16.2.4.2 
Parkinson’s Disease History 
Listing 16.2.4.3 
Medical History 
Listing 16.2.4.4.1 
Prior Medications (Excluding Antiparkinsonian Medications) 
Listing 16.2.4.4.2 
Concomitant Medications (Excluding Antiparkinsonian Medications) 
Listing 16.2.4.5.1 
Prior Antiparkinsonian Medications 
Listing 16.2.4.5.2 
Concomitant Antiparkinsonian Medications 
Listing 16.2.5.1 
Study Drug Dosing Record and Compliance 
Listing 16.2.5.2 
Study Drug Dose Adjustment 
Listing 16.2.6 
Patient Global Impression - Improvement  
Listing 16.2.7.1 
Adverse Events 
Listing 16.2.7.2 
Serious Adverse Events and Deaths 
Listing 16.2.7.3 
Adverse Events Leading to Discontinuation from the Study 
Listing 16.2.8.1 
Laboratory Assessments - Hematology 
Listing 16.2.8.2 
Laboratory Assessments – Blood Chemistry 
Listing 16.2.8.3 
Laboratory Assessments – Urinalysis 
Listing 16.2.8.4 
Pregnancy Test 
Listing 16.2.8.5 
Follicle Stimulating Hormone 
Listing 16.2.8.6 
Laboratory Assessments - Comments 
Listing 16.2.9.1 
Vital Signs and Body Weight 
Listing 16.2.9.2 
12-Lead Electrocardiogram Report – Qualitative Data by Subject 
Listing 16.2.9.3 
Physical Examination 
Listing 16.2.9.4 
Neurological Examination 
 


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Table 14.1.1 
Subject Enrollment by Center 
Enrolled Subjects 
 
 
Center 
 
Investigator 
 
Total 
Number 
Name 
All Safety[1] ITT[2] 
1 
Xxxxxxx  
xx    xx      xx 
 
 
 
 
Yyyyyyy  
xx    xx      xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total 
 
xx      xx 
  
[1] Safety Analysis Set: Includes all subjects who received at least one dose of assigned study drug (even a partial 
dose).  
[2] Intent-to-Treat (ITT) set includes all subjects with both a valid baseline and at least one valid post-baseline 
assessment. 
 
  Data source: xyzabc.sas7bdat    Program source: myprogram.sas        Listing source:  16.x.y.z 
 
 
 
 
 
NOTE TO PROGRAMMER: Add source to all tables following the same format. 
 
 


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Table 14.1.2 
Subject Disposition 
Enrolled Subjects 
 
Status 
Total 
Randomized 
   xx (100%) 
ITT Analysis Set [1] 
xx (xx.x) 
Safety Analysis Set [2] 
xx (xx.x) 
Completed 
 
Week 12 
xx (xx.x) 
Week 26 
xx (xx.x) 
Week 52 
xx (xx.x) 
Completed Treatment Period 
xx (xx.x) 
 
 
Discontinued Prematurely 
xx (xx.x) 
 
 
Adverse Event 
xx (xx.x) 
Prohibited Concomintant Medication 
xx (xx.x) 
Subject withdrew consent 
xx (xx.x) 
Investigator decision 
xx (xx.x) 
Noncompliance 
Administrative reasons 
Pregnancy 
Subject did not meet entry criteria 
Other 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   [1] Intent-to-Treat (ITT) set includes all subjects with both a valid baseline and at least one valid post-
baseline assessment. 
  
[2] All subjects who received at least one dose of assigned study drug (even a partial dose). 
 
 


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Table 14.1.3 
Demographic and Baseline Characteristics 
Safety Analysis Set 
 
 
Total 
Variable 
(N=) 
Age (years) 
 
n 
xx 
Mean 
xx.x 
SD 
  x.xx 
Median 
xx.x 
Range 
(xx,xx) 
 
 
Gender n (%) 
 
Male 
xx (xx.x) 
Female 
xx (xx.x) 
 
 
Race n (%) 
 
White 
xx (xx.x) 
Asian 
xx (xx.x) 
Black  
xx (xx.x) 
American Indian or Alaska Native 
xx (xx.x) 
Native Hawaiian or Other Pacific Islander 
xx (xx.x) 
Other 
Not Applicable 
xx (xx.x) 
xx (xx.x) 
 
 
Ethnicity n (%) 
 
Hispanic or Latino 
xx (xx.x) 
Not Hispanic or Latino 
xx (xx.x) 
 
 
 
 
 


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Table 14.1.3 
Demographic and Baseline Characteristics 
Safety Analysis Set 
 
 
Total 
Variable 
(N=) 
 
 
Height (cm) 
 
n 
xx 
Mean 
xx.x 
SD 
  x.xx 
Median 
xx.x 
Range 
(xx,xx) 
 
 
Weight (kg)  
 
n 
xx 
Mean 
xx.x 
SD 
  x.xx 
Median 
xx.x 
Range 
(xx,xx) 
 
 
BMI (kg/m2) 
 
n 
xx 
Mean 
xx.x 
SD 
  x.xx 
Median 
xx.x 
Range 
(xx,xx) 
 
 
 
 


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Table 14.1.3 
Demographic and Baseline Characteristics 
Safety Analysis Set 
 
 
Total 
Variable 
(N=) 
 
 
Current Smoker n (%) 
 
Yes 
xx (xx.x) 
No 
xx (xx.x) 
 
 
Number of Cigarettes Smoked per Day n (%) 
 
<= 5 cigarettes per day 
xx (xx.x) 
> 5 cigarettes per day 
xx (xx.x) 
 
 
Number of Cups (8 Ounces) per Day of  
Any Caffeinated Beverage 
 
n 
xx 
Mean 
xx.x 
SD 
  x.xx 
Median 
xx.x 
Range 
 
(xx,xx) 
 
 
 
 
 
 
 
 
 
 
 
           NOTE TO PROGRAMMER: Additional baseline characteristics may be added as needed.  
 
 
 
 
 


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Table 14.1.4 
Parkinson’s Disease History 
Safety Analysis Set 
 
Variable 
Total 
  Statistics 
(N=) 
 
 
Time Since Diagnosis (years) n (%) 
 
< 1 year 
xx (xx.x) 
1-3 years 
4-7 years 
>= 8 years  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
Time Since Initiation of Levodopa (years) 
 
n 
xx 
Mean 
xx.x 
SD 
  x.xx 
Median 
xx.x 
Range 
(xx,xx) 
 
 
Time Since Onset of Motor Complications (years) 
 
n 
xx 
Mean 
xx.x 
SD 
  x.xx 
Median 
xx.x 
Range 
(xx,xx) 
 
 
 
  
Programming note: The data in this table will be brought forward from the Kyowa 6002-14 Study 
 
 


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Table 14.1.5.1 
Prior Medications (Excluding Antiparkinsonian Medications) 
Safety Analysis Set 
 
Therapeutic Class/ 
Total 
  Preferred Term [1] 
(N=) 
Subjects who took prior medications 
xx (xx.x) 
Therapeutic Class 1 
Preferred Term 1 
Preferred Term 1 
Etc. 
... 
 
 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: This table includes medications that were taken within 30 days prior to the first dose of Iistradefyline. 
[1] WHODRUG Dictionary Version 2013 SEP was used for coding.  
 
NOTE TO PROGRAMMER:  
Please present medications in descending order of total frequency by therapeutic class and then by descending order of total frequency of preferred term 
within the therapeutic class. 
 
 


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Statistical Analysis Plan 
Istradefylline 6002-018 
Table 14.1.5.2 
Concomitant Medications (Excluding Antiparkinsonian Medications) 
Safety Analysis Set 
 
 
NOTE TO PROGRAMMER:  
 
Follow the same format as Table 14.1.5.1: Change “Subjects who took prior medications” to: “Subjects who took concomitant medications.” 
Change note to “This table includes medications having a start date on or after the date of the first dose of  Istradefyline  or with a start date prior to the 
first dose of Istradefyline  and continuing beyond the first dose of Istradefyline.”. 
 
 
 
Table 14.1.6.1 
Prior Antiparkinsonian Medications 
Safety Analysis Set 
NOTE TO PROGRAMMER:  
 
Follow the same format as Table 14.1.5.1: Change “Subjects who took prior medications” to: “Subjects who took prior antiparkinsonian medications” 
 
 
 
Table 14.1.6.2 
Concomitant Antiparkinsonian Medications 
Safety Analysis Set 
NOTE TO PROGRAMMER:  
 
Follow the same format as Table 14.1.5.2: Change “Subjects who took concomitant medications” to: “Subjects who took concomitant antiparkinsonian 
medications.” 
 
 


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Table 14.1.7.1 
Duration of Therapy (Weeks) 
 
Safety Analysis Set 
 
 
 
 
Total 
Statistics 
(N=) 
Duration of Therapy (weeks) [1] n (%) 
 
<=12 
xx (xx.x) 
>12 to <=26 
xx (xx.x) 
>26 to <=52 
xx (xx.x) 
>52  
xx (xx.x) 
 
 
 
xx 
n 
xx.x 
Mean 
  x.xx 
SD 
xx.x 
Median 
(xx,xx) 
Range 
xx 
Total Duration (subject weeks) 
 
xx 
 
 [1] Duration of therapy = ([Last dose date  First dose date] + 1)/7 
 
 


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Table 14.1.7.2 
Compliance Rate 
Safety Analysis Set 
 
 
 
 
 
Total 
Statistics 
(N=) 
Compliance Rate Category 
 
  Treatment Period n (%) 
 
    <60% 
xx (xx.x%) 
    60 to 69% 
xx (xx.x%) 
    70 to 79% 
xx (xx.x%) 
    80 to 89% 
xx (xx.x%) 
    90 to 99% 
xx (xx.x%) 
    100 to 109% 
xx (xx.x%) 
    >110% 
xx (xx.x%) 
 
 
    n 
xx 
    Mean Rate 
xx.x 
    Median Rate 
xx.x 
 
 
  Week 12  n (%) 
 
    <60% 
xx (xx.x%) 
    60 to 69% 
xx (xx.x%) 
    ... 
xx (xx.x%) 
 
 
    n 
xx 
    Mean Rate 
xx.x 
    Median Rate 
xx.x 
 
 
NOTE TO PROGRAMMER: please also summarize compliance rate at each study visit (weeks 12, 26,  & 52) 


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Table 14.1.7.3 
Treatment Adjustments 
Safety Analysis Set 
 
 
Time Period 
 
Total 
   Exposure Adjustment 
(N=) 
 
 
Baseline to <Week 12 
 
    Remained on Istradefyline 20 mg 
xx (xx.x%) 
    Escalated to Istradefyline 40 mg 
xx (xx.x%) 
    Escalated to Istradefyline 40 mg and de-escalated to Istradefyline 20 mg 
xx (xx.x%) 
 
 
Week 12 to <Week 26 
 
    Remained on Istradefyline 20 mg 
xx (xx.x%) 
    Remained on Istradefyline 40 mg 
xx (xx.x%) 
    Escalated to Istradefyline 40 mg 
xx (xx.x%) 
    Escalated to Istradefyline 40 mg and de-escalated to Istradefyline 20 mg 
xx (xx.x%) 
 
 
≥ Week 26  
 
    Remained on Istradefyline 20 mg 
xx (xx.x%) 
    Remained on Istradefyline 40 mg 
xx (xx.x%) 
 
 
Total 
 
    Remained on Istradefyline 20 mg (without escalation to 40 mg) 
xx (xx.x%) 
    Escalated and Remained on Istradefyline 40 mg 
xx (xx.x%) 
    Escalated to Istradefyline 40 mg and De-escalated to Istradefyline 20 mg 
xx (xx.x%) 
 
 
Note: time period: Baseline to < Week 12, 1 to 84 study days; Week 12 to < Week 26, 85 to 183 study days; ≥ Week 26, ≥ 184 study days 


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Table 14.2.1.1 
Patient Global Impression – Improvement by Study Visit – Overall Condition 
ITT Analysis Set 
 
 
Treatment in 6002-014 
 
Visit/ 
  Score 
Placebo 
(N=) 
Istradefylline 
(N=) 
Total 
(N=) 
 
 
 
 
Week 12 [n(%)] 
xx (100%) 
xx (100%) 
xx (100%) 
  1=Moderate improvement (or greater)  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  2=Mild improvement  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  3=No change from Baseline  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  4=Mild deterioration  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  5=Moderate deterioration (or greater)  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
Week 26 [n(%)] 
 
 
 
  ... 
(Note to Programmer: Repeat for week 52) 
 
 
 
 
 
 
 
 
 
 
 


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Table 14.2.1.2 
Patient Global Impression – Improvement by Study Visit – Fatigue 
ITT Analysis Set 
 
Note to Programmer: Repeat Table 14.2.1.1 
 
 
 
 
Table 14.2.1.3 
Patient Global Impression – Improvement by Study Visit – Sleep 
ITT Analysis Set 
Note to Programmer: Repeat Table 14.2.1.1 
 
 
 
 
Table 14.2.1.4 
Patient Global Impression – Improvement by Study Visit – Motivated to Get Things Done 
ITT Analysis Set 
Note to Programmer: Repeat Table 14.2.1.1 
 
 
 
 
Table 14.2.1.5 
Patient Global Impression – Improvement by Study Visit – Key Symptoms 
ITT Analysis Set 
Note to Programmer: Repeat Table 14.1.5.1 


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Table 14.3.1.1 
Overall Summary of Treatment-Emergent Adverse Events (TEAE) 
Safety Analysis Set 
 
 
  
 
Total 
 (N=) 
 
Subjects with any TEAE n (%) 
xx (xx.x) 
 
Subjects with any serious TEAE n (%) 
xx (xx.x) 
 
Subjects with any TEAE leading to discontinuation n (%) 
xx (xx.x) 
 
Subjects with any Related [1] TEAE n (%) 
xx (xx.x) 
 
Subjects with any Severe TEAE n (%) 
xx (xx.x) 
 
Subjects who died n (%) 
xx (xx.x) 
 
 
[1] Related = includes probably, possibly, and definitely study drug related. 
 
 
 
 
 
 


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Table 14.3.1.2 
Subjects with Treatment-Emergent Adverse Events (TEAE) by System Organ Class and Preferred Term 
Safety Analysis Set 
 
 
System Organ Class/ 
 Preferred Term 
Total 
 (N=) 
 
Subjects with any TEAE n (%) 
xx (xx.x) 
 
System Organ Class 1 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
  ... 
 
 
System Organ Class 2 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
  ... 
 
 
 
Note: If a subject experienced more than 1 TEAE within a system organ class, the subject is counted once under that 
SOC. If a subject has more than 1 count of a particular preferred term, the subject was counted once for that 
preferred term. MedDRA dictionary Version 16.1 was used for coding. 
 
Programming Notes: For all TEAE tables (where applicable), present the data within an SOC by frequency of occurrence in decreasing 
order (NOT alphabetically)then by PT within SOC by frequency of occurance. 
 
Same format will be followed for Tables 14.3.1-3, 14.3.1-4. 
 
 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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                                                                       39 
 
Table 14.3.1.3 
Subjects with Treatment-Emergent Adverse Events (TEAE)  
by System Organ Class, Preferred Term, and Maximum Severity 
Safety Analysis Set 
 
System Organ Class/ Preferred Term 
Severity 
Total 
 (N=) 
Subjects with any TEAE n (%) 
Mild 
xx (xx.x) 
 
Moderate 
xx (xx.x) 
 
Severe 
xx (xx.x) 
 
 
 
System Organ Class 1 
Mild 
xx (xx.x) 
 
Moderate 
xx (xx.x) 
 
Severe 
xx (xx.x) 
 
 
 
  Preferred Term 1 
Mild 
xx (xx.x) 
   
Moderate 
xx (xx.x) 
  ... 
Severe 
xx (xx.x) 
 
 
 
Note: If a subject experienced more than 1 TEAE within a system organ class, the subject is counted once under 
that SOC. If a subject has more than 1 count of a particular preferred term, the subject was counted once for that 
preferred term. If a subject experienced more than 1 severity within a TEAE, the subject is counted once under 
maximum severity. MedDRA dictionary Version 16.1 was used for coding. 
 
 
NOTE TO PROGRAMMER: Please present in descending order by total count in SOC, and then in descending order by total 
count for PT within SOC. 
 
 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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                                                                       40 
Table 14.3.1.4 
Subjects with Treatment-Emergent Adverse Events (TEAE)  
by System Organ Class, Preferred Term, and Relationship to Study Drug 
Safety Analysis Set 
 
 
System Organ Class/ Preferred Term 
Relation to Study 
Drug 
Total 
 (N=) 
Subjects with any TEAE n (%) 
Related 
xx (xx.x) 
 
Not Related 
xx (xx.x) 
 
 
 
System Organ Class 1 
Related 
xx (xx.x) 
 
Not Related 
xx (xx.x) 
 
 
 
  Preferred Term 1 
Related 
xx (xx.x) 
   
Not Related 
xx (xx.x) 
  ... 
 
 
 
 
 
 
Note: If a subject experienced more than 1 TEAE within a system organ class, the subject is counted once under 
that SOC. If a subject has more than 1 count of a preferred term, the subject was counted once for that preferred 
term. MedDRA dictionary Version 16.1 was used for coding. 
 
 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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                                                                       41 
 
Table 14.3.2.1 
Subjects with any Treatment-Emergent Adverse Events Leading to Death  
by System Organ Class and Preferred Term 
Safety Analysis Set 
 
System Organ Class/ 
 Preferred Term 
Total 
 (N=) 
Dose at 
Occurrence  
 
 
20 mg 
40 mg 
 
Subjects with any TEAE leading to death n (%) 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
System Organ Class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ... 
 
 
 
 
System Organ Class 2 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ... 
 
 
 
 
 
 
 
Note: If a subject experienced more than 1 TEAE within a system organ class, the subject is counted once under that 
SOC. If a subject has more than 1 count of a particular preferred term, the subject was counted once for that 
preferred term. MedDRA dictionary Version 16.1 was used for coding. 
 
NOTE TO PROGRAMMER: Please present in descending order by frequency in SOC, and then by frequency in descending 
order by PT within SOC. 
 
 
 
 
 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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                                                                       42 
 
Table 14.3.2.2 
Subjects with Serious Treatment-Emergent Adverse Events (TEAE) by System Organ Class and Preferred Term 
Safety Analysis Set 
 
 
System Organ Class/ 
 Preferred Term 
Total 
 (N=) 
Dose at 
Occurrence  
 
 
20 mg 
40 mg 
 
Subjects with any Serious TEAE n (%) 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
 
System Organ Class 1 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ... 
 
 
 
 
System Organ Class 2 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
  Preferred Term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Preferred Term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ... 
 
 
 
 
 
 
 
 
 
 
 
Note: If a subject experienced more than 1 TEAE within a system organ class, the subject is counted once under that 
SOC. If a subject has more than 1 count of a particular preferred term, the subject was counted once for that 
preferred term. MedDRA dictionary Version 16.1 was used for coding. 
 
NOTE TO PROGRAMMER: Please present in descending order by frequency in SOC, and then in descending order by 
frequency PT within SOC. 
 
 
 
 
 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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                                                                       43 
Table 14.3.2.3 
Subjects with Treatment-Emergent Adverse Events (TEAE) Leading to Discontinuation from the Study 
by System Organ Class and Preferred Term 
Safety Analysis Set 
 
 
System Organ Class/ 
 Preferred Term 
Total 
 (N=) 
Dose at 
Occurrence
 
 
20 mg
40 mg
 
Subjects with any TEAE Leading to Discontinuation n (%) 
xx (xx.x) 
 
xx (xx.x)
 
xx (xx.x)
 
System Organ Class 1 
xx (xx.x) 
 
xx (xx.x)
 
xx (xx.x)
  Preferred Term 1 
xx (xx.x) 
xx (xx.x)
xx (xx.x)
  Preferred Term 2 
xx (xx.x) 
xx (xx.x)
xx (xx.x)
  ... 
 
 
 
 
System Organ Class 2 
xx (xx.x) 
 
xx (xx.x)
 
xx (xx.x)
  Preferred Term 1 
xx (xx.x) 
xx (xx.x)
xx (xx.x)
  Preferred Term 2 
xx (xx.x) 
xx (xx.x)
xx (xx.x)
  ... 
 
 
 
 
 
 
 
Note: If a subject experienced more than 1 TEAE within a system organ class, the subject is counted once under that 
SOC. If a subject has more than 1 count of a particular preferred term, the subject was counted once for that 
preferred term. MedDRA dictionary Version 16.1 was used for coding. 
 
 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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                                                                       44 
 
Table 14.3.4.1 
Summary Statistics by Laboratory Test: Hematology 
Actual and Change from Baseline Values 
Safety Analysis Set 
Parameter (Unit) 
 
Visit/ 
 
Total 
(N=) 
  Statistics 
 
 
Actual 
Change 
Screening 
 
 
 
 
  n 
 
 
xx 
 
  Mean 
 
 
xx.xx 
 
  SD 
 
 
x.xxx 
 
  Median 
 
 
xx.xx 
 
  Range 
 
 
xx.x-xx.x 
 
 
 
 
 
 
Week 26 
 
 
 
 
  n 
 
 
xx 
xx 
  Mean 
 
 
xx.xx 
xx.xx 
  SD 
 
 
x.xxx 
x.xxx 
  Median 
 
 
xx.xx 
xx.xx 
  Range 
 
 
xx.x-xx.x 
xx.x-xx.x 
 
 
 
 
 
Week 52 
 
 
 
 
 
 
Table 14.3.4.2 
Summary Statistics by laboratory Test: Blood Chemistry 
Actual and Change from Baseline Values 
Safety Analysis Set 
 
Note to Programmer: Repeat Table 14.3.4.1 for Blood Chemistry 
 
Table 14.3.4.3 
Summary Statistics by laboratory Test: Urinalysis 
Actual and Change from Baseline Values 
Safety Analysis Set 
 
Note to Programmer: Repeat Table 14.3.4.1 for Urinalysis 
 
 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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                                                                       45 
 
Table 14.3.4.4 
Shift Table by Laboratory Test: Hematology 
Safety Analysis Set 
Parameter: Hemoglobin (Unit) 
Post-Baseline 
Visit 
 
Baseline n (%) 
 
 
 
High 
Low 
Normal 
Total 
 
 
 
 
 
 
 
 
 
High 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
Week 26 
 
Normal 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
 
 
Low 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
 
 
Total 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
100% 
 
 
 
 
 
 
 
Week 52 
 
 
 
 
 
 
 
 
High 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
 
 
Normal 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
 
 
Low 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
 
 
Total 
xx.x(xx.x) 
xx.x(xx.x) 
xx.x(xx.x) 
100% 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: High = above upper limit of normal reference range; Normal = within limit of normal reference range; Low = below low limit of 
normal reference range.  
Reference range: see Preface A. 
 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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Table 14.3.4.5 
Shift Table by Laboratory Test: Blood Chemistry 
Safety Analysis Set 
 
Note to Programmer: Repeat Table 14.3.4.4 for Blood Chemistry 
 
 
 
 
 
 
 
Table 14.3.4.6 
Shift Table by Laboratory Test: Urinalysis – Continuous Parameters 
Safety Analysis Set 
 
Note to Programmer: Repeat Table 14.3.4.4 for Urinalysis – Continuous Parameters 
 
 
 
 
 
 
 
Table 14.3.4.7 
Shift Table by Laboratory Test: Urinalysis – Categorical Parameters  
Safety Analysis Set 
 
Note to Programmer: Repeat Table 14.3.4.4 for Urinalysis – Categorical Parameters 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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Listing 16.2.1.1 
Subject Completion/Discontinuation  
 
 
Clinical 
Site 
Subject 
No. 
Date of First Dose/ 
Date of Last Dose/ 
Day of Last Dose [1] 
Date/Day of 
Final Visit 
 
Dose at 
Final 
Visit (mg) 
Completed 
Study 
Reason for 
Discontinuation 
Analysis 
Population 
 
 
 
 
 
 
 
xxxx-xxx 
DDMMMYYYY/ 
DDMMMYYYY/XX  
Yes 
 
ITT, Safety  
 
DDMMMYYYY/XX 
 
 
 
 
 
 
 
 
 
 
 
 
xxxx-xxx 
DDMMMYYYY/ 
DDMMMYYYY/XX  
No 
Adverse Event 
ITT, Safety 
 
DDMMMYYYY/XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Relative to first dose of study drug. 
Source: Data source: xyzabc.sas7bdat    Program source: myprogram.sas 
 
Note to Programmer: Add source to all listings 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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Listing 16.2.1.2 
Screen Failures  
 
 
Clinical Site 
Subject No. 
Reason for Screen Failure 
xxxx-xxx 
 
 
 
 
 
 
 
 
 
 
 
xxxx-xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Data source: xyzabc.sas7bdat    Program source: myprogram.sas 
 
Note to Programmer: Add source to all listings 
 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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Listing 16.2.2.1 
Major Protocol Deviations 
 
 
Clinical Site 
Subject No. 
Protocol Deviation 
Visit Impacted by 
Deviation 
Description 
xxxx-xxx 
 
Screening 
xxxxxxxxxxxxxxxxxxxx 
 
 
 
xxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
xxxxxxxxxxxxxxxxxxxx 
 
 
 
xxxxxxxxxxxxxxxxxxxx 
 
 
 
xxxxxxxxxxxxxxxxxxxx 
xxxx-xx 
 
Screening 
 
 
 
 
 
 
NOTE TO PROGRAMMER: This will be programmed based on data provided by clinical. 
 


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Listing 16.2.2.2 
Inclusion/Exclusion Criteria Violations 
 
 
 
Clinical Site 
Subject No 
Date of 
Informed Consent 
Satisfy All Eligibility 
Criteria? 
Criteria Not 
Met 
Protocol Subject 
Initially Consented 
xxxx-xxx 
DDMMMYYYY 
No 
xx 
Amendment 2 
 
 
 
 
 
xxxx-xxx 
DDMMMYYYY 
No 
I01 E01 
Amendment 3 
 
 
 
 
 
xxxx-xxx 
DDMMMYYYY 
No 
I02 E05 
Amendment 4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 16.2.3 
Subjects Excluded from Analysis Sets 
 
 
 
 
 
 
Clinical Site 
Subject No. 
 
 
Analysis Set 
 
 
Exclusion 
Yes/No 
Reason for Exclusion  
xxxx-xxx 
ITT 
No 
 
 
Safety 
Yes 
xxxxxxxxxxxxxxxxxxxx 
 
 
 
 
xxxx-xxx 
ITT 
No 
 
 
Safety 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 16.2.4.1 
Demography 
 
 
Clinical 
Site 
Subject No. 
Age 
(yrs) 
Gender 
Race 
Ethnicity 
Height (cm)/ 
Weight (kg)/ 
BMI (kg/m2) 
Smoker/ 
Cigar- 
ettes  
per Day 
Caffeine 
Intake 
per Day 
Number of 
Years of 
Education 
Of Child-
Bearing 
Potential? 
xxxx-xxx 
xx 
Female 
xxxx
x 
xxxxxxxxxx 
xxx.x/ 
xx.x/  
xx.x 
Yes/<=5
/ >5 
2 
12 Years 
Yes/No 
 
 
 
 
 
 
 
 
 
 
 
xx 
Male 
xxxx
x 
xxxxxxxxxx 
xxx.x 
No 
1 
>12Years 
 
xxxx-xxx 
 
 
 
 
 
 
 
 
 
 
xx 
Female 
xxxx
x 
xxxxxxxxxx 
xxx.x 
No 
3 
>12Years 
Yes/No 
 
 
 
 
 
 
 
 
 
 
xxxx-xxx 
xx 
Male 
xxxx
x 
xxxxxxxxxx 
xxx.x 
Yes/xx 
4 
12Years 
 
 
 
 
 
 
 
 
 
 
 
 
xx 
Male 
xxxx
x 
xxxxxxxxxx 
xxx.x 
Yes/xx 
 
 
 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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Listing 16.2.4.2 
Parkinson’s Disease History 
 
 
 
Clinical Site 
Subject No. 
Screening Visit 
Date/Day [1] 
PD Diagnosis 
Duration 
Levodopa Initiated 
Onset of Motor Complications 
Date 
Duration (Yrs) 
Date 
Duration (Yrs) 
 
 
 
 
 
 
 
xxxx-xxx 
DDMMMYYYY/XXX 
< 1 year 
DDMMMYYYY 
XX 
DDMMMYYYY 
XX 
 
 
 
 
 
 
 
xxxx-xxx 
DDMMMYYYY/XXX 
1-3 years 
DDMMMYYYY 
XX 
DDMMMYYYY 
XX 
 
 
 
 
 
 
 
xxxx-xxx 
DDMMMYYYY/XXX 
4-7 years 
DDMMMYYYY 
XX 
DDMMMYYYY 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: data from Study 6002-014. 
[1] Relative to first dose of study drug. 


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Listing 16.2.4.3 
Medical History 
 
 
 
Clinical Site 
Subject No. 
Reported Term 
Start Date 
Ongoing? 
xxxx-xxx 
XXXXXXXXXXXXXXX 
DDMMMYYYY 
No 
 
 
 
 
xxxx-xxx 
XXXXXXXXXXXXXXX 
DDMMMYYYY 
Yes 
 
 
 
 
xxxx-xxx 
XXXXXXXXXXXXXXX 
DDMMMYYYY 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 16.2.4.4.1 
Prior Medications (Excluding AntiParkinsonian Medications) 
 
  
Clinical Site 
Subject No. 
Preferred 
Term [1] 
Medication 
Total Daily 
Dose (Unit) 
Start 
Date/Day[2] 
Stop 
Date/Day[2] 
Indication 
xxxx-xxx 
xxxxx 
xxxxx 
10 mg 
DDMMMYYYY/xx 
Ongoing 
xxxxxxxxxx 
 
 
 
 
 
 
 
xxxx-xxx 
xxxxx 
xxxxx 
10 mg 
DDMMMYYYY/xx 
DDMMMYYYY/xx 
xxxxxxxxxx 
 
 
 
 
 
 
 
xxxx-xxx 
xxxxx 
xxxxx 
10 mg 
DDMMMYYYY/xx 
DDMMMYYYY/xx 
xxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] XXX dictionary Version YYY was used for coding. 
[2] Relative to first dose of study drug. 
 
 
 


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Listing 16.2.4.4.2 
Concomitant Medications (Excluding AntiParkinsonian Medications) 
 
  
Clinical Site 
Subject No. 
Preferred 
Term [1] 
Medication 
Total Daily 
Dose (Unit) 
Start 
Date/Day[2] 
Stop 
Date/Day[2] 
Indication 
xxxx-xxx 
xxxxx 
xxxxx 
10 mg 
DDMMMYYYY/xx 
Ongoing 
xxxxxxxxxx 
 
 
 
 
 
 
 
xxxx-xxx 
xxxxx 
xxxxx 
10 mg 
DDMMMYYYY/xx 
DDMMMYYYY/xx 
xxxxxxxxxx 
 
 
 
 
 
 
 
xxxx-xxx 
xxxxx 
xxxxx 
10 mg 
DDMMMYYYY/xx 
DDMMMYYYY/xx 
xxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] XXX dictionary Version YYY was used for coding. 
[2] Relative to first dose of study drug. 
 
 
 


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Listing 16.2.4.5.1 
Prior Antiparkinsonian Medications 
 
  
Clinical Site 
Subject No. 
Preferred 
Term [1] 
Medication 
Total Daily 
Dose (Unit) 
Start 
Date/Day[2] 
Stop 
Date/Day[2] 
Indication 
xxxx-xxx 
xxxxx 
xxxxx 
10 mg 
DDMMMYYYY/xx 
Ongoing 
xxxxxxxxxx 
 
 
 
 
 
 
 
xxxx-xxx 
xxxxx 
xxxxx 
10 mg 
DDMMMYYYY/xx 
DDMMMYYYY/xx 
xxxxxxxxxx 
 
 
 
 
 
 
 
xxxx-xxx 
xxxxx 
xxxxx 
10 mg 
DDMMMYYYY/xx 
DDMMMYYYY/xx 
xxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] XXX dictionary Version YYY was used for coding. 
[2] Relative to first dose of study drug. 


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Listing 16.2.4.5.2 
Concomitant Antiparkinsonian Medications 
 
  
Clinical Site 
Subject No. 
Preferred 
Term [1] 
Medication 
Total Daily 
Dose (Unit) 
Start 
Date/Day[2] 
Stop 
Date/Day[2] 
Indication 
xxxx-xxx 
xxxxx 
xxxxx 
10 mg 
DDMMMYYYY/xx 
Ongoing 
xxxxxxxxxx 
 
 
 
 
 
 
 
xxxx-xxx 
xxxxx 
xxxxx 
10 mg 
DDMMMYYYY/xx 
DDMMMYYYY/xx 
xxxxxxxxxx 
 
 
 
 
 
 
 
xxxx-xxx 
xxxxx 
xxxxx 
10 mg 
DDMMMYYYY/xx 
DDMMMYYYY/xx 
xxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] XXX dictionary Version YYY was used for coding. 
[2] Relative to first dose of study drug. 
 


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Listing 16.2.5.1 
Study Drug Dosing Record and Compliance 
 
 
Clinical 
Site 
Subject 
No. 
Visit 
Date Dispensed-day/ 
Returned-day [1] 
Bottle 
Number 
Dose 
Level 
Number of 
Tablets 
Dispensed 
40 mg/20mg 
Number of 
Tablets 
Returned  
40mg/20mg 
Compliance 
Rate [2] 
70% or 
Greater 
Compl-
iant? 
Reason for 
Non-
compliance 
xxxx-xxx 
xxx 
DDMMMYYYY-xx/ 
DDMMMYYYY-xx 
xxx 
20 mg/d
xxx/xxx 
xxx/xxx 
xx.x% 
No 
AE 
 
 
 
 
 
 
 
 
 
 
xxxx-xxx 
xxx 
DDMMMYYYY-xx/ 
DDMMMYYYY-xx 
xxx 
40 mg/d
xxx/xxx 
xxx/xxx 
xx.x% 
No 
Other:XXXX 
 
 
 
 
 
 
 
 
 
 
xxxx-xxx 
xxx 
DDMMMYYYY-xx/ 
DDMMMYYYY-xx 
xxx 
20 mg/d
xxx/xxx 
xxx/xxx 
xx.x% 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 
[1] Relative to first dose of study drug. 
[2] Compliance rate = [(Number of tablets dispensed – Number of tablets returned) / (Number of tablets expected to 
be taken)] * 100. 
 
 
 


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Listing 16.2.5.2 
Study Drug Dose Adjustment 
 
 
Clinical 
Site 
Subject No. 
Visit 
Assessment 
Date/Day [1] 
Was the Dose 
Level 
Adjusted? 
Reason for Dose 
Adjustment 
If AE, Specify 
If Other, 
specify 
xxxx-xxx 
xxx 
DDMMMYYYY/XX 
Yes 
xxxxxxxxxxx 
xxxxxxxxxxx 
xxxxxxxxxxx 
 
 
 
 
 
 
 
xxxx-xxx 
xxx 
DDMMMYYYY/XX 
No 
 
 
 
 
 
 
 
 
 
 
xxxx-xxx 
xxx 
 
No 
 
 
 
 
 
DDMMMYYYY/XX 
 
 
 
 
 
 
 
 
 
 
 
Note:  
[1] Relative to first dose of study drug.


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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Listing 16.2.6 
Patient Global Impression - Improvement 
 
 
 
Clinical Site 
Subject No. 
Visit 
Assessment 
Date/Day [1] 
Overall 
Condition 
[2] 
Fatigue 
[2] 
Sleep [2] 
Motivated 
to Get 
Tasks Done 
[2] 
Key Symptom 
xxxx-xxx 
End of 6002-014 
DDMMMYYYY/XX 
 
 
 
 
XXXXXXX/4 
 
Baseline 
DDMMMYYYY/XX 
 
 
 
 
XXXXXXX/5 
 
Week 12 
DDMMMYYYY/XX 
1 
2 
3 
4 
XXXXXXX/5 
 
Week 26 
DDMMMYYYY/XX 
1 
2 
3 
4 
XXXXXXX/5 
 
Week 52 
DDMMMYYYY/XX 
1 
2 
3 
4 
XXXXXXX/5 
 
 
 
 
 
 
 
 
xxxx-xxx 
End of 6002-014 
DDMMMYYYY/XX 
 
 
 
 
XXXXXXX/4 
 
Baseline 
DDMMMYYYY/XX 
 
 
 
 
XXXXXXX/3 
 
Week 12 
DDMMMYYYY/XX 
1 
2 
3 
4 
XXXXXXX/3 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Relative to first dose of study drug. 
[2] PGI-I Scale: 1=Moderate improvement (or greater), 2=Mild improvement, 3=No change from Baseline, 4=Mild 
deterioration, 5=Moderate deterioration (or greater). 
                


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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Listing 16.2.7.1 
Adverse Events 
 
 
 
 
AE Start
AE Stop
 
Clinical 
Site 
Subject 
No. 
SOC/PT/Verbatim 
Date/    
Day [1]
Date/    
Day [1]
Istra- 
defylline 
dose at  
AE onset
SAE
Severity
[2]
Relation
[3]
Action 
taken 
[4]
Outcome 
[5]
xxxx 
xxxxxxxxx 
/xxxxxxxxxx 
/xxxxxxxxxxxxxx 
DDMMMYYYY/
XX 
DDMMMYYYY/
XX
Yes
Mild/ 
Mod/ 
Severe
Def/ 
Prob/ 
Poss/ 
Unlike/
Not R/ 
N/A
Drug 
W/D/ 
Dose 
Int/ 
No Chg;
N/A
Res/ 
Res’ing/
Not Res/
Res Seq/
Fatal/ 
Unk
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: XXX dictionary Version YYY was used for coding. AE=Adverse Event; SOC=System Organ Class; PT=Preferred Term; 
SAE=Serious Adverse Event. 
[1] Relative to first dose of study drug. Negative days at AE Start indicate the AE occured prior to first dose. 
[2] Severity: Mod=Moderate. 
[3] Relationship to Study Drug: Def=Definitely; Prob=Probably; Poss=Possibly; Unlike=Unlikely; Not R=Not Related; 
N/A=Not Applicable. 
[4] Action taken:  Drug W/D=Drug Withdrawn; Dose Int=Dose Interrupted; No Chg=Dose Not Changed; N/A=Not Applicable. 
[5] Outcome:  Res=Recovered/Resolved; Res’ing=Recovering/Resolving; Not Res=Not Recovered/Not Resolved; Res Seq= 
Recovered/Resolved with Sequelae; Unk=Unknown. 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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Listing 16.2.7.2 
Serious Adverse Events and Deaths 
 
 
 
 
AE Start
AE Stop
 
Clinical 
Site 
Subject 
No. 
SOC/PT/Verbatim 
Date/    
Day [1]
Date/    
Day [1]
Istra- 
defylline 
dose at AE 
onset
Sever- 
ity 
[2] 
Relation 
[3]
Action 
taken 
[4]
Outcome 
[5]
xxxx 
xxxxxxxxx 
/xxxxxxxxxx 
/xxxxxxxxxxxxxx 
DDMMMYYYY/ 
XX
DDMMMYYYY/ 
XX
Mild/ 
Mod/ 
Severe 
Def/ 
Prob/ 
Poss/ 
Unlike/ 
Not R/ 
N/A
Drug 
W/D/ 
Dose 
Int/ 
No Chg; 
N/A
Res/ 
Res’ing/ 
Not Res/ 
Res Seq/ 
Fatal/ 
Unk
 
 
 
 
 
 
 
 
 
 
 
 
Note: XXX dictionary Version YYY was used for coding. AE=Adverse Event; SOC=System Organ Class; PT=Preferred Term; 
SAE=Serious Adverse Event. 
[1] Relative to first dose of study drug. Negative days at AE Start indicate the AE occured prior to first dose. 
[2] Severity: Mod=Moderate. 
[3] Relationship to Study Drug: Def=Definitely; Prob=Probably; Poss=Possibly; Unlike=Unlikely; Not R=Not Related; 
N/A=Not Applicable. 
[4] Action taken:  Drug W/D=Drug Withdrawn; Dose Int=Dose Interrupted; No Chg=Dose Not Changed; N/A=Not Applicable. 
[5] Outcome:  Res=Recovered/Resolved; Res’ing=Recovering/Resolving; Not Res=Not Recovered/Not Resolved; Res Seq= 
Recovered/Resolved with Sequelae; Unk=Unknown. 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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Listing 16.2.7.3 
Adverse Events Leading to Discontinuation from the Study 
 
Note to Programmer: Repeat listing 16.2.7.1 for AE Leading to Discontinuation from the Study. 
 


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Listing 16.2.8.1 
Laboratory Assessments – Hematology 
 
 
Clinical 
Site 
Subject No. 
 
Parameter 
Unit 
Normal Range 
Low-High 
Visit 
Sample Date/Time/Day 
[1] 
Lab Value 
Flag* 
   xxx-xxx 
 
xxxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x   
H 
 
 
 
 
 
xxxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x   
H 
    
 
 
 
 
xxxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x   
H 
 
 
 
 
 
xxxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  xxx-xxx 
 
xxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x   
H 
 
 
 
 
 
xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x   
H 
 
 
 
 
 
xxxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxx 
 
xxxxxxxxxxxxxxx 
xxx 
xx.x – xx.x 
xxxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x 
 
 
 
 
 
 
xxxxxxx 
DDMMMYYYY/HH:MM/XXX 
  xx.x   
H 
 
 
 
 
 
xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: CS = clinically significant.  
[1] Relative to first dose of study drug. 
* H = above upper limit of normal reference range; L = below lower limit of normal reference range. 
 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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Listing 16.2.8.2 
Laboratory Assessments – Blood Chemistry 
 
Note to Programmer: Repeat listing 16.2.8.1 for blood chemistry parameters  
 
 
Listing 16.2.8.3 
Laboratory Assessments – Urinalysis 
 
Note to Programmer: Repeat listing 16.2.8.1 for urinalysis parameters 


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Listing 16.2.8.4 
Pregnancy Test 
 
Clinical Site 
Subject No. 
Visit 
Assessment 
Date/Day [] 
Sample Type 
Result 
xxxx-xxx 
Screening 
DDMMMYYYY/XXX 
Serum 
Negative 
 
Day 1 
DDMMMYYYY/XXX 
Urine 
Negative 
 
Week 26 
DDMMMYYYY/XXX 
Serum 
Negative 
 
Week 52 
DDMMMYYYY/XXX 
Serum 
Negative 
 
 
 
 
 
xxxx-xxx 
Screening 
DDMMMYYYY/XXX 
Serum 
Negative 
 
Day 1 
DDMMMYYYY/XXX 
Urine 
Negative 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Relative to first dose of study drug. 


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Listing 16.2.8.5 
Follicle Stimulating Hormone 
 
 
 
Clinical Site 
Subject No. 
Visit 
Assessment Date/Day 
[1] 
FSH > 30 IU/L 
xxxx-xxx 
Screening 
DDMMMYYYY/XX 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Relative to first dose of study drug. 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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Listing 16.2.8.6 
Laboratory Assessments - Comments 
 
 
 
Clinical 
Site 
Subject No. 
Parameter (Unit) 
Normal 
Range 
Low-High 
Visit 
Sample Date/Day 
[1]/Time 
Lab 
Value 
Comment 
 
xxx-xxxxxx 
xxxxxxx (xxxxxx) 
x.x-x.x 
Week xx 
ddMMMyyyy/xx/hh:mm 
x.x 
<---text----------> 
 
 
xxxxxxx (xxxxxx) 
x.x-x.x 
Week xx 
ddMMMyyyy/xx/hh:mm 
x.x 
<---text----------> 
 
 
 
Week xx 
ddMMMyyyy/xx/hh:mm 
x.x 
<---text----------> 
 
 
 
 
 
 
 
 
(Programming Note:Only list lab data having an associated comment in SDTM dataset SUPPLB.) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 16.2.9.1  
Vital Signs and Body Weight 
 
 
 
Clinical Site 
Subject No. 
Visit  
Assessment 
Date/Day [1] 
Height 
(cm) 
Weight 
(kg) 
Systolic 
BP 
(mmHg) 
Diastolic 
BP (mmHg) 
Heart 
Rate 
(bpm) 
Respiratory 
Rate 
(resp/min) 
Temp 
(C) 
xxxx-xxx 
Screening 
DDMMMYYYY/ 
XX 
  XXX    XXX 
  XXX 
  XXX 
  XXX 
    XX 
 XX.X 
 
 
 
 
 
 
 
 
    XX 
 XX.X 
 
Unscheduled  DDMMMYYYY/XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxx-xxx 
Screening 
DDMMMYYYY/XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unscheduled  DDMMMYYYY/XX 
 
 
 
 
 
 
 
Note: Height was only collected at screening. Only screening systolic/diastolic blood pressure and heart rate are 
presented on this listing..  
[1] Relative to first dose of study drug. 
 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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Listing 16.2.9.2 
12-Lead Electrocardiogram Report – Qualitative Data by Subject 
 
 
 
Clinical Site 
Subject No. 
Visit  
Assessment Date/Day 
[1] 
Assessment Time 
Investigator 
Interpretation of ECG 
Result [2] 
xxxx-xxx 
Screening 
DDMMMYYYY/XX 
 
 
. . . 
Unscheduled  
DDMMMYYYY/XX 
XX:XX 
Abnormal, CS 
 
 
 
 
 
 
xxxx-xxx 
Screening 
DDMMMYYYY/XX 
 
 
. . . 
 
 
XX:XX 
Abnormal, CS 
 
Unscheduled  
DDMMMYYYY/XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Relative to first dose of study drug. 
[2] CS=Clinically significant. 


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Listing 16.2.9.3 
Physical Examination 
 
 
 
Clinical Site 
Subject No. 
Visit 
Assessment Date/Day [1] 
Assessment Time 
Physical Exam 
Findings [2] 
xxxx-xxx 
Screening 
DDMMMYYYY/XX 
 
 
 
Unscheduled  
DDMMMYYYY/XX 
 
 
 
 
 
 
 
xxxx-xxx 
Screening 
DDMMMYYYY/XX 
 
 
 
 
 
 
 
 
Unscheduled  
DDMMMYYYY/XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Relative to first dose of study drug. 
[2] CS=Clinically significant. 


Kyowa Kirin Pharmaceutical Development, Inc.                                                                                                                                                  DDMMMYYYY 
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Listing 16.2.9.4 
Neurological Examination 
 
 
 
Clinical Site 
Subject No. 
Visit 
Assessment Date/Day [1] 
Assessment Time 
Neurological Exam 
Findings [2] 
xxxx-xxx 
Screening 
DDMMMYYYY/XX 
XX:XX 
Normal 
 
 
 
 
 
 
Unscheduled  
DDMMMYYYY/XX 
 
 
 
 
 
 
 
xxxx-xxx 
Screening 
DDMMMYYYY/XX 
 
 
 
 
 
 
 
 
Unscheduled  
DDMMMYYYY/XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Relative to first dose of study drug. 
[2] CS=Clinically significant.