Conditions: Healthy Volunteers
Keywords: Drug Therapy
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 6
Healthy volunteers: yes

Brief summary:
The purpose of this study is to determine ABA of TAK-906 following single oral (capsule) administration of 50 milligram (mg) of TAK-906 and single intravenous (IV) microtracer dose administration of 100 microgram (μg) (approximately 1 microcurie \[μCi\]) of \[14C\]-TAK-906 in Period 1 (ABA), and to determine the mass balance of TAK-906 in urine and feces following a single oral (solution) administration of 50 mg (approximately 100 μCi) of \[14C\]-TAK-906 in Period 2 (absorption, distribution, metabolism, and elimination \[ADME\]).

Detailed description:
The drug being tested in this study is called TAK-906. The study will determine ABA in Period 1, and ADME, and mass balance of TAK-906 after single oral administration in Period 2 in healthy adult male participants. Plasma and urine samples will be collected for PK determination; plasma, whole blood, urine, and feces samples will be collected for total radioactivity (TRA) determination; and plasma, urine, and feces samples will be collected to characterize the metabolite profiles of TAK-906.

The study will enroll approximately 6 participants. The study is designed to consist of 2 periods: Period 1 (ABA study period) and Period 2 (ADME study period). In Period 1 (ABA study period), all participants will receive single unlabeled oral 50 mg dose of TAK-906 as capsule followed by microdose of 100 μg (approximately 1 μCi) \[14C\]-TAK-906 as intravenous infusion followed by a washout period of at least 7 days before the dose in Period 2. In Period 2 (ADME study period), all participants will receive a single dose of 50 mg (approximately 100 μCi) \[14C\]-TAK-906 as an oral solution.

This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 65 days including screening period. Participants will be contacted approximately 30 days after the last dose of study drug for a follow-up assessment.

Arms:
arm 1: TAK-906 50 mg, capsule, orally, once on Day 1, followed by \[14C\]-TAK-906 100 micrograms (μg) \[approximately 1 microcurie (μCi)\], IV infusion, once on Day 1 of Treatment Period 1, followed by a Washout Period of 7 days, further followed by \[14C\]-TAK-906 50 mg (approximately 100 μCi), solution, orally, once on Day 1 of Treatment Period 2.

Interventions: intervention 1: TAK-906 Oral Capsule intervention 2: [14C]-TAK-906 Intravenous Infusion intervention 3: [14C]-TAK-906 Oral Solution
Intervention descriptions: intervention 1: TAK-906 capsule. intervention 2: \[14C\]-TAK-906 intravenous infusion. intervention 3: \[14C\]-TAK-906 oral solution.

Protocol document:
Prot_000.pdf: 



Title: A Phase 1 Study to Assess Absolute Bioavailability of TAK-906 and to Characterize Mass 
Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]-TAK-906 in Healthy Male 
Subjects
NCT Number: NCT04454918
Protocol Approve Date: 30 March 2020
Certain information within this protocol has been redacted (ie, specific content is masked irreversibly from 
view with a black/blue bar) to protect either personally identifiable information (PPD) or company 
confidential information (CCI). 
This may include, but is not limited to, redaction of the following: 
Named persons or organizations associated with the study.
Proprietary information, such as scales or coding systems, which are considered confidential 
information under prior agreements with license holder.
Other information as needed to protect confidentiality of Takeda or partners, personal information, or 
to otherwise protect the integrity of the clinical study.


TAKEDA PHARMACEUTICALS
PROTOCOL
A Phase 1 Study to Assess Absolute Bioavailability of TAK-906 and to Characterize Mass 
Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]-TAK-906 in Healthy Male 
Subjects
Study Identifier:
TAK-906-1007
Compound:
TAK-906
Date:
30 March 2020
Version/Amendment 
Number:
1
ial Use Only and Subject to the Applicable Terms of Use
ass
s
ass
y Male 
rms
y Male 
Property of Takeda: For
or Non-Commercia


TAK-906
Study ID TAK-906-1007
Page 2 of 81
Protocol
30 March 2020
TABLE OF CONTENTS
1.0
STUDY SUMMARY ......................................................................................................7
2.0
STUDY SCHEMATIC..................................................................................................12
3.0
SCHEDULE OF STUDY PROCEDURES ....................................................................13
4.0
INTRODUCTION.........................................................................................................23
4.1
Background .............................................................................................................23
4.2
Rationale for the Proposed Study.............................................................................25
4.3
Benefit/Risk Profile .................................................................................................25
5.0
TRIAL OBJECTIVES AND ENDPOINTS ...................................................................26
5.1
Hypothesis...............................................................................................................26
5.2
Trial Objectives .......................................................................................................26
5.2.1
Trial Primary Objectives ....................................................................................26
5.2.2
Trial Secondary Objectives ................................................................................26
5.2.3
..............................................................................26
5.2.4
Trial Safety Objectives.......................................................................................27
5.3
Endpoints.................................................................................................................27
5.3.1
Primary Endpoints .............................................................................................27
5.3.2
Secondary Endpoints..........................................................................................27
5.3.3
.......................................................................................28
5.3.4
Safety Endpoints................................................................................................28
6.0
TRIAL DESIGN AND DESCRIPTION ........................................................................29
6.1
Trial Design.............................................................................................................29
6.2
Dose Escalation .......................................................................................................30
6.3
Rationale for Trial Design, Dose, and Endpoints......................................................30
6.3.1
Rationale of Trial Design ...................................................................................30
6.3.2
Rationale for Dose .............................................................................................31
6.3.3
Rationale for Endpoints......................................................................................31
6.3.4
Critical Procedures Based on Trial Objectives: Timing of Procedures ................31
6.4
Trial Design/Dosing/Procedures Modifications Permitted Within Protocol 
Parameters...............................................................................................................32
6.5
Trial Beginning and End/Completion.......................................................................32
6.5.1
Definition of Beginning of the Trial ...................................................................32
6.5.2
Definition of End of the Trial.............................................................................32
6.5.3
Definition of Trial Completion...........................................................................32
6.5.4
Definition of Trial Discontinuation ....................................................................32
CCI
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TAK-906
Study ID TAK-906-1007
Page 3 of 81
Protocol
30 March 2020
6.5.5
Criteria for Premature Termination or Suspension of the Trial............................32
6.5.6
Criteria for Premature Termination or Suspension of a Site................................32
7.0
SELECTION AND DISCONTINUATION/WITHDRAWAL OF SUBJECTS..............33
7.1
Inclusion Criteria .....................................................................................................33
7.2
Exclusion Criteria ....................................................................................................33
7.3
Excluded Medications, Supplements, Dietary Products............................................35
7.4
Diet, Fluid, Activity.................................................................................................35
7.4.1
Diet and Fluid ....................................................................................................35
7.4.2
Activity..............................................................................................................36
7.5
Criteria for Discontinuation or Withdrawal of a Subject...........................................36
7.6
Procedures for Discontinuation or Withdrawal of a Subject......................................36
7.7
Subject Replacement................................................................................................36
8.0
CLINICAL STUDY MATERIAL MANAGEMENT.....................................................37
8.1
Clinical Study Drug .................................................................................................37
8.1.1
Clinical Study Drug Labeling.............................................................................37
8.1.2
Clinical Study Drug Inventory and Storage ........................................................37
8.1.3
Clinical Study Drug Blinding.............................................................................38
8.1.4
Randomization Code Creation and Storage ........................................................38
8.1.5
Clinical Trial Blind Maintenance/Unblinding Procedure ....................................38
8.1.6
Accountability and Destruction of Sponsor-Supplied Drugs...............................38
9.0
STUDY PROCEDURES...............................................................................................39
9.1
Administrative Procedures.......................................................................................39
9.1.1
Assignment of Screening and Randomization Numbers......................................39
9.1.2
Study Drug Assignment .....................................................................................39
9.1.3
Inclusion and Exclusion .....................................................................................39
9.1.4
Medical History/Demography ............................................................................39
9.1.5
Concomitant Medications...................................................................................39
9.2
Clinical Procedures and Assessments.......................................................................39
9.2.1
Full Physical Exam ............................................................................................40
9.2.2
Height and Weight .............................................................................................40
9.2.3
BMI ...................................................................................................................40
9.2.4
Vital Signs .........................................................................................................40
9.2.5
12-Lead ECG.....................................................................................................40
9.2.6
Taste Questionnaire............................................................................................41
9.2.7
Study Drug Administration ................................................................................41
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 4 of 81
Protocol
30 March 2020
9.2.8
AE Monitoring...................................................................................................41
9.2.9
Laboratory Procedures and Assessments............................................................41
9.3
PK Samples .............................................................................................................43
9.3.1
PK Measurements..............................................................................................44
9.3.2
Biomarker Measurements...................................................................................46
9.3.3
PGx Measurements............................................................................................47
9.3.4
Confinement ......................................................................................................47
10.0
ADVERSE EVENTS ....................................................................................................48
10.1
Definitions and Elements of AEs .............................................................................48
10.1.1 SAEs..................................................................................................................50
10.1.2 Special Interest AEs...........................................................................................51
10.2
AE Procedures.........................................................................................................51
10.2.1 Assigning Severity/Intensity of AEs...................................................................51
10.2.2 Assigning Causality of AEs................................................................................51
10.2.3 Start Date...........................................................................................................52
10.2.4 End Date............................................................................................................52
10.2.5 Pattern of Adverse Event (Frequency)................................................................52
10.2.6 Action Taken With Study Treatment..................................................................52
10.2.7 Outcome ............................................................................................................52
10.2.8 Collection and Reporting of AEs, SAEs, Special Interest AEs, and Abnormal 
LFTs ..................................................................................................................53
10.2.9 Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities.....55
11.0
STATISTICAL METHODS..........................................................................................56
11.1
Statistical and Analytical Plans ................................................................................56
11.1.1 Analysis Sets......................................................................................................56
11.1.2 Analysis of Demography and Other Baseline Characteristics .............................56
11.1.3 PK Analysis .......................................................................................................56
11.1.4 Analysis of Mass Balance ..................................................................................57
11.1.5 Whole Blood to Plasma Partitioning Ratio .........................................................57
11.1.6 Metabolite Profiling ...........................................................................................57
11.1.7 PD Analysis .......................................................................................................57
11.1.8 Safety Analysis ..................................................................................................57
11.2
Interim Analysis and Criteria for Early Termination ................................................58
11.3
Determination of Sample Size..................................................................................58
12.0
QUALITY CONTROL AND QUALITY ASSURANCE...............................................59
12.1
Study-Site Monitoring Visits ...................................................................................59
keda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 5 of 81
Protocol
30 March 2020
12.2
Protocol Deviations..................................................................................................59
12.3
Quality Assurance Audits and Regulatory Agency Inspections ................................59
13.0
ETHICAL ASPECTS OF THE STUDY........................................................................60
13.1
IRB and/or IEC Approval ........................................................................................60
13.2
Subject Information, Informed Consent, and Subject Authorization .........................61
13.3
Subject Confidentiality ............................................................................................62
13.4
Publication, Disclosure, and Clinical Trial Registration Policy.................................62
13.4.1 Publication and Disclosure.................................................................................62
13.4.2 Clinical Trial Registration..................................................................................63
13.4.3 Clinical Trial Results Disclosure ........................................................................63
13.5
Insurance and Compensation for Injury....................................................................63
14.0
ADMINISTRATIVE AND REFERENCE INFORMATION.........................................64
14.1
Administrative Information......................................................................................64
14.1.1 Study Contact Information .................................................................................64
14.1.2 INVESTIGATOR AGREEMENT......................................................................65
14.1.3 Study-Related Responsibilities...........................................................................66
14.1.4 List of Abbreviations .........................................................................................66
15.0
DATA HANDLING AND RECORDKEEPING............................................................69
15.1
CRFs (Electronic and Paper)....................................................................................69
15.2
Record Retention .....................................................................................................69
16.0
REFERENCES..............................................................................................................71
17.0
APPENDICES...............................................................................................................72
LIST OF IN-TEXT TABLES
Table 3.a
Blood and Plasma Sampling Schedule (Period 1 - ABA Study Period)...............18
Table 3.b
Urine and Fecal Sampling Schedule (Period 1 – ABA Study Period)..................19
Table 3.c
Blood and Plasma Sampling Schedule (Period 2 - ADME Study Period)............20
Table 3.d
Urine and Fecal Sampling Schedule (Period 2 - ADME Study Period) ...............21
Table 6.a
Planned TAK-906 and [14C]-TAK-906 Doses ....................................................30
Table 7.a
Excluded Medications, Supplements, and Dietary Products................................35
Table 9.a
Primary Specimen Collections ...........................................................................43
Table 10.a
Takeda Medically Significant AE List................................................................51
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TAK-906
Study ID TAK-906-1007
Page 6 of 81
Protocol
30 March 2020
LIST OF APPENDICES
Appendix A
Taste Questionnaire............................................................................................72
Appendix B
Responsibilities of the Investigator.....................................................................73
Appendix C
Elements of the Subject Informed Consent.........................................................75
Appendix D
Investigator Consent to the Use of Personal Information ....................................78
Appendix E
Pregnancy and Contraception.............................................................................79
Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 7 of 81
Protocol
30 March 2020
1.0
STUDY SUMMARY
Name of Sponsor:
Millennium Pharmaceuticals, Inc. a wholly owned subsidiary of 
Takeda Pharmaceutical Company, Ltd
40 Landsdowne Street
Cambridge, Massachusetts USA 02139
Telephone: +1 (617) 679-7000
Compound:
TAK-906
Study Identifier: TAK-906-1007 
Phase: 1
Protocol Title: A Phase 1 Study to Assess Absolute Bioavailability of TAK-906 and to Characterize Mass Balance, 
Pharmacokinetics, Metabolism, and Excretion of [14C]-TAK-906 in Healthy Male Subjects
Trial Design:
This is an open-label, 2-period, single-dose study in 6 male healthy subjects. 
On Day 1 of Period 1 (absolute bioavailability [ABA] Study Period), after at least a 10-hour fast, 6 subjects will 
receive a single unlabeled oral 50 mg dose of TAK-906 as capsules. At approximately 45 minutes post oral dosing 
(0.75 hour) (ie, 15 minutes prior to the median tmax for the oral unlabeled dose [~ 1.1 hours]), subjects will receive a 
15-minute intravenous (IV) infusion of a microtracer dose of 100 µg (approximately equivalent to 1 microcurie 
~[1 µCi]) [14C]-TAK-906. Serial blood sampling will be performed to determine the pharmacokinetics (PK) of 
TAK-906 and its metabolite (M23) in the plasma for the oral dose and total radioactivity (TRA) and PK of 
[14C]-TAK-906 in the plasma for the IV dose. Urine and fecal output will also be collected up to the morning of Day 5 
(ie, Hour 96) to determine TRA levels and until a discharge criterion is met (ie, 80% or greater of the total dose of 
radioactivity administered is recovered in urine and fecal samples or the excretion of radioactivity in the urine and 
feces combined has declined to ≤1% of the total administered radioactivity per 24-hour interval for at least 2 
consecutive intervals where both a urine and fecal sample are collected) but no less than Day 5 for [14C]-TRA 
excretion in urine and feces. 
In Period 1, subjects will be confined in the clinical research unit (CRU) for at least 5 days (until after the last PK 
sample and morning urine and fecal sample [when passed] are collected) and until discharge criterion is met or up to 
Day 7. Subjects will return to the clinic on Day -1 of Period 2 for Check-in procedures. There will be a washout period 
of at least 7 days between the dose in Period 1 and the dose in Period 2. As per site preference, subjects may be 
confined throughout the washout period. 
On Day 1 of Period 2 (absorption, distribution, metabolism, and elimination [ADME] Study Period), after at least a 
10-hour fast, the subjects will receive a single dose of 50 mg (~100 μCi) [14C]-TAK-906 as an oral solution. Serial 
blood sampling and urine and feces output will be collected. PK of TAK-906 and its metabolite, M23, will be 
determined in plasma and urine; plasma, whole blood, urine, and feces will be collected for TRA determination; and 
plasma, urine, and feces will be collected to characterize the metabolite profiles of TAK-906. Complete urinary and 
fecal output will be collected until at least the morning of Day 6 (ie, Hour 120). Subjects will be confined in the clinic 
until at least this time and until a discharge criterion is met (ie, 90% or greater of the total dose of radioactivity 
administered is recovered in urine and fecal samples or the excretion of radioactivity in the urine and feces combined 
has declined to ≤1% of the total administered radioactivity per 24 hour interval for at least 2 consecutive intervals 
where both a urine and fecal sample are collected) or up to 14 days postdose (ie, Day 15). After Day 15, if subjects 
have not met the discharge criteria, the subject may need to return to  the CRU to collect urine and fecal samples in two 
blocks of 24-hour periods on Days 20, 21, or 22 and Days 27, 28, or 29 based on the discretion of the Sponsor. Release 
of subjects who do not meet a discharge criterion by Day 15 in Period 2 will be reviewed on a case-by-case basis. In 
each of the 2 consecutive intervals, both urine and fecal samples have to be collected and counted for TRA, ie, if only 
urine or feces is collected in a day, this day is not considered to be one of the 2 consecutive intervals. Since up to an 
approximate 24-hour time lag is anticipated for radioactivity counting of samples, actual subject release from the CRU 
may occur 1 day after discharge criteria are met.
In both Periods 1 and 2, any subject who experiences emesis within 3 hours post oral dose will be excluded in the final 
data analysis and will be replaced with a new subject. If a subject experiences emesis after dosing in Period 2, vomitus 
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TAK-906
Study ID TAK-906-1007
Page 8 of 81
Protocol
30 March 2020
will need to be collected as much as possible and assayed for TRA. For a subject who drops out in Period 2, the 
replacement subject will be required to complete Period 2 only.
The clinic will contact all subjects (including subjects who terminate the study early) via phone call 30 ± 2 days after 
the last study drug administration to determine if any adverse events (AEs) have occurred since the last study visit. The 
subjects may be requested to return the site for further safety assessment, due to reported AEs, at the Investigator's 
discretion.
Period 1 - ABA
Trial Primary Objective:

To determine the oral absolute bioavailability 
(F) of TAK-906 following single oral (capsule) 
administration of 50 mg of TAK-906 and single 
IV microtracer dose administration of 100 µg 
(~1 µCi) of [14C]-TAK-906.
Trial Secondary Objectives:

To determine the plasma PK parameters of 
TAK-906 and metabolite, M23, following single 
oral (capsule) administration of 50 mg of 
TAK-906.

To determine plasma PK parameters of TRA 
following a single IV administration of 100 µg 
(~1 µCi) of [14C]-TAK-906.

To determine plasma PK parameters of 
[14C]-TAK 906 following a single IV 
administration of 100 µg (~1 µCi) of 
[14C]-TAK-906.
Trial Safety Objective:

To evaluate the safety and tolerability of 
TAK-906, administered as a single oral dose 
(capsule) of TAK-906 followed by single IV 
microtracer dose administration of 
[14C]-TAK-906.
Period 2 - ADME
Trial Primary Objective:

To determine the mass balance of TAK-906 in 
urine and feces following a single oral (solution) 
administration of 50 mg (~100 µCi) of 
[14C]-TAK-906.
Trial Secondary Objectives:

To determine the plasma PK parameters of 
TAK-906 and metabolite, M23, following a 
single oral (solution) administration of 50 mg 
(~100 µCi) of [14C]-TAK-906. 

To determine plasma and whole blood PK 
parameters for TRA following a single oral 
(solution) administration of 50 mg (~100 µCi) 
of [14C]-TAK-906. 
Trial Safety Objective:

To evaluate the safety and tolerability of 
TAK-906, administered as a single oral dose 
(solution) of [14C]-TAK-906.
Trial Subject Population: Healthy adult male subjects
Planned Number of Subjects:
6
Planned Number of Sites:
1
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O
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TAK-906
Study ID TAK-906-1007
Page 9 of 81
Protocol
30 March 2020
Dose Levels:
Period 1:
50 mg of TAK-906
100 µg (1 µCi) [14C]-TAK-906
Period 2:
50 mg (~100 µCi) [14C]-TAK-906
Route of Administration:
Period 1:
Oral (capsules)
IV infusion
Period 2:
Oral (solution)
Duration of Treatment:
Period 1:
On Day 1, subjects will receive a single oral dose 
followed by a 15 minute IV dose at ~0.75 hours post oral 
dose.
Period 2:
On Day 1, subjects will receive a single oral dose.
Planned Trial Duration:
Approximately 65 ± 2 days including the Screening 
Period and through follow-up.
Main Criteria for Inclusion:
In order to be eligible for study participation, subjects must:
1.
Healthy, adult, male, 19-55 years of age, inclusive, at screening.
2.
Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first 
dosing and throughout the study. 
3.
Body mass index (BMI) ≥18.0 and ˂ 30.0 kg/m2 at screening.
4.
Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital 
signs or ECGs performed at the screening visit and before administration of the initial dose of trial drug, as 
deemed by the Investigator or designee.
5.
A non-vasectomized male subject must agree to use a condom with spermicide or abstain from sexual intercourse 
during the study until 90 days after the last dosing. (No restrictions are required for a vasectomized male provided 
his bilateral vasectomy procedure has been performed at least 1 year prior to the first dosing of study drug. A male 
who has been vasectomized less than 1 year prior to study first dosing must follow the same restrictions as a 
non-vasectomized male). Appropriate documentation of surgical procedures should be provided.
6.
Male must agree not to donate sperm from the first dosing until 90 days after the last dosing (refer to Appendix E 
for detailed guidance on contraception and pregnancy avoidance procedures).
7.
Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the 
protocol.
Main Criteria for Exclusion:
The subject must be excluded from participating in the study if the subject: 
1.
Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or 
expected during the conduct of the study.
2.
History or presence of clinically significant endocrine, gastrointestinal (including motility
disorder and intestinal obstruction), cardiovascular, hematological, hepatic, immunological, renal, respiration, 
genitourinary, major neurological (including stroke and chronic seizures), or malignancy, or any other clinically 
significant abnormalities or disease in the opinion of the Investigator or designee.
3.
History of any illness that, in the opinion of the Investigator or designee, might confound the results of the study 
or poses an additional risk to the subject by their participation in the study.
4.
History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
5.
History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds.
ct to the Applicable Terms of Use
of
of
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lica
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Non-Commercial Use Only and Subject
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Prope
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TAK-906
Study ID TAK-906-1007
Page 10 of 81
Protocol
30 March 2020
6.
Positive urine drug or cotinine, or alcohol results at screening or first check-in.
7.
Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or 
hepatitis C virus (HCV).
8.
QTcF interval is >450 msec or ECG findings are deemed abnormal with clinical significance by the Investigator 
or designee at screening.
9.
Estimated creatinine clearance <90 mL/min at screening.
10. Has tattoo(s) or scarring at or near the site of IV infusion or any other condition which may interfere with infusion 
site examination, in the opinion of the Investigator.
11. Subject has infrequent bowel movements (less than approximately once per day) within 30 days prior to first 
dosing.
12. Recent history of abnormal bowel movements, such as diarrhea, loose stools, or constipation, within 2 weeks of 
first dosing.
13. Has received radiolabeled substances or has been exposed to radiation sources within 12 months of first dosing or 
is likely to receive radiation exposure or radioisotopes within 12 months of last dosing such that participation in 
this study would increase their total exposure beyond the recommended levels considered safe (ie, weighted 
annual limit recommended by the ICRP of 3000 mrem).
14. Unable to refrain from or anticipates the use of:

Any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements 
within 14 days prior to the first dosing and throughout the study. Acetaminophen (up to 2 g per 24 hr period) 
and Milk of Magnesia® (ie, magnesium hydroxide [≤ 60 mL per day after Day 3 in Period 1 and after Day 8 in 
Period 2]) may be permitted during the study, only after dosing, if necessary to treat AEs. Additional 
administration of Milk of Magnesia® may be administered on other days at discretion of the Investigator. 

Any drugs known to significantly affect the absorption, distribution, metabolism or elimination of TAK-906 
within 28 days prior to the first dosing and throughout the study. Appropriate sources (eg, Flockhart TableTM) 
will be consulted to confirm lack of PK/pharmacodynamics interaction with study drug.
15. Has been on a diet incompatible with the on-study diet, in the opinion of the Investigator or designee, within the 
30 days prior to the first dosing and throughout the study.
16. Donation of blood or significant blood loss within 56 days prior to the first dosing.
17. Plasma donation within 7 days prior to the first dosing.
18. Participation in another clinical study within 30 days prior to the first dosing. The 30-day window will be derived 
from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of Period 1 
of the current study.
Main Criteria for Evaluation and Analyses:
Period 1 - ABA
The primary endpoint will be assessed through 
evaluation of the following:

Ratio of dose normalized AUC∞of TAK-906 
and [14C]-TAK-906 in plasma (or AUClast in the 
case AUC∞ is incalculable).
The secondary endpoints will be assessed through 
evaluation of the following: 

PK parameters for oral TAK-906 and M23 in 
plasma: Cmax, Tmax, AUClast, AUC%extrap, and 
t1/2; for TAK-906 only in plasma: Vz/F, CL/F.

PK parameters for IV TRA in plasma: Ceoi, Tmax, 
Main Criteria for Evaluation and Analyses:
Period 2 - ADME
The primary endpoint will be assessed through 
evaluation of the following:

Cumulative recovery of radioactivity in urine 
(Cum%Dose[UR]) and feces (Cum%Dose[FE])
separately and both routes combined, expressed 
as a percent of total oral radioactive dose 
administered.
The secondary endpoints will be assessed through 
evaluation of the following:

PK parameters for plasma TAK-906 and M23: 
Cmax, Tmax, AUClast, AUC∞, AUC%extrap, and t1/2; 
or Non-Commercial Use Only and Subject to the Applicable Terms of Use
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pe
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TAK-906
Study ID TAK-906-1007
Page 11 of 81
Protocol
30 March 2020
AUClast, AUC∞, and t1/2.

PK parameters for IV [14C]-TAK-906 in plasma: 
C , CL, V , AUC
, AUC
and t
.
The safety endpoint will be assessed through 
evaluation of the following:

AE reporting, laboratory tests, ECGs, and vital 
sign parameters after administration of a single 
oral dose (capsule) of TAK-906 followed by 
single IV microtracer dose administration of 
[14C]-TAK-906.
for TAK-906 only: Vz/F and CL/F.

PK parameters for plasma and whole blood 
TRA: Cmax, Tmax, time-matched AUCt (where t is 
the last common time point at which TRA and 
plasma TAK-906 are quantifiable in all 
subjects), AUC
, AUC , and t
The safety endpoint will be assessed through 
evaluation of the following:

AE reporting, laboratory tests, ECGs, and vital 
sign parameters after a single oral dose 
(solution) of [14C]-TAK-906.
Statistical Considerations:
Descriptive statistics will be provided for the TRA (whole blood [Period 2], plasma, urine, feces [Periods 1 and 2], and 
if applicable, emesis [Period 2]), TAK-906 and metabolite concentrations and PK parameters (plasma and urine 
[Period 2]), and [14C]-TAK-906 concentrations (plasma, urine, feces [Period 1]), and the metabolite profile of 
TAK-906 (plasma, urine, feces [Period 2]), using appropriate summary statistics to be fully specified in the SAP.
ABA of TAK-906 (Period 1) will be estimated using a ninety percent (90%) confidence interval (CI) constructed for 
the difference in least-squares (LS) mean on the log scale for dose normalized AUC∞ between a single oral and the IV 
microtracer dose. Exponentiating the log-scale 90% CI will provide a 90% CI for the dose normalized AUC∞
geometric mean ratio (GMR); TAK-906 administered as oral dose / [14C]-TAK-906 administered as IV microtracer 
dose. AUClast will be analyzed in a similar fashion if AUC∞ cannot be calculated.
Mass balance will be calculated as a sum of the percent of the TRA recovered in urine and feces relative to the 
administered radioactivity dose minus any radioactivity lost due to emesis (if any occurred).
Sample Size Justification: The sample size of 6 male healthy subjects was selected empirically without statistical 
considerations and is deemed adequate to meet the study objectives. In addition, this sample size is limited based on 
clinical considerations for this type of study and in order to limit exposure to radioactivity.
CCI
CCI
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is
o
is
and
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of
Non-Commercial Use Only and Subject to
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to the Applicable Ter


TAK-906
Study ID TAK-906-1007
Page 12 of 81
Protocol
30 March 2020
2.0
STUDY SCHEMATIC
Screening
Treatment Period 1 a
Within 28 days of first 
dosing on Period 1 
Day -1
Day 1
Days 2 - 7
Check-in
Oral Dosing 
at Hour 0
IV Dosing at 
Hour 0.75 
Plasma, urine, and fecal sampling for ABA and safety monitoring for at least 
96 hours post oral dose b
< - - - - - - - - - - - -  confinement b - - - - - - - - - - - - >
a  Dosing in each period will be separated by at least 7 days.
b Subjects will be confined in the clinic until at least the morning of Day 5 (until after the last PK sample and morning 
urine and fecal sample [when passed] are collected) and until a discharge criterion is met (ie, 80% or greater of the 
total dose of radioactivity administered is recovered in urine and fecal samples or the excretion of radioactivity in the 
urine and feces combined has declined to ≤1% of the total administered radioactivity per 24-hour interval for at least 
2 consecutive intervals where both a urine and fecal sample are collected) or up to Day 7.
Treatment Period 2 c
Follow-up
Day -1
Day 1
Days 2 – 15
30 ± 2 days after last 
dosing
Check-in
Oral Dosing at Hour 0
Plasma, whole blood, urine, and fecal sampling for PK, TRA, and metabolite 
profiling, and safety monitoring for at least 120 hours posdose, or up to 
approximately 336 hours postdose if discharge criteria are not met. 
Additional urine and feces samples may be taken in two blocks of Days 20, 
21, 22 and Days 27, 28, and 29.
< - - - - - - - - - - - -  confinement d - - - - - - - - - - - - >
c Day -1 of Period 2 may be the same day as Day 7 of Period 1. 
d Subjects will be confined in the clinic until at least the morning of Day 6 and until discharge criterion is met (ie, 90% 
or greater of the total dose of radioactivity administered is recovered in urine and fecal samples or the excretion of 
radioactivity in the urine and feces combined has declined to ≤1% of the total administered radioactivity per 24-hour 
interval for at least 2 consecutive intervals where both a urine and fecal sample are collected) or up to 14 days postdose 
(ie, Day 15). After Day 15, if subjects have not met the discharge criteria, the subject may need to return to the CRU to 
collect urine and fecal samples in two blocks of 24-hour periods on Days 20, 21, or 22 and Days 27, 28, or 29 based on 
the discretion of the Sponsor. Release of subjects who do not meet a discharge criterion by Day 15 will be reviewed on 
a case-by-case basis. Since up to an approximate 24-hour time lag is anticipated for radioactivity counting of samples, 
actual subject release from the CRU may occur 1 day after discharge criteria are met.
Use Only and Subject to the Applicable Terms of Use
f
of
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Property of Takeda: For 
or


TAK-906
Study ID TAK-906-1007
Page 13 of 81
Protocol
30 March 2020
CONFIDENTIAL
3.0
SCHEDULE OF STUDY PROCEDURES 
Study Procedures a
Days →Screening b
Study Days in Period 1 c
-1 (Check-In d) 
1
2
3
4
5
6-7 e
Administrative Procedures
Informed Consent
X
Inclusion/Exclusion Criteria
X
X
Medical History 
X
X
Safety Evaluations 
Physical Examination f
X
X
Demographics
X
Height
X
Weight
X
BMI
X
12-Lead Safety Electrocardiograms
X
X g
X o
Vital Signs (pulse rate and blood pressure)
X
X g
X o
Vital Signs (respiratory rate and temperature)
X
X g
X o
Hematology, Serum Chemistry h, and Urinalysis
X
X
X
X o
Urine Drug and Alcohol Screen
X
X
Urine cotinine screen
X
X
Human immunodeficiency virus /Hepatitis Screen
X
Adverse Event Monitoring
X
X
Concomitant Medication Monitoring/Medication History
X
X
X
Study Drug Administration / Pharmacokinetics
TAK-906 Administration (oral)
X i
[14C]-TAK-906 Administration (intravenous infusion)
X j
Blood for TAK-906 and M23 Plasma pharmacokinetics k
X
X
X
X
X
Blood for [14C]-TAK-906 Plasma Pharmacokinetics and for Total 
X
X
X
X
X
mmercial Use Only and Subject to the Applicable Terms of Use
Te
Days in P
lica
Days in P
ca
2
Ap
2
pli
pli
pl
he
he Ap
Ap
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th
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bje
Subjbjeje
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bje
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X
Sub
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ly
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Us
X
se
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For Non-Commer
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er
mm
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No
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No
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For
dication 
or
da: F
macokin
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macokin
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on (intrav
Take
on (intrav
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M23 Plas
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M23 Plas
Ta
906 Plas
ty o
906 Plas
of
Property
rty


TAK-906
Study ID TAK-906-1007
Page 14 of 81
Protocol
30 March 2020
CONFIDENTIAL
Study Procedures a
Days →Screening b
Study Days in Period 1 c
-1 (Check-In d) 
1
2
3
4
5
6-7 e
Radioactivity Plasma Pharmacokinetics k
Urine for [14C]-TAK-906 Pharmacokinetics and for Total 
Radioactivity l
X
X
Feces for [14C]-TAK-906 Pharmacokinetics and for Total 
Radioactivity l
X
X
Other Procedures
Confinement in the Clinical Research Unit (e, m)
X
X
Visit
X
ct to the Applicable Terms of Use
Te
in Period
ble
in Period
e
3
b
3
ab
lic
lic
licic
plic
X
Ap
X
App
th
bje
Subje
bjbjeject 
ct
bje
bje
Property of Takeda: For Non-Commercial Use Only and Subje
bje
Su
d


TAK-906
Study ID TAK-906-1007
Page 15 of 81
Protocol
30 March 2020
CONFIDENTIAL
Study Procedures a
Study Days in Period 2 c
FU n
-1 
(C-I d)
1
2
3
4
5
6
7
8
9
10
11-15
Safety Evaluations 
Physical Examination f
X
12-Lead Safety Electrocardiogram
X g
X o
Vital Signs (pulse rate and blood pressure)
X g
X o
Vital Signs (respiratory rate and temperature)
X g
X o
Hematology, Serum Chemistry h, and Urinalysis
X
X
X o
Urine Drug and Alcohol Screen
X
Adverse Event Monitoring
X
Concomitant Medication Monitoring
X
Study Drug Administration / Pharmacokinetics
[14C]- TAK-906 Administration (oral)  
X i
Blood for Total Radioactivity whole blood 
Pharmacokinetics p
X
X
X
X
X
X
X
X 
Blood for Total Radioactivity Plasma Pharmacokinetics p
X
X
X
X
X
X
X
X
Blood for TAK-906 and M23 Plasma Pharmacokinetics p
X
X
X
X
X
X
X
X
Blood for TAK-906 Plasma Metabolite Profiling p
X
X
X
X
X
X
X
Urine for Total Radioactivity, Metabolite Profiling, and 
TAK-906 and M23 Pharmacokinetics q
X
Feces for Total Radioactivity and Metabolite Profiling q
X
Other Procedures
Taste Questionnaire r
X
Confinement in the CRU s
X
Phone call
X
a For details on Procedures, refer to Section 9.0.
b Within 28 days prior to the first dosing.
c There will be a washout period of at least 7 days between the dose in Period 1 and the dose in Period 2. Day -1 of Period 2 may be the same day as Day 7 of 
Use Only and Subject to the Applicable Terms of Use
Te
e
7
lica
7
ab
ab
p
cab
Ap
App
pp
Ap
A
t
A
th
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to
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je
bj
S
j
Su
n
S
nd
a
On
On y
Only
O
X
se
X i
e
i
e O
Non-Commercial Us
X
U
X
Us
al U
cia
me
mm
om
and 
n-C
and 
Co
Takeda: For No
o
Profiling
r No
Profiling
No
For 
or
F
da
ke
Property of Ta
Ta
s, refer to
of T
s, refer to
to the fir
y of
to the fir
shout per
rty 
shout per


TAK-906
Study ID TAK-906-1007
Page 16 of 81
Protocol
30 March 2020
CONFIDENTIAL
Period 1.
d Subjects will be admitted to the CRU on Day -1, at the time indicated by the CRU. If the CRU decides to confine the subjects throughout the washout period, some 
safety events at check-in (eg, clinical laboratory tests, urine drug and alcohol screen, cotinine test, vital signs, and ECGs) may not be performed, following a 
decision by Investigator.
e Subjects who do not meet a discharge criterion in Period 1 (ie, 80% or greater of the total dose of radioactivity administered is recovered in urine and fecal samples 
or the excretion of radioactivity in the urine and feces combined has declined to ≤1% of the total administered radioactivity per 24-hour interval for at least 
2 consecutive intervals where both a urine and fecal sample are collected) by Day 5, will remain confined and undergo study procedures until a discharge criterion 
is met or up to Day 7.
f A full physical examination will be conducted at screening. Abbreviated physical examinations are to be conducted on Day -1 of each period. These examinations 
will be repeated at the discharge day in Period 2 (ie, Day 15 or earlier). If the subject is required to return to the clinic facility to collect urine and fecal samples in 
two blocks of 24 hour periods on Days 20, 21, or 22 and Days 27, 28, or 29 at the discretion of the Sponsor, those exams will be repeated at the applicable block 
discharge day. Symptom-driven physical examination may be performed at additional times, at the Investigator’s or designee’s discretion. Release of subjects who 
do not meet a discharge criterion by Day 15 in Period 2 will be reviewed on a case-by-case basis.
g 12-Lead ECG and Vital signs (ie, pulse rate and blood pressure) are to be assessed within 24 hours prior to Day 1 oral dosing and at 1- and 4-hour post oral drug 
administration on Day 1; Vital signs (ie, respiratory rate and temperature) are to be assessed within 24 hours prior to Day 1 oral dosing, and at 4-hour post oral drug 
administration on Day 1. All ECG and vital sign assessments will be performed after the subjects have rested for at least 5 minutes.
h Samples for serum chemistry will be obtained following a fast of at least 8 hours, however, in case of dropouts or rechecks, subjects may not have fasted for 
8 hours prior to the serum chemistry sample being taken. Coagulation tests (prothrombin/international normalized ratio) will be performed if subjects have on-study 
aspartate aminotransferase or alanine aminotransferase elevated ≥3x the upper limit of normal.
i Oral drug administration will be performed at Hour 0 of Day 1.
j A 15 minute IV drug administration will begin at approximately 45 minutes post oral dose (Hour 0.75) on Day 1 of Period 1.
k For a detailed blood sampling schedule refer to Table 3.a.
l For a detailed urine and fecal sampling schedule refer to Table 3.b.
m As per site preference, subjects may be confined throughout the washout period. If subjects are confined throughout the washout period, some safety events at 
check-in of Period 2 (eg, clinical laboratory tests, urine drug and alcohol screen, cotinine test, vital signs, and ECGs) may not be performed, following a decision by 
the Investigator.
n The clinic will contact via phone call all subjects (including subjects who terminate the study early) 30 ±2 days after the last study drug administration to determine 
if any AEs have occurred since the last study visit. The subjects may be requested to return the site for further safety assessment, due to reported AEs, at the 
Investigator's discretion.
o To be performed at the end of Period 1 or Period 2 (prior to discharge) or prior to early termination from the study.
p For a detailed blood sampling schedule refer to Table 3.c.
q For a detailed urine and fecal sampling schedule refer to Table 3.d.
r A taste questionnaire will be completed within 5 minutes of [14C]-TAK-906 administration. 
s Subjects will remain confined to the CRU until at least the morning of Day 6 in Period 2. If discharge criteria are not met within 5 days post dose, the subject will 
continue to stay in the clinic until a discharge criterion is met (ie, ≥ 90% of the total dose of radioactivity administered is recovered in urine and fecal samples or the 
excretion of radioactivity in the urine and feces combined has declined to ≤1% of the total administered radioactivity per 24-hour interval for at least 2 consecutive 
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
Te
bjects thr
cab
bjects thr
CGs) may
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administe
App
administe
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and und
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and und
to be con
ct t
to be con
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to return
f the Spo
Subje
f the Spo
s, at the I
Su
s, at the I
ase basis
d S
ase basis
within 24
and
within 24
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Only
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TAK-906
Study ID TAK-906-1007
Page 17 of 81
Protocol
30 March 2020
CONFIDENTIAL
intervals) or up to a maximum of 14 days postdose (ie, day 15) is reached, whichever occurs first. Subjects can be released after Day 15 collection of excreta. After 
Day 15, if subjects have not met the discharge criteria, the subject may need to return to the clinic facility to collect urine and fecal samples in two blocks of 24-hour 
period on Days 20, 21, or 22 and Days 27, 28, or 29 at the discretion of the Sponsor. Release of subjects who do not meet a discharge criterion by Day 15 in Period 2 
will be reviewed on a case-by-case basis.
Abbreviations: CRU = Clinical Research Unit, ECG = Electrocardiogram, IV = Intravenous.
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 18 of 81
Protocol
30 March 2020
CONFIDENTIAL
Table 3.a
Blood and Plasma Sampling Schedule (Period 1 - ABA Study Period)
Time (hour)
(relative to oral dosing)
Time (hour)
(relative to intravenous infusion)
Sample Collection
Matrix
Plasma 1 a
Plasma 2 b
0 (predose)
X
0.5 hr postdose (± 2 min)
X
0.75 hr postdose (- 2 min) c
0 (predose)
X
1 hr postdose (- 2 min) d
End of infusion
X
X
10 min after the end of infusion (± 2 min)
X
20 min after the end of infusion (± 2 min)
X
1.5 hr postdose (± 2 min)
30 min after the end of infusion (± 2 min)
X
X
2 hr postdose (± 2 min)
1 hr after the end of infusion (± 2 min)
X
X
4 hr postdose (± 2 min)
3 hr after the end of infusion (± 2 min)
X
X
6 hr postdose (± 2 min)
5 hr after the end of infusion (± 2 min)
X
X
8 hr postdose (± 2 min)
7 hr after the end of infusion (± 2 min)
X
X
12 hr postdose (± 5 min)
11 hr after the end of infusion (± 2 min)
X
X
24 hr postdose (± 5 min)
23 hr after the end of infusion (± 5 min)
X
X
36 hr postdose (± 10 min)
35 hr after the end of infusion (± 10 min)
X
X
48 hr postdose (± 10 min)
47 hr after the end of infusion (± 10 min)
X
X
72 hr postdose (± 10 min)
71 hr after the end of infusion (± 10 min)
X
X
96 hr postdose (± 15 min)
95 hr after the end of infusion (± 15 min)
X
X
a. Plasma 1: For determination of TAK-906 and M23 in plasma. Predose samples should be stored separately away from the postdose samples to avoid cross 
contamination. 
b. Plasma 2: For determination of TRA and [14C]-TAK-906 in plasma. Predose samples should be stored separately away from the postdose samples to avoid cross 
contamination.
c. To be withdrawn within 2 minutes prior to start of infusion.
d. To be withdrawn within 2 minutes prior to end of infusion. 
or Non-Commercial Use Only and Subject to the Applicable Terms of Use
Te
lililic
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fusion (± 
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and
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TAK-906
Study ID TAK-906-1007
Page 19 of 81
Protocol
30 March 2020
CONFIDENTIAL
Table 3.b
Urine and Fecal Sampling Schedule (Period 1 – ABA Study Period)
Study Day
Time Interval (hour)
(Relative to Oral Dosing)
Sample Collection
Matrix
Urine (a)
Feces (b)
Day -2 to Day 1
-48 to 0 hr (predose)
X (c)
X (d)
Day 1
0-12 hr
X
X (0-24 hr)
Day 1 to Day 2
12-24 hr
X
Day 2 to Day 3
24-48 hr
X
X
Day 3 to Day 4
48-72 hr
X
X
Day 4 to Day 5
72-96 hr
X (e)
X (e)
Day 5 to Day 6 (f)
96-120 hr
X (f)
X (f)
Day 6 to Day 7 (f)
120-144 hr
X (f)
X (f)
(a) Urine sample for TRA and [14C]-TAK-906.
(b) Feces sample for TRA and [14C]-TAK-906.
(c) Predose urine sample is to be obtained within 24 hours prior to IV infusion and prior to oral dosing. Predose samples should be stored separately away from the 
postdose samples to avoid cross contamination.
(d) Predose fecal sample is to be obtained within 48 hours prior to oral dosing. Subjects will be asked to bring a fecal sample at check-in (if produced within 
48 hours prior to oral dosing). Feces produced between check-in and dosing will also be collected as a predose sample with the sample produced nearest to oral 
dosing to be retained as the only predose sample. Predose samples should be stored separately away from the postdose samples to avoid cross contamination.
(e) Including the urine and fecal sample collected on the morning of Day 5 (ie, Hour 96, as/when passed) prior to release.
(f)
Collection only for subjects who have not met discharge criteria.
e Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 20 of 81
Protocol
30 March 2020
CONFIDENTIAL
Table 3.c
Blood and Plasma Sampling Schedule (Period 2 - ADME Study Period)
Time (hour)
(Relative to Oral Dosing)
Sample Collection
Matrix
Blood 1 (a)
Plasma 1 (b),
Plasma 2 (b)
Plasma 3 (b)
0 (predose) (c)
X
X
X
0.5 hr postdose (±2 min)
X
X
X
1 hr postdose (± 2 min)
X
X
X
1.5 hr postdose (± 2 min)
X
X
2 hr postdose (± 2 min)
X
X
X
3 hr postdose (± 2 min)
X
X
4 hr postdose (± 2 min)
X
X
X
6 hr postdose (± 2 min)
X
X
8 hr postdose (± 2 min)
X
X
X
12 hr postdose (± 5 min)
X
X
X
24 hr postdose (± 5 min)
X
X
X
48 hr postdose (± 10 min)
X
X
X
72 hr postdose (± 10 min)
X
X
X
96 hr postdose (± 15 min)
X
X
X
120 hr postdose (± 15 min)
X
X
X
168 hr postdose (± 1 hr) (d)
X
X
X
240 hr postdose (± 1 hr) (d)
X
X
336 hr or before discharge (± 1 hr) (d)
X
X
(a) Blood sample for TRA (Blood 1). 
(b) Plasma sample for TAK-906 PK and M23 metabolite (Plasma 1), Plasma sample for TRA (Plasma 2), and plasma sample for metabolite profiling (Plasma 3).
(c) Predose blood and plasma samples should be stored separately away from the postdose samples to avoid cross contamination.
(d) Collection only for subjects confined beyond the morning of Day 6 (ie, Hour 120) and not discharged at the collection time.
Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 21 of 81
Protocol
30 March 2020
CONFIDENTIAL
Table 3.d
Urine and Fecal Sampling Schedule (Period 2 - ADME Study Period)
Study Day
Time Interval (hour)
(Relative to Oral Dosing)
Sample Collection
Sample Collection
Matrix
Urine 1 (a), Urine 2 (a)
Feces (b)
Day -2 to Day 1
-48 to 0 hr (predose)
X (c)
X (d)
Day 1
0-12 hr
X
X (0-24 hr)
Day 1 to Day 2
12-24 hr
X
Day 2 to Day 3
24-48 hr
X
X
Day 3 to Day 4
48-72 hr
X
X
Day 4 to Day 5
72-96 hr
X
X
Day 5 to Day 6
96-120 hr (e)
X
X
Day 6 to Day 7
120-144 hr (f)
X
X
Day 7 to Day 8
144-168 hr (f)
X
X
Day 8 to Day 9
168-192 hr (f)
X
X
Day 9 to Day 10
192-216 hr (f)
X
X
Day 10 to Day 11
216-240 hr (f)
X
X
Day 11 to Day 12
240-264 hr (f)
X
X
Day 12 to Day 13
264-288 hr (f)
X
X
Day 13 to Day 14
288-312 hr (f)
X
X
Day 14 to Day 15
312-336 hr (f)
X
X
(a) Urine sample for TAK-906 and M23 PK (Urine 1); Urine sample for TRA and urine sample for metabolite profiling (Urine 2). 
(b) Feces sample for TRA and feces sample for metabolite profiling (Feces).
(c) Predose urine sample is to be obtained within 24 hours prior to dosing. Predose urine samples should be stored separately away from the postdose samples to 
avoid cross contamination.
(d) Predose fecal sample is to be obtained within 48 hours prior to dosing. If applicable, for subject(s) who are released in Period 1 and return for Period 2, subjects 
will be asked to bring a fecal sample at check-in (if produced within 48 hours prior to dosing). Feces produced between check-in and dosing will also be 
collected as a predose sample with the sample produced nearest to dosing to be retained as the only predose sample. Predose fecal samples should be stored 
separately away from the postdose samples to avoid cross contamination.
on-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 22 of 81
Protocol
30 March 2020
CONFIDENTIAL
(e) Including the urine and fecal sample collected on the morning of Day 6 (ie, Hour 120, as/when passed) prior to release.
(f)
Collected for subjects who have not met the discharge criteria. Samples will continue to be collected in 24-hour intervals until a discharge criterion is met (ie, 
90% or greater of the total dose of radioactivity administered is recovered in urine and fecal samples or the excretion of radioactivity in the urine and feces 
combined has declined to ≤1% of the total administered radioactivity per 24 hour interval for at least 2 consecutive intervals where both a urine and fecal 
sample are collected) or up to 14 days postdose (ie, Day 15). After Day 15, if subjects have not met the discharge criteria, the subject may need to return to the 
CRU to collect urine and fecal samples in two blocks of 24-hour periods on Days 20, 21, or 22 and Days 27, 28, or 29 based on the discretion of the Sponsor. 
Release of subjects who do not meet a discharge criterion by Day 15 in Period 2 will be reviewed on a case-by-case basis.
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 23 of 81
Protocol
30 March 2020
4.0
INTRODUCTION
4.1
Background
The intended indication for TAK-906 is to treat patients with gastroparesis, a disorder of the 
stomach characterized by delayed gastric emptying in the absence of mechanical obstruction. 
Symptoms are chronic and include nausea, vomiting, early satiety, abdominal pain, and 
postprandial fullness with episodic exacerbation [1]. The prevalence of gastroparesis in the United 
States (US) is estimated to be approximately 24.2 per 100,000 [2]. In cases of chronic 
gastroparesis, diabetic (29%), postsurgical (13%), and idiopathic (36%) etiologies comprise the 
majority of cases in the tertiary referral setting [3]. 
TAK-906 is a peripherally selective (eg, limited penetration of the blood brain barrier [BBB]) 
dopamine D2/D3 receptor antagonist. It has demonstrated suitable PK and pharmacodynamic (PD) 
activity in a phase 1 study and other completed studies. Therefore TAK-906 is expected to reduce 
nausea and vomiting, without the side effects which restrict the use of other D2/D3 antagonists. 
Because of its low BBB penetration and a weak human Ether-a-go-go-Related Gene channel 
affinity indicative of a low potential cardiac risk, TAK-906 is anticipated to have an improved 
safety profile, compared to other D2/D3 antagonists (eg, metoclopramide and domperidone).
To date, at least 259 subjects have been dosed in the completed and ongoing clinical studies in the 
TAK-906 program, of which approximately 149 subjects have received at least 1 dose of active 
treatment with TAK-906. The results from these clinical studies indicate that TAK-906 was well 
tolerated with no significant safety issues attributed to TAK-906 in healthy subjects, patients with 
diabetic gastroparesis, or with idiopathic gastroparesis.
To date, 5 clinical studies have been completed: a phase 1 randomized, double-blind, 
placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study to 
evaluate the safety, PK, PD, effect of food, and optimal oral dose of TAK-906M in healthy 
subjects (Study AT-01C), a phase 1 itraconazole-interaction study in healthy subjects 
(Study TAK-906-1003), a phase 1 SAD and MAD study in Japanese healthy male subjects in 
Japan (Study TAK-906-1004), a phase 1 drug-drug interaction study with esomeprazole 
(Study TAK-906-1006), and a phase 2 randomized, double-blind and open-label, placebo- and 
active-comparator controlled study to evaluate the safety, PK, and PD of TAK-906 in subjects 
with diabetes mellitus and gastroparesis or idiopathic gastroparesis (TAK-906-1002).
Preclinical Pharmacokinetics
Following oral administration of [14C]-TAK-906M at 3.66 mg/kg (3 mg/kg as TAK-906) to fasted 
male rats and dogs, the t1/2z values of TRA were 1.6 and 6.1 hours, respectively. TAK-906 
radioactivity was almost completely eliminated from circulation by 24 and 120 hours in rats and 
dogs, respectively. Excretion of radioactivity in male rats was almost complete by 48 hours, with 
6.0% and 94.7% of the dosed radioactivity excreted in urine and feces, respectively, and 0.0% 
excreted in expired air. In bile duct-cannulated rats, 86.0%, 5.1%, and 11.0% of the dosed 
radioactivity were excreted into bile, urine, and feces, respectively, by 24 hours. Thus, biliary 
excretion represented the major excretion route for TAK-906 and related substances in rats. 
For Non-Commercial Use Only and Subject to the Applicable Terms of Use
ion. 
erm
ion. 
d d 
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TAK-906
Study ID TAK-906-1007
Page 24 of 81
Protocol
30 March 2020
Similarly, in fasted male dogs, urinary and fecal excretion of TAK-906 were 8.0% and 91.3%, 
respectively, over 96 hours.
TAK-906 is a substrate of P-glycoprotein and organic anion transporting polypeptide (OATP) 1B1 
and OATP1B3. Further uptake and kinetic studies using OATP1B1/1B3-expressing cells and 
human hepatocytes as a reference of pravastatin suggested that almost all the in vivo TAK-906 
uptake into human hepatocytes is by a saturable process of transporters, not by a passive process 
and TAK-906 is taken up into the human hepatocytes predominantly by OATP1B1. 
The in vitro metabolism showed that TAK-906 was mainly metabolized by cytochrome P450 
(CYP)3A4/5 and CYP2C8. M23 (pharmacologically inactive) was the metabolite formed by 
human liver cytosol, but not formed by CYP-expressing microsomes. The relative contribution 
ratio of CYP and non-CYP toward in vitro metabolism of TAK-906 using human hepatic S9 with 
or without typical CYP inhibitor was 43.3% and 56.7%, respectively.
Clinical Pharmacokinetics
In Study AT-01C, TAK-906M was administered as a single oral dose (ranging from 5 to 300 mg)
and repeated oral doses (ranging from 50 to 100 mg twice daily) for 5 days to healthy male and 
female non-Japanese subjects. Additionally, the effect of food on the PK of TAK-906 was 
evaluated at a single dose level of 25 mg TAK-906M in this study. TAK-906 showed rapid 
absorption and rapid elimination following oral administration. Median Tmax was ~1.1 hours 
postdose. The half-life (mean) following a single oral dose was ~4 hours when administered in the 
fasted state. Following administration of single oral doses of TAK-906 maleate between 5 and 
300 mg, exposure to TAK-906 increased in a manner generally proportional to dose increment. 
Food had a significant impact on reducing the exposure to TAK-906 in healthy subjects. The ratio 
of geometric LS means for Cmax was 58.06% (90% CI: 38.97% to 86.51%) for the test (fed) to 
reference (fasting) doses. For AUC∞and AUC12, the ratios were 58.23% (90% CI: 45.08% to 
75.21%) and 53.69% (90% CI: 42.79% to 67.37%), respectively. Confidence interval testing 
showed that all parameters were below and generally outside the comparison interval of 80% to 
125%. 
Drug-drug interaction potential of TAK-906 was evaluated. Coadministration of itraconazole, 200 
mg for 5 days, with TAK-906 maleate increased TAK-906 mean Cmax by approximately 2.0-fold 
and AUC∞by approximately 1.3-fold. TAK-906 is not classified as a sensitive CYP3A4 substrate. 
Following coadministration of esomeprazole (40 mg oral capsule) and TAK-906 (25 mg oral 
capsule) to healthy subjects, the AUClast, AUC∞, and Cmax of TAK-906 decreased approximately 
12 to 13% compared to TAK-906 administration alone. The AUClast and AUC∞ of M23 were 
similar, but the Cmax of M23 increased by approximately 20% when TAK-906 was coadministered 
with esomeprazole compared to TAK-906 administration alone.
Refer to the TAK-906 Investigator’s Brochure for complete information on the investigational 
product [4].
For Non-Commercial Use Only and Subject to the Applicable Terms of Use
B1 
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TAK-906
Study ID TAK-906-1007
Page 25 of 81
Protocol
30 March 2020
4.2
Rationale for the Proposed Study
The primary purposes of the present study are to characterize the ABA (Period 1) and the 
absorption, distribution, metabolism, excretion, and mass balance of TAK-906 after single oral 
administration (Period 2) in healthy adult male subjects, by collecting plasma and urine samples 
for TAK-906 and M23 analysis, plasma, urine, whole blood, and fecal samples for TRA analysis 
and, plasma, urine, and fecal samples for metabolite profiling. The study will provide data required 
to evaluate the ABA, mass balance, and the metabolite profile of TAK-906 in humans. 
4.3
Benefit/Risk Profile
The single dose of 50 mg TAK-906 is selected for this study and has been demonstrated to be safe 
and well tolerated in healthy subjects in studies conducted to date (IB, 2018).
The estimated radiation dose from a single IV administration of [14C]-TAK-906 (~1 µCi) and a 
single oral dose of [14C]-TAK-906 (~100 μCi) is below the radiation dose limits set forth in 
21 CFR 361 for the whole body, active blood forming organs, lens of the eye, gonads, and other 
organs (see Section 6.3.2). Thus, the health risk resulting from exposure to radiation in the study 
drug is very low.
The inclusion and exclusion criteria, screening, and safety monitoring practices employed by this 
protocol (ie, 12-lead ECG, vital signs, clinical laboratory tests, AE questioning, and physical 
examination) are adequate to protect the subjects’ safety and should detect all TEAEs.
There will be no direct health benefit for study participants from receipt of study drug. An indirect 
health benefit to the healthy subjects enrolled in this study is the free medical tests received at 
screening and during the study.
ubject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 26 of 81
Protocol
30 March 2020
5.0
TRIAL OBJECTIVES AND ENDPOINTS
5.1
Hypothesis
Not applicable.
5.2
Trial Objectives
5.2.1
Trial Primary Objectives
Trial Primary Objective – Period 1 (ABA):

To determine the oral absolute bioavailability (F) of TAK-906 following single oral 
(capsule) administration of 50 mg of TAK-906 and single IV microtracer dose 
administration of 100 µg (~1 µCi) of [14C]-TAK-906.
Trial Primary Objective – Period 2 (ADME):

To determine the mass balance of TAK-906 in urine and feces following a single oral 
(solution) administration of 50 mg (~100 µCi) of [14C]-TAK-906.
5.2.2
Trial Secondary Objectives
Trial Secondary Objectives – Period 1 (ABA):

To determine the plasma PK parameters of TAK-906 and metabolite, M23, following 
single oral (capsule) administration of 50 mg of TAK-906.

To determine plasma PK parameters of TRA following a single IV administration of 
100 µg (~1 µCi) of [14C]-TAK-906.

To determine plasma PK parameters of [14C]-TAK 906 following a single IV 
administration of 100 µg (~1 µCi) of [14C]-TAK-906.
Trial Secondary Objectives – Period 2 (ADME):

To determine the plasma PK parameters of TAK-906 and metabolite M23 following a 
single oral (solution) administration of 50 mg (~100 µCi) of [14C]-TAK-906. 

To determine plasma and whole blood PK parameters for TRA following a single oral 
(solution) administration of 50 mg (~100 µCi) of [14C]-TAK-906. 
CCI
mmercial Use Only and Subject to the Applicable Terms of Use
o
A
owing s
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TAK-906
Study ID TAK-906-1007
Page 27 of 81
Protocol
30 March 2020
5.2.4
Trial Safety Objectives
Trial Safety Objective - Period 1 (ABA):

To evaluate the safety and tolerability of TAK-906, administered as a single oral dose 
(capsule) of TAK-906 followed by single IV microtracer dose administration of 
[14C]-TAK-906.
Trial Safety Objective - Period 2 (ADME):

To evaluate the safety and tolerability of TAK-906, administered as a single oral dose 
(solution) of [14C]-TAK-906.
5.3
Endpoints
5.3.1
Primary Endpoints
Period 1 (ABA):

Ratio of dose normalized AUC∞of TAK-906 and [14C]-TAK-906 in plasma (or AUClast in 
the case AUC∞is incalculable).
Period 2 (ADME):  

Cumulative recovery of radioactivity in urine (Cum%Dose[UR]) and feces
(Cum%Dose[FE]) separately and both routes combined, expressed as a percent of total oral 
radioactive dose administered.
5.3.2
Secondary Endpoints 
Period 1 (ABA):

PK parameters for oral TAK-906 and M23 in plasma: Cmax, Tmax, AUClast, AUC%extrap, and 
t1/2; for TAK-906 only in plasma: Vz/F and CL/F.

PK parameters for IV TRA in plasma: Ceoi, Tmax, AUClast, AUC∞, and t1/2.

PK parameters for IV [14C]-TAK-906 in plasma: Ceoi, CL, Vss, AUClast, AUC%extrap, and t1/2.
Period 2 (ADME):

PK parameters for plasma TAK-906 and M23: Cmax, Tmax, AUClast, AUC∞, AUC%extrap, and 
t1/2; for TAK-906 only: Vz/F and CL/F.

PK parameters for plasma and whole blood TRA: Cmax, Tmax, time-matched AUCt (where t 
is the last common time point at which TRA and plasma TAK-906 are quantifiable in all 
subjects), AUClast, AUC∞, and t1/2.
CCI
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TAK-906
Study ID TAK-906-1007
Page 28 of 81
Protocol
30 March 2020
5.3.4
Safety Endpoints
Period 1 (ABA):

AE reporting, laboratory tests, ECGs, and vital sign parameters after administration of a 
single oral dose (capsule) of TAK-906 followed by single IV microtracer dose 
administration of [14C]-TAK-906.
Period 2 (ADME):

AE reporting, laboratory tests, ECGs, and vital sign parameters after a single oral dose 
(solution) of [14C]-TAK-906.
CCI
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 29 of 81
Protocol
30 March 2020
6.0
TRIAL DESIGN AND DESCRIPTION
6.1
Trial Design 
This is an open-label, 2-period, single-dose study in 6 male healthy subjects. 
On Day 1 of Period 1 (ABA Study Period), after at least a 10-hour fast, 6 subjects will receive a 
single unlabeled oral 50 mg dose of TAK-906 as capsules. At approximately 45 minutes post oral 
dosing (0.75 hour) (ie, 15 minutes prior to the median tmax for the oral unlabeled dose 
[~ 1.1 hours]), subjects will receive a 15-minute IV infusion of a microtracer dose of 100 µg 
(approximately equivalent to 1 µCi ~[1 µCi]) [14C]-TAK-906. Serial blood sampling will be 
performed to determine the PK of TAK-906 and its metabolite (M23) in the plasma for the oral 
dose and TRA and PK of [14C]-TAK-906 in the plasma for the IV dose. Urine and fecal output will 
also be collected up to the morning of Day 5 (ie, Hour 96) to determine TRA levels and 
[14C]-TAK-906 PK and until a discharge criterion is met (ie, 80% or greater of the total dose of 
radioactivity administered is recovered in urine and fecal samples or the excretion of radioactivity 
in the urine and feces combined has declined to ≤1% of the total administered radioactivity per 
24-hour interval for at least 2 consecutive intervals where both a urine and fecal sample are 
collected) but no less than Day 5 for [14C]-TRA excretion in urine and feces. 
In Period 1, subjects will be confined in the CRU for at least 5 days (until after the last PK sample 
and morning urine and fecal sample [when passed] are collected) and until discharge criterion is 
met or up to Day 7. Subjects will return to the clinic on Day -1 of Period 2 for Check-in procedures. 
There will be a washout period of at least 7 days between the dose in Period 1 and the dose in 
Period 2. As per site preference, subjects may be confined throughout the washout period. 
On Day 1 of Period 2 (ADME Study Period), after at least a 10-hour fast, the subjects will receive 
a single dose of 50 mg (~100 μCi) [14C]-TAK-906 as an oral solution. Serial blood sampling and 
urine and feces output will be collected. PK of TAK-906 and its metabolite, M23, will be 
determined in plasma and urine; plasma, whole blood, urine, and feces will be collected for TRA 
determination; and plasma, urine, and feces will be collected to characterize the metabolite profiles 
of TAK-906. Complete urinary and fecal output will be collected until at least the morning of Day 
6 (ie, Hour 120). Subjects will be confined in the clinic until at least this time and until a discharge 
criterion is met (ie, 90% or greater of the total dose of radioactivity administered is recovered in 
urine and fecal samples or the excretion of radioactivity in the urine and feces combined has 
declined to ≤1% of the total administered radioactivity per 24 hour interval for at least 
2 consecutive intervals where both a urine and fecal sample are collected) or up to 14 days 
postdose (ie, Day 15). After Day 15, if subjects have not met the discharge criteria, the subject may 
need to return to the CRU to collect urine and fecal samples in two blocks of 24-hour periods on 
Days 20, 21, or 22 and Days 27, 28, or 29 based on the discretion of the Sponsor. Release of 
subjects who do not meet a discharge criterion by Day 15 in Period 2 will be reviewed on a 
case-by-case basis. In each of the 2 consecutive intervals, both urine and fecal samples have to be 
collected and counted for TRA, ie, if only urine or feces is collected in a day, this day is not 
considered to be one of the 2 consecutive intervals. Since up to an approximate 24-hour time lag is 
r Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 30 of 81
Protocol
30 March 2020
anticipated for radioactivity counting of samples, actual subject release from the CRU may occur 
1 day after discharge criteria are met.
In both Periods 1 and 2, any subject who experiences emesis within 3 hours post oral dose will be 
excluded in the final data analysis and will be replaced with a new subject. If a subject experiences 
emesis after dosing in Period 2, vomitus will need to be collected as much as possible and assayed 
for TRA. For a subject who drops out in Period 2, the replacement subject will be required to 
complete Period 2 only. 
The clinic will contact all subjects (including subjects who terminate the study early) via phone 
call, 30 ± 2 days after the last study drug administration to determine if any AEs have occurred 
since the last study visit. The subjects may be requested to return the site for further safety 
assessment, due to reported AEs, at the Investigator's discretion.
The planned dose levels of TAK-906 to be evaluated are outlined in Table 6.a. 
Table 6.a
Planned TAK-906 and [14C]-TAK-906 Doses
Dose
Route of 
Administration
Period 1 (Treatment A)
TAK-906
50 mg
Oral capsule
[14C]-TAK-906
100 µg (~1 µCi)
IV
Period 2 (Treatment B)
[14C]-TAK-906
50 mg (~100 µCi)
Oral solution
6.2
Dose Escalation
Not applicable.
6.3
Rationale for Trial Design, Dose, and Endpoints
6.3.1
Rationale of Trial Design 
In Period 1 of the study, the ABA of TAK-906 will be estimated using a labeled IV microtracer 
administered at ~0.75 hours ie, approximately 45 min post oral dose (over approximately 
15 minutes) after an unlabeled oral dose in order to characterize the disposition properties of 
TAK-906. In order to determine ABA accurately and reliably, a healthy adult population is chosen.
Characterization of the disposition of a drug following IV administration facilitates the 
understanding of fundamental aspects of TAK-906’s PK that cannot be determined from oral 
dosing alone, including bioavailability, intrinsic clearance, and volume of distribution. The results 
of this trial will contribute to a robust understanding of the PK characteristics of TAK-906.
In Period 2 of the study, characterization of the absorption, distribution, metabolism, excretion, 
and mass balance of TAK-906 after oral administration of a single 50 mg (~100 μCi) 
[14C]-TAK-906 will be achieved by collecting plasma and urine samples for drug concentration 
analysis; plasma, whole blood, urine, and fecal samples for TRA analysis; and plasma, urine, and 
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 31 of 81
Protocol
30 March 2020
feces for metabolite profiling The study will provide data required to evaluate the mass balance 
and the metabolite profile of TAK-906 in humans.
6.3.2
Rationale for Dose 
A single oral dose of 50 mg of unlabeled and [14C]-TAK-906 will be used in the study in Periods 1 
and 2. This is the highest dose of TAK-906 which is being evaluated in a dose range phase-IIb trial 
in gastroparesis patients. Safety and tolerability of TAK-906 were studied up to a single dose of 
300 mg and 100 mg twice daily for 4 days via the oral route in healthy subjects and found to be safe 
and tolerable. 
Radiolabeled doses [14C] were administered to male Sprague-Dawley and Long-Evans rats (blood 
and pigmented skin only). Tissue concentration versus time profiles showed that 
elimination/tissue release of radioactivity from all tissues was generally very rapid and 
concentrations for many tissues were below the limit of quantitation (BLQ). 
The calculated radiation absorbed doses were relatively low (< 2.000 mrem and < 0.020 mSv) for 
most tissues (except bladder) for male human subjects following a single oral dose of 
[14C]TAK-906 of 100 μCi. The highest estimated absorbed dose was in the bladder, which had a 
value of 4.854 mrem (0.049 mSv) and represented 0.097% of the allowable 5000 mrem United 
States (US)-Food and Drug Administration (FDA) exposure limit for a single tissue. In descending 
order, the next highest radiation absorbed doses (> 0.200 mrem) were in the small intestine 
(1.270 mrem, 0.013 mSv), the liver (0.917 mrem, 0.009 mSv), the mesenteric lymph node (0.221 
mrem, 0.002 mSv), and the kidney (0.219 mrem, 0.002 mSv). Blood, blood-forming organs, and 
lymph nodes each had an estimated dose of ≤0.221 mrem (0.002 mSv), which represented 
0.0074% of the allowable 3000 mrem US-FDA exposure limit. Radioactive concentrations in the 
eyes and testis (gonads) were BLQ at all sampled time-points, which represented 0% of the 
allowable 3000 mrem exposure limit. The overall human male whole-body exposure was 
calculated to be 0.3143 mrem (0.0031 mSv), which represented approximately 0.010% of the 
allowable 3000 mrem US-FDA exposure limit, and 0.31% of the allowable 1 mSv ICRP 
(International Committee on Radiation Protection) limit and is considered to be safe. A single oral 
dose of up to 100 μCi (3.70 MBq) of [14C]-TAK-906 is not expected to represent a major 
whole-body radiation exposure risk to human male subjects as defined in the US-FDA and ICRP 
guidelines.
6.3.3
Rationale for Endpoints
Not applicable
6.3.4
Critical Procedures Based on Trial Objectives: Timing of Procedures 
For this study, the blood, plasma, urine, and feces collections for total radioactivity, plasma and 
urine concentrations, and plasma, urine, and feces for metabolite profiling for TAK-906 and M23, 
as appropriate, are the critical procedures and are required to be collected, as appropriate, as close 
to the scheduled times defined in this protocol as possible.
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TAK-906
Study ID TAK-906-1007
Page 32 of 81
Protocol
30 March 2020
6.4
Trial Design/Dosing/Procedures Modifications Permitted Within Protocol 
Parameters
The dose and administration of the study drug to any subject may not be modified. If necessary a 
subjects must be discontinued for the reasons described in Section 7.5.
6.5
Trial Beginning and End/Completion
6.5.1
Definition of Beginning of the Trial
The beginning of the trial will be defined as the beginning of the screening (ie, signing of the ICF) 
of the first subject.
6.5.2
Definition of End of the Trial
The end of study is defined as the date of the last scheduled study procedure as outlined in the 
Schedule of Study Procedures (Section 3.0).
6.5.3
Definition of Trial Completion
The end of the study is scheduled after completion of the evaluations in the follow-up phone call 
for the last subject in the study.
This time period may change in the event that the study is terminated early or the last subject is lost 
to follow-up.
6.5.4
Definition of Trial Discontinuation
Celerion reserves the right to terminate the study in the interest of subject welfare.
The Sponsor reserves the right to suspend or terminate the study at any time.
6.5.5
Criteria for Premature Termination or Suspension of the Trial
Celerion reserves the right to terminate the study in the interest of subject welfare.
Sponsor reserves the right to suspend or terminate the study at any time.
6.5.6
Criteria for Premature Termination or Suspension of a Site
6.5.6.1
Criteria for Premature Termination or Suspension of a Site 
Not Applicable.
6.5.6.2
Procedures for Premature Termination or Suspension of a Site
Not Applicable.
or Non-Commercial Use Only and Subject to the Applicable Terms of Use
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6.5


TAK-906
Study ID TAK-906-1007
Page 33 of 81
Protocol
30 March 2020
7.0
SELECTION AND DISCONTINUATION/WITHDRAWAL OF SUBJECTS
7.1
Inclusion Criteria 
Subjects must fulfill the following inclusion criteria to be eligible for participation in the study:
1. Healthy, adult, male, 19-55 years of age, inclusive, at screening.
2. Continuous non-smoker who has not used nicotine-containing products for at least 3 months 
prior to the first dosing and throughout the study. 
3. BMI ≥18.0 and ˂ 30.0 kg/m2 at screening.
4. Medically healthy with no clinically significant medical history, physical examination, 
laboratory profiles, vital signs or ECGs performed at the screening visit and before 
administration of the initial dose of trial drug, as deemed by the Investigator or designee.
5. A non-vasectomized male subject must agree to use a condom with spermicide or abstain from 
sexual intercourse during the study until 90 days after the last dosing. (No restrictions are 
required for a vasectomized male provided his bilateral vasectomy procedure has been 
performed at least 1 year prior to the first dosing of study drug. A male who has been 
vasectomized less than 1 year prior to study first dosing must follow the same restrictions as a 
non-vasectomized male). Appropriate documentation of surgical procedures should be 
provided.
6. Male must agree not to donate sperm from the first dosing until 90 days after the last dosing 
(refer to Appendix E for detailed guidance on contraception and pregnancy avoidance 
procedures).
7. Understands the study procedures in the ICF, and be willing and able to comply with the 
protocol.
7.2
Exclusion Criteria
Subjects must not be enrolled in the study if they meet any of the following criteria:
1. Is mentally or legally incapacitated or has significant emotional problems at the time of the 
screening visit or expected during the conduct of the study.
2. History or presence of clinically significant endocrine, gastrointestinal (including motility
disorder and intestinal obstruction), cardiovascular, hematological, hepatic, immunological,
renal, respiration, genitourinary, major neurological (including stroke and chronic seizures), or 
malignancy, or any other clinically significant abnormalities or disease in the opinion of the 
Investigator or designee.
3. History of any illness that, in the opinion of the Investigator or designee, might confound the 
results of the study or poses an additional risk to the subject by their participation in the study.
4. History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
dy:
ms
dy:
ast 3 mo
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ast 3 mo
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TAK-906
Study ID TAK-906-1007
Page 34 of 81
Protocol
30 March 2020
5. History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related 
compounds.
6. Positive urine drug or cotinine, or alcohol results at screening or first check-in.
7. Positive results at screening for HIV, HBsAg, or HCV.
8. QTcF interval is >450 msec or ECG findings are deemed abnormal with clinical significance 
by the Investigator or designee at screening.
9. Estimated creatinine clearance <90 mL/min at screening.
10. Has tattoo(s) or scarring at or near the site of IV infusion or any other condition which may 
interfere with infusion site examination, in the opinion of the Investigator.
11. Subject has infrequent bowel movements (less than approximately once per day) within 
30 days prior to first dosing.
12. Recent history of abnormal bowel movements, such as diarrhea, loose stools, or constipation, 
within 2 weeks of first dosing.
13. Has received radiolabeled substances or has been exposed to radiation sources within 
12 months of first dosing or is likely to receive radiation exposure or radioisotopes within 
12 months of last dosing such that participation in this study would increase their total 
exposure beyond the recommended levels considered safe (ie, weighted annual limit 
recommended by the ICRP of 3000 mrem).
14. Unable to refrain from or anticipates the use of:

Any drug, including prescription and non-prescription medications, herbal remedies, or 
vitamin supplements within 14 days prior to the first dosing and throughout the study. 
Acetaminophen (up to 2 g per 24 hr period) and Milk of Magnesia® (ie, magnesium 
hydroxide [≤ 60 mL per day after Day 3 in Period 1 and after Day 8 in Period 2]) may be 
permitted during the study, only after dosing, if necessary to treat AEs. Additional 
administration of Milk of Magnesia® may be administered on other days at discretion of 
the Investigator. 

Any drugs known to significantly affect the absorption, distribution, metabolism or 
elimination of TAK-906 within 28 days prior to the first dosing and throughout the study. 
Appropriate sources (eg, Flockhart TableTM) will be consulted to confirm lack of 
PK/pharmacodynamics interaction with study drug.
15. Has been on a diet incompatible with the on-study diet, in the opinion of the Investigator or 
designee, within the 30 days prior to the first dosing and throughout the study.
16. Donation of blood or significant blood loss within 56 days prior to the first dosing.
17. Plasma donation within 7 days prior to the first dosing.
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 35 of 81
Protocol
30 March 2020
18. Participation in another clinical study within 30 days prior to the first dosing. The 30-day 
window will be derived from the date of the last blood collection or dosing, whichever is later, 
in the previous study to Day 1 of Period 1 of the current study.
7.3
Excluded Medications, Supplements, Dietary Products
Concomitant medications will be prohibited as listed in the exclusion criteria in Section 7.2.
If deviations occur, the Investigator or designee in consultation with the Sponsor if needed will 
decide on a case-by-case basis whether the subject may continue participation in the study.
All medications taken by subjects during the course of the study will be recorded.
Use of excluded agents (prescription or nonprescription) or dietary products is outline in Table 7.a
Table 7.a
Excluded Medications, Supplements, and Dietary Products
Category
Between Screening and First Dosing (Days 
-28 to predose [Day 1 Period 1])
Post-First Dosing (Day 1 
Period 1) to Follow-Up 
Alcohol
Prohibited from 48 hours prior to first dosing.
Prohibited until end of PK 
collection in Period 2
Xanthine and/or caffeine
Prohibited from 24 hours prior to first dosing a
Prohibited 24 hours prior to each 
dosing until end of PK collection 
in each period a
Medications
See Sections 7.2 and 7.3 b
See Sections 7.2 and 7.3 b
Food substance
Grapefruit/Seville orange
Prohibited from 14 days prior to first dosing 
Prohibited until end of PK 
collection in Period 2
a small amounts of caffeine derived from normal foodstuffs eg, 250 mL/8 oz./1 cup decaffeinated coffee or other 
decaffeinated beverage, per day, with the exception of espresso; 45 g/1.5 oz. chocolate bar, per day, would not be 
considered a deviation to this restriction.
b Acetaminophen (up to 2 g per 24 hr period) and Milk of Magnesia® (ie, magnesium hydroxide [≤ 60 mL per day after 
Day 3 in Period 1 and after Day 8 in Period 2]) may be permitted during the study, only after dosing, if necessary to 
treat AEs. Additional administration of Milk of Magnesia® may be administered on other days at discretion of the 
Investigator.
7.4
Diet, Fluid, Activity 
7.4.1
Diet and Fluid
Water (except water provided with each oral dosing) will be restricted 1 hour prior to and 1 hour 
after each oral study drug administration, but will be allowed ad libitum at all other times, when 
dosing occurs at the CRU. Other fluids may be given as part of meals and snacks but will be 
restricted at all other times throughout the confinement period.
Subjects will fast overnight for at least 10 hours prior to each oral study drug administration and 
will continue to fast for at least 4 hours following the oral study drug administration.
f Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 36 of 81
Protocol
30 March 2020
When confined, standard meals and snacks will be provided at appropriate times, except when 
they are required to fast. When confined in the CRU, subjects will be required to fast from all food 
and drink except water between meals and snacks.
7.4.2
Activity
Subjects will remain ambulatory or seated upright for the first 4 hours post oral dose, except when 
they are supine or semi-reclined for study procedures (eg, IV dosing on Day 1 of Period 1).
7.5
Criteria for Discontinuation or Withdrawal of a Subject
Subjects are free to withdraw from the study at any time for any reason. 
In addition, subjects may be withdrawn from the study by the Investigator or designee for the 
following reasons:

AEs.

Positive urine drug or alcohol results.

Difficulties in blood collection.
Any subject who experiences emesis within 3 hours post the oral dose will be discontinued, 
excluded from the final data analysis, and may be replaced with a new subject. In Period 2, if a 
subject experiences emesis after dosing, vomitus will need to be collected as much as possible and 
assayed for TRA.
A subject may be withdrawn by the Investigator (or designee) or the Sponsor if enrollment into the 
study is inappropriate, the study plan is violated, or for administrative and/or other safety reasons.
7.6
Procedures for Discontinuation or Withdrawal of a Subject
The Investigator may discontinue a subject’s study participation at any time during the study when 
the subject meets the study termination criteria described in Section 7.5. In addition, a subject may 
discontinue his participation without giving a reason at any time during the study. Should a 
subject’s participation be discontinued, the primary criterion for termination must be recorded by 
the Investigator. In addition, efforts should be made to perform all procedures scheduled for the 
end-of-study or early termination as described in Section 3.0
7.7
Subject Replacement
Discontinued subjects may be replaced at the discretion of the Sponsor and the Investigator. For a 
subject who drops out in Period 2, the replacement subject will be required to complete Period 2 
only.
For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 37 of 81
Protocol
30 March 2020
8.0
CLINICAL STUDY MATERIAL MANAGEMENT
8.1
Clinical Study Drug 
TAK-906 Capsule 
A single unlabeled 50 mg dose of TAK-906 capsules will be administered in Period 1 of the study. 
The drug product, TAK-906 capsules, for oral administration consists of TAK-906 maleate 
(TAK-906M), nominally 50 mg of TAK-906 (free base) per capsule, along with microcrystalline 
cellulose.
[14C]-TAK-906 IV Sterile Solution
An IV dose of approximately 100 μg [14C]-TAK-906 (~1 µCi) will be administered at ~0.75 hours 
(ie, ~45 min) after the TAK-906 oral dose in Period 1 of the study. 
The drug product is prepared in the CRU pharmacy as an IV solution. The solution will be 
prepared and labeled by licensed pharmacy staff according to the procedures outlined in the 
pharmacy manual. 
[14C]-TAK-906 Oral Solution
A dose of 50 mg [14C]-TAK-906 (~100 µCi) as an oral solution will be administered in Period 2 of 
the study.
The drug product is prepared in the CRU pharmacy as an oral solution. The solution will be 
prepared and labeled by licensed pharmacy staff according to the procedures outlined in the 
pharmacy manual.
8.1.1
Clinical Study Drug Labeling
All study drug preparations will be affixed with a clinical label in accordance with local regulatory 
requirements.
8.1.2
Clinical Study Drug Inventory and Storage
The Sponsor will supply sufficient quantities of TAK-906 products to allow completion of this 
study. 
Celerion will provide sufficient quantities of preparation and/or dilution solutions to allow 
completion of the study. The same lot number will be used throughout the study.
The lot numbers and expiration dates (where available) of the study drugs supplied will be
recorded in the final report.
Records will be made of the receipt, preparation, dispensing, and final disposition of the study 
drugs supplied. All TAK-906 products will be prepared and labeled by licensed pharmacy staff 
according to the procedures outlined in the pharmacy manual.
Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 38 of 81
Protocol
30 March 2020
8.1.3
Clinical Study Drug Blinding
This is an open-label study.
8.1.4
Randomization Code Creation and Storage 
Not applicable.
8.1.5
Clinical Trial Blind Maintenance/Unblinding Procedure
Not applicable.
8.1.6
Accountability and Destruction of Sponsor-Supplied Drugs
Not applicable.
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use


TAK-906
Study ID TAK-906-1007
Page 39 of 81
Protocol
30 March 2020
9.0
STUDY PROCEDURES
9.1
Administrative Procedures
The purpose of the study, the procedures to be carried out and the potential hazards will be 
described to the subjects in non-technical terms. Subjects will be required to read, sign and date an 
ICF summarizing the discussion prior to screening, and will be assured that they may withdraw 
from the study at any time without jeopardizing their medical care.
Subjects will be given a copy of their signed ICF.
9.1.1
Assignment of Screening and Randomization Numbers 
Each subject will be assigned a unique identification number upon screening. Subjects who 
complete the study screening assessments and meet all the eligibility criteria will be assigned a 
unique identification number at the time of the first dosing, different from the screening number.
9.1.2
Study Drug Assignment
This is a fixed-sequence study. All subjects will receive the same treatments as detailed in Table 
6.a.
9.1.3
Inclusion and Exclusion 
Please refer to Sections 7.1 and 7.2.
9.1.4
Medical History/Demography
Medical history and demographic data, including name, sex, age, race, ethnicity, and history of 
tobacco use will be recorded.
9.1.5
Concomitant Medications
Concomitant medications will be prohibited as listed in Section 7.2 and in Section 7.3. All 
medications taken by subjects during the course of the study will be recorded.
9.2
Clinical Procedures and Assessments
The Schedule of Study Procedures (Section 3.0) summarizes the clinical procedures to be 
performed at each visit. Individual clinical procedures are described in detail below. Additional 
evaluations/testing may be deemed necessary by the Investigator or designee and/or the Sponsor 
for reasons related to subject safety.
For this study, the collection for blood, plasma, urine, and feces for TRA, TAK-906, M23, and 
[14C]-TAK-906 concentrations, and for metabolite profiling, as appropriate, are the critical 
parameter and need to be collected as close to the exact time point as possible. All other procedures 
should be completed as close to the prescribed/scheduled time as possible, but can be performed 
prior or after the prescribed/scheduled time.
Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 40 of 81
Protocol
30 March 2020
Any nonscheduled procedures required for urgent evaluation of safety concerns take precedence 
over all routine scheduled procedures.
9.2.1
Full Physical Exam
Full and abbreviated physical examination will be performed as outlined in the Schedule of Study 
Procedures (Section 3.0). An abbreviated physical examination will include at the minimum, 
examination of respiratory, cardiovascular, and gastrointestinal systems, with the option for 
further examination of additional systems as necessary based on reported symptoms/AEs. 
9.2.2
Height and Weight
Body height (cm) and weight (kg) will be reported as outlined in the Schedule of Study Procedures 
(Section 3.0).
9.2.3
BMI
BMI will be calculated based on the height and weight measured at screening.
9.2.4
Vital Signs
Single measurements of body temperature, respiratory rate, blood pressure, and pulse rate, will be 
measured as outlined in the Schedule of Study Procedures (Section 3.0). Additional vital signs 
may be taken at any other times, if deemed necessary.
Blood pressure and pulse rate measurements will be performed with subjects in a seated position, 
except when they are supine or semi-reclined because of study procedures and/or AEs (eg, nausea, 
dizziness) or if deemed necessary by the Investigator or designee. All vital sign assessments will 
be performed after the subjects have rested for at least 5 minutes.
Blood pressure, pulse rate, respiratory rate, and temperature will be measured within 24 hours 
prior to Day 1 oral dosing of each period for the predose time point. When scheduled postdose, 
vital signs will be performed within approximately 15 minutes of the scheduled time point.
9.2.5
12-Lead ECG
Single 12-lead ECGs will be performed as outlined in the Schedule of Study Procedures 
(Section 3.0). Additional ECGs may be taken at any other times, if deemed necessary by the 
Investigator or designee.
ECGs will be performed with subjects in a supine position. All ECG assessments will be 
performed after the subjects have rested for at least 5 minutes. All ECG tracings will be reviewed 
by the Investigator or designee.
ECGs will be measured within 24 hours prior to Day 1 oral dosing of each period for the predose 
time point. When scheduled postdose, ECGs will be performed within approximately 20 minutes 
of the scheduled time point.
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 41 of 81
Protocol
30 March 2020
9.2.6
Taste Questionnaire
Subjects will complete a taste questionnaire (Appendix A) evaluating the taste of the TAK-906 
oral solution administered in Period 2. The questionnaire will be completed within 5 minutes of 
dosing.
9.2.7
Study Drug Administration
TAK-906 oral capsule and [14C]-TAK-906 oral and IV solution will be provided as described in 
Section 8.1.
Subjects will be instructed not to crush, split, or chew the TAK-906 capsules.
Treatments A and B are described as follows: 
Treatment A:
50 mg TAK-906 capsules administered at Hour 0 on Day 1 followed by a 100 µg 
(~1 μCi) [14C]-TAK-906 IV infusion administered at Hour 0.75 for approximately 
15 minutes (Period 1).
Treatment B:
50 mg (~100 μCi) [14C]-TAK-906 oral solution administered at Hour 0 on Day 1 
(Period 2).
The oral doses of TAK-906 and [14C]-TAK-906 will be administered following an overnight fast 
with approximately 240 mL of water. The total volume of liquid administered will not exceed 
240 mL. The exact clock time of oral dosing will be recorded. 
The start and end time of the IV infusion will be recorded.
The pharmacy at the CRU will provide for each subject, the IV dose and the oral capsule dose (in 
individual unit dose containers) for dosing in Period 1, and the oral solution dose (prepared in a 
dosing container) for dosing in Period 2.
9.2.8
AE Monitoring
Subjects will be monitored throughout the study for AEs to the study formulations and/or 
procedures as described in Section 10.0.
9.2.9
Laboratory Procedures and Assessments
All tests listed below will be performed as outlined in the Schedule of Study Procedures 
(Section 3.0). In addition, laboratory safety tests may be performed at various unscheduled time 
points, if deemed necessary by the Investigator or designee.
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TAK-906
Study ID TAK-906-1007
Page 42 of 81
Protocol
30 March 2020
9.2.9.1
Clinical Laboratory Tests
Hematology
Hematology will consist of the following tests:
Hemoglobin
Red blood cell count
Hematocrit
Platelet count
Total and differential leukocyte count
Chemistry* 
Chemistry evaluations will consist of the following standard chemistry panel:
Total protein
Sodium
Blood urea nitrogen
Potassium
Bilirubin (total and direct)
Chloride
Alkaline phosphatase
Glucose
Aspartate aminotransferase ***
Creatinine**
Alanine aminotransferase***
Albumin
*
Serum chemistry tests will be performed after at least a 8-hour fast; however, in case of dropouts or rechecks, subjects 
may not have fasted for 8 hours prior to the serum chemistry sample is taken.
**
At screening, creatinine clearance will be calculated using the Cockcroft-Gault formula.
***
Coagulation tests (prothrombin/international normalized ratio) will be performed if subjects have on-study aspartate 
aminotransferase or alanine aminotransferase elevated ≥3x the upper limit of normal.
Urinalysis
Urinalysis will consist of the following tests:
pH
Nitrite*
Specific gravity
Urobilinogen
Protein*
Leukocyte esterase*
Glucose
Ketones
Bilirubin
Blood*
*
If urinalysis is positive for protein, blood, nitrite and/or leukocyte esterase, a microscopic examination (for red 
blood cells, white blood cells, bacteria, casts, and epithelial cells) will be performed.
keda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 43 of 81
Protocol
30 March 2020
Other 
HIV test
Urine Drug Screen
HBsAg
Amphetamines
HCV (if antibody positive, confirm RNA negative)
Barbiturates
Urine alcohol screen
Benzodiazepines
Urine cotinine test
Cocaine
Cannabinoids
Opiates (includes morphine, heroin (diacetylmorphine), 
codeine, 6-acetylmorphine, dihydrocodeine, 
hydrocodone, thebaine, and, hydromorphone)
9.3
PK Samples
Primary specimen collection parameters are provided in Table 9.a. Instructions for plasma, urine, 
fecal samples processing and handling will be provided in a separate document(s). 
Table 9.a
Primary Specimen Collections
Specimen Name
Primary 
Specimen
Primary 
Specimen 
Derivative
Description of Intended Use
Sample 
Collection
Period 1
Plasma for TAK-906 and M23 
PK
Plasma
PK analysis
Mandatory
Plasma for TRA and 
[14C]-TAK-906 PK
Plasma
TRA and PK analysis
Mandatory
Urine for TRA and 
[14C]-TAK-906 PK 
Urine
TRA recovery and PK analysis
Mandatory
Feces for TRA and 
[14C]-TAK-906 PK 
Feces
TRA recovery and PK analysis
Mandatory
Period 2
Blood for TRA
Whole Blood
TRA
Mandatory
Plasma for TRA
Plasma
TRA
Mandatory
Plasma for TAK-906 and M23 
PK
Plasma
PK analysis
Mandatory
Plasma for TAK-906 
Metabolite Profiling
Plasma
Metabolite profiling
Mandatory
Urine for TRA 
Urine
TRA
Mandatory
Urine for TAK-906 and M23  
PK
Urine
PK analysis
Mandatory
Urine for TAK-906 Metabolite 
Profiling
Urine
Metabolite profiling
Mandatory
Feces for TRA
Feces
TRA
Mandatory
Feces for TAK-906 Metabolite 
Profiling
Feces
Metabolite profiling
Mandatory
mercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 44 of 81
Protocol
30 March 2020
9.3.1
PK Measurements 
9.3.1.1
Plasma and Whole Blood PK Measurements
PK parameters for whole blood and plasma radioactivity concentration equivalents (Period 2) and 
for plasma TAK-906 and metabolite concentrations (Periods 1 and 2) following oral 
administration will be calculated as follows, as appropriate and not limited to:
AUClast:
The area under the concentration versus time curve, from time 0 to the last 
observed non-zero concentration, as calculated by the linear trapezoidal 
method.
AUC∞:
The area under the concentration versus time curve, from time 0 
extrapolated to infinity. AUC∞is calculated as AUCt plus the ratio of the last 
measurable blood concentration to the elimination rate constant.
AUCt:
The area under the concentration-time curve from time 0 to time of the last 
common time point “t” at which total radioactivity and TAK-906 are 
quantifiable for all subjects. 
AUC%extrap:
Percent of AUC∞ extrapolated, represented as (1 - AUCt/AUC∞)*100.
CL/F:
Apparent total plasma clearance after oral (extravascular) administration, 
calculated as Dose/AUC0-∞ (parent only)
Cmax:
Maximum observed concentration.
Tmax:
Time to reach Cmax. If the maximum value occurs at more than one time 
point, Tmax is defined as the first time point with this value.
t½:
Apparent first-order terminal elimination half-life will be calculated as 
0.693/Kel.
Vz/F:
Apparent volume of distribution during the terminal elimination phase after 
oral (extravascular) administration, calculated as Dose/(AUC0-∞x Kel) 
(parent only)
Kel:
Kel is the apparent first-order terminal elimination rate constant calculated 
from a semi-log plot of the plasma concentration versus time curve. The 
parameter will be calculated by linear least-squares regression analysis 
using the maximum number of points in the terminal log-linear phase (eg, 
three or more non-zero plasma concentrations).
PK parameters for plasma concentrations of [14C]-TAK-906 and plasma radioactivity 
concentration equivalents following IV infusion (Period 1) will be calculated as follows, as 
appropriate and not limited to:
Commercial Use Only and Subject to the Applicable Terms of Use
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PK
er
PK


TAK-906
Study ID TAK-906-1007
Page 45 of 81
Protocol
30 March 2020
AUClast:
The area under the concentration versus time curve, from time 0 to the last 
observed non-zero concentration, as calculated by the linear trapezoidal 
method.
AUC∞:
The area under the concentration versus time curve, from time 0 
extrapolated to infinity. AUC∞is calculated as AUCt plus the ratio of the last 
measurable blood concentration to the elimination rate constant.
AUC%extrap:
Percent of AUC∞ extrapolated, represented as (1 - AUCt/AUC∞)*100.
Ceoi:
Concentration at the end of infusion.
CL:
Total clearance after intravenous administration.
t½:
Apparent first-order terminal elimination half-life will be calculated as 
0.693/Kel.
Kel:
The apparent first-order terminal elimination rate constant calculated from a 
semi-log plot of the plasma concentration versus time curve. The parameter 
will be calculated by linear least-squares regression analysis using the 
maximum number of points in the terminal log-linear phase (eg, three or 
more non-zero plasma concentrations).
Vss:
Volume of distribution during the terminal disposition phase after 
intravenous administration.
In all above-listed PK parameter calculations, no value for Kel, AUC∞, AUC%extrap, t½, CL/F, Vz/F, 
CL, or Vss will be reported for cases that do not exhibit a terminal log-linear phase in the 
concentration versus time profile and AUClast would be used for the further calculations, wherever 
necessary if AUC∞would not be available. 
No PK parameters will be calculated for subjects with detectable concentrations or radioactivity 
concentration equivalents at 2 or fewer consecutive time points. 
Individual and mean plasma concentration- or radioactivity concentration equivalent-time curves 
(both linear and log-linear) will be included in the final report.
The absolute bioavailability parameters for TAK-906 (Period 1) will be calculated as follows:
F:
Absolute bioavailability, calculated for plasma TAK-906, calculated as:
Dose (IV) x AUC∞(oral) / Dose (oral) x AUC∞ (IV).
%F:
Percent absolute bioavailability, calculated for plasma TAK-906 as 
[Dose (IV) x AUC∞(oral)] / [Dose (oral) x AUC∞(IV)] x 100.
If AUC∞ cannot not be calculated, AUClast will be used for the F determination.
For Non-Commercial Use Only and Subject to the Applicable Terms of Use
f
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%F:
If
e
If


TAK-906
Study ID TAK-906-1007
Page 46 of 81
Protocol
30 March 2020
9.3.1.2
Urine for PK Measurements
PK parameters for urine concentrations of [14C]-TAK-906 (Period 1; IV dose), for urine TAK-906 
and metabolite concentrations (Period 2), and for urine TRA (Periods 1 and 2) will be calculated as 
follows, as appropriate:
Aet1-t2:
Amount of unchanged drug excreted in the urine collection interval 
from t1 to t2.
Ae(UR):
Cumulative amount of TRA excreted in urine.
%Dose(UR):
Percent of administered radioactive dose excreted in urine within a 
given collection interval.
Cum%Dose(UR):
Cumulative percent of administered dose excreted in urine.
TRA excreted in urine will be presented in mass equivalent units.
9.3.1.3
Feces for PK Measurements
PK parameters for fecal concentrations of [14C]-TAK-906 (Period 1; IV dose) and for fecal TRA 
(Periods 1 and 2) will be calculated as follows:
Ae(FE):
Cumulative amount of TRA excreted in feces.
%Dose(FE):
Percent of administered radioactive dose excreted in feces within a given 
collection interval.
Cum%Dose(FE):
Cumulative percent of administered dose excreted in feces.
TRA excreted in feces will be presented in mass equivalent units.
9.3.1.4
Additional PK Measurements
PK parameter for combined urine and fecal [14C]-TAK-906 concentrations (Period 1; IV dose) and 
for urine and fecal TRA (Periods 1 and 2) will be calculated as follows:
Combined Cum%Dose:
Cumulative combined percent of administered dose excreted in urine 
and feces.
If technically feasible, cumulative [14C]-M23 excreted in urine and feces in Period 1 will be 
measured.
9.3.2
Biomarker Measurements 
Not applicable.
CCI
o the Applicable Terms of Use
d as
o
d as
nt
T
nterval
Ter
erval
d in uri
Appl
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m
bject to t


TAK-906
Study ID TAK-906-1007
Page 47 of 81
Protocol
30 March 2020
9.3.3
PGx Measurements
Not applicable. 
9.3.4
Confinement
In Period 1, subjects will be housed on Day -1, at the time indicated by the CRU until at least after 
the 96-hour blood draw and morning urine and fecal sample [when passed] (Day 5) and/or study 
procedures and if a discharge criterion is met, or up to Day 7. As per site preference, subjects may 
be confined throughout the washout period.
In Period 2, subjects will be housed on Day -1, at the time indicated by the CRU, and confined until 
at least after the 120-hour blood draw and morning urine and fecal sample [when passed] (Day 6) 
and/or study procedures and if a discharge criterion is met, or up to Day 15. 
All urine and fecal collections will be analyzed for radioactivity levels in both periods to determine 
if the discharge criteria are met. In each of the 2 consecutive periods, both urine and fecal samples 
have to be collected and counted for TRA, ie, if only urine or feces is collected in a day, this day is 
not considered to be one of the 2 consecutive intervals. Subjects will be eligible for discharge if 
they meet either of the following discharge criteria on Day 5 (Period 1) or Day 6 (Period 2):

≥80% (following Period 1 dose) and ≥90%* (following Period 2 dose) of the total dose of 
radioactivity administered has been recovered in the urine and feces; or 

There is ≤1% of the total administered radioactivity in each of two consecutive 24-hour 
intervals where both a urine and fecal sample is provided.
*The specified discharge criteria (ie, ≥90%) for Period 2 is implemented to maximize the 
radioactive dose recovered in the ADME period.
Subjects can be released after Day 15 collection of excreta in Period 2. After Day 15, if subjects 
have not met the discharge criteria, the subject may need to return to the clinic facility to collect 
urine and fecal samples in two blocks of 24-hour periods on Days 20, 21, or 22 and Days 27, 28, or 
29 based on the discretion of the Sponsor. Release of subjects who do not meet a discharge 
criterion by Day 15 in Period 2 will be reviewed on a case-by-case basis.
Since up to an approximate 24-hour time lag is anticipated for radioactivity counting of samples, 
actual subject release from the CRU may occur 1 day after discharge criteria are met.
At all times, a subject may be required to remain at the CRU for longer at the discretion of the 
Investigator or designee. 
The clinic will contact all subjects (including subjects who terminate the study early) via phone 
call, 30 ± 2 days after the last study drug administration to determine if any AEs have occurred 
since the last study visit.
Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 48 of 81
Protocol
30 March 2020
10.0
ADVERSE EVENTS
10.1
Definitions and Elements of AEs
An AE is defined as any untoward medical occurrence in a clinical investigation subject who has 
signed informed consent to participate in a study; it does not necessarily have to have a causal 
relationship with the treatment.
An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or 
not it is considered related to the drug.
An untoward finding generally may:

Indicate a new diagnosis or unexpected worsening of a preexisting condition. (Intermittent 
events for pre-existing conditions or underlying disease should not be considered AEs.)

Necessitate therapeutic intervention.

Require an invasive diagnostic procedure.

Require discontinuation or a change in dose of study medication or a concomitant medication.

Be considered unfavorable by the Investigator for any reason.
Diagnoses versus signs and symptoms:

Each event should be recorded to represent a single diagnosis. Accompanying signs (including 
abnormal laboratory values or ECG findings) or symptoms should NOT be recorded as 
additional AEs. If a diagnosis is unknown, sign(s) or symptom(s) should be recorded 
appropriately as an AE(s).
Laboratory values and ECG findings:

Changes in laboratory values or ECG parameters maybe considered AEs if they are judged to 
be clinically significant (ie, if some action or intervention is required or if the Investigator 
judges the change to be beyond the range of normal physiologic fluctuation). A laboratory 
re-test and/or continued monitoring of an abnormal value are not considered an intervention. In 
addition, repeated or additional noninvasive testing for verification, evaluation or monitoring 
of an abnormality is not considered an intervention.

If abnormal laboratory values or ECG findings are the result of pathology for which there is an 
overall diagnosis (eg, increased creatinine in renal failure), the diagnosis only should be 
reported appropriately as an AE.
Pre-existing conditions:

A pre-existing condition (present at the time of signing of informed consent) is considered a 
concurrent medical history condition and should NOT be recorded as an AE. A baseline 
evaluation (eg, laboratory test, ECG, X-ray, etc) should NOT be recorded as an AE unless 
related to a study procedure. However, if the subject experiences a worsening or complication 
Non-Commercial Use Only and Subject to the Applicable Terms of Use
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P
e
P


TAK-906
Study ID TAK-906-1007
Page 49 of 81
Protocol
30 March 2020
of such a concurrent medical history condition, the worsening or complication should be 
recorded appropriately as an AE (worsening or complication occurs after informed consent is 
signed). Investigators should ensure that the event term recorded captures the change in the 
condition (eg, “worsening of…”).

If a subject has a pre-existing episodic condition (eg, asthma, epilepsy), any occurrence of an 
episode should only be captured as an AE if the episodes become more frequent, serious, or 
severe in nature, that is, Investigators should ensure that the AE term recorded captures the 
change from Baseline in the condition (eg, “worsening of…”).

If a subject has a degenerative concurrent condition (eg, cataracts, rheumatoid arthritis), 
worsening of the condition should only be captured as an AE if occurring to a greater extent to 
that which would be expected. Again, Investigators should ensure that the AE term recorded 
captures the change in the condition (eg, “worsening of…”).
Worsening of AEs:

If the subject experiences a worsening or complication of an AE after the first administration of 
study medication or after any change in study medication, the worsening or complication 
should be recorded as a new AE. Investigators should ensure that the AE term recorded 
captures the change in the condition (eg, “worsening of…”).
Changes in severity of AEs:

If the subject experiences a change in the severity of an AE that is not associated with a change 
in study medication, the event should be captured once with the maximum severity recorded.
Preplanned surgeries or procedures:

Preplanned procedures (surgeries or therapies) that were scheduled prior to signing of 
informed consent are not considered AEs. However, if a preplanned procedure is performed 
early (eg, as an emergency) due to a worsening of the pre-existing condition, the worsening of 
the condition should be captured appropriately as an AE. Complications resulting from any 
planned surgery should be reported as AEs.
Elective surgeries or procedures:

Elective procedures performed where there is no change in the subject’s medical condition 
should not be recorded as AEs but should be documented in the subject’s source documents. 
Complications resulting from an elective surgery should be reported as AEs.
Overdose:

An overdose is defined as a known deliberate or accidental administration of investigational 
drug, to or by a study subject, at a dose above that which is assigned to that individual subject 
according to the study protocol. It is up to the Investigator or the reporting physician to decide 
whether a dose is to be considered an overdose, in consultation with the Sponsor.

All cases of overdose (with or without associated AEs) will be documented on an Overdose 
page of the (e)CRF, in order to capture this important safety information consistently in the 
akeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
nce of an
Term
nce of an
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captures
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
erty



TAK-906
Study ID TAK-906-1007
Page 50 of 81
Protocol
30 March 2020
database. AEs associated with an overdose will be documented on AE CRF(s) according to 
Section 10.0.

Serious adverse events (SAEs) of overdose should be reported according to the procedure 
outlined in Section 10.2.8.

In the event of drug overdose, the subject should be treated symptomatically.
10.1.1 SAEs
An SAE is defined as any untoward medical occurrence that at any dose:
1. Results in DEATH.
2. Is LIFE THREATENING.

The term “life threatening” refers to an event in which the subject was at risk of death at the 
time of the event; it does not refer to an event that hypothetically might have caused death 
if it were more severe.
3. Requires inpatient HOSPITALIZATION or prolongation of existing hospitalization.
4. Results in persistent or significant DISABILITY/INCAPACITY.
5. Is a CONGENITAL ANOMALY/BIRTH DEFECT.
6. Is an IMPORTANT MEDICAL EVENT that satisfies any of the following:

May require intervention to prevent items 1 through 5 above.

May expose the subject to danger, even though the event is not immediately life 
threatening or fatal or does not result in hospitalization.

Includes any event or synonym described in the Takeda Medically Significant AE List 
(Table 10.a).
ercial Use Only and Subject to the Applicable Terms of Use
subject 
ct to
subject 
othetica
bject
othetica
gation o
d S
gation o
Y/INCA
an
Y/INCA
DEFECT
Only
DEFECT
T that s
se O
T that s
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danger, 
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Property of Takeda: For Non-Comm
oes not 
mer
oes not 
or synon
Com
or synon


TAK-906
Study ID TAK-906-1007
Page 51 of 81
Protocol
30 March 2020
Table 10.a
Takeda Medically Significant AE List 
Term
Acute respiratory failure/acute respiratory 
distress syndrome
Hepatic necrosis
Acute liver failure
Torsade de pointes / ventricular fibrillation / 
ventricular tachycardia
Anaphylactic shock
Acute renal failure
Malignant hypertension
Pulmonary hypertension
Convulsive seizures
Pulmonary fibrosis
Agranulocytosis
Confirmed or suspected endotoxin shock
Aplastic anemia
Confirmed or suspected transmission of infectious agent by 
a medicinal product
Toxic epidermal necrolysis/
Stevens-Johnson syndrome
Neuroleptic malignant syndrome / malignant hyperthermia
Spontaneous abortion / stillbirth and fetal death
AEs that fulfill 1 or more of the serious criteria above are to be considered SAEs and should be 
reported and followed up in the same manner (see Sections 10.1 and 10.1.1).
10.1.2 Special Interest AEs
There were no AEs of special interest defined for reporting in this study.
10.2
AE Procedures
10.2.1 Assigning Severity/Intensity of AEs
The different categories of severity/intensity are:
Mild:
An adverse event that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere 
with usual activities of daily living.
Moderate:
An adverse event that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research 
participant.
Severe:
An adverse event that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention.
10.2.2 Assigning Causality of AEs
The relationship of each AE to study medication(s) will be assessed using the following 
categories:
Related:
An AE that follows a reasonable temporal sequence from administration of a 
drug (including the course after withdrawal of the drug), or for which a causal 
Commercial Use Only and Subject to the Applicable Terms of Use
f
shock
ppli
shock
mission of
Ap
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syndrome
to th
syndrome
on / stillb
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on / stillb
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to be co
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to be co
ions
d S
ions 10.
S
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for rep
On
for rep
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ity of A
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me
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Com
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Property of Takeda: For Non-C
ent or t
n-C
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Non
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An adv
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f T
ere:
10
e
10


TAK-906
Study ID TAK-906-1007
Page 52 of 81
Protocol
30 March 2020
relationship is at least a reasonable possibility, ie, the relationship cannot be 
ruled out, although factors other than the drug, such as underlying diseases, 
complications, concomitant drugs and concurrent treatments, may also be 
responsible.
Not Related:
An AE that does not follow a reasonable temporal sequence from administration 
of a drug and/or that can reasonably be explained by other factors, such as 
underlying diseases, complications, concomitant medications and concurrent 
treatments.
10.2.3 Start Date 
The start date of the AE is the date that the first signs/symptoms were noted by the subject and/or 
Investigator.
10.2.4 End Date 
The end date of the AE is the date at which the subject recovered, the event resolved but with 
sequelae or the subject died.
10.2.5 Pattern of Adverse Event (Frequency) 
Episodic AEs (eg, headache) or those which occur repeatedly over a period of consecutive days are 
intermittent. All other events are continuous.
10.2.6 Action Taken With Study Treatment

Drug withdrawn – a study medication is stopped due to the particular AE.

Dose not changed – the particular AE did not require stopping a study medication.

Unknown – only to be used if it has not been possible to determine what action has been taken.

Not applicable – a study medication was stopped for a reason other than the particular AE 
eg, the study has been terminated, the subject died, dosing with study medication had not yet 
started or dosing with study medication was already stopped before the onset of the AE.

Drug interrupted – the dose was interrupted due to the particular AE.
10.2.7 Outcome 

Recovered/resolved – subject returned to first assessment status with respect to the AE.

Recovering/resolving – the intensity is lowered by one or more stages: the diagnosis has or 
signs/symptoms have almost disappeared; the abnormal laboratory value improved, but has 
not returned to the normal range or to the baseline value; the subject died from a cause other 
than the particular AE with the condition remaining “recovering/resolving.”

Not recovered/not resolved – there is no change in the diagnosis, signs or symptoms; the 
intensity of the diagnosis, signs/symptoms or laboratory value on the last day of the observed 
r Non-Commercial Use Only and Subject to the Applicable Terms of Use
istratio
erm
istratio
uch as 
e Te
uch as 
concur
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e noted b
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occur rep
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Us
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Treatme
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Property of Takeda: 
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y o
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
e



TAK-906
Study ID TAK-906-1007
Page 53 of 81
Protocol
30 March 2020
study period has become worse than when it started; is an irreversible congenital anomaly; the 
subject died from another cause with the particular AE state remaining “Not recovered/not 
resolved.”

Recovered/ Resolved with sequelae – the subject recovered from an acute AE but was left with 
permanent/significant impairment (eg, recovered from a cardiovascular accident but with 
some persisting paresis).

Fatal – an AE that is considered as the cause of death.

Unknown – the course of the AE cannot be followed up due to hospital change or residence 
change at the end of the subject’s participation in the study.
10.2.8 Collection and Reporting of AEs, SAEs, Special Interest AEs, and Abnormal LFTs
10.2.8.1 Collection Period
Collection of AEs (ie, AEs, SAEs, Special Interest AEs, and Abnormal LFTs) will commence at 
the time the subject signs the informed consent. Routine collection of AEs will continue until the 
follow-up phone call on approximately 30 (± 2 days) days after the last dose of investigational 
product. For subjects who discontinue prior to the administration of study medication, AEs will be 
followed until the subject discontinues study participation. 
10.2.8.2 Reporting AEs
At each study visit, the Investigator will assess whether any subjective AEs have occurred. A 
neutral question, such as “How have you been feeling since your last visit?” may be asked. 
Subjects may report AEs occurring at any other time during the study. Subjects experiencing an 
SAE prior to the first exposure to investigational product must be monitored until the symptoms 
subside and any clinically relevant changes in laboratory values have returned to Baseline or there 
is a satisfactory explanation for the change. Nonserious AEs that begin prior to the first exposure 
to investigational product, related or unrelated to the study procedure, need not be followed-up for 
the purposes of the protocol.
All subjects experiencing AEs, whether considered associated with the use of the study medication 
or not, must be monitored until the symptoms subside and any clinically relevant changes in 
laboratory values have returned to Baseline or until there is a satisfactory explanation for the 
changes observed. All AEs will be documented in the AE page of the CRF, whether or not the 
Investigator concludes that the event is related to the drug treatment. The following information 
will be documented for each event:

Event term.

Start and end date and time.

Pattern of AE (frequency).

Severity/Intensity.
keda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
ft with
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


TAK-906
Study ID TAK-906-1007
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Protocol
30 March 2020

Causality (Investigator’s opinion of the causal relationship between the event and 
administration of study drug[s]).

Action taken with trial drug.

Outcome of event.

Seriousness.
10.2.8.3 Reporting SAEs
When an SAE occurs through the AE collection period it should be reported according to the 
procedure outlined below:
A Takeda SAE form must be completed, in English and signed by the Investigator immediately or 
within 24 hours of first onset or notification of the event. The information should be completed as 
fully as possible but contain, at a minimum:

A short description of the event and the reason why the event is categorized as serious.

Subject identification number.

Investigator’s name.

Name of the study medication(s).

Causality assessment.
The SAE form should be transmitted within 24 hours to the attention of the contact listed in 
Section 14.1.1.
Any SAE spontaneously reported to the Investigator following the AE collection period should be 
reported to the Sponsor if considered related to study participation.
Reporting of SAEs that begin before first administration of investigational product will follow the 
same procedure for SAEs occurring on treatment.
SAE Follow-Up
If information is not available at the time of the first report becomes available at a later date, the 
Investigator should complete a follow-up SAE form or provide other written documentation and 
fax it immediately within 24 hours of receipt. Copies of any relevant data from the hospital notes 
(eg, ECGs, laboratory tests, discharge summary, postmortem results) should be sent to the 
addressee, if requested.
All SAEs should be followed up until resolution or permanent outcome of the event. The timelines 
and procedure for follow-up reports are the same as those for the initial report.
10.2.8.4 Reporting Special Interest AEs 
There are no AEs of Special Interest defined for reporting in this study.
da: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 55 of 81
Protocol
30 March 2020
10.2.8.5 Reporting of Abnormal LFTs
If a subject is noted to have ALT or AST elevated >3 ×ULN on 2 consecutive occasions, the 
abnormality should be recorded as an AE. In addition, an LFT Increases CRF must be completed 
providing additional information on relevant recent history, risk factors, clinical signs and 
symptoms and results of any additional diagnostic tests performed.
If a subject is noted to have ALT or AST >3 ×ULN, concurrently with total bilirubin >2 ×ULN for 
which an alternative etiology has not been identified, the event should be recorded as an SAE and 
reported as per Section 10.2.8.3. The Investigator must contact the Medical Monitor for discussion 
of the relevant subject details and possible alternative etiologies, such as acute viral hepatitis A or 
B or other acute liver disease. Follow-up laboratory tests as described in Section 9.2.9 must also be 
performed. In addition, an LFT Increases CRF must be completed and transmitted with the Takeda 
SAE form (as per Section 10.2.9). 
10.2.9 Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities 
The Sponsor will be responsible for reporting all suspected unexpected serious adverse reactions 
(SUSARs) and any other applicable SAEs to regulatory authorities, Investigators and IRBs or 
IECs, as applicable, in accordance with national regulations in the countries where the study is 
conducted. Relative to the first awareness of the event by/or further provision to the Sponsor or 
Sponsor’s designee, SUSARs will be submitted within 7 days for fatal and life-threatening events 
and 15 days for other serious events, unless otherwise required by national regulations. The 
Sponsor will also prepare an expedited report for other safety issues where these might materially 
alter the current benefit-risk assessment of an investigational medicinal product or that would be 
sufficient to consider changes in the investigational medicinal products administration or in the 
overall conduct of the trial. The investigational site also will forward a copy of all expedited 
reports to his or her IRB or IEC in accordance with national regulations.
and Subject to the Applicable Terms of Use
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mm
EC in ac


TAK-906
Study ID TAK-906-1007
Page 56 of 81
Protocol
30 March 2020
11.0
STATISTICAL METHODS
11.1
Statistical and Analytical Plans
Detailed methodology for summary and statistical analyses of the data collected in this study will 
be documented in a SAP. The SAP will be prepared by Celerion and agreed upon with the 
Sponsor. This document may modify the plans outlined in the protocol; however, any major 
modifications of the primary endpoints definition and/or its analysis will also be reflected in a 
protocol amendment. Additional statistical analyses other than those described in this section may 
be performed if deemed appropriate. A clinical pharmacology analysis plan will also be generated 
for the study.
11.1.1 Analysis Sets
11.1.1.1 Safety Set
All subjects who received at least one dose of the study drug will be included in the safety 
evaluations.
11.1.1.2 PK Set
Samples from all subjects will be assayed even if the subjects do not complete the study. All 
subjects who comply sufficiently with the protocol and display an evaluable PK profile (eg, 
exposure to treatment, availability of measurements and absence of major protocol violations) will 
be included in the statistical analyses.
11.1.1.3 PD Set
Not applicable
11.1.2 Analysis of Demography and Other Baseline Characteristics
Continuous demographic data (ie, age, weight, height, and BMI) will be listed and summarized 
using appropriate summary statistics. Categorical demographic data (ie, gender, race, and 
ethnicity) will also be listed and tabulated.
11.1.3 PK Analysis
Descriptive statistics will be provided for the TRA (whole blood [Period 2], plasma, urine, feces 
[Periods 1 and 2], and if applicable, emesis [Period 2]), TAK-906 and metabolite concentrations 
and PK parameters (plasma and urine [Period 2]), and [14C]-TAK-906 concentrations (plasma, 
urine, feces [Period 1]), and the metabolite profile of TAK-906 (plasma, urine, feces [Period 2]), 
using appropriate summary statistics to be fully specified in the SAP.
PK parameters for whole blood, plasma, and TRA concentrations will be calculated as described in 
Section 9.3.1.1 and for urine and feces, as described in Sections 9.3.1.2 and 9.3.1.3, respectively. 
Further details would be specified in the Clinical Pharmacology Analysis Plan.
Non-Commercial Use Only and Subject to the Applicable Terms of Use
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and PK
urin
erty
urin
e


TAK-906
Study ID TAK-906-1007
Page 57 of 81
Protocol
30 March 2020
ABA of TAK-906 (Period 1) will be estimated using a ninety percent (90%) CI constructed for the 
difference in LS mean on the log scale for dose normalized AUC∞ between a single oral and the IV 
microtracer dose. Exponentiating the log-scale 90% CI will provide a 90% CI for the dose 
normalized AUC∞GMR; TAK-906 administered as oral dose / [14C]-TAK-906 administered as IV 
microtracer dose. AUClast will be analyzed in a similar fashion if AUC∞ cannot be calculated.
Mass balance will be calculated as a sum of the percent of the TRA recovered in urine and feces 
relative to the administered radioactivity dose minus any radioactivity lost due to emesis (if any 
occurred).
11.1.4 Analysis of Mass Balance
In Period 2, mass balance will be calculated as a sum of the percent of the TRA recovered in urine 
and feces relative to the administered radioactivity dose minus any radioactivity lost due to emesis 
(if any occurred).
11.1.5 Whole Blood to Plasma Partitioning Ratio 
In Period 2, the fraction of [14C]-radioactivity associated with red blood cells and other cellular 
components of whole blood will also be determined by using the concentration of 
[14C]-radioactivity in whole blood and plasma to calculate the whole blood:plasma partitioning 
ratio. 
11.1.6 Metabolite Profiling
In Period 2, TAK-906 metabolite profiling will be performed in plasma, urine, and feces 
containing sufficient amounts of radioactivity. The percent of dose represented by each of the 
metabolites, if any, will be calculated using the radioactivity concentration equivalent data 
combined with the metabolite profiling data. The percentage of each identified metabolite, if any, 
to total radioactivity in the plasma will be estimated based on plasma metabolite profiling data.
11.1.7 PD Analysis 
Not applicable.
11.1.8 Safety Analysis
All safety data will be populated in the individual CRFs. 
Dosing dates and times will be listed by subject.
Quantitative safety data as well as the difference to baseline, when appropriate, will be 
summarized using the appropriate descriptive statistics.
11.1.8.1 AEs
AEs will be coded using the most current version of Medical Dictionary for Regulatory Activities 
(MedDRA®) available at Celerion and summarized by treatment for the number of subjects 
and Subject to the Applicable Terms of Use
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s o
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sum
erty
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TAK-906
Study ID TAK-906-1007
Page 58 of 81
Protocol
30 March 2020
reporting the TEAE and the number of TEAEs reported. A by-subject AE data listing including 
verbatim term, coded term, treatment, severity, and relationship to treatment will be provided.
11.1.8.2 Clinical Laboratory Evaluation
Clinical laboratory results will be summarized by treatment and point of time of collection and a 
shift table describing out of normal range shifts will be provided.
11.1.8.3 Vital Signs
Vital signs assessments will be summarized by treatment and point of time of collection.
11.1.8.4
ECG Assessment
ECGs will be summarized by treatment and point of time of collection.
11.1.8.5 Other Safety Parameters
Physical examination findings will be presented in the data listings.
Medical history, and concurrent conditions will be coded using the MedDRA® and concomitant 
medications will be coded using the World Health Organization drug and will be listed by subject.
11.2
Interim Analysis and Criteria for Early Termination
NA
11.3
Determination of Sample Size
The sample size of 6 male healthy subjects was selected empirically without statistical 
considerations and is deemed adequate to meet the study objectives. In addition, this sample size is 
limited based on clinical considerations for this type of study and in order to limit exposure to 
radioactivity.
and Subject to the Applicable Terms of Use
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Property of Takeda: For Non-Co
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Com
onsider


TAK-906
Study ID TAK-906-1007
Page 59 of 81
Protocol
30 March 2020
12.0
QUALITY CONTROL AND QUALITY ASSURANCE
12.1
Study-Site Monitoring Visits
Monitoring visits to the study site will be made periodically during the study to ensure that all 
aspects of the protocol are followed. Source documents will be reviewed for verification of data 
recorded on the CRFs. Source documents are defined as original documents, data, and records. 
The Investigator and study site guarantee access to source documents by the Sponsor or its 
designee (CRO) and by the IRB or IEC.
All aspects of the study and its documentation will be subject to review by the Sponsor or the 
Sponsor’s designee (as long as blinding is not jeopardized), including but not limited to the 
Investigator’s Binder, trial drug, subject medical records, informed consent documentation, and 
review of CRFs and associated source documents. It is important that the Investigator and other 
study personnel are available during the monitoring visits and that sufficient time is devoted to the 
process.
12.2
Protocol Deviations
The Investigator should not deviate from the protocol, except where necessary to eliminate an 
immediate hazard to trial subjects. Should other unexpected circumstances arise that will require 
deviation from protocol-specified procedures, the Investigator should consult with the Sponsor or 
designee (and IRB or IEC, as required) to determine the appropriate course of action. There will be 
no exemptions (a prospectively approved deviation) from the inclusion or exclusion criteria.
Significant deviations include, but are not limited to, those that involve fraud or misconduct, 
increase the health risk to the subject, or confound interpretation of primary study assessment. 
12.3
Quality Assurance Audits and Regulatory Agency Inspections
The study site also may be subject to quality assurance audits by the Sponsor or designees. In this 
circumstance, the Sponsor-designated auditor will contact the site in advance to arrange an 
auditing visit. The auditor may ask to visit the facilities where laboratory samples are collected, 
where the medication is stored and prepared, and any other facility used during the study. In 
addition, there is the possibility that this study may be inspected by regulatory agencies, including 
those of foreign governments (eg, the FDA, the United Kingdom Medicines and Healthcare 
products Regulatory Agency, the Pharmaceuticals and Medical Devices Agency of Japan). If the 
study site is contacted for an inspection by a regulatory body, the Sponsor should be notified 
immediately. The Investigator guarantees access for quality assurance auditors to all study 
documents as described in Section 12.1.
f Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
ll
m
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of data 
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records
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TAK-906
Study ID TAK-906-1007
Page 60 of 81
Protocol
30 March 2020
13.0
ETHICAL ASPECTS OF THE STUDY
This study will be conducted with the highest respect for the individual participants (ie, subjects) 
according to the protocol, the ethical principles that have their origin in the Declaration of 
Helsinki, and the International Conference on Harmonisation (ICH) Harmonised Tripartite 
Guideline for GCP. Each Investigator will conduct the study according to applicable local or 
regional regulatory requirements and align his or her conduct in accordance with the 
“Responsibilities of the Investigator” that are listed in Appendix B. The principles of Helsinki are 
addressed through the protocol and through appendices containing requirements for informed 
consent and Investigator responsibilities.
13.1
IRB and/or IEC Approval
IRBs and IECs must be constituted according to the applicable state and federal/local requirements 
of each participating region. The Sponsor or designee will require documentation noting all names 
and titles of members who make up the respective IRB or IEC. If any member of the IRB or IEC 
has direct participation in this study, written notification regarding his or her abstinence from 
voting must also be obtained. Those Americas sites unwilling to provide names and titles of all 
members due to privacy and conflict of interest concerns should instead provide a Federal Wide 
Assurance Number or comparable number assigned by the Department of Health and Human 
Services.
The Sponsor or designee will supply relevant documents for submission to the respective IRB or 
IEC for the protocol’s review and approval. This protocol, the Investigator’s Brochure, a copy of 
the informed consent form, and, if applicable, subject recruitment materials and/or advertisements 
and other documents required by all applicable laws and regulations, must be submitted to a 
central or local IRB or IEC for approval. The IRB’s or IEC’s written approval of the protocol and 
subject informed consent must be obtained and submitted to the Sponsor or designee before 
commencement of the study (ie, before shipment of the Sponsor-supplied drug or study specific 
screening activity). The IRB or IEC approval must refer to the study by exact protocol title, 
number, and version date; identify versions of other documents (eg, informed consent form) 
reviewed; and state the approval date. The Sponsor will ship drug/notify site once the Sponsor has 
confirmed the adequacy of site regulatory documentation and, when applicable, the Sponsor has 
received permission from competent authority to begin the trial. Until the site receives 
drug/notification no protocol activities, including screening, may occur.
Sites must adhere to all requirements stipulated by their respective IRB or IEC. This may include 
notification to the IRB or IEC regarding protocol amendments, updates to the informed consent 
form, recruitment materials intended for viewing by subjects, local safety reporting requirements, 
reports and updates regarding the ongoing review of the study at intervals specified by the 
respective IRB or IEC, and submission of the Investigator’s final status report to IRB or IEC. All 
IRB and IEC approvals and relevant documentation for these items must be provided to the 
Sponsor or its designee.
Subject incentives should not exert undue influence for participation. Payments to subjects must 
be approved by the IRB or IEC and Sponsor.
f Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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of Helsi
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TAK-906
Study ID TAK-906-1007
Page 61 of 81
Protocol
30 March 2020
13.2
Subject Information, Informed Consent, and Subject Authorization
Written consent documents will embody the elements of informed consent as described in the 
Declaration of Helsinki and the ICH Guidelines for GCP and will be in accordance with all 
applicable laws and regulations. The informed consent form, subject authorization form (if 
applicable), and subject information sheet (if applicable) describe the planned and permitted uses, 
transfers, and disclosures of the subject’s personal and personal health information for purposes of 
conducting the study. The informed consent form and the subject information sheet (if applicable) 
further explain the nature of the study, its objectives, and potential risks and benefits, as well as the 
date informed consent is given. The informed consent form will detail the requirements of the 
participant and the fact that he is free to withdraw at any time without giving a reason and without 
prejudice to his or her further medical care.
The Investigator is responsible for the preparation, content, and IRB or IEC approval of the 
informed consent form and, if applicable, the subject authorization form. The informed consent 
form, subject authorization form (if applicable), and subject information sheet (if applicable) must 
be approved by both the IRB or IEC and the Sponsor prior to use.
The informed consent form, subject authorization form (if applicable), and subject information 
sheet (if applicable) must be written in a language fully comprehensible to the prospective subject. 
It is the responsibility of the Investigator to explain the detailed elements of the informed consent 
form, subject authorization form (if applicable), and subject information sheet (if applicable) to the 
subject. Information should be given in both oral and written form whenever possible and in the 
manner deemed appropriate by the IRB or IEC. In the event the subject is not capable of rendering
adequate written informed consent, then the subject’s legally acceptable representative may 
provide such consent for the subject in accordance with applicable laws and regulations.
The subject, or the subject’s legally acceptable representative, must be given ample opportunity to: 
(1) inquire about details of the study, and (2) decide whether or not to participate in the study. If the 
subject, or the subject’s legally acceptable representative, determines he or she will participate in 
the study, then the informed consent form and subject authorization form (if applicable) must be 
signed and dated by the subject, or the subject’s legally acceptable representative, at the time of 
consent and prior to the subject entering into the study. The subject or the subject’s legally 
acceptable representative should be instructed to sign using their legal names, not nicknames, 
using blue or black ballpoint ink. The Investigator must also sign and date the informed consent 
form and subject authorization (if applicable) at the time of consent and prior to subject entering 
into the study; however, the Sponsor may allow a designee of the Investigator to sign to the extent
permitted by applicable law.
Once signed, the original informed consent form, subject authorization form (if applicable), and 
subject information sheet (if applicable) will be stored in the Investigator’s site file. The 
Investigator must document the date the subject signs the informed consent in the subject’s 
medical record. Copies of the signed informed consent form, the signed subject authorization form 
(if applicable), and subject information sheet (if applicable) shall be given to the subject.
eda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 62 of 81
Protocol
30 March 2020
All revised informed consent forms must be reviewed and signed by relevant subjects or the 
relevant subject’s legally acceptable representative in the same manner as the original informed 
consent. The date the revised consent was obtained should be recorded in the subject’s medical 
record, and the subject should receive a copy of the revised informed consent form.
Subjects who consented and provided a PGx sample for DNA and RNA analysis can withdraw 
their consent and request disposal of a stored sample at any time prior to analysis. Notify Sponsor 
of consent withdrawal.
13.3
Subject Confidentiality
The Sponsor and designees affirm and uphold the principle of the subject’s right to protection 
against invasion of privacy. Throughout this study, a subject’s source data will only be linked to 
the Sponsor’s clinical study database or documentation via a unique identification number. As 
permitted by all applicable laws and regulations, limited subject attributes, such as sex, age, or date 
of birth, and subject initials may be used to verify the subject and accuracy of the subject’s unique 
identification number.
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the Sponsor 
requires the Investigator to permit its monitor or designee’s monitor, representatives from any 
regulatory authority (eg, FDA, Medicines and Healthcare products Regulatory Agency, 
Pharmaceuticals and Medical Devices Agency), the Sponsor’s designated auditors, and the 
appropriate IRBs and IECs to review the subject’s original medical records (source data or 
documents), including, but not limited to, laboratory test result reports, ECG reports, admission 
and discharge summaries for hospital admissions occurring during a subject’s study participation, 
and autopsy reports. Access to a subject’s original medical records requires the specific 
authorization of the subject as part of the informed consent process (see Section 13.2).
Copies of any subject source documents that are provided to the Sponsor must have certain 
personally identifiable information removed (ie, subject name, address, and other identifier fields 
not collected on the subject’s CRF).
13.4
Publication, Disclosure, and Clinical Trial Registration Policy
13.4.1 Publication and Disclosure
The Investigator is obliged to provide the Sponsor with complete test results and all data derived 
by the Investigator from the study. During and after the study, only the Sponsor may make study 
information available to other study Investigators or to regulatory agencies, except as required by 
law or regulation. Except as otherwise allowable in the clinical study site agreement, any public 
disclosure (including publicly accessible websites) related to the protocol or study results, other 
than study recruitment materials and/or advertisements, is the sole responsibility of the Sponsor.
The Sponsor may publish any data and information from the study (including data and information 
generated by the investigator) without the consent of the Investigator. Manuscript authorship for 
any peer-reviewed publication will appropriately reflect contributions to the production and 
review of the document. All publications and presentations must be prepared in accordance with 
y of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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sc
t


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this section and the Clinical Study Site Agreement. In the event of any discrepancy between the 
protocol and the Clinical Study Site Agreement, the Clinical Study Site Agreement will prevail.
13.4.2 Clinical Trial Registration 
In order to ensure that information on clinical trials reaches the public in a timely manner and to 
comply with applicable laws, regulations and guidance, Takeda will, at a minimum register all 
interventional clinical trials it Sponsors anywhere in the world on ClinicalTrials.gov and/or other 
publicly accessible websites before start of study, as defined in Takeda Policy/Standard. Takeda 
contact information, along with Investigator’s city, state (for Americas Investigators), country, and 
recruiting status will be registered and available for public viewing. 
For some registries, Takeda will assist callers in locating study sites closest to their homes by 
providing the Investigator name, address, and phone number to the callers requesting trial 
information. Once subjects receive Investigator contact information, they may call the site 
requesting enrollment into the trial. The investigative sites are encouraged to handle the trial 
inquiries according to their established subject screening process. If the caller asks additional 
questions beyond the topic of trial enrollment, they should be referred to the Sponsor.
Any Investigator who objects to the Sponsor providing this information to callers must provide the 
Sponsor with a written notice requesting that their information not be listed on the registry site.
13.4.3 Clinical Trial Results Disclosure 
Takeda will post the results of clinical trials on ClinicalTrials.gov or other publicly accessible 
websites, as required by Takeda Policy/Standard, applicable laws and/or regulations.
13.5
Insurance and Compensation for Injury
Each subject in the study must be insured in accordance with the regulations applicable to the site 
where the subject is participating. If a local underwriter is required, then the Sponsor or Sponsor’s 
designee will obtain clinical study insurance against the risk of injury to study subjects. Refer to 
the study site agreement regarding the Sponsor’s policy on subject compensation and treatment for 
injury. If the Investigator has questions regarding this policy, he or she should contact the Sponsor 
or Sponsor’s designee.
Use Only and Subject to the Applicable Terms of Use
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designe


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14.0
ADMINISTRATIVE AND REFERENCE INFORMATION
14.1
Administrative Information
14.1.1 Study Contact Information 
Contact Type / Role
Contact
Serious adverse event and pregnancy reporting
PPD
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
Ter
T
App
Applicable T


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14.1.2 INVESTIGATOR AGREEMENT 
I confirm that I have read and that I understand this protocol, the Investigator’s Brochure, package 
insert, as appropriate, and any other product information provided by the Sponsor. I agree to 
conduct this study in accordance with the requirements of this protocol and also to protect the 
rights, safety, privacy, and well-being of study subjects in accordance with the following:

The ethical principles that have their origin in the Declaration of Helsinki.

International Conference on Harmonisation, E6 Good Clinical Practice: Consolidated 
Guideline.

All applicable laws and regulations, including, without limitation, data privacy laws and 
regulations.

Regulatory requirements for reporting serious adverse events defined in Section 10.2.9 of this 
protocol.

Terms outlined in the study site agreement.

Responsibilities of the Investigator (Appendix B).
I further authorize that my personal information may be processed and transferred in accordance 
with the uses contemplated in Appendix D of this protocol.
Signature of Investigator
Date
Investigator Name (print or type)
Investigator’s Title
Location of Facility (City, State/Provence)
Location of Facility (Country)
on-Commercial Use Only and Subject to the Applicable Terms of Use
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o
ge
t the
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t the
ng:
T
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on
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F
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ati
f T
ation o
f Ta
on o
Ta


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14.1.3 Study-Related Responsibilities 
The Sponsor will perform all study-related activities with the exception of those identified in the 
Study-Related Responsibilities template. The vendors identified for specific study-related 
activities will perform these activities in full or in partnership with the Sponsor.
14.1.4 List of Abbreviations
μCi
Microcurie
µg
Microgram
%Dose(FE)
Percent of administered radioactive dose excreted in feces within a given collection 
interval
%Dose(UR)
Percent of administered radioactive dose excreted in urine within a given collection 
interval
%F
Percent absolute oral bioavailability
ABA
Absolute bioavailability
ADME
Absorption, distribution, metabolism, and elimination
AE
Adverse event
Ae
Amount excreted
Aet1-t2
Amount of unchanged drug excreted in the urine collection interval from t1 to t2.
Ae(FE)
Amount of total radioactivity excreted in feces within a given collection interval
Ae(UR)
Amount of total radioactivity excreted in urine within a given collection interval
ALT
Alanine aminotransferase
AUC
Area under the concentration-time curve
AUC%extrap
Percent of AUC∞ extrapolated 
AUClast
Area under the concentration-time curve, from time 0 to the last observed non-zero 
concentration
AUCt
Area under the concentration versus time curve, from 0 to the time of the last common 
time point “t” at which plasma total radioactivity and plasma TAK-788 are quantifiable 
for all subjects
AUC∞
Area under the concentration-time curve, from time 0 extrapolated to infinity
AUC12
Area under the concentration-time curve, from time 0 to Hour 12 concentration
BBB
Blood brain barrier
BLQ
Below the limit of quantitation
BMI
Body mass index
bpm
Beats per minute
[14C]
Carbon-14; radiocarbon
Ceoi
Concentration at end of infusion
CFR
Code of Federal Regulations
CI
Confidence interval
CL/F
Apparent total plasma clearance after oral (extravascular) administration
Cmax
Maximum observed concentration 
CCI
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
hin a giv
App
hin a giv
ne within
the
ne within
eliminat
Subj
eliminat
creted in 
ly a
creted in 
ty excret
Only
ty excret
tivity ex
se O
tivity ex
erase
Us
erase
oncentra
ial U
oncentra
UC
r
UC∞
erc
∞extr
rci
extr
er the co
me
er the co
tration
mm
tration
ea under 
Com
ea under 
time poin
n-C
time poin
for all
Non
for all
Ar
N
Ar
m
o
m
[
t
[ 4C]
ty o
C]
C
erty
Ceoi
rty
eoi
C
e
C


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CRF
Case report form
CRU
Clinical Research Unit
Cum%Dose(FE):
Cumulative percent of administered dose excreted in feces.
Cum%Dose(UR):
Cumulative percent of administered dose excreted in urine.
CYP
Cytochrome P450
ECG
Electrocardiogram
F
Bioavailability
FDA
Food and Drug Administration
g
Gram
GCP
Good Clinical Practice
GMR
Geometric mean ratio
HBsAg
Hepatitis B surface antigen
HCV
Hepatitis C virus 
HIV
Human immunodeficiency virus
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Council for Harmonisation
ICRP
Commission on Radiological Protection
IEC
Independent Ethics Committee
IRB
Institutional Review Board
IV
Intravenous
Kel
Apparent first-order terminal elimination rate constant
kg
Kilogram
LFT
Liver function tests
LS
Least-squares
m2
Meters squared
MAD
Multiple ascending dose
MBq
Megabecquerel
MedDRA®
Medical Dictionary for Regulatory Activities®
mg
Milligram
min
Minute
mL
Milliliter
mrem
Millirem
msec
Millisecond
mSv
Millisievert
OATP
Organic anion transporting polypeptide 
Oz
Ounce
PD
Pharmacodynamic(s)
PK
Pharmacokinetic(s)
QTcF
QT interval corrected for heart rate using Fridericia’s formula
SAD
Single ascending dose
Commercial Use Only and Subject to the Applicable Terms of Use
tion
nd
tion
otection
y an
otection
ee
O
ee
d
er termin
l U
er termin
ion tests
merc
ion tests
quares
mm
quares
ters squa
Com
ters squa
Property of Takeda: For Non
Multiple
n-C
Multiple
Mega
Non
Mega
M
N
M
ec
of
ec
mSv
ty o
mSv
OAT
erty
OAT
O


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SAE
Serious adverse event
SAP
Statistical analysis plan
SUSARs
Suspected unexpected serious adverse reactions
t½
Apparent first-order terminal elimination half-life
TEAE
Treatment-emergent adverse event
tmax
Time to reach maximum observed concentration [Cmax]
TRA
Total radioactivity
ULN
Upper limit of normal
US
United States
USA
United States of America
Vz/F
Apparent volume of distribution during the terminal elimination phase after oral 
(extravascular) administration
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
nation ph
he A
nation ph


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15.0
DATA HANDLING AND RECORDKEEPING
The full details of procedures for data handling will be documented in the Data Management Plan. 
AEs, medical history, and concurrent conditions will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). Drugs will be coded using the World Health Organization Drug 
Dictionary.
15.1
CRFs (Electronic and Paper)
Completed CRFs are required for each subject who signs an informed consent.
The Sponsor or its designee will supply investigative sites with access to CRFs. The Sponsor will 
make arrangements to train appropriate site staff in the use of the CRF. These forms are used to 
transmit the information collected in the performance of this study to the Sponsor and regulatory 
authorities. CRFs must be completed in English. Data are transcribed directly onto CRFs.
After completion of the entry process, computer logic checks will be run to identify items, such as 
inconsistent dates, missing data, and questionable values. Queries may be issued by Takeda 
personnel (or designees) and will be answered by the site. 
Corrections are recorded in an audit trail that captures the old information, the new information, 
identification of the person making the correction, the date the correction was made, and the reason 
for change. Reasons for significant corrections should additionally be included. 
The Principal Investigator must review the CRFs for completeness and accuracy and must sign and 
date the appropriate CRFs as indicated. Furthermore, the Investigator must retain full 
responsibility for the accuracy and authenticity of all data entered on the CRFs.
After the lock of the clinical study database, any change of, modification of, or addition to the data 
on the CRFs should be made by the Investigator with use of change and modification records of 
the CRFs. The Principal Investigator must review the data change for completeness and accuracy, 
and must sign and date.
CRFs will be reviewed for completeness and acceptability at the study site during periodic visits 
by study monitors. The Sponsor or its designee will be permitted to review the subject’s medical 
and hospital records pertinent to the study to ensure accuracy of the CRFs. The completed CRFs 
are the sole property of the Sponsor and should not be made available in any form to third parties, 
except for authorized representatives of appropriate governmental health or regulatory authorities, 
without written permission of the Sponsor.
15.2
Record Retention
The Investigator agrees to keep the records stipulated in Section 15.1 and those documents that 
include (but are not limited to) the study-specific documents, the identification log of all 
participating subjects, medical records, temporary media such as thermal sensitive paper, source 
worksheets, all original signed and dated informed consent forms, subject authorization forms 
regarding the use of personal health information (if separate from the informed consent forms), 
electronic copy of CRFs, including the audit trail, and detailed records of drug disposition to 
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
r r 
Drug
ms 
Drug
RFs. Th
App
RFs. Th
These fo
e Ap
These fo
the Spo
the
the Spo
bed direc
to t
bed direc
will be ru
ject 
will be ru
ueries m
ubje
ueries m
e.
d
e.
es the ol
and
es the ol
the date
ly a
the date
shoul
Only
should
y
d
CRFs fo
se O
CRFs fo
Further
l Us
Further
thent
ial U
thentic
U
ic
y
m
y d
e
d
y ataba
merc
ataba
by
m
by the In
mme
the In
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m
y
vest
Com
vestigat
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igat
wed for c
Non
wed for c
s. The S
or N
s. The S
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propert
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enable evaluations or audits from regulatory authorities, the Sponsor or its designees. Any source 
documentation printed on degradable thermal sensitive paper should be photocopied by the site 
and filed with the original in the subject’s chart to ensure long-term legibility. Furthermore, ICH 
E6 Section 4.9.5 requires the Investigator to retain essential documents specified in ICH E6 
(Section 8) until at least 2 years after the last approval of a marketing application for a specified 
drug indication being investigated or, if an application is not approved, until at least 2 years after 
the investigation is discontinued and regulatory authorities are notified. In addition, ICH E6 
Section 4.9.5 states that the study records should be retained until an amount of time specified by 
applicable regulatory requirements or for a time specified in the Clinical Study Site Agreement 
between the Investigator and Sponsor.
Refer to the Clinical Study Site Agreement for the Sponsor’s requirements on record retention. 
The Investigator and the head of the institution should contact and receive written approval from 
the Sponsor before disposing of any such documents.
Applicable Terms of Use
H 
H 
cified 
erms
cified 
years aft
Ter
years aft
ICH
ble T
ICH E6
T
E6
me spec
able
me spec
y
p
y Si
lic
Si
he
te Ag
plica
te Ag
iti
lic
iti
nts on r
he A
nts on r
Property of Takeda: For Non-Commercial Use Only and Subject to t
ceive w
o the
ceive w


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16.0
REFERENCES
1. Parkman HP, Hasler WL, Fisher RS. American Gastroenterological A. American 
Gastroenterological Association technical review on the diagnosis and treatment of 
gastroparesis. Gastroenterology 2004;127(5):1592-622.
2. Camilleri M, Parkman HP, Shafi MA, Abell TL. Gerson L, American College of G. Clinical 
guideline: management of gastroparesis. Am J Gastroenterol 2013;108(1):18-37.
3. Hyett B, Martinez FJ, Gill BM, Mehra S, Lembo A, Kelly CP, et al. Delayed radionucleotide 
gastric emptying studies predict morbidity in diabetics with symptoms of gastroparesis. 
Gastroenterology 2009;137(2):445-52.
4. Takeda Pharmaceuticals, Inc. Global Investigator Brochure. Edition 3.0, Dec 2018.
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
Clinica
Ter
Clinica
radionu
cab
radionu
gastropa
plic
gastropa
n 3.0, D
the A
n 3.0, D


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17.0
APPENDICES
Appendix A
Taste Questionnaire
This assessment would be done within 5 minutes of completion of dosing in Period 2. Subjects will 
be isolated from other subjects during the evaluation session in such a way that they do not see 
each other’s facial impression or body gestures. Subjects will be asked to refrain from 
communicating their opinions in a manner that could bias other subjects. Talking will be restricted. 
The taste area will be monitored for compliance by the site personnel. 
Subject Number: ________
Treatment Period: ________
Please evaluate the following attributes by circling the number that best represents your response
TASTE:
1
Definitely 
disliked
2
Disliked 
moderately
3
Disliked 
slightly
4
Neither 
dislike or 
liked
5
Liked slightly
6
Liked 
moderately
7
Definitely 
liked
AFTERTASTE:
1
Definitely 
disliked
2
Disliked 
moderately
3
Disliked 
slightly
4
Neither 
dislike or 
liked
5
Liked slightly
6
Liked 
moderately
7
Definitely 
liked
Do you have any additional comments regarding this formulation? No ___ Yes __
If yes, please print your comments here: _________________________________________________
_________________________________________________________________________________
_________________________________________________________________________________
_________________________________________________________________________________
What is the taste of the product? Please use the following scale and circle all that applies
Sweetness
0 (nothing)
1
2
3
4
5 (Very 
strong)
Bitterness
0 (nothing)
1
2
3
4
5 (Very 
strong)
Sourness
0 (nothing)
1
2
3
4
5 (Very 
strong)
Saltiness
0 (nothing)
1
2
3
4
5 (Very 
strong)
Other
0 (nothing)
1
2
3
4
5 (Very 
strong)
Please describe other taste: 
Non-Commercial Use Only and Subject to the Applicable Terms of Use
s will 
ms o
s will 
t see 
erm
t see 
l be rest
ble T
l be rest
lic
ur respon
he A
ur respon
A
the
slightly
ect 
slightly
o
to
S
her 
ly
her 
like o
Only
like or
ly
roro
ly
oro
liked
e O
liked
nd
nd
nd
and
his formu
Use
his formu
________
al U
________
______
ci
______
_____
e
_____
______
mm
______
e
t? Please
Com
t? Please
mm
)
C
Property of Takeda: For Non-Co
Co
-C
othing)
r No
othing)
No
0 (not
a: F
0 (not
Fo
ed
ess
k
ess
ed
ed
ed
ed
Other
of T
Other
f T
perty
Plea
erty
Plea
rty
pe
pe
pe
pe
pe


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Appendix B
Responsibilities of the Investigator
Clinical research studies sponsored by the Sponsor are subject to ICH GCP and all the applicable 
local laws and regulations. The responsibilities imposed on Investigators by the FDA are 
summarized in the “Statement of Investigator” (Form FDA 1572), which must be completed and 
signed before the Investigator may participate in this study.
The Investigator agrees to assume the following responsibilities by signing a Form FDA 1572:
1. Conduct the study in accordance with the protocol.
2. Personally conduct or supervise the staff that will assist in the protocol.
3. If the Investigator/institution retains the services of any individual or party to perform 
trial-related duties and functions, the Investigator/institution should ensure that this individual 
or party is qualified to perform those trial-related duties and functions and should implement 
procedures to ensure the integrity of the trial-related duties and functions performed and any 
data generated.
4. Ensure that study related procedures, including study specific (nonroutine/nonstandard panel) 
screening assessments are NOT performed on potential subjects, prior to the receipt of written 
approval from relevant governing bodies/authorities.
5. Ensure that all colleagues and employees assisting in the conduct of the study are informed of 
these obligations.
6. Secure prior approval of the study and any changes by an appropriate IRB/IEC that conform to 
21 CFR Part 56, ICH, and local regulatory requirements.
7. Ensure that the IRB/IEC will be responsible for initial review, continuing review, and approval 
of the protocol. Promptly report to the IRB/IEC all changes in research activity and all 
anticipated risks to subjects. Make at least yearly reports on the progress of the study to the 
IRB/IEC, and issue a final report within 3 months of study completion.
8. Ensure that requirements for informed consent, as outlined in 21 CFR Part 50, ICH and local 
regulations, are met.
9. Obtain valid informed consent from each subject who participates in the study, and document 
the date of consent in the subject’s medical chart. Valid informed consent is the most current 
version approved by the IRB/IEC. Each informed consent form should contain a subject 
authorization section that describes the uses and disclosures of a subject’s personal 
information (including personal health information) that will take place in connection with the 
study. If an informed consent form does not include such a subject authorization, then the 
Investigator must obtain a separate subject authorization form from each subject or the 
subject’s legally acceptable representative.
10. Prepare and maintain adequate case histories of all persons entered into the study, including 
CRFs, hospital records, laboratory results, etc, and maintain these data for a minimum of 
2 years following notification by the Sponsor that all investigations have been discontinued or 
that the regulatory authority has approved the marketing application. The Investigator should 
da: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
d and
ms
d and
DA 1572
e Te
DA 1572
party
Ap
party to 
App
to 
y
Ap
y
ensure
he A
ensure
ct
o
ctio
o t
ions a
o th
ns a
d
t
d fu
t to
funct
to
nct
specific 
Subj
specific 
nt
d
ntia
d S
ial sub
d S
l sub
tie
a
ies.
and
s.
sist
Onl
sisting i
nly 
ing i
d any ch
Use
d any ch
gulatory
al U
gulatory
e respon
ercia
e respon
eport to 
me
eport to 
ects. Ma
omm
ects. Ma
final rep
Com
final rep
rements
Non
rements
e m
r N
e met.
No
et.
d infor
Fo
d infor
of cons
da: 
of cons
Taked
o
k
on appr
keda
n appr
thori
Take
thoriza
k
za
Property of T
inform
f Ta
inform
stud
y of
stud
I
y
I


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contact and receive written approval from the Sponsor before disposing of any such 
documents.
11. Allow possible inspection and copying by the regulatory authority of GCP-specified essential 
documents.
12. Maintain current records of the receipt, administration, and disposition of Sponsor-supplied 
drugs, and return all unused Sponsor-supplied drugs to the Sponsor. 
13. Report adverse reactions to the Sponsor promptly. In the event of an SAE, notify the Sponsor 
within 24 hours.
ble Terms of Use
iaial
o
l
upplied
Ter
upplied
Property of Takeda: For Non-Commercial Use Only and Subject to the Applica
otify the
cab
otify the


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Protocol
30 March 2020
Appendix C
Elements of the Subject Informed Consent
In seeking informed consent, the following information shall be provided to each subject:
1. A statement that the study involves research.
2. An explanation of the purposes of the research.
3. The expected duration of the subject’s participation.
4. A description of the procedures to be followed, including invasive procedures.
5. The identification of any procedures that are experimental.
6. The estimated number of subjects involved in the study.
7. A description of the subject’s responsibilities.
8. A description of the conduct of the study.
9. A statement describing the treatment(s) and the probability for random assignment to each 
treatment.
10. A description of the possible side effects of the treatment that the subject may receive.
11. A description of any reasonably foreseeable risks or discomforts to the subject and, when 
applicable, to an embryo, fetus, or nursing infant.
12. A description of any benefits to the subject or to others that reasonably may be expected from 
the research. When there is no intended clinical benefit to the subject, the subject should be 
made aware of this.
13. Disclosures of appropriate alternative procedures or courses of treatment, if any, that might be 
advantageous to the subject and their important potential risks and benefits.
14. A statement describing the extent to which confidentiality of records identifying the subject 
will be maintained, and a note of the possibility that regulatory agencies, auditor(s), IRB/IEC, 
and the monitor may inspect the records. By signing a written informed consent form, the 
subject or the subject’s legally acceptable representative is authorizing such access.
15. For research involving more than minimal risk, an explanation as to whether any compensation 
and an explanation as to whether any medical treatments are available if injury occurs and, if 
so, what they consist of or where further information may be obtained.
16. The anticipated prorated payment(s), if any, to the subject for participating in the study.
17. The anticipated expenses, if any, to the subject for participating in the study.
18. An explanation of whom to contact for answers to pertinent questions about the research 
(Investigator), subject’s rights, and IRB/IEC and whom to contact in the event of a 
research-related injury to the subject.
19. A statement that participation is voluntary, that refusal to participate will involve no penalty or 
loss of benefits to which the subject otherwise is entitled, and that the subject or the subject’s 
Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 76 of 81
Protocol
30 March 2020
legally acceptable representative may discontinue participation at any time without penalty or 
loss of benefits to which the subject is otherwise entitled.
20. The consequences of a subject’s decision to withdraw from the research and procedures for 
orderly termination of participation by the subject.
21. A statement that the subject or the subject’s legally acceptable representative will be informed 
in a timely manner if information becomes available that may be relevant to the subject’s 
willingness to continue participation in the study.
22. A statement that results of PGx analysis will not be disclosed to an individual, unless 
prevailing laws require the Sponsor to do so.
23. The foreseeable circumstances or reasons under which the subject’s participation in the study 
may be terminated.
24. A written subject authorization (either contained within the informed consent form or provided 
as a separate document) describing to the subject the contemplated and permissible uses and
disclosures of the subject’s personal information (including personal health information) for 
purposes of conducting the study. The subject authorization must contain the following 
statements regarding the uses and disclosures of the subject’s personal information:
a) that personal information (including personal health information) may be processed by or 
transferred to other parties in other countries for clinical research and safety reporting 
purposes, including, without limitation, to the following: (1) Takeda, its affiliates, and 
licensing partners; (2) business partners assisting Takeda, its affiliates, and licensing 
partners; (3) regulatory agencies and other health authorities; and (4) IRBs/IECs;
b) it is possible that personal information (including personal health information) may be 
processed and transferred to countries that do not have data protection laws that offer 
subjects the same level of protection as the data protection laws within this country; 
however, Takeda will make every effort to keep your personal information confidential, 
and your name will not be disclosed outside the clinic unless required by law;
c) that personal information (including personal health information) may be added to 
Takeda’s research databases for purposes of developing a better understanding of the 
safety and effectiveness of the study medication(s), studying other therapies for patients, 
developing a better understanding of disease, and improving the efficiency of future 
clinical studies;
d) that subjects agree not to restrict the use and disclosure of their personal information 
(including personal health information) upon withdrawal from the study to the extent that 
the restricted use or disclosure of such information may impact the scientific integrity of 
the research; and
e) that the subject’s identity will remain confidential in the event that study results are 
published.
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 77 of 81
Protocol
30 March 2020
25. Male subjects must use highly effective contraception (as defined in the informed consent) 
from signing the informed consent throughout the duration of the study and for 90 days after 
the last dose of study drug.
26. A statement that clinical trial information from this trial will be publicly disclosed in a publicly 
accessible website, such as ClinicalTrials.gov.
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
ublicly 
ms 
ublicly 


TAK-906
Study ID TAK-906-1007
Page 78 of 81
Protocol
30 March 2020
Appendix D
Investigator Consent to the Use of Personal Information 
Takeda will collect and retain personal information of Investigator, including his or her name, 
address, and other personally identifiable information. In addition, Investigator’s personal 
information may be transferred to other parties located in countries throughout the world (eg, the 
United Kingdom, United States, and Japan), including the following:

Takeda, its affiliates, and licensing partners.

Business partners assisting Takeda, its affiliates, and licensing partners.

Regulatory agencies and other health authorities.

IRBs and IECs.
Investigator’s personal information may be retained, processed, and transferred by Takeda and 
these other parties for research purposes including the following:

Assessment of the suitability of Investigator for the study and/or other clinical studies.

Management, monitoring, inspection, and audit of the study.

Analysis, review, and verification of the study results.

Safety reporting and pharmacovigilance relating to the study.

Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to the study.

Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to other medications used in other clinical studies that may contain 
the same chemical compound present in the study medication.

Inspections and investigations by regulatory authorities relating to the study.

Self-inspection and internal audit within Takeda, its affiliates, and licensing partners.

Archiving and audit of study records.

Posting Investigator site contact information, study details and results on publicly accessible 
clinical trial registries, databases, and websites.
Investigator’s personal information may be transferred to other countries that do not have data 
protection laws that offer the same level of protection as data protection laws in Investigator’s own 
country.
Investigator acknowledges and consents to the use of his or her personal information by Takeda 
and other parties for the purposes described above.
on-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 79 of 81
Protocol
30 March 2020
Appendix E
Pregnancy and Contraception
Contraception and Pregnancy Avoidance Procedure
Male Subjects and Their Female Partners
From signing of informed consent, throughout the duration of the study, and for 90 days after last 
dose of study drug, male subjects who are sexually active with a female partner of childbearing 
potential* must use barrier contraception (eg, condom with spermicide). In addition, they must be 
advised not to donate sperm throughout the duration of the study, and for 90 days after last dose of 
study drug. Females of childbearing potential who are partners of male subjects are also advised to 
use additional contraception as shown in the list containing highly effective contraception below. 
Total abstinence (no sexual intercourse) may be considered an acceptable method of birth control 
if it agrees with the subject’s preferred and usual lifestyle.
Definitions and Procedures for Contraception and Pregnancy Avoidance
The following definitions apply for contraception and pregnancy avoidance procedures.
* A woman is considered a woman of childbearing potential (WOCBP), ie, fertile, following 
menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization 
methods include hysterectomy, and bilateral oophorectomy. A postmenopausal state is defined as 
no menses for 12 months without an alternative medical cause.
The following procedures apply for contraception and pregnancy avoidance.
1. Highly effective methods of contraception are defined as “those, alone or in combination, that 
result in a low failure rate (ie, less than 1% failure rate per year when used consistently and 
correctly). Acceptable methods of contraception are: 

Non-Hormonal Methods: 
–
Intrauterine device (IUD).
–
Bilateral tubal occlusion.
–
Vasectomised subject (has received medical assessment of the surgical success).
–
True sexual abstinence, only if this is in line with the preferred and usual lifestyle of the 
subject. True abstinence is defined as refraining from heterosexual intercourse during 
the entire period of the study, from 1 month prior to the first dose until 90 days after the 
last dose.

Hormonal Methods:
–
Combined (estrogen and progestogen) hormonal contraception associated with 
inhibition of ovulation initiated at least 3 months prior to the first dose of study drug 
OR combined with a barrier method (male condom, female condom or diaphragm) if 
for shorter duration until she has been on contraceptive for 3 months;

Oral.
Use Only and Subject to the Applicable Terms of Use
after la
Term
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TAK-906
Study ID TAK-906-1007
Page 80 of 81
Protocol
30 March 2020

Intravaginal (eg, ring).

transdermal.
–
Progestogen-only hormonal contraception associated with inhibition of ovulation 
initiated at least 3 months prior to the first dose of study drug OR combined with a 
barrier method (male condom, female condom or diaphragm) if shorter till she has been 
on contraceptive for 3 months;

oral.

Injectable.

Implantable.
2. Unacceptable methods of contraception are:

Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods).

Spermicides only.

Withdrawal.

No method at all.

Use of female and male condoms together.

Cap/diaphragm/sponge without spermicide and without condom.
3. Subjects will be provided with information on highly effective methods of contraception as 
part of the subject informed consent process and will be asked to sign a consent form stating 
that they understand the requirements for avoidance of pregnancy and sperm donation during 
the course of the study.
4. During the course of the study, all subjects will receive continued guidance with respect to the 
avoidance of pregnancy and sperm donation as part of the study procedures. Such guidance 
should include a reminder of the following:
a.
contraceptive requirements of the study
b. reasons for use of barrier methods (ie, condom) in subjects with pregnant 
partners
c.
assessment of subject compliance through questions such as
i. Have you used the contraception consistently and correctly since the last visit?
ii. Have you forgotten to use contraception since the last visit?
General Guidance With Respect to the Avoidance of Pregnancy
Such guidance should include a reminder of the following:

contraceptive requirements of the study.
ercial Use Only and Subject to the Applicable Terms of Use
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TAK-906
Study ID TAK-906-1007
Page 81 of 81
Protocol
30 March 2020

reasons for use of barrier methods (ie, condom) in subjects with pregnant partners.

assessment of subject compliance through questions such as:
–
Have you used the contraception consistently and correctly since the last visit?
–
Have you forgotten to use contraception since the last visit? 
Procedures for Reporting Drug Exposure During Pregnancy and Birth Events
Women will not be included in this study.
If a female partner of a subject becomes pregnant during the subject’s participation in this study, 
the Sponsor must be contacted immediately by faxing a completed pregnancy form to the Takeda 
Global Pharmacovigilance department or designee (see Section 14.1.1). 
Any pregnancies in the partner of a male subject during the study or for 90 days after the last dose, 
should also be recorded following authorization from the subject’s partner.
If the female partner of a subject agrees to the primary care physician being informed, the 
Investigator should notify the primary care physician that the female partner became pregnant at 
the time when her partner (male subject) was participating in a clinical study and provide details of 
the study drug the subject received (blinded or unblinded, as applicable).
All pregnancies of female partners of subjects on active study drug (including comparator, if 
applicable) will be followed up to final outcome, using the pregnancy form. Pregnancies will 
remain blinded to the study team. The outcome, including any premature termination, must be 
reported to the Sponsor. An evaluation after the birth of the child will also be conducted.
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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ELECTRONIC SIGNATURES 
Signed by 
Meaning of Signature 
Server Date 
(dd-MMM-yyyy HH:mm ‘UTC’) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
090101d680d443c6
A Phase 1 Study to Assess Absolute Bioavailability of TAK-906 and to Characterize Mass Balance,
Pharmacokinetics, Metabolism, and Excretion of [14C]-TAK-906 in Healthy Male Subjects
Biostatistics Approval
01-Apr-2020 16:01 UTC
Clinical Science Approval
03-Apr-2020 00:52 UTC
Clinical Pharmacology Approval
03-Apr-2020 02:25 UTC
PPD
ble Terms of Use
e Te
ate 
T
ate 
ble T
HH:mm ‘U
ble 
HH:mm ‘U
Ter
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable
ble
:01 UTC
able
:01 UTC
020 00:52
ppli
020 00:52
-Apr-2020
he A
-Apr-2020

SAP_001.pdf: 


Other information as needed to protect confidentiality of Takeda or partners, personal
information, or to otherwise protect the integrity of the clinical study.
Title: A Phase 1 Study to Assess Absolute Bioavailability of TAK-906 and to Characterize Mass 
Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]-TAK-906 in Healthy Male 
Subjects
NCT Number: NCT04454918
SAP Approve Date: 10 August 2020
Certain information within this Statistical Analysis Plan has been redacted (ie, specific content is masked 
irreversibly from view with a black/blue bar) to protect either personally identifiable (PPD) information 
or company confidential information (CCI). 
This may include, but is not limited to, redaction of the following: 
Named persons or organizations associated with the study.
Proprietary information, such as scales or coding systems, which are considered confidential 
information under prior agreements with license holder.


1.0
TITLE PAGE
STATISTICAL ANALYSIS PLAN
STUDY NUMBER: TAK-906-1007
CELERION STUDY NUMBER: CA24217
A Phase 1 Study to Assess Absolute Bioavailability of TAK-906 and to Characterize Mass
Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]-TAK-906 in 
Healthy Male Subjects
Version: Final
Date: 10 August 2020
Prepared by:
Based on:
Protocol Dated: 30 March 2020
Protocol Clarification Letter Dated: 15 June 2020
da: For 
ol
F
ol Date
Fo
Date
l
F
l
P
rty of Taked
otocol
eda
otocol C
a
C
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a
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906 an
ct t
906 an
retion o
bjec
retion o
cts
Su
cts
al
nd
al
ugust 20
ly a
ugust 20
PPD


TAK-906-1007
Page 2 of 25
Statistical Analysis Plan 
10 August 2020
Study Title:
A Phase 1 Study to Assess Absolute Bioavailability of TAK-906 and to 
Characterize Mass Balance, Pharmacokinetics, Metabolism, and Excretion 
of [14C]-TAK-906 in Healthy Male Subjects
Property of Takeda: For Non-Commercial Use Only and Subject to 
s of Use
n 
s
n 
PPD


TAK-906-1007
Page 3 of 25
Statistical Analysis Plan 
10 August 2020
2.0
TABLE OF CONTENTS
1.0
TITLE PAGE ..................................................................................................................1
2.0
TABLE OF CONTENTS.................................................................................................3
List of In-Text Tables............................................................................................................4
3.0
LIST OF ABBREVIATIONS..........................................................................................5
4.0
OBJECTIVES .................................................................................................................7
4.1
Primary Objectives ....................................................................................................7
4.2
Secondary Objective..................................................................................................7
4.3
..............................................................................................7
4.4
Safety Objectives.......................................................................................................8
4.5
Study Design .............................................................................................................8
5.0
ANALYSIS ENDPOINTS.............................................................................................11
5.1
Primary Endpoint.....................................................................................................11
5.2
Secondary Endpoints ...............................................................................................11
5.3
.............................................................................................12
5.4
Safety Endpoints......................................................................................................12
6.0
DETERMINATION OF SAMPLE SIZE.......................................................................12
7.0
METHODS OF ANALYSIS AND PRESENTATION...................................................12
7.1
General Principles....................................................................................................12
7.2
Definition of Study Days .........................................................................................14
7.3
Analysis Sets ...........................................................................................................14
7.4
Study Information....................................................................................................14
7.5
Disposition of Subjects ............................................................................................14
7.6
Demographic and Other Baseline Characteristics.....................................................15
7.7
Medical History and Concurrent Medical Conditions...............................................15
7.8
Medication History and Concomitant Medications...................................................15
7.9
Study Drug Exposure and Compliance.....................................................................15
7.10
Efficacy Analysis.....................................................................................................15
7.11
Pharmacokinetic/Pharmacodynamic Analysis ..........................................................16
7.11.1 Pharmacokinetic Analysis ..................................................................................16
7.11.2 Pharmacodynamic Analysis ...............................................................................21
7.12
Other Outcomes.......................................................................................................21
7.13
Safety Analysis........................................................................................................21
7.13.1 Adverse Events..................................................................................................21
7.13.2 Clinical Laboratory Evaluations .........................................................................22
n-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906-1007
Page 4 of 25
Statistical Analysis Plan 
10 August 2020
7.13.3 Vital Signs .........................................................................................................23
7.13.4 12-Lead ECGs ...................................................................................................24
7.13.5 Physical Exams..................................................................................................24
7.13.6 Taste Questionnaire............................................................................................24
7.13.7 Overdose............................................................................................................24
7.14
Interim Analysis ......................................................................................................25
7.15
Preliminary Analysis................................................................................................25
7.16
Changes in the Statistical Analysis Plan...................................................................25
8.0
REFERENCES..............................................................................................................25
LIST OF IN-TEXT TABLES
Table 4.a
Study Schematic ................................................................................................10
Table 4.b
Planned TAK-906 and [14C]-TAK-906 Doses ....................................................11
Table 7.a
Plasma Sampling Schedule (Period 1 - ABA Study Period)................................16
Table 7.b
Urine and Fecal Sampling Schedule (Period 1 – ABA Study Period)..................17
Table 7.c
Blood and Plasma Sampling Schedule (Period 2 - ADME Study Period)............17
Table 7.d
Urine and Fecal Sampling Schedule (Period 2 - ADME Study Period) ...............19
Table 7.e
Collection of Vital Signs....................................................................................23
Table 7.f
Collection of Electrocardiograms .......................................................................24
Only and Subject to the Applicable Terms of Use
24
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TAK-906-1007
Page 5 of 25
Statistical Analysis Plan 
10 August 2020
3.0
LIST OF ABBREVIATIONS
ABA
absolute bioavailability; F (often expressed as a percent, ie, %F)
ADME
absorption, distribution, metabolism, and elimination
Ae
amount of drug eliminated
AE
adverse event
AUC
area under the curve
AUCextrap%
area under the concentration-time curve from the last quantifiable concentration to infinity 
calculated using the observed value of the last quantifiable concentration, expressed as a 
percentage of AUC.
AUC∞
area under the concentration-time curve from time 0 extrapolated to infinity calculated using the 
observed value of the last quantifiable concentration
AUClast
area under the concentration-time curve from time 0 to the time of the last quantifiable 
concentration
AUCt
area under the concentration-time curve from time 0 to time t at which the both the analyte of 
interest and total radioactivity are quantifiable, ie, time-matched AUC.
BLQ
below the limit of quantitation
BMI
body mass index
Ceoi
concentration at the end of infusion
CL/F
apparent clearance after extravascular administration, calculated using the observed value of the 
last quantifiable concentration.
CL
total clearance after intravenous administration, calculated using the observed value of the last 
quantifiable concentration.
CLR
renal clearance
Cmax
maximum observed concentration
CPAP
Clinical Pharmacology Analysis Plan
CRF
case report form
CRU
clinical research unit
CS
clinically significant
CSR
clinical study report
CV
coefficient of variation
DMP
Data Management Plan
ECG
electrocardiogram
Geom CV
geometric coefficient of variation
Geom Mean
geometric mean
ICF
informed consent form
ICH
International Conference on Harmonisation
IV
intravenous
ln
natural log
LSM
least-square means
Mean
arithmetic mean
MedDRA
Medical Dictionary for Regulatory Activities
PD
pharmacodynamics
or Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906-1007
Page 6 of 25
Statistical Analysis Plan 
10 August 2020
PI
Principal Investigator
PK
pharmacokinetics
SAE
serious adverse event
SD
standard deviation
SEM
standard error of the mean
SOC
system organ class
t1/2z
terminal disposition phase half-life
TEAE
treatment-emergent adverse event
TFL
tables, figures and listings
tmax
time of maximum observed concentration
Vss
volume of distribution at steady state after intravenous administration, calculated using the 
observed value of the last quantifiable concentration.
Vz/F
apparent volume of distribution during the terminal disposition phase after extravascular 
administration, calculated using the observed value of the last quantifiable concentration.
WHO
World Health Organization
Note: The PK parameters presented in the clinical study report (CSR) and in the in-text tables will be subscripted, 
whereas the PK parameters presented in the end-of-text tables will not be subscripted. In addition, AUC∞and z will 
be presented as AUCinf and Lambdaz in the end-of-text tables, respectively.
Subject to the Applicable Terms of Use
tion, calc
he A
tion, calc
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t to 
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Property of Takeda: For Non-Commercial Use Only and 
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TAK-906-1007
Page 7 of 25
Statistical Analysis Plan 
10 August 2020
4.0
OBJECTIVES
4.1
Primary Objectives
Period 1 (Absolute Bioavailability [ABA])

To determine the oral ABA (F) of TAK-906 following single oral (capsule) administration of 
50 mg of TAK-906 and single intravenous (IV) microtracer dose administration of 100 µg 
(~1 µCi) of [14C]-TAK-906.
Period 2 (Absorption, Distribution, Metabolism, and Elimination [ADME])

To determine the mass balance of TAK-906 in urine and feces following a single oral 
(solution) administration of 50 mg (~100 µCi) of [14C]-TAK-906.
4.2
Secondary Objective
Period 1 (ABA)

To determine the plasma pharmacokinetic (PK) parameters of TAK-906 and metabolite, 
M23, following single oral (capsule) administration of 50 mg of TAK-906.

To determine plasma PK parameters of total radioactivity following a single IV 
administration of 100 µg (~1 µCi) of [14C]-TAK-906.

To determine plasma PK parameters of [14C]-TAK 906 following a single IV administration 
of 100 µg (~1 µCi) of [14C]-TAK-906.
Period 2 (ADME)

To determine the plasma PK parameters of TAK-906 and metabolite M23 following a single 
oral (solution) administration of 50 mg (~100 µCi) of [14C]-TAK-906. 

To determine plasma and whole blood PK parameters for total radioactivity following a 
single oral (solution) administration of 50 mg (~100 µCi) of [14C]-TAK-906.
P
mmercial Use Only and Subject to the Applicable Terms of Use
istration
Te
istration
n of 100 
ble 
n of 100 
wing a s
he Ap
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ameters
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ameters
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CCI


TAK-906-1007
Page 8 of 25
Statistical Analysis Plan 
10 August 2020
4.4
Safety Objectives
Period 1 (ABA)

To evaluate the safety and tolerability of TAK-906, administered as a single oral dose 
(capsule) of TAK-906 followed by single IV microtracer dose administration of 
[14C]-TAK-906.
Period 2 (ADME)

To evaluate the safety and tolerability of TAK-906, administered as a single oral dose 
(solution) of [14C]-TAK-906.
4.5
Study Design
This is an open-label, 2-period, single-dose study in 6 male healthy subjects. 
On Day 1 of Period 1 (ABA Study Period), after at least a 10-hour fast, 6 subjects will receive a 
single unlabeled oral 50 mg dose of TAK-906 as capsules. At approximately 45 minutes 
(0.75 hour) post oral dosing (ie, 15 minutes prior to the median tmax for the oral unlabeled dose 
[~ 1.1 hours]), subjects will receive a 15-minute IV infusion of a microtracer dose of 100 µg 
(~1 µCi) [14C]-TAK-906. Serial blood sampling will be performed up to Day 5 (ie, Hour 96) to 
determine the PK of TAK-906 and M23 in plasma for the oral dose and total radioactivity and 
PK of [14C]-TAK-906 in plasma for the IV dose. Urine and fecal output will also be collected up 
to the morning of Day 5 (ie, Hour 96) to determine total radioactivity levels and [14C]-TAK-906 
PK and until a discharge criterion is met (ie, 80% or greater of the total dose of radioactivity 
administered is recovered in urine and fecal samples or the excretion of radioactivity in the urine 
and feces combined has declined to ≤1% of the total administered radioactivity per 24-hour 
interval for at least 2 consecutive intervals where both a urine and fecal sample are collected) but 
no less than Day 5 for total radioactivity excretion in urine and feces. 
In Period 1, subjects will be confined in the CRU for at least 5 days (until after the last PK 
sample and morning urine and fecal sample [when passed] are collected) and until a discharge 
criterion is met or up to Day 7. Subjects will return to the clinic on Day -1 of Period 2 for 
Check-in procedures. There will be a washout period of at least 7 days between the dose in 
Period 1 and the dose in Period 2. As per site preference, subjects may be confined throughout 
the washout period. 
On Day 1 of Period 2 (ADME Study Period), after at least a 10-hour fast, the subjects will 
receive a single dose of 50 mg (~100 μCi) [14C]-TAK-906 as an oral solution. Serial blood 
sampling and urine and feces output will be collected. The PK of TAK-906 and M23 will be 
determined in plasma and urine; plasma, whole blood, urine, and feces will be collected for total 
radioactivity determination; and plasma, urine, and feces will be collected to characterize the 
metabolite profiles of TAK-906. Complete urinary and fecal output will be collected until at least 
the morning of Day 6 (ie, Hour 120). Subjects will be confined in the clinic until at least this 
time and until a discharge criterion is met (ie, 90% or greater of the total dose of radioactivity 
administered is recovered in urine and fecal samples or the excretion of radioactivity in the urine 
and feces combined has declined to ≤1% of the total administered radioactivity per 24 hour 
f Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906-1007
Page 9 of 25
Statistical Analysis Plan 
10 August 2020
interval for at least 2 consecutive intervals where both a urine and fecal sample are collected) or 
up to 14 days postdose (ie, Day 15). After Day 15, if subjects have not met the discharge criteria, 
the subject may need to return to the CRU to collect urine and fecal samples in two blocks of 
24-hour periods on Days 20, 21, or 22 and Days 27, 28, or 29 based on the discretion of the 
Sponsor. Release of subjects who do not meet a discharge criterion by Day 15 in Period 2 will be 
reviewed on a case-by-case basis. In each of the 2 consecutive intervals, both urine and fecal 
samples have to be collected and counted for total radioactivity, ie, if only urine or feces is 
collected in a day, this day is not considered to be one of the 2 consecutive intervals. Since up to 
an approximate 24-hour time lag is anticipated for radioactivity counting of samples, actual 
subject release from the CRU may occur 1 day after discharge criteria are met.
In both Periods 1 and 2, any subject who experiences emesis within 3 hours post oral dose will 
be excluded in the final data analysis and will be replaced with a new subject. If a subject 
experiences emesis after dosing in Period 2, vomitus will need to be collected as much as 
possible and assayed for total radioactivity. For a subject who drops out in Period 2, the 
replacement subject will be required to complete Period 2 only. 
The clinic will contact all subjects (including subjects who terminate the study early) via phone 
call, 30 ± 2 days after the last study drug administration to determine if any adverse event (AEs) 
have occurred since the last study visit. The subjects may be requested to return the site for 
further safety assessment, due to reported AEs, at the Investigator’s discretion.
The study schematic is presented in Table 4.a.
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TAK-906-1007
Page 10 of 25
Statistical Analysis Plan 
10 August 2020
Table 4.a
Study Schematic
Screening
Treatment Period 1 a
Within 28 days of first 
dosing on Period 1
Day -1
Day 1
Days 2 - 7
Check-in
Oral Dosing at Hour 0
IV Dosing at Hour 0.75
Plasma, urine, and fecal sampling for ABA and safety monitoring for 
at least 96 hours post oral dose b
< - - - - - - - - - - - -  confinement b - - - - - - - - - - - - >
a  Dosing in each period will be separated by at least 7 days.
b Subjects will be confined in the clinic until at least the morning of Day 5 (until after the last PK sample and 
morning urine and fecal sample [when passed] are collected) and until a discharge criterion is met (ie, 80% or 
greater of the total dose of radioactivity administered is recovered in urine and fecal samples or the excretion of 
radioactivity in the urine and feces combined has declined to ≤1% of the total administered radioactivity per 24-hour 
interval for at least 2 consecutive intervals where both a urine and fecal sample are collected) or up to Day 7.
Treatment Period 2 c
Follow-up
Day -1
Day 1
Days 2 – 15
30 ± 2 days 
after last 
dosing
Check-in
Oral Dosing at Hour 0
Plasma, whole blood, urine, and fecal sampling for PK, total radioactivity, and 
metabolite profiling, and safety monitoring for at least 120 hours postdose, or up to 
approximately 336 hours postdose if discharge criteria are not met. Additional urine and 
feces samples may be taken in two blocks of Days 20, 21, 22 and Days 27, 28, and 29.
< - - - - - - - - - - - -  confinement d - - - - - - - - - - - - >
c Day -1 of Period 2 may be the same day as Day 7 of Period 1. 
d Subjects will be confined in the clinic until at least the morning of Day 6 and until discharge criterion is met 
(ie, 90% or greater of the total dose of radioactivity administered is recovered in urine and fecal samples or the 
excretion of radioactivity in the urine and feces combined has declined to ≤1% of the total administered radioactivity 
per 24-hour interval for at least 2 consecutive intervals where both a urine and fecal sample are collected) or up to 
14 days postdose (ie, Day 15). After Day 15, if subjects have not met the discharge criteria, the subject may need to 
return to the CRU to collect urine and fecal samples in two blocks of 24-hour periods on Days 20, 21, or 22 and 
Days 27, 28, or 29 based on the discretion of the Sponsor. Release of subjects who do not meet a discharge criterion 
by Day 15 will be reviewed on a case-by-case basis. Since up to an approximate 24-hour time lag is anticipated for 
radioactivity counting of samples, actual subject release from the CRU may occur 1 day after discharge criteria are 
met.
The treatment descriptions and planned dose levels of TAK-906 and [14C]-TAK-906 are outlined 
in Table 4.b.
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906-1007
Page 11 of 25
Statistical Analysis Plan 
10 August 2020
Table 4.b
Planned TAK-906 and [14C]-TAK-906 Doses
Dose
Route of Administration
Period 1 (Treatment A)
TAK-906
50 mg
Oral (capsule)
[14C]-TAK-906
100 µg (~1 µCi)
IVa
Period 2 (Treatment B)
[14C]-TAK-906
50 mg (~100 µCi)
Oral (solution)
aAdministered over 15 minutes from 0.75 to 1 hour after the oral dose of TAK-906.
5.0
ANALYSIS ENDPOINTS
5.1
Primary Endpoint
Period 1 (ABA):

Ratio of dose normalized AUCof TAK-906 and [14C]-TAK 906 in plasma (or AUClast in 
the case AUCis incalculable).
Period 2 (ADME):  

Cumulative recovery of radioactivity in urine (Cum%Dose[UR]) and feces 
(Cum%Dose[FE]) separately and both routes combined, expressed as a percent of total oral 
radioactive dose administered.
5.2
Secondary Endpoints
Period 1 (ABA):

PK parameters for oral TAK-906 and M23 in plasma: Cmax, tmax, AUClast, AUCextrap%, and 
t1/2z; for TAK-906 only in plasma: Vz/F and CL/F.

PK parameters for IV total radioactivity in plasma: Ceoi, tmax, AUClast, AUC∞, and t1/2z.

PK parameters for IV [14C]-TAK-906 in plasma: Ceoi, CL, Vss, AUClast, AUCextrap%, and t1/2z.
Period 2 (ADME):

PK parameters for plasma TAK-906 and M23: Cmax, tmax, AUClast, AUC∞, AUCextrap%, and 
t1/2z; for TAK-906 only: Vz/F and CL/F.

PK parameters for plasma and whole blood total radioactivity: Cmax, tmax, time-matched AUCt
(where t is the last common time point at which total radioactivity and TAK-906 are 
quantifiable in the plasma of all subjects), AUClast, AUC∞, and t1/2z.
da: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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PK


TAK-906-1007
Page 12 of 25
Statistical Analysis Plan 
10 August 2020
5.4
Safety Endpoints
Period 1 (ABA):

AE reporting, laboratory tests, electrocardiograms (ECGs), and vital sign parameters after 
administration of a single oral dose (capsule) of TAK-906 followed by single IV microtracer 
dose administration of [14C]-TAK-906.
Period 2 (ADME):

AE reporting, laboratory tests, ECGs, and vital sign parameters after a single oral dose 
(solution) of [14C]-TAK-906.
6.0
DETERMINATION OF SAMPLE SIZE
The sample size of 6 healthy male subjects was selected empirically without statistical 
considerations and is deemed adequate to meet the study objectives. In addition, this sample size 
is limited based on clinical considerations for this type of study and in order to limit exposure to 
radioactivity.
7.0
METHODS OF ANALYSIS AND PRESENTATION
7.1
General Principles 
All statistical analyses will be conducted using SAS® Version 9.4. All data recorded on the case 
report form (CRF) will be listed by subject. 
The number of observations (n) is presented as an integer (no decimal places), arithmetic mean 
(mean), median, and geometric mean (Geom Mean) values will be presented to 1 more level of 
precision than the individual values. Standard deviation (SD) and standard error of the mean 
(SEM) will be presented to 2 more levels of precision than the individual values. Minimum and 
maximum values will be presented to the same precision as the individual values. Arithmetic 
percent coefficient of variation (CV%) and geometric percent coefficient of variation (Geom 
CV%) will be presented to 1 decimal place. In the tables presenting summary statistics of 
Property of Takeda: For Non-Commercial Use Only and Subject to
Gs), an
Subj
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K-
d
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d Su
906 f
d vital s
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AMPLE
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CCI


TAK-906-1007
Page 13 of 25
Statistical Analysis Plan 
10 August 2020
concentration data, the number of observations that are above the level of quantification 
(n_ABLQ) will also be presented.
Geometric least-squares means (LSMs) will be reported with 1 more level of precision than the 
recorded data. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) around the 
ratio will be reported using 2 decimal places. 
Concentration values below the limit of quantitation (BLQ) will be presented as ‘BLQ’ in the 
concentration table listings and footnoted accordingly. BLQ values will be treated as zero for the 
calculation of summary statistics, the generation of concentration plots, and the calculation of PK 
parameters, unless they are obvious outliers (eg, BLQ value between measurable values), in 
which case they will be treated as missing.
A subject’s PK parameter data will be included in the listings but excluded from the descriptive 
statistics if one or more of the following criteria are met: 

A predose (0 hr) concentration is greater than 5% of that subject’s maximum concentration 
value in that period,

A subject did not meet inclusion/exclusion criteria that may have an effect on the PK (as 
determined by the Takeda Clinical Pharmacology Lead and Celerion Pharmacokinetic 
Scientist).

A subject deviates substantially from the protocol defined study procedures including but not 
limited to dosing, dose timing, sample collection, meal timing, etc. (as determined by the 
Takeda Clinical Pharmacology Lead and Celerion Pharmacokinetic Scientist).
The details on PK parameter calculations and TFLs for both Periods 1 and 2 will be outlined in 
the Clinical Pharmacology Analysis Plan (CPAP) and TFL Shell document including specifics 
on the following:

Insufficient data to determine a reliable t1/2z value and other terminal disposition phase rate 
constant (z)-dependent parameters.

PK parameters presented by period/treatment, including the units, precision, and summary 
statistics that will be presented in in-text and end-of-text tables.

Concentration data presented by period/treatment, including the units, precision, and 
summary statistics that will be presented in end-of-text tables.

Concentration data file used for PK analysis.

PK parameter WinNonlin® output file used to generate the TFLs.

Mixed effects modelling results presented in in-text and end-of-text table(s). 

Concentration-time and PK parameter data will be plotted.

Concentration versus time and cumulative percentage of dose recovered versus time figures 
for individual subjects presented in Appendix 16.2.6.
ercial Use Only and Subject to the Applicable Terms of Use
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he
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


TAK-906-1007
Page 14 of 25
Statistical Analysis Plan 
10 August 2020
For demographic data where appropriate, variables will be summarized descriptively over all 
subjects. For the categorical variables, the count and proportions of each possible value will be 
tabulated over all subjects, where applicable. The denominator for the proportion will be based 
on the number of subjects who provided non missing responses to the categorical variable. For 
continuous variables, the number of subjects with non-missing values, mean, SD, minimum, 
median, and maximum values will be tabulated.
7.2
Definition of Study Days
Day 1 for each period is defined as the date on which a subject is administered their first dose of 
the study drug(s) in each period. Other study days are defined relative to Day 1 with Day -1 
being the day prior to Day 1 of each period. Study day prior to the first dose of each 
period/treatment will be calculated as: date of assessment/event - date of period/treatment 
(Day 1); study day on or after the date of first dose will be calculated as: date of 
assessment/event - date of period/treatment (Day 1) + 1.
7.3
Analysis Sets
PK Set:
Samples from all subjects will be assayed even if the subjects do not complete the study. All 
subjects who comply sufficiently with the protocol and display an evaluable PK profile 
(eg, exposure to treatment, availability of measurements and absence of major protocol 
violations) will be included in the statistical analyses. In terms of criteria for evaluable subjects, 
please see CPAP.
Safety Set:
All subjects who received at least one dose of the study drug(s) will be included in the safety set. 
7.4
Study Information
A study information table will be generated including the following items: date of first subject’s 
signed informed consent form, date of first dose, date of last dose, date of last subject’s last 
visit/contact, date of last subject’s last procedure for collection of data for primary endpoint, the 
version of Medical Dictionary for Regulatory Activities (MedDRA®), the version of World 
Health Organization (WHO) Dictionary, and SAS version used for creating the datasets.
7.5
Disposition of Subjects
Disposition of subjects (number of subjects dosed, completed the study, discontinued from the 
study, and reason(s) for discontinuation) will be summarized overall. Individual subject’s dosing
status by period/treatment, study completion status, including reason for discontinuation, will 
also be listed by subject in a table. 
For Non-Commercial Use Only and Subject to the Applicable Terms of Use
or 
ms
or 
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TAK-906-1007
Page 15 of 25
Statistical Analysis Plan 
10 August 2020
7.6
Demographic and Other Baseline Characteristics
Demographic and baseline characteristics will be summarized over all subjects. Summary 
statistics (number of subjects [n], mean, SD, minimum, median, and maximum) will be 
generated for continuous variables (age [calculated from the date of signed Informed Consent 
Form [ICF]], weight, height and body mass index [BMI]) and the number and percentage of 
subjects within each category will be presented for categorical variables (sex, race, and 
ethnicity). Height, weight, and BMI collected at screening will be used in the baseline 
summaries. Demographics data will also be listed as recorded on the CRF, including the date of 
informed consent.
7.7
Medical History and Concurrent Medical Conditions
Medical history to be obtained will include any significant conditions or diseases that resolved at 
or before signing the ICF. Concurrent medical conditions are those significant ongoing 
conditions or diseases that are present at signing the ICF. Each subject’s medical history and 
concurrent medical conditions will be listed. Any medical condition started after taking the study 
drug will be classified as an adverse event. All medical and surgical history recorded during the 
study will be coded using the Medical Dictionary for Regulatory Activities (MedDRA®), 
Version 23.0 or later, and listed. The medical history listing will include whether the event was 
medical or surgical, the body system or organ class involved, the MedDRA system organ class 
(SOC) and preferred term (PT), the start date (if known) and end date or whether the condition 
was ongoing, and a description of the condition or event. There will be no statistical analysis of 
medical history.
7.8
Medication History and Concomitant Medications
Medication history to be obtained includes any medication relevant to eligibility criteria and 
safety evaluation stopped at or within 28 days prior to signing the ICF. Concomitant medication 
includes any medication other than study drug taken at any time between time of signing the ICF 
through the end of the study (including follow-up visit). All medication history and concomitant 
medications recorded during the study will be coded with the World Health Organization (WHO) 
Dictionary, Version 01-Mar-2020 b3 or later, and listed. The listing will include the medication 
name, coded term, dosage, route of administration, start date and time (if known), end date and 
time, or whether it continued after study completion, and indication for use. 
7.9
Study Drug Exposure and Compliance
Not applicable.
7.10
Efficacy Analysis
Not applicable.
For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906-1007
Page 16 of 25
Statistical Analysis Plan 
10 August 2020
7.11
Pharmacokinetic/Pharmacodynamic Analysis
7.11.1
Pharmacokinetic Analysis
Blood, plasma, urine, and feces were collected as specified in Table 7.a to Table 7.d.
Table 7.a
Plasma Sampling Schedule (Period 1 - ABA Study Period)
Time (hour)
(relative to oral dosing)
Time (hour)
(relative to intravenous infusion)
Sample Collection
Matrix
Plasma 1 a
Plasma 2 b
0 (predose)
X
0.5 hr postdose (± 2 min)
X
0.75 hr postdose (- 2 min) c
0 (predose)
X
1 hr postdose (+ 2 min) d
End of infusion
X
X
10 min after the end of infusion (± 2 min)
X
20 min after the end of infusion (± 2 min)
X
1.5 hr postdose (± 2 min)
30 min after the end of infusion (± 2 min)
X
X
2 hr postdose (± 2 min)
1 hr after the end of infusion (± 2 min)
X
X
4 hr postdose (± 2 min)
3 hr after the end of infusion (± 2 min)
X
X
6 hr postdose (± 2 min)
5 hr after the end of infusion (± 2 min)
X
X
8 hr postdose (± 2 min)
7 hr after the end of infusion (± 2 min)
X
X
12 hr postdose (± 5 min)
11 hr after the end of infusion (± 2 min)
X
X
24 hr postdose (± 5 min)
23 hr after the end of infusion (± 5 min)
X
X
36 hr postdose (± 10 min)
35 hr after the end of infusion (± 10 min)
X
X
48 hr postdose (± 10 min)
47 hr after the end of infusion (± 10 min)
X
X
72 hr postdose (± 10 min)
71 hr after the end of infusion (± 10 min)
X
X
96 hr postdose (± 15 min)
95 hr after the end of infusion (± 15 min)
X
X
a. Plasma 1: For determination of TAK-906 and M23 in plasma. Predose samples should be stored separately away
from the postdose samples to avoid cross contamination. 
b. Plasma 2: For determination of total radioactivity and [14C]-TAK-906 in plasma. Predose samples should be 
stored separately away from the postdose samples to avoid cross contamination.
c. To be withdrawn within 2 minutes prior to start of infusion.
d. To be withdrawn within 2 minutes after the end of infusion. 
mercial Use Only and Subject to the Applicable Terms of Use
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TAK-906-1007
Page 17 of 25
Statistical Analysis Plan 
10 August 2020
Table 7.b
Urine and Fecal Sampling Schedule (Period 1 – ABA Study Period)
Study Day
Time Interval (hour)
(Relative to Oral Dosing)
Sample Collection
Matrix
Urine a
Feces b
Day -2 to Day 1
-48 to 0 hr (predose)
X c
X d
Day 1
0-12 hr
X
X (0-24 hr)
Day 1 to Day 2
12-24 hr
X
Day 2 to Day 3
24-48 hr
X
X
Day 3 to Day 4
48-72 hr
X
X
Day 4 to Day 5
72-96 hr
X e
X e
Day 5 to Day 6 f
96-120 hr
X f
X f
Day 6 to Day 7 f
120-144 hr
X f
X f
a. Urine sample for total radioactivity and [14C]-TAK-906.
b. Feces sample for total radioactivity and [14C]-TAK-906.
c. Predose urine sample is to be obtained within 24 hours prior to IV infusion and prior to oral dosing. Predose 
samples should be stored separately away from the postdose samples to avoid cross contamination.
d. Predose fecal sample is to be obtained within 48 hours prior to oral dosing. Subjects will be asked to bring a fecal 
sample at check-in (if produced within 48 hours prior to oral dosing). Feces produced between check-in and 
dosing will also be collected as a predose sample with the sample produced nearest to oral dosing to be retained 
as the only predose sample. Predose samples should be stored separately away from the postdose samples to 
avoid cross contamination.
e. Including the urine and fecal sample collected on the morning of Day 5 (ie, Hour 96, as/when passed) prior to 
release.
f. Collection only for subjects who have not met discharge criteria.
Table 7.c
Blood and Plasma Sampling Schedule (Period 2 - ADME Study Period)
Time (hour)
(Relative to Oral Dosing)
Sample Collection
Matrix
Blood 1 a
Plasma 1 b,
Plasma 2 b
Plasma 3 b
0 (predose) c
X
X
X
0.5 hr postdose (±2 min)
X
X
X
1 hr postdose (± 2 min)
X
X
X
1.5 hr postdose (± 2 min)
X
X
2 hr postdose (± 2 min)
X
X
X
3 hr postdose (± 2 min)
X
X
4 hr postdose (± 2 min)
X
X
X
6 hr postdose (± 2 min)
X
X
8 hr postdose (± 2 min)
X
X
X
12 hr postdose (± 5 min)
X
X
X
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TAK-906-1007
Page 18 of 25
Statistical Analysis Plan 
10 August 2020
Table 7.c
Blood and Plasma Sampling Schedule (Period 2 - ADME Study Period)
Time (hour)
(Relative to Oral Dosing)
Sample Collection
Matrix
Blood 1 a
Plasma 1 b,
Plasma 2 b
Plasma 3 b
24 hr postdose (± 5 min)
X
X
X
48 hr postdose (± 10 min)
X
X
X
72 hr postdose (± 10 min)
X
X
X
96 hr postdose (± 15 min)
X
X
X
120 hr postdose (± 15 min)
X
X
X
168 hr postdose (± 1 hr) d
X
X
X
240 hr postdose (± 1 hr) d
X
X
336 hr or before discharge (± 1 hr) d
X
X
a. Blood sample for total radioactivity (Blood 1). 
b. Plasma sample for TAK-906 PK and M23 metabolite (Plasma 1), Plasma sample for total radioactivity 
(Plasma 2), and plasma sample for metabolite profiling (Plasma 3).
c. Predose blood and plasma samples should be stored separately away from the postdose samples to avoid cross 
contamination.
d. Collection only for subjects confined beyond the morning of Day 6 (ie, Hour 120) and not discharged at the 
collection time.
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
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asma 3
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TAK-906-1007
Page 19 of 25
Statistical Analysis Plan 
10 August 2020
Table 7.d
Urine and Fecal Sampling Schedule (Period 2 - ADME Study Period)
Study Day
Time Interval (hour)
(Relative to Oral Dosing)
Sample Collection
Sample Collection
Matrix
Urine 1 a, Urine 2 a
Feces b
Day -2 to Day 1
-48 to 0 hr (predose)
X c
X d
Day 1
0-12 hr
X
X (0-24 hr)
Day 1 to Day 2
12-24 hr
X
Day 2 to Day 3
24-48 hr
X
X
Day 3 to Day 4
48-72 hr
X
X
Day 4 to Day 5
72-96 hr
X
X
Day 5 to Day 6
96-120 hr e
X
X
Day 6 to Day 7
120-144 hr f
X
X
Day 7 to Day 8
144-168 hr f
X
X
Day 8 to Day 9
168-192 hr f
X
X
Day 9 to Day 10
192-216 hr f
X
X
Day 10 to Day 11
216-240 hr f
X
X
Day 11 to Day 12
240-264 hr f
X
X
Day 12 to Day 13
264-288 hr f
X
X
Day 13 to Day 14
288-312 hr f
X
X
Day 14 to Day 15
312-336 hr f
X
X
a. Urine sample for TAK-906 and M23 PK (Urine 1); Urine sample for total radioactivity and urine sample for 
metabolite profiling (Urine 2). 
b. Feces sample for total radioactivity and feces sample for metabolite profiling (Feces).
c. Predose urine sample is to be obtained within 24 hours prior to dosing. Predose urine samples should be stored 
separately away from the postdose samples to avoid cross contamination.
d. Predose fecal sample is to be obtained within 48 hours prior to dosing. If applicable, for subject(s) who are 
released in Period 1 and return for Period 2, subjects will be asked to bring a fecal sample at check-in (if 
produced within 48 hours prior to dosing). Feces produced between check-in and dosing will also be collected as 
a predose sample with the sample produced nearest to dosing to be retained as the only predose sample. Predose 
fecal samples should be stored separately away from the postdose samples to avoid cross contamination.
e. Including the urine and fecal sample collected on the morning of Day 6 (ie, Hour 120, as/when passed) prior to 
release.
f. Collected for subjects who have not met the discharge criteria. Samples will continue to be collected in 24-hour 
intervals until a discharge criterion is met (ie, 90% or greater of the total dose of radioactivity administered is 
recovered in urine and fecal samples or the excretion of radioactivity in the urine and feces combined has 
declined to ≤1% of the total administered radioactivity per 24 hour interval for at least 2 consecutive intervals 
where both a urine and fecal sample are collected) or up to 14 days postdose (ie, Day 15). After Day 15, if 
subjects have not met the discharge criteria, the subject may need to return to the CRU to collect urine and fecal 
samples in two blocks of 24-hour periods on Days 20, 21, or 22 and Days 27, 28, or 29 based on the discretion of 
the Sponsor. Release of subjects who do not meet a discharge criterion by Day 15 in Period 2 will be reviewed 
on a case-by-case basis.
The actual date and time of sample collection will be recorded on the source document in the 
case report form (CRF).
l Use Only and Subject to the Applicable Terms of Use
ion
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TAK-906-1007
Page 20 of 25
Statistical Analysis Plan 
10 August 2020
Concentration (or concentration equivalent) data for the total radioactivity (whole blood 
[Period 2]; plasma, urine, and feces [Periods 1 and 2]; and if applicable, emesis [Period 2]), 
TAK-906 and M23 (plasma [Periods 1 and 2]; and urine [Period 2]), and [14C]-TAK-906 
(plasma, urine, and feces [Period 1]) 
Excluded concentrations will be presented and footnoted as such in the concentration table 
listings, and those values will be excluded from the descriptive statistics. 
Excluded parameters will be presented and footnoted as such in the PK parameter table listings, 
and those values will be excluded from the descriptive statistics.
Individual urine sample weight, fecal homogenate weight, analyte concentrations, analyte 
amounts, and percentage of dose will be listed by time interval. Amounts and percentage of dose 
recovered will also be summarized descriptively for each collection interval, and the overall 
collection period. Summary will be done by period/treatment using the summary statistics listed 
in the CPAP. Excluded data will be presented and footnoted as such in the table listings, and 
those values will be excluded from the descriptive summary statistics. Whole blood and plasma 
concentration-time profiles will be plotted on linear and semi-log scales. Arithmetic mean and 
median linear scale plots will be plotted with and without SD. For arithmetic mean and median 
whole blood and plasma concentration-time plots by sampling time, nominal PK sampling times
will be used; for individual subject whole blood and plasma concentration-time plots by 
sampling time, actual PK sampling times will be used. Cumulative percentage of the dose 
recovered versus time will be plotted on linear scale versus nominal collection interval end time. 
Arithmetic mean and median linear scale plots will be plotted with and without SD.
A mixed effects model will be performed on ln-transformed, dose-normalized AUC∞with route 
(treatment) as the fixed effect and subject as the random effect. The estimate of ABA and its 
90% CI will be obtained by exponentiating the difference in LS means between dosing routes 
and its 90% CI based on the mixed effects of AUC∞ on the log scale. This will provide the 
estimate of ABA and 90% CI for the dose-normalized AUC∞GMR (TAK-906 administered as 
oral dose / [14C]-TAK-906 administered as IV microtracer dose), respectively. AUClast will be 
analyzed in a similar fashion if AUC∞cannot be calculated. The mixed effects modelling
analysis will be performed using the following SAS® code:
PROC MIXED;
CLASS ROUTE SUBJECT;
MODEL LN(PK_PARAMETER) = ROUTE/ DDFM = KR;
RANDOM SUBJECT;
ESTIMATE “Oral vs Intravenous” ROUTE 1 -1 / cl alpha=0.1 e;
RUN;
Programmer Note: The coefficient estimates will be adjusted according to the route of 
administration decodes. PK_PARAMETER is dose-normalized AUC∞.
r Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906-1007
Page 21 of 25
Statistical Analysis Plan 
10 August 2020
7.11.1.1
Analysis of Mass Balance
In Period 2, mass balance will be summarized using the following descriptive statistics: n, Mean, 
SD, CV%, SEM, minimum, median, maximum, Geom Mean, and Geom CV%.
7.11.1.2
Whole Blood to Plasma Partitioning Ratio
In Period 2, ratios of the total radioactivity concentration equivalents in whole blood relative to 
plasma (ie, whole blood:plasma partitioning ratios) will be summarized using the following 
descriptive statistics: n, Mean, SD, CV%, SEM, minimum, median, maximum, Geom Mean, and 
Geom CV%.
7.11.1.3
Metabolite Profiling
TAK-906 metabolite profiling will be performed by Takeda in plasma, urine, and feces samples 
from Period 2 containing sufficient amounts of radioactivity. The percentage of the dose 
represented by each of the metabolites, if any, will be calculated using the radioactivity 
concentration equivalent data combined with the metabolite profiling data. The percentage of 
each identified metabolite, if any, to total radioactivity in the plasma will be estimated based on 
plasma metabolite profiling data.
7.11.2
Pharmacodynamic Analysis
Not applicable. 
7.12
Other Outcomes
Not applicable.
7.13
Safety Analysis
Safety will be evaluated by the incidence of TEAEs, severity and relationship to study drug of 
TEAEs, changes from baseline in the subjects’ clinical laboratory results, vital signs, and ECG’s 
using the safety set. All clinical safety data will be listed by subject and assessment time points, 
including rechecks, unscheduled assessments, and early termination, chronologically. 
Continuous variables will be summarized using n, mean, SD, minimum, median, and maximum. 
Frequency counts and percentages will be reported for categorical data when appropriate. Where 
individual data points are missing because of dropouts or other reasons, the data will be 
summarized based on reduced denominators.
7.13.1
Adverse Events 
All AEs captured in the database will be listed in by-subject data listings including verbatim 
term, coded term, severity (Mild, Moderate, and Severe), relationship to study drug (related or 
not related), action relative to the study drug, outcome, and procedures. All AEs occurring during 
this study will be coded using MedDRA®, Version 23.0 or later where appropriate. However, 
only TEAEs occurring after administration of the first dose of study drug and through the follow-
n-Commercial Use Only and Subject to the Applicable Terms of Use
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7.13
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7.13
A


TAK-906-1007
Page 22 of 25
Statistical Analysis Plan 
10 August 2020
up phone call (30 +/- 2 days after the last study drug administration) will be summarized. A 
TEAE is defined as an AE that is starting or worsening at the time of or after study drug 
administration. TEAEs occurring at or after Period 1 Day 1 oral dosing and prior to Period 2 Day 
1 dosing will be considered treatment-emergent to Treatment A (i.e., single oral dose of 50 mg 
TAK-906 followed by a single intravenous dose of 100 µg (~1 µCi) [14C]-TAK-906 [Period 1])
and those occurring at or after Period 2 Day 1 dosing up to safety follow up visit by phone call 
will be considered treatment-emergent to Treatment B (i.e., single oral dose of 50 mg (~100 μCi) 
[14C]-TAK-906 [Period 2]).
For each period/treatment, TEAEs will be coded using MedDRA® and tabulated by SOC and 
Preferred Term. Summary tables will include number of subjects reporting the AE and as percent 
of safety set by period/treatment. The most commonly reported TEAEs (i.e., those events 
reported by >5% of all subjects in each period/treatment, excluding SAEs) will also be 
summarized separately. For the list of all AE summary tables see CPAP. In addition, TEAEs will 
be summarized as number of AEs and percentage of AEs for each period/treatment for the 
overview of TEAEs. Additional TEAE summary tables will be presented by severity and 
relationship to study drug. Similarly, a table of the events per subject will be included where if a 
subject has multiple AEs with different severity levels within the same term, the subject will be 
counted in the most severe category only. If a subject has both related and unrelated AEs with 
the same term, the subject will be counted as having related TEAEs only. Should any SAEs 
(including all-cause mortalities) occur, they will be listed and summarized the same way as 
TEAE. All AEs will be displayed in the data listings and TEAEs will be discussed in the text of 
the study report. 
7.13.2
Clinical Laboratory Evaluations
Hematology, serum chemistry, and urinalysis will be performed at screening, check-in (Day -1) 
of Period 1 and Period 2 (Note: subjects were being confined for washout, Period 2 check-in
events were not performed in the current study), Day 3 in each period, and prior to discharge in 
Period 2 or early termination. In addition, laboratory safety tests may be performed at various 
unscheduled time points, if deemed necessary by the Principal Investigator (PI). Coagulation 
tests (PT/INR) will be performed if subjects has on-study aspartate aminotransferase or alanine 
aminotransferase elevated ≥3x the upper limit of normal.
For all laboratory values that are numeric, summary statistics (n, mean, SD, minimum, median, 
and maximum) will be presented for each laboratory test by period/treatment and assessment 
time points. Change from baseline will be summarized in a similar way. Baseline is defined as 
the last assessment including rechecks taken prior to oral dosing on Day 1 of Period 1 (Day -1 
Check-in of Period 1). 
For each laboratory test, a shift table will be developed comparing the frequency of the results at 
period/treatment baseline (above normal (H), normal (N), or below normal (L)) with those 
postdose time point for each period/treatment. For urinalysis tests, the categories are normal (N) 
and abnormal (A). Out-of-range values and corresponding recheck results will be listed. 
Non-Commercial Use Only and Subject to the Applicable Terms of Use
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TAK-906-1007
Page 23 of 25
Statistical Analysis Plan 
10 August 2020
Out-of-normal range flags will be recorded as follows: high (H) and low (L) for numerical 
results and did-not-match (*) for categorical results. If a value fails the reference range, it will 
automatically be compared to a clinically significant (CS) range. If the value falls within the CS 
range, it will be noted as “N” for not clinically significant. If the value fails the CS range, it will 
be flagged with a “Y” which prompts the PI to determine how the out-of-range value should be 
followed using 4 Investigator flags: “N”, not clinically significant, “R”, requesting a recheck, 
“^”, checking at the next scheduled visit, or “Y”, clinically significant. To distinguish the PI flag 
from the computer CS range flags, the PI flags of “N” and “Y” will be presented as “-“ and “+”, 
respectively, in the data listing. Additionally, the PI will provide a 4th flag when the 3rd flag 
indicates “R” or “^”. This 4th flag is intended to capture final CS (+)/NCS (-) when the 3rd flag 
does not document significance. All clinically significant laboratory tests, as indicated by the PI, 
and the corresponding values will be listed by subject. All clinical laboratory data will be 
presented in by-subject data listings.
7.13.3
Vital Signs
Single measurements of vital signs will be collected as outlined in Table 7.e. 
Table 7.e
Collection of Vital Signs
Measurement Type
Period
Day
Time Point
Vital Signs (Pulse Rate and Blood Pressure)
Screen
1
-1
1
1 and 4 hours post oral dose
End of Period 1^
2
-1^
1
1 and 4 hours post oral dose
Discharge or ET*
Vital Signs (Respiratory Rate and Temperature)
Screen
1
-1
1
4 hours post oral dose
End of Period 1^
2
-1^
1
4 hours post oral dose
Discharge or ET*
* ET = Early termination.
^ Note: subjects were being confined for washout, Period 2 check-in (Day -1) and End of Period 1 events were not 
performed in the current study.
Additional unscheduled vital signs measurements may be taken at other times, if deemed 
necessary by the PI.
Summary statistics (n, mean, SD, minimum, median, and maximum) will be reported for vital 
sign results by period/treatment and time point of collection. Change from baseline will be 
summarized in a similar way. Baseline is defined as the last assessment including rechecks taken 
prior to Day 1 oral dosing in Period 1 (Day -1 Check-in of Period 1). Vital signs will also be 
displayed in a data listing by subject.
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TAK-906-1007
Page 24 of 25
Statistical Analysis Plan 
10 August 2020
7.13.4
12-Lead ECGs
Standard 12-lead ECGs will be recorded as outlined in Table 7.f.
Table 7.f
Collection of Electrocardiograms
Measurement Type
Period
Day
Time Point
12-Lead ECG
Screen
1
-1
1
1 and 4 hours post oral dose
End of Period 1^
2
-1^
1
1 and 4 hours post oral dose
Discharge or ET*
* ET = Early termination.
^ Note: subjects were being confined for washout, Period 2 check-in (Day -1) and End of Period 1 events were not 
performed in the current study.
Additional unscheduled ECGs may be recorded at other times if deemed necessary by the PI. 
Summary statistics (n, mean, SD, minimum, median, and maximum) will be reported for ECG 
results and change from baseline by period/treatment and time point of collection. Baseline is 
defined as the last assessment including rechecks taken prior to Day 1 oral dosing in Period 1 
(Day -1 Check-in of Period 1). ECG data will also be displayed in a data listing by subject with 
QTcF > 450 ms and QTcF change from baseline >30 ms flagged.
7.13.5
Physical Exams
A full physical exam will be performed at screening. Abbreviated physical examinations will be 
performed at Day -1 of each period and prior to Period 2 discharge or early termination. 
Symptom-driven physical exams may be performed at other times at the discretion of the PI. 
Physical exam findings, as recorded on the CRF, will be presented in a data listing by subject. 
7.13.6
Taste Questionnaire
Subjects will complete a taste questionnaire evaluating the taste of the TAK-906 oral solution 
administered in Period 2. The questionnaire will be completed within 5 minutes of dosing. Taste 
questionnaire results will be presented in a data listing by subject.
7.13.7
Overdose 
All cases of overdose will be presented in a data listing by subject. Any AEs associated with 
overdose will be documented as AEs. 
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TAK-906-1007
Page 25 of 25
Statistical Analysis Plan 
10 August 2020
7.14
Interim Analysis
No interim analysis will be performed. 
7.15
Preliminary Analysis
If requested, QCed whole blood and plasma concentration data will be plotted using nominal 
times to aid in the determination of samples for repeat bioanalysis. If requested, a preliminary 
PK analysis will be completed as described in the CPAP and Section 7.11.1 of the SAP, with the 
following changes: 1) QCed data will be used (not QAed); 2) nominal times (not actual sampling 
times) will be used for the calculation of PK parameters in whole blood and plasma; 3) tables 
and figures will be created using Phoenix® WinNonlin® Version 8.1 or higher for whole blood 
and plasma data, and using SAS® Version 9.4, or higher for urine and feces data.
7.16
Changes in the Statistical Analysis Plan 
The analyses in the SAP are the same as those specified in the protocol.
8.0
REFERENCES
Clinical Pharmacology Analysis Plan (CPAP). Study Number: TAK-906-1007. A phase 1 study 
to assess absolute bioavailability of TAK-906 and to characterize mass balance, 
pharmacokinetics, metabolism, and excretion of [14C]-TAK-906 in healthy male subjects.
Tables, Figures, Listings (TFL) Shells. Study Number: TAK-906-1007. Celerion Study Number: 
CA24217. A phase 1 study to assess absolute bioavailability of TAK-906 and to characterize 
mass balance, pharmacokinetics, metabolism, and excretion of [14C]-TAK-906 in healthy male 
subjects.
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable Terms of Use
minal
Term
minal
eliminar
le T
eliminar
SAP, w
able
SAP, w
ot actua
lica
ot actua
plasma;
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plasma;
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feces da
the A
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and
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On
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ELECTRONIC SIGNATURES 
Signed by 
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Server Date 
(dd-MMM-yyyy HH:mm ‘UTC’) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
090101d680e37221
16-1-9-1 Statistical Analysis Plan 2020-08-10
Biostatistics Approval
21-Aug-2020 14:42 UTC
ble Terms of Use
e Te
ate 
T
ate 
ble T
HH:mm ‘U
ble 
HH:mm ‘U
Ter
Property of Takeda: For Non-Commercial Use Only and Subject to the Applicable
ble
:42 UTC
able
:42 UTC
PPD