Clinical trial NCT03316976
Conditions: Healthy Volunteers
Keywords: Drug therapy
Sponsor: Takeda
Start date: 2017-11-22; Completion date: 2018-02-08
Enrollment: 40 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess the pharmacokinetics after a single dose of dexlansoprazole 30 and 60 mg delayed-release capsules in healthy Chinese participants.

Detailed description:
The drug being tested in this study is called Dexlansoprazole. This study will assess the pharmacokinetics, safety and tolerability of a single oral dose of Dexlansoprazole 30 mg and 60 mg delayed-release capsules in healthy participants.

The study will enroll approximately 40 participants, 20 participants in each parallel arm. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:

* Group 1: A single oral dose of Dexlansoprazole 30 mg delayed-release capsule
* Group 2: A single oral dose of Dexlansoprazole 60 mg delayed-release capsule

All participants will be asked to take single dose of study drug on Day 1.

This single center trial will be conducted in China. The overall time to participate in this study is approximately 40 days. Participants will be contacted by telephone or will make a final visit to the clinic 5 to 10 days after receiving their last dose of study drug for a follow-up assessment.

Arms: arm 1: Dexlansoprazole 30 mg, delayed-release, capsule, orally, administered as single dose on Day 1. arm 2: Dexlansoprazole 60 mg, delayed-release, capsule, orally, administered as single dose on Day 1.
Interventions: intervention 1: Dexlansoprazole
Intervention descriptions: intervention 1: Dexlansoprazole delayed-release capsule.

Protocol documents:
Prot_001.pdf: 
This may include, but is not limited to, redaction of the following: 


•
Title: A Phase 1, Single-Center, Open-Label, 2-Arm Parallel Group, Single-Dose Study to
Evaluate the Pharmacokinetics of Dexlansoprazole 30 mg and 60 mg Delayed-Release
Capsules in Healthy Chinese Subjects
NCT Number:  NCT03316976
Protocol Approve Date: 28 November 2017
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 or company confidential information. 
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.


TITLE PAGE
PROTOCOL AMENDMENT
A Phase 1, Single-Center, Open-Label, 2-Arm Parallel Group, Single-Dose Study to 
Evaluate the Pharmacokinetics of Dexlansoprazole 30 mg and 60 mg Delayed-Release 
Capsules in Healthy Chinese Subjects 
Phase 1 Dexlansoprazole PK Study in Healthy Chinese Subjects
Sponsor:
Takeda Development Center Asia, Pte. Ltd.
21 Biopolis Road, Nucleos North Tower, Level 4, Singapore 138567
Study Number:
TAK-390MR_106
IND Number:
Not Applicable
EudraCT Number:
Not Applicable 
Compound:
TAK-390MR Dexlansoprazole
Date:
28 November 2017
Amendment Number:
03
Amendment History: 
Date
Amendment Number
Amendment Type
Region
20 June 2011
Initial Protocol
Not applicable
China
22 June 2016
01
Nonsubstantial
China
28 March 2017
02
Nonsubstantial
China
28 November 2017
03
Nonsubstantial
China
CONFIDENTIAL PROPERTY OF TAKEDA
This document is a confidential communication of Takeda. Acceptance of this document constitutes the agreement by 
the recipient that no information contained herein will be published or disclosed without written authorization from 
Takeda except to the extent necessary to obtain informed consent from those persons to whom the drug may be 
administered. Furthermore, the information is only meant for review and compliance by the recipient, his or her staff, 
and applicable institutional review committee and regulatory agencies to enable conduct of the study.


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1.0
ADMINISTRATIVE INFORMATION
1.1
Contacts 
A separate contact information list will be provided to each site.
TDC Asia sponsored Asia Pacific investigators will be provided with emergency medical contact 
information cards to be carried by each subject.
General advice on protocol procedures should be obtained through the monitor assigned to the 
study site. Information on service providers is given in Section 3.1 and relevant guidelines should 
be provided to the site.
Contact Type / Role
Contact
Serious adverse event and pregnancy reporting
Medical Monitor (medical advice on protocol 
and compound, and medical management of 
subjects)
Responsible Medical Officer 
(carries overall responsibility for the conduct of 
the study)
Personally Protected Data


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1.2
Approval
REPRESENTATIVES OF TAKEDA
This study will be conducted with the highest respect for the individual participants in accordance 
with the requirements of this clinical study protocol and also 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, clinical 
trial disclosure laws, and regulations.
SIGNATURES
Electronic Signatures may be found on the last page of this document.
Personally Protected Data


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INVESTIGATOR AGREEMENT
I confirm that I have read and that I understand this protocol, the Investigator’s Brochure, 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 of this 
protocol.

Terms outlined in the Clinical Study Site Agreement.

Appendix B – Responsibilities of the Investigator.
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)


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1.3
Protocol Amendment 03 Summary of Changes
Rationale for Amendment 03
This document describes the changes in reference to the protocol incorporating Amendment 
No. 03. The primary reasons for this amendment are to update blood volume collected for 
genotype analysis and total volume of blood, and to make minor modifications to specify the 
relative centrifugal force, remove plasma first to be transferred into 1 aliquot after centrifugation, 
and to extend the duration for blood collection to freezing plasma sample on processing of plasma 
samples for pharmacokinetic analysis to allow greater flexibility in Appendix E, and update the 
reference to lab manual for processing of blood samples for genotype analysis in Appendix E.
For specific descriptions of the changes listed below and where these changes are located, see 
Appendix F.
Changes in Amendment 03
1. Updated Appendix E Collection, Storage, and Shipment of Bioanalytical Samples.
2. Correct blood volume for genotype analysis and total blood volume.


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TABLE OF CONTENTS
1.0
ADMINISTRATIVE INFORMATION ...........................................................................2
1.1
Contacts.....................................................................................................................2
1.2
Approval....................................................................................................................3
1.3
Protocol Amendment 03 Summary of Changes ..........................................................5
2.0
STUDY SUMMARY ....................................................................................................10
3.0
STUDY REFERENCE INFORMATION ......................................................................12
3.1
Study-Related Responsibilities.................................................................................12
3.2
Principal Investigator...............................................................................................12
3.3
List of Abbreviations ...............................................................................................13
3.4
Corporate Identification...........................................................................................14
4.0
INTRODUCTION.........................................................................................................15
4.1
Background .............................................................................................................15
4.2
Rationale for the Proposed Study.............................................................................16
5.0
STUDY OBJECTIVES AND ENDPOINTS..................................................................17
5.1
Objectives................................................................................................................17
5.1.1
Primary Objective .......................................................................................17
5.1.2
Secondary Objective ...................................................................................17
5.2
Endpoints.................................................................................................................17
5.2.1
Primary Endpoints.......................................................................................17
5.2.2
Additional Endpoints ..................................................................................17
5.2.3
Safety Endpoints.........................................................................................17
6.0
STUDY DESIGN AND DESCRIPTION.......................................................................18
6.1
Study Design ...........................................................................................................18
6.2
Justification for Study Design, Dose, and Endpoints ................................................18
6.3
Premature Termination or Suspension of Study or Investigational Site.....................19
6.3.1
Criteria for Premature Termination or Suspension of the Study...................19
6.3.2
Criteria for Premature Termination or Suspension of Investigational Sites ..19
6.3.3
Procedures for Premature Termination or Suspension of the Study or the 
Participation of Investigational Site(s).........................................................19
7.0
SELECTION AND DISCONTINUATION/WITHDRAWAL OF SUBJECTS..............20
7.1
Inclusion Criteria .....................................................................................................20
7.2
Exclusion Criteria ....................................................................................................20
7.3
Excluded Medications and Dietary Products ............................................................22
7.4
Diet, Fluid, and Activity Control..............................................................................23


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7.5
Criteria for Discontinuation or Withdrawal of a Subject...........................................24
7.6
Procedures for Discontinuation or Withdrawal of a Subject......................................25
8.0
CLINICAL TRIAL MATERIAL MANAGEMENT ......................................................26
8.1
Study Medication and Materials...............................................................................26
8.1.1
Dosage Form, Manufacturing, Packaging, and Labeling..............................26
8.1.2
Storage........................................................................................................26
8.1.3
Dose and Regimen ......................................................................................26
8.1.4
Overdose.....................................................................................................27
8.2
Investigational Drug Assignment and Dispensing Procedures ..................................27
8.3
Accountability and Destruction of Sponsor-Supplied Drugs.....................................27
9.0
STUDY PLAN ..............................................................................................................29
9.1
Study Procedures.....................................................................................................29
9.1.1
Informed Consent Procedure.......................................................................29
9.1.2
Demographics, Medical History, and Medication History Procedure...........29
9.1.3
Physical Examination Procedure .................................................................29
9.1.4
Weight, Height and BMI.............................................................................30
9.1.5
Vital Sign Procedure ...................................................................................30
9.1.6
Documentation of Concomitant Medications...............................................30
9.1.7
Documentation of Concurrent Medical Conditions......................................30
9.1.8
Procedures for Clinical Laboratory Samples................................................30
9.1.9
Contraception and Pregnancy Avoidance Procedure....................................32
9.1.10
Pregnancy ...................................................................................................33
9.1.11
ECG Procedure ...........................................................................................34
9.1.12
Sample Collection for Genotype Analysis ...................................................34
9.1.13
Pharmacokinetic Sample Collection ............................................................34
9.1.13.1
Collection of Blood for Pharmacokinetic Sampling ................................34
9.1.14
Pharmacokinetic Parameters........................................................................35
9.1.15
Documentation of Screen Failure ................................................................35
9.1.16
Documentation of Study Entrance...............................................................35
9.2
Monitoring Subject Treatment Compliance..............................................................36
9.3
Schedule of Observations and Procedures................................................................36
9.4
Blood Volume .........................................................................................................36
10.0
PRETREATMENT EVENTS AND ADVERSE EVENTS ............................................37
10.1
Definitions...............................................................................................................37
10.1.1
PTEs...........................................................................................................37


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10.1.2
AEs.............................................................................................................37
10.1.3
Additional Points to Consider for PTEs and AEs.........................................37
10.1.4
SAEs...........................................................................................................39
10.1.5
Severity of PTEs and AEs ...........................................................................40
10.1.6
Causality of AEs .........................................................................................40
10.1.7
Relationship to Study Procedures................................................................40
10.1.8
Start Date....................................................................................................41
10.1.9
Stop Date ....................................................................................................41
10.1.10
Frequency ...................................................................................................41
10.1.11
Action Concerning Study Drug ...................................................................41
10.1.12
Outcome .....................................................................................................41
10.2
Procedures...............................................................................................................42
10.2.1
Collection and Reporting of AEs.................................................................42
10.2.1.1
PTE and AE Collection Period ...............................................................42
10.2.1.2
PTE and AE Reporting ...........................................................................42
10.2.2
Collection and Reporting of SAEs...............................................................43
10.2.3
Reporting of Abnormal Liver Function Tests ..............................................43
10.3
Follow-up of SAEs ..................................................................................................43
10.3.1
Safety Reporting to Investigators, IRBs or IECs, and Regulatory 
Authorities ..................................................................................................44
11.0
STUDY-SPECIFIC COMMITTEES .............................................................................45
12.0
DATA HANDLING AND RECORDKEEPING............................................................46
12.1
CRFs (Electronic and Paper)....................................................................................46
12.2
Record Retention .....................................................................................................46
13.0
STATISTICAL METHODS..........................................................................................48
13.1
Statistical and Analytical Plans ................................................................................48
13.1.1
Analysis Sets...............................................................................................48
13.1.2
Analysis of Demographics and Other Baseline Characteristics ....................48
13.1.3
Pharmacokinetic Analysis ...........................................................................48
13.1.4
Safety Analysis ...........................................................................................48
13.2
Interim Analysis and Criteria for Early Termination ................................................49
13.3
Determination of Sample Size..................................................................................49
14.0
QUALITY CONTROL AND QUALITY ASSURANCE...............................................50
14.1
Study-Site Monitoring Visits ...................................................................................50
14.2
Protocol Deviations..................................................................................................50
14.3
Quality Assurance Audits and Regulatory Agency Inspections ................................51


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15.0
ETHICAL ASPECTS OF THE STUDY........................................................................52
15.1
IRB and/or IEC Approval ........................................................................................52
15.2
Subject Information, Informed Consent, and Subject Authorization .........................53
15.3
Subject Confidentiality ............................................................................................54
15.4
Publication, Disclosure, and Clinical Trial Registration Policy.................................54
15.4.1
Publication and Disclosure..........................................................................54
15.4.2
Clinical Trial Registration...........................................................................55
15.4.3
Clinical Trial Results Disclosure .................................................................55
15.5
Insurance and Compensation for Injury....................................................................55
16.0
REFERENCES..............................................................................................................56
LIST OF IN-TEXT TABLES
Table 6.a
Parallel Groups ..................................................................................................18
Table 7.a
Prohibited Medications, Supplements, and Dietary Products ..............................23
Table 8.a
Study Medication Supplies.................................................................................26
Table 9.a
Clinical Laboratory Tests...................................................................................31
Table 9.b
Collection of Blood Samples for Pharmacokinetic Analysis ...............................34
Table 9.c
Approximate Blood Volume ..............................................................................36
Table 10.a
Takeda Medically Significant AE List................................................................40
Table 14.a
Windows for Pharmacokinetic Sample Collection..............................................51
LIST OF IN-TEXT FIGURES
Figure 6.a
Schematic of Study Design ................................................................................18
LIST OF APPENDICES
Appendix A
Schedule of Study Procedures............................................................................57
Appendix B
Responsibilities of the Investigator.....................................................................59
Appendix C
Elements of the Subject Informed Consent.........................................................61
Appendix D
Investigator Consent to Use of Personal Information..........................................64
Appendix E
Collection, Storage, and Shipment of Bioanalytical Samples..............................65
Appendix F
Detailed Description of Amendments to Text.....................................................68


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2.0
STUDY SUMMARY
Name of Sponsor(s):
Takeda Development Center Asia, Pte. Ltd.
Compound:
TAK-390MR Dexlansoprazole
Title of Protocol: A Phase 1, Single-Center, Open-Label, 
2-Arm Parallel Group, Single-Dose Study to Evaluate the 
Pharmacokinetics of Dexlansoprazole 30 mg and 60 mg 
Delayed-Release Capsules in Healthy Chinese Subjects 
IND No.: 
Not Applicable
EudraCT No.:
Not Applicable
Study Number: TAK-390MR_106
Phase: 1
Study Design:
This is a phase 1, open-label, single dose, 2-arm parallel study to evaluate the pharmacokinetics (PK) of a single oral 
dose of dexlansoprazole 30 and 60 mg delayed-release capsules in healthy Chinese subjects. Forty subjects will be 
enrolled in the study, 20 subjects in Group 1 and 20 subjects in Group 2. 
Objectives:
Primary:
The primary objective of this study is to assess the PK of single doses of dexlansoprazole 30 and 60 mg 
delayed-release capsules in healthy Chinese subjects.
Secondary:
The secondary objective of this study is to evaluate the safety and tolerability of dexlansoprazole following oral 
administration of a single 30 or 60 mg dexlansoprazole delayed-release capsule.
Subject Population:
Healthy men and women of Chinese descent aged 18 to 45, inclusive, at the time of informed consent and study 
medication dose.
Number of Subjects:
Estimated Total: 40
Number of Sites:
Estimated total: 1 in China
Dose Level(s):
Dexlansoprazole 30 mg
Dexlansoprazole 60 mg
Route of Administration:
Oral
Duration of Treatment:
Single dose on Day 1
Period of Evaluation:
Approximately 40 days (including Screening to 
Follow-up)
Main Criteria for Inclusion:
Men and women subjects aged 18 to 45, inclusive, and of Chinese descent who are in good health as determined by a 
physician.
Main Criteria for Exclusion:
Subjects who have hypersensitivity to dexlansoprazole or related compounds, or have a history or clinical 
manifestations of serious neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, 
urological, endocrine, hematologic, dermatologic, immunologic, psychiatric disorders, or other abnormality which 
may impact the ability of the subjects to participate or potentially confound the study results. Subject has a positive test 
result for alcohol or drugs of abuse at Screening or Check-in (Day -1), or a positive test result for hepatitis B surface 
antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at Screening, 
or an abnormal (clinically significant) ECG or laboratory values at Screening or Check-in (Day -1). In addition, 
subjects who has taken any excluded medication, supplements, or food products during the time periods listed in the 
protocol.


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Main Criteria for Evaluation and Analyses:
Primary Endpoints:
The primary endpoints for this study are the PK parameters of dexlansoprazole following a single oral dose of 
dexlansoprazole 30 and 60 mg delayed-release capsules:

Maximum observed concentration (Cmax).

Area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUClast).

Area under the plasma concentration-time curve from time zero to infinity (AUC∞).
Additional Endpoints:
In addition, the following PK variables will be additional endpoints:

Time of first occurrence of Cmax (tmax).

Terminal disposition phase rate constant (λz).

Terminal disposition phase half-life (t1/2z).

Volume of distribution during the terminal disposition phase after extravascular administration (Vz/F).

Apparent clearance after extravascular administration (CL/F).
Safety Endpoints:
Safety will be assessed by summarizing the incidence of adverse events (AEs), clinical laboratory values, physical 
examinations, ECGs, and vital signs.
Statistical Considerations:
Pharmacokinetics:
Plasma dexlansoprazole concentrations and the PK parameters will be tabulated and descriptive statistics computed.
Sample Size Justification:
A sample size of 40 subjects, 20 per parallel arm, will be used in this study. This sample size is deemed to be sufficient 
for the assessment of the PK of dexlansoprazole 30 and 60 mg delayed-release capsules in Chinese population. The 
study is not statistically powered.


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3.0
STUDY REFERENCE INFORMATION
3.1
Study-Related Responsibilities
The sponsor will perform all study-related activities with the exception of those identified in the
Study-Related Responsibilities template. The identified vendors in the template for specific 
study-related activities will perform these activities in full or in partnership with the sponsor.
3.2
Principal Investigator
Personal Protected Data


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3.3
List of Abbreviations
λz
terminal disposition phase rate constant
%CV
coefficient of variation
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the plasma concentration-time curve
AUClast
area under the plasma concentration-time curve from time 0 to time of the last quantifiable 
concentration
AUC∞
area under the plasma concentration-time curve from time 0 to infinity
BMI
body mass index
bpm
beats per minute
CFDA
China Food and Drug Administration
CL/F
apparent clearance after extravascular administration
Cmax
maximum observed concentration
CRF
case report form
CRO
contract research organization
CS
clinically significant
CSR
clinical study report
CYP
cytochrome P450
ECG
electrocardiogram
EE
erosive esophagitis
EM
extensive metabolizer
FDA
Food and Drug Administration
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
GERD
gastroesophageal reflux disease
GGT
-glutamyl transferase
HBsAg
hepatitis B surface antigen
hCG
human chorionic gonadotropin
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HLT
high level term
HRT
hormone replacement therapy
IBD
international birth date
ICH
International Conference on Harmonisation
IEC
independent ethics committee
INR
international normalized ratio
IRB
institutional review board
IUD
intrauterine devices


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K2EDTA
potassium ethylenediamine tetraacetic acid.
LFT
liver function test
MedDRA
Medical Dictionary for Regulatory Activities
MR
modified release
NCS
not clinically significant
PK
pharmacokinetics
PM
poor metabolizer
PPI
proton pump inhibitor
PT
preferred term
PTE
pretreatment event
QD
once daily
OTC
over-the-counter
RBC
red blood cell
RCF
relative centrifugal force
SAE
serious adverse event
SAP
statistical analysis plan
SOC
system organ class
SOP
standard operating procedure
SUSAR
suspected unexpected serious adverse reaction
t1/2z
terminal disposition phase half-life
TEAE
treatment-emergent adverse event
tmax
time of first occurrence of Cmax
ULN
upper limit of normal
Vz/F
volume of distribution during the terminal disposition phase after extravascular 
administration
WBC
white blood cell
WHO
World Health Organization
3.4
Corporate Identification
Takeda
TDC Asia, TDC Europe, TDC Americas, TCH, and/or TPC, as applicable
TCH
Takeda (China) Holdings Co., Ltd.
TDC
TDC Asia, TDC Europe and/or TDC Americas, as applicable
TDC Americas
Takeda Development Center Americas, Inc.
TDC Asia
Takeda Development Center Asia, Pte Ltd
TDC Europe
Takeda Development Centre Europe Ltd.
TPC
Takeda Pharmaceutical Company Limited


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4.0
INTRODUCTION
4.1
Background
Dexlansoprazole is a proton pump inhibitor (PPI) with prolonged elevation of intragastric pH. 
PPIs inhibit the secretion of H+ ions in the stomach by inhibiting the (H+, K+)-ATPase enzyme 
(proton pump) at the secretory surface of the gastric parietal cell [1]. Dexlansoprazole is the 
R-enantiomer of the racemate lansoprazole. Lansoprazole, initially approved in France in 1990 
and in China in 1994, is currently marketed in over 90 countries and has a well-established safety 
profile. 
Takeda Development Center Americas, Inc. developed dexlansoprazole delayed-release capsules 
(also referred to as dexlansoprazole modified-release capsules) as a new therapy for treating 
acid-related disorders including symptomatic non-erosive gastroesophageal reflux disease
(GERD), erosive esophagitis (EE), and maintenance of healed EE and relief of heartburn. 
Dexlansoprazole capsules are approved for use in adults (≥18 years of age) in over 35 countries in 
North and South America, Europe, Asia, and the Middle East. Dexlansoprazole capsules were first 
approved for use in adults in the United States in January 2009. The international birth date (IBD) 
is 30 January 2009.
The clinical pharmacology program for dexlansoprazole capsules was extensive and evaluated the 
pharmacokinetics (PK), pharmacodynamics, extrinsic factors (eg, drug-drug interactions and food 
effect), and intrinsic factors (eg, age, gender, race, hepatic impairment) [1]. Dexlansoprazole mean 
maximum observed plasma concentration (Cmax) and mean area under the plasma 
concentration-time curve (AUC) values appeared to increase proportionally to the dose following 
oral administration of dexlansoprazole delayed-release capsule single-doses or multiple-doses 
ranging from 30 to 120 mg. The apparent terminal disposition phase half-life (t1/2z) of 
dexlansoprazole typically ranged from 1 to 2 hours, regardless of the dose, and no appreciable 
accumulation of dexlansoprazole was observed following once daily (QD) dosing. In addition, the 
PK of dexlansoprazole were shown to be time independent based on the similar systemic exposure 
after oral administration of a single dose of dexlansoprazole capsules and that which was observed 
following QD oral dosing [2].
Dexlansoprazole is primarily metabolized by the cytochrome P450 (CYP) enzymes CYP3A4 and 
polymorphic CYP2C19 [1]. The CYP2C19 poor metabolizer (PM) phenotype is present in 12% to 
23% of the Asian population, and the prevalence of CYP2C19 PMs in Chinese subjects is similar 
to that of other Asian populations [3]. Study TAK-390MR/CPH-002 assessed the PK of multiple 
doses of dexlansoprazole 30 and 60 mg capsule doses in male Japanese PM and extensive 
metabolizer (EM) subjects. In the Japanese PMs, dexlansoprazole t1/2z was approximately 3 times 
longer than in EMs, and apparent clearance after extravascular administration (CL/F) in the EMs 
was approximately 4-times greater than PMs. Although the availability of PK data in PMs in the 
Caucasian and African American population is limited, it is expected that dexlansoprazole 
exposure in these races will be affected by CYP2C19 phenotypes as well.


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The majority of the dexlansoprazole capsule phase 1 studies were conducted in the United States. 
As development of dexlansoprazole expands to other countries, additional studies are needed to 
bridge between the data acquired previously in North American and Asian populations.
4.2
Rationale for the Proposed Study
The rationale for the current study is to add to the current knowledge of dexlansoprazole by 
assessing the PK and safety of dexlansoprazole 30 and 60 mg capsules in healthy Chinese subjects.


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5.0
STUDY OBJECTIVES AND ENDPOINTS
5.1
Objectives
5.1.1
Primary Objective
The primary objective of this study is to assess the PK after a single dose of dexlansoprazole 
30 and 60 mg delayed-release capsules in healthy Chinese subjects.
5.1.2
Secondary Objective
The secondary objective of this study is to evaluate the safety and tolerability of dexlansoprazole 
following oral administration of a single 30 or 60 mg dexlansoprazole delayed-release capsule.
5.2
Endpoints
5.2.1
Primary Endpoints
The primary endpoints for this study are the PK parameters of dexlansoprazole following a single 
oral dose of dexlansoprazole 30 and 60 mg delayed-release capsules:

Cmax.

Area under the plasma concentration-time curve from time 0 to time of the last quantifiable
concentration (AUClast).

Area under the plasma concentration-time curve from time zero to infinity (AUC∞).
5.2.2
Additional Endpoints

Time of first occurrence of Cmax (tmax).

Terminal disposition phase rate constant (λz).

t1/2z.

Volume of distribution during the terminal disposition phase after extravascular administration 
(Vz/F).

CL/F.
5.2.3
Safety Endpoints
Safety will be assessed by summarizing the incidence of treatment-related AEs, clinical laboratory 
tests (hematology, serum chemistry, and urinalysis), vital sign measurements, electrocardiograms 
(ECGs), and physical examinations.


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6.0
STUDY DESIGN AND DESCRIPTION
6.1
Study Design
This is a phase 1, open-label, single dose, 2-arm parallel study to assess the PK of a single oral dose 
of dexlansoprazole 30 and 60 mg delayed-release capsules. Forty subjects will be enrolled in the 
study, 20 subjects in Group 1 and 20 subjects in Group 2 (Table 6.a).
Table 6.a
Parallel Groups
Group
Regimen
1
A single oral dose of dexlansoprazole 30 mg delayed-release capsule
2
A single oral dose of dexlansoprazole 60 mg delayed-release capsule
A schematic of the study design is included as Figure 6.a. A schedule of study procedures is listed 
in Appendix A.
Figure 6.a
Schematic of Study Design
Pretreatment Period
Treatment Period
Follow-Up
Screening
Check-in
Dexlansoprazole
Delayed-Release Capsule
Single Dose 
(30 or 60 mg)
Discharge/Study 
Exit/Premature 
Termination
Follow-up Site/ 
Telephone Visit
Days -28 to -2
Day -1
Day 1
Day 2
5 to 10 days postdose
Confinement to Clinic
Note: A follow-up site/telephone visit will be made for collection of adverse events, serious adverse events, and 
concomitant medications taken since final dose.
6.2
Justification for Study Design, Dose, and Endpoints
This study was designed based on the requirements of the China Food and Drug Administration 
(CFDA) for successful registration of dexlansoprazole in China. Phase 3 safety and efficacy trials 
with dexlansoprazole will be performed concurrently in China. A single-dose study will provide 
adequate information on the PK of dexlansoprazole in Chinese subjects to allow the data to be 
bridged to data previously acquired in North American and Japanese populations at both the 
30 and 60 mg doses.
This is a single-center, open-label, single-dose, 2-arm parallel study using dexlansoprazole 
delayed-release capsules (30 and 60 mg). Healthy adult Chinese subjects will be enrolled. Since 
PPIs are intended to be used by both genders, effort will be made to enroll an equal number of men 
and women. The study will assess the PK of dexlansoprazole 30 and 60 mg delayed-release 
capsules.
The CYP2C19 PM phenotype is present in 12% to 23% of the Asian population, and the
prevalence of CYP2C19 PMs in Chinese subjects is similar to that of other Asian populations [3].


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The CYP2C19 isozyme is a polymorphic enzyme that is involved in the metabolism of 
dexlansoprazole, and administration of dexlansoprazole may result in higher plasma levels in 
subjects who are CYP2C19 PMs [1]. Therefore, the CYP2C19 metabolizer status of the subjects 
will be determined and, if appropriate, the effect of metabolizer status on the PK of 
dexlansoprazole will be assessed.
The objective of the study is to evaluate the PK of dexlansoprazole at both doses that will be 
included in the phase 3 studies. Standard PK parameters will be calculated. The design of the study 
will provide information on the PK of a single dose of dexlansoprazole 30 and 60 mg in healthy 
Chinese subjects. The safety of dexlansoprazole delayed-release capsules has been evaluated 
following oral administration in phases 1 and 3 studies. In the previous phase 3 studies, 
dexlansoprazole 30 and 60 mg had a comparable safety profile to lansoprazole 30 mg. 
Dexlansoprazole delayed-release capsule doses of 30 and 60 mg were well tolerated.
6.3
Premature Termination or Suspension of Study or Investigational Site
6.3.1
Criteria for Premature Termination or Suspension of the Study
The study will be completed as planned unless one or more of the following criteria are satisfied 
that require temporary suspension or early termination of the study.

New information or other evaluation regarding the safety or efficacy of the study medication 
that indicates a change in the known risk/benefit profile for the compound, such that the 
risk/benefit is no longer acceptable for subjects participating in the study.

Significant violation of Good Clinical Practice (GCP) that compromises the ability to achieve 
the primary study objectives or compromises subject safety.
6.3.2
Criteria for Premature Termination or Suspension of Investigational Sites
A study site may be terminated prematurely or suspended if the site (including the investigator) is 
found in significant violation of GCP, protocol, or contractual agreement, is unable to ensure 
adequate performance of the study, or as otherwise permitted by the contractual agreement.
6.3.3
Procedures for Premature Termination or Suspension of the Study or the 
Participation of Investigational Site(s)
In the event that the sponsor, an institutional review board (IRB)/ independent ethics committee 
(IEC), or regulatory authority elects to terminate or suspend the study or the participation of an 
investigational site, a study-specific procedure for early termination or suspension will be 
provided by the sponsor; the procedure will be followed by applicable investigational sites during 
the course of termination or study suspension.


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7.0
SELECTION AND DISCONTINUATION/WITHDRAWAL OF SUBJECTS
All entry criteria, including test results, need to be confirmed prior to first dose of study medication 
on Day 1.
7.1
Inclusion Criteria
Subject eligibility is determined according to the following criteria prior to entry into the study:
1. In the opinion of the investigator, the subject is capable of understanding and complying with 
protocol requirements.
2. The subject or, when applicable, the subject’s legally acceptable representative signs and dates 
a written, informed consent form and any required privacy authorization prior to the initiation 
of any study procedures including requesting that a subject fast for any laboratory evaluations.
3. The subject is a healthy adult man or woman of Chinese descent.
4. The subject is aged 18 to 45 years, inclusive, at the time of informed consent and study 
medication dose.
5. The subject weighs at least 50 kg and has a body mass index (BMI) from 19.0 to 26.0 kg/m2, 
inclusive at Screening Visit.
6. A man who is nonsterilized* and sexually active with a woman of childbearing potential*
agrees to use adequate contraception* from signing of informed consent throughout the 
duration of the study and for 30 days after last dose of study drug. 
7. If a woman of childbearing potential* is sexually active with a nonsterilized* man, she agrees 
to routinely use adequate contraception* from signing of informed consent throughout the 
duration of the study and for 30 days following the last dose of study drug. Women of 
childbearing potential* must have a negative pregnancy test at Screening and Check-in (Day -1 
of Period 1) and they must not be nursing.
*Definitions and acceptable methods of contraception are defined in Section 9.1.9
Contraception and Pregnancy Avoidance Procedure and reporting responsibilities 
are defined in Section 9.1.10 Pregnancy.
8. Subject has clinical chemistry, hematology, and complete urinalysis (fasted for at least 8 hours)
at the Screening Visit and Check-in (Day -1) results within the reference range for the testing
laboratory unless the out of range results are deemed not clinically significant by both the
investigator and Medical Monitor.
7.2
Exclusion Criteria
Any subject who meets any of the following criteria will not qualify for entry into the study: 
1. The subject has received any investigational compound within 3 months prior to Check-in 
(Day -1).


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2. The subject has received dexlansoprazole in a previous clinical study or has received 
dexlansoprazole or lansoprazole as a therapeutic agent within 30 days prior to Check-in 
(Day -1 of Period 1).
3. Subject has a known hypersensitivity to any component of the formulation of dexlansoprazole
or other drug with the same mechanism of action (including lansoprazole, omeprazole,
esomeprazole, rabeprazole, ilaprazole, or pantoprazole), or related compounds.
4. The subject is an immediate family member, study site employee, or is in a dependant 
relationship with a study site employee who is involved in the conduct of this study 
(eg, spouse, parent, child, sibling) or may consent under duress.
5. The subject has a history of significant gastrointestinal (GI) disorders manifested with 
persistent, chronic or intermittent nausea, vomiting, diarrhea, or has a current or recent (within 
6 months) GI disease that would influence the absorption of drugs (eg, a history of 
malabsorption, severe esophageal reflux, peptic ulcer disease or erosive esophagitis with 
frequent [more than once per week] occurrence of heartburn).
6. The subject has a history or clinical manifestations of serious neurologic, cardiovascular, 
pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, endocrine, hematologic, 
dermatologic, immunologic, psychiatric disorders, or other abnormality which may impact the 
ability of the subjects to participate or potentially confound the study results. 
7. Subject has received any known hepatic or renal clearance altering agents (eg, erythromycin, 
cimetidine, barbiturates, phenothiazines, fluvoxamine, etc.) within 28 days prior to the 
Check-in (Day -1) Visit.
8. Subject has had an acute, clinically significant illness within 30 days prior to Day 1.
9. The subject has a positive test result for alcohol or drugs of abuse at the Screening Visit or 
Check-in (Day -1) Visit.
10. The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol 
abuse within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol 
for 48 hours prior to Check-in (Day -1) throughout the confinement and for 48 hours prior to 
each clinic visit and drugs throughout the study. 
11. Subject has taken any excluded medication, supplements, or food products during the time 
periods listed in the Excluded Medications, Supplements, and Dietary Products Table 7.a listed 
in Section 7.3.
12. If a woman is pregnant or lactating or intending to become pregnant before, during, or within 
30 days after participating in this study; or is intending to donate ova during such time period.
13. If a man intends to donate sperm during the course of this study or for 30 days thereafter.
14. Subject has a history of cancer, except basal cell carcinoma which has been in remission for at 
least 5 years prior to Day 1.


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15. Subject has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus 
(HCV) antibody, or human immunodeficiency virus (HIV) antibody at Screening.
16. Subject has used nicotine-containing products (including but not limited to cigarettes, pipes, 
cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in 
(Day -1) or is unwilling to abstain from these products for the duration of the study.
17. The subject has poor peripheral venous access.
18. Subject has donated blood products (such as plasma), whole blood or had a significant blood 
loss (450 mL) within 56 days of Day 1.
19. Subject has a Screening or Check-in (Day -1) abnormal (clinically significant) ECG. Entry of 
any subject with an abnormal (not clinically significant) ECG must be approved, and 
documented by signature by both the principal investigator and the medical monitor.
20. Subject has abnormal Screening or Check-in (Day -1) laboratory values that suggest a 
clinically significant underlying disease or subject with the following lab abnormalities:
creatinine >1.5 mg/dL, alanine aminotransferase (ALT) and/or aspartate aminotransferase 
(AST) >2.5x the upper limits of normal (ULN), or total bilirubin >2.0 mg/dL.
7.3
Excluded Medications and Dietary Products
Use of the agents in Table 7.a (prescription or nonprescription) is prohibited from the time points 
specified until completion of all study activities. 


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Table 7.a
Prohibited Medications, Supplements, and Dietary Products
28 days prior to Check-in 
(Day -1)
7 days prior to Check-in 
(Day -1)
72 hours prior to Check-in 
(Day -1)
Prescription medications (a)
Over-the-counter (OTC) medications (b)
Products containing caffeine 
and/or xanthine
Nicotine-containing products
Vitamin supplements
Poppy seeds
Nutraceuticals (eg, St. John’s wort, 
ginseng, kava kava, ginkgo biloba, 
Chinese herbs, and melatonin)
Foods or beverages containing grapefruit 
or grapefruit juice, star fruit or star fruit 
juice, Seville-type (sour) oranges and 
marmalade, apple, orange, or pineapple 
juice, vegetables from the mustard green 
family (eg, kale, broccoli, watercress, 
collard greens, kohlrabi, Brussels 
sprouts, mustard), and charbroiled meats
Hepatic or renal clearance altering 
agents
Immunization/Vaccines (c)
Alcohol-containing products
Intake of known OTC 
inhibitors/inducers of CYPs 3A4/5, 
2C9, 2C19, 2D6, 1A2, 2B6, 2E1, and 
2A6 (d)
(a) Hormonal contraception and HRT are allowed, as long as the subject has been on a stable dose for a minimum of 90 
days prior to Day 1.
(b) Occasional use of acetaminophen (≤2 g/day) is allowed or other medication as approved by Takeda on a 
case-by-case basis. Acetaminophen is not allowed on Day 1.
(c) Inclusive of but not limited to H1N1 and flu vaccinations.
(d) Examples include: omeprazole, cimetidine, ranitidine, and chlorpheniramine.
Subjects must be instructed not to take any medications including OTC products without first 
consulting with the investigator.
7.4
Diet, Fluid, and Activity Control
Diet and Fluid
During each day of the confinement period, subjects will receive standardized meals and an 
evening snack. The menu of the standardized meals from the clinical research site needs to be 
approved by Takeda before the implementation. The clinical research site will ensure the same 
meals are served to all subjects on Day 1. All subjects may consume water ad libitum except for 
1 hour before and 1 hour after drug administration.
During confinement, foods, and beverages listed in Table 7.a will be prohibited, and all subjects 
will be limited to only standardized meals and snacks provided by the site.
Subjects will fast for a minimum of 8 hours prior to dosing. On Day 1, breakfast will be served 
1 hour postdose. Lunch will be served approximately 4 hours postdose. Dinner will be served 
approximately 9 hours postdose. A snack will be served approximately 12 hours postdose. No 


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additional meals will be served on Day 1. The start and stop times of meals on Day 1 will be 
recorded in the source documentation and on the case report form (eCRF). Subjects will be fasting 
for a minimum of 8 hours prior to collection of safety labs on Day 2.
Activity Control
Subjects will refrain from strenuous exercise beginning upon confinement and for the duration of 
their participation in the study.
7.5
Criteria for Discontinuation or Withdrawal of a Subject
The primary reason for discontinuation or withdrawal of the subject from the study should be 
recorded in the eCRF using the following categories. For screen failure subjects, refer to 
Section 9.1.15.
1. Pretreatment event (PTE) or adverse event (AE). The subject has experienced a PTE or AE that 
requires early termination because continued participation imposes an unacceptable risk to the 
subject’s health or the subject is unwilling to continue because of the PTE or AE.
2. Significant protocol deviation. The discovery after the first dose of study drug that the subject 
failed to meet protocol entry criteria or did not adhere to protocol requirements, and continued 
participation poses an unacceptable risk to the subject’s health.
3. Lost to follow-up. The subject did not return to the clinic and attempts to contact the subject 
were unsuccessful. Attempts to contact the subject must be documented.
4. Voluntary withdrawal. The subject (or subject’s legally acceptable representative) wishes to 
withdraw from the study. The reason for withdrawal, if provided, should be recorded in the 
eCRF.
Note: All attempts should be made to determine the underlying reason for the withdrawal and, 
where possible, the primary underlying reason should be recorded (ie, withdrawal due to an 
AE should not be recorded in the “voluntary withdrawal” category).
5. Study termination. The sponsor, IRB, IEC, or regulatory agency terminates the study.
6. Pregnancy. The subject is found to be pregnant.
Note: If the subject is found to be pregnant, the subject must be withdrawn immediately. The 
procedure is described in Section 9.1.10.
7. Other.
Note: The specific reasons should be recorded in the “specify” field of the eCRF.


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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 or her 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. In 
addition, efforts should be made to perform all procedures scheduled for Early Termination as 
noted in Appendix A. Discontinued or withdrawn subjects will not be replaced after enrollment.


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8.0
CLINICAL TRIAL MATERIAL MANAGEMENT
This section contains information regarding all medication and materials provided directly by the 
sponsor, and/or sourced by other means, that are required by the study protocol, including 
important sections describing the management of clinical trial material.
8.1
Study Medication and Materials
8.1.1
Dosage Form, Manufacturing, Packaging, and Labeling
The following study medications manufactured by Takeda Pharmaceutical Company Limited, 
Osaka, Japan will be provided for this study: 

Dexlansoprazole 30 mg delayed-release capsules.

Dexlansoprazole 60 mg delayed-release capsules.
The study drug will be foil/foil blistered and packaged in 1-day child resistant blister cards 
containing 1 capsule. The card label will be compliant with requirement of CFDA.
8.1.2
Storage
All clinical drug supplies used to conduct this study should be stored at: 20°C to 25°C; excursions 
allowed between 15°C and 30°C. 
Investigational drug must be kept in an appropriate, limited-access, secure place until it is used or 
returned to the sponsor or designee for destruction. Investigational drug must be stored under the 
conditions specified on the label, and remain in the original container until dispensed. A daily 
temperature log of the drug storage area must be maintained every working day.
8.1.3
Dose and Regimen
Subjects will fast for a minimum of 8 hours prior to dosing. On Day 1, breakfast will be served 
1 hour postdose. Subjects may consume water ad libitum except for 1 hour before and 1 hour after 
drug administration. Dosing will commence at approximately 0800 hours on Day 1. Study drug 
will be administered with 240 mL of water. Subjects must drink all of the water provided with the 
dose.
Following administration of the study drug, hand and mouth checks will be performed to ensure 
that the study drug was swallowed. Although the timing of events requires that each subject will be 
consistently administered the appropriate study drug at specific times, the exact dose time of 
consecutive subjects may be staggered to obviate the need to have all subjects on precisely the 
same study schedule.
Table 8.a
Study Medication Supplies
Parallel Group
Dose
1
Single oral dose of dexlansoprazole 30 mg delayed-release capsule
2
Single oral dose of dexlansoprazole 60 mg delayed-release capsule


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8.1.4
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.
All cases of overdose (with or without associated AEs) will be documented on an Overdose page 
of the eCRF, in order to capture this important safety information consistently in the database. 
Cases of overdose without manifested signs or symptoms are not considered AEs. AEs associated 
with an overdose will be documented on AE eCRF(s) according to Section 10.0, Pretreatment 
Events and Adverse Events.
Serious adverse events (SAEs) associated with overdose should be reported according to the 
procedure outlined in Section 10.2.2, Collection and Reporting of SAEs.
In the event of drug overdose, the subject should be treated symptomatically by the investigator.
8.2
Investigational Drug Assignment and Dispensing Procedures
The site will assign a 4-digit enrollment number in the order subjects become eligible for 
enrollment starting from 1001. This enrollment sequence number will be entered onto the eCRF. 
This 4-digit number will be used by the clinical site to facilitate the prelabeling of PK samples, and 
will be the only subject identifier used on all sample collections. It should also be contained on the 
PK transport vials shipped to the bioanalytical laboratory, and will be used by the laboratory to 
report the subject data results. This 4-digit number should only be used for the purposes described 
in this section. It does not replace the 3-digit subject screening number which is assigned at the 
time the informed consent is obtained (Section 9.1.1) and which is used for all other procedures to 
identify the subjects throughout the study.
8.3
Accountability and Destruction of Sponsor-Supplied Drugs
Drug supplies will be counted and reconciled at the site before being returned to a designated 
facility for destruction. 
The investigator or designee must ensure that the study medication is used in accordance with the 
approved protocol and is dispensed only to subjects enrolled in the study. To document appropriate 
use of study medication, the investigator must maintain records of all study medication delivery to 
the site, site inventory, dispensation and use by each subject, and return to the sponsor or designee.
Upon receipt of sponsor-supplied drug, the investigator or designee must verify the contents of the 
shipments against the packing list. The verifier should ensure that the quantity is correct, and the 
medication is in good condition. If quantity and conditions are acceptable, investigator or designee 
should acknowledge the receipt of the shipment by signing bottom half of the packing list and 
faxing per instructions provided on the form. If there are any discrepancies between the packing 
list versus the actual product received, Takeda must be contacted to resolve the issue. The packing 
list should be filed in the investigator’s essential document file.


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The investigator must maintain 100% accountability for all study medication received and 
dispensed during his or her entire participation in the study. Proper drug accountability includes, 
but is not limited to:

Continuously monitoring expiration dates if expiry date is provided to the investigator. 

Frequently verifying that actual inventory matches documented inventory.

Verifying that the log is completed for the drug lot used to prepare each dose.

Verifying that all containers used are documented accurately on the log.

Verifying that required fields are completed accurately and legibly.
If any dispensing errors or discrepancies are discovered, the sponsor must be notified immediately.
The investigator must record the current inventory of all study medication on a sponsor-approved 
drug accountability log. The following information will be recorded at a minimum: protocol 
number and title, name of investigator, site identifier and number, description of study medication, 
expiry date and amount dispensed, including the initials of the person dispensing the drug. The log 
should include all required information as a separate entry for each subject to whom study 
medication is dispensed.
Prior to site closure or at appropriate intervals, a representative from the sponsor or its designee 
will perform clinical trial material accountability and reconciliation before clinical trial materials 
are returned to the sponsor or its designee for destruction. The investigator will retain the original 
documentation regarding clinical trial material accountability, return, and destruction, and copies 
will be sent to the sponsor or designee.
The investigator will be notified of any expiry date or retest date extension of clinical trial material 
during the study conduct. On expiry date notification from the sponsor or designee, the site must 
complete all instructions outlined in the notification, including segregation of expired clinical trial 
material for return to the sponsor or its designee for destruction.
In the event of expiry date extension of supplies already at the study site, clinical trial material may 
be relabeled with the new expiry date at that site. In such cases, Takeda or its designee will prepare 
additional labels, and all necessary documentation for completion of the procedure at the sites.


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9.0
STUDY PLAN
9.1
Study Procedures
The following sections describe the study procedures and data to be collected. For each procedure, 
subjects are to be assessed by the same investigator or site personnel whenever possible. The 
Schedule of Study Procedures is located in Appendix A.
9.1.1
Informed Consent Procedure
The requirements of the informed consent are described in Section 15.2.
Informed consent must be obtained prior to the subject entering into the study, and before any 
protocol-directed procedures are performed, including requesting that a subject fast for laboratory 
evaluations.
A unique subject identification number (site number + subject number) will be assigned to each 
subject at the time informed consent is obtained; this subject number will be used throughout the 
study.
9.1.2
Demographics, Medical History, and Medication History Procedure
Demographic information to be obtained will include date of birth, gender, race as described by the 
subject, height, weight, and smoking status of the subject at Screening. Caffeine consumption and 
alcohol history will also be collected at Screening. Medical history to be obtained will include 
determining whether the subject has any significant conditions or diseases that stopped at or prior 
to signing of informed consent. Ongoing conditions are considered concurrent medical conditions 
(see Section 9.1.7).
Medication history information to be obtained includes any medication relevant to eligibility 
criteria stopped at or within 28 days prior to signing of informed consent.
9.1.3
Physical Examination Procedure
A baseline physical examination (defined as the pretreatment assessment immediately prior to the 
start of investigational drug) will consist of the following body systems: (1) eyes; (2) ears, nose, 
throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; 
(6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; 
(10) lymph nodes; and (11) other.
Any abnormal findings from the baseline physical examination must be assessed as not clinically 
significant (NCS) or clinically significant (CS) by the investigator and recorded in the source 
document and eCRF. All CS findings/changes will be recorded as a PTE or concurrent medical 
condition in the source document and on the appropriate eCRF described in Section 10.0 or 
Section 9.1.7.
On subsequent examinations, any abnormal change from the pretreatment physical examination 
assessment occurring immediately prior to the start of the investigational drug (Day1) must be 
assessed as NCS or CS by the investigator and recorded in the source document and eCRF. Any 


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CS change or new diagnosis as a result of a CS change, as determined by the investigator, will be 
recorded as an AE in source documentation and on the PTE/AE eCRF described in Section 10.0.
9.1.4
Weight, Height and BMI
A subject should have weight and height measured while wearing indoor clothing and with shoes 
off. The BMI is calculated using metric units with the formula provided below:
Metric:
BMI = weight (kg)/[height (m)]2
Height will be collected in centimeters to 1 decimal place and weight will be collected in 
kilograms (kg) to 1 decimal place. BMI will only be calculated at the Screening Visit and results
for BMI will be expressed with 1 decimal place.
Example: Height=176.2 cm (or 1.762 m), weight=79.2 kg; BMI=79.2/1.7622=25.5 kg/m2.
9.1.5
Vital Sign Procedure
Vital signs will include oral or axillary body temperature measurement, sitting blood pressure 
(after 5 minutes resting), respiration rate and pulse beats per minute (bpm). Only blood pressure 
and pulse will be taken on Check-in (Day -1) through Day 2.
When vital signs are scheduled at the same time as blood draws, the blood draw will take priority 
and vital signs will be obtained within 0.5 hour before or after the scheduled blood draw.
9.1.6
Documentation of Concomitant Medications
Concomitant medication is any drug given in addition to the study medication. These may be 
prescribed by a physician or obtained by the subject over the counter. Concomitant medication is 
not provided by Takeda. At each study visit, subjects will be asked whether they have taken any 
medication other than the study medication (used from signing of informed consent through the 
end of the study), and all medication including vitamin supplements, over-the-counter 
medications, and oral herbal preparations, must be recorded in the eCRF. Documentation will 
include generic medication name, dose, unit, frequency, route of administration, start and end 
dates, and reason for use.
9.1.7
Documentation of Concurrent Medical Conditions
Concurrent medical conditions are those significant ongoing conditions or diseases that are present 
at signing of informed consent. This includes clinically significant laboratory, ECG, or physical 
examination abnormalities noted at Screening. The condition (ie, diagnosis) should be described.
9.1.8
Procedures for Clinical Laboratory Samples
All samples will be collected in accordance with acceptable laboratory procedures. The maximum 
volume of blood at any single visit is approximately 84 mL, and the total volume of blood for the 
study is approximately 152 mL. Laboratory samples will be taken following a minimum 8-hour 
overnight fast on the days stipulated in the Schedule of Study Procedures (Appendix A).


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Table 9.a lists the tests that will be obtained for each laboratory specimen.
Table 9.a
Clinical Laboratory Tests
Hematology
Serum Chemistry
Urinalysis
Red blood cells (RBC)
White blood cells (WBC)
with differential
Hemoglobin
Hematocrit
Platelets
ALT
Albumin
Alkaline phosphatase
AST
Glucose
Total bilirubin
Total protein
Total cholesterol
Triglycerides
Serum creatinine
Blood urea nitrogen or urea
Uric acid
-Glutamyl transferase (GGT)
Calcium
Phosphorus
Potassium
Sodium
Chloride
Bicarbonate or carbon dioxide
pH
Specific gravity
Protein
Glucose
Ketones
Bilirubin
Microscopic Analysis
(RBCs, WBCs, epithelial 
cells, casts) if significant 
findings on dipstick 
urinalysis
Diagnostic Screening:
Serum
Urine
Breath
HIV test – Screening Visit only
Hepatitis panel, including HBsAg and anti-HCV
– Screening Visit only
Women only
FSH (if menopause is suspected)
Women of childbearing potential only
serum hCG (for pregnancy)
– Screening, Day -1, Day 2, or if a subject 
prematurely terminates from the study.
Drug screen, including amphetamines, 
barbiturates, benzodiazepines, cannabinoids, 
cocaine, and opiates.
Alcohol test
hCG=human chorionic gonadotropin, FSH=follicle stimulating hormone.
The local laboratory will perform laboratory tests for hematology, serum chemistries, and 
urinalysis. The results of laboratory tests will be returned to the investigator, who is responsible for 
reviewing and filing these results. All laboratory safety data will be transferred electronically to 
Takeda or designee in the format requested by Takeda. If the laboratory is unable to electronically 
transfer data, the study site coordinator or designee is responsible for transcribing laboratory 
results to the eCRF. The investigator will maintain a copy of the laboratory accreditation and the 
reference ranges for the laboratory used.


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If subjects experience ALT or AST >3×ULN, follow-up laboratory tests (at a minimum, serum 
alkaline phosphatase, ALT, AST, total bilirubin, GGT, and INR) should be performed within a 
maximum of 7 days and preferably within 48-72 hours after the abnormality was found.
(Please refer to Section 10.2.3 for the appropriate guidance on Reporting of Abnormal Liver 
Function Tests in relation to ALT or AST >3×ULN in conjunction with total bilirubin >2×ULN.)
If the ALT or AST remains elevated >3×ULN on these 2 consecutive occasions, the investigator 
must contact the Medical Monitor for consideration of additional testing, close monitoring, 
possible discontinuation of study medication, discussion of the relevant subject details and 
possible alternative etiologies. The abnormality should be recorded as an AE (please refer to 
Section 10.2.3 Reporting of Abnormal Liver Function Tests for reporting requirements).
Laboratory reports must be signed and dated by the principal investigator or the study doctor 
delegated by the principal investigator indicating that the report has been reviewed and any 
abnormalities have been assessed for clinical significance.
All clinically significant laboratory abnormalities must be recorded as a PTE/AE in the subject’s 
source documents and on the appropriate eCRF. A clinically significant laboratory abnormality 
that has been verified by retesting will be followed until the abnormality returns to an acceptable 
level or a satisfactory explanation has been obtained.
9.1.9
Contraception and Pregnancy Avoidance Procedure
From signing of informed consent, throughout the duration of the study, and for 30 days after last 
dose of study medication, nonsterilized** men who are sexually active with a woman of 
childbearing potential* must use barrier contraception (eg, condom with spermicidal cream or 
jelly). In addition, they must be advised not to donate sperm during this period.
From signing of informed consent, throughout the duration of the study, and for 30 days after last 
dose of study medication, female subjects of childbearing potential* who are sexually active with a 
nonsterilized male partner** must use adequate contraception. In addition they must be advised 
not to donate ova during this period.
*Women NOT of childbearing potential are defined as those who have been surgically sterilized 
(hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (defined as
continuous amenorrhea of at least 1 year and FSH>40 IU/L or at least 5 years since last regular 
menses, confirmed before any study medication is implemented, confirmed before any study 
medication is administered). Subject without bilateral tubal ligation documentation must follow 
one of the other methods of contraception as described below.
**Sterilized men should be at least 1 year postvasectomy and have confirmed that they have 
obtained documentation of the absence of sperm in the ejaculate.
An acceptable method of contraception is defined as one that has no higher than a 1% failure rate. 
In this study, where medications and devices containing hormones are included (provided the 
subject has been on a stable dose for a minimum of 90 days prior to Day 1), the only acceptable 
methods of contraception are:


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Barrier methods (each time the 
subject has intercourse):
Intrauterine devices 
(IUDs):
Hormonal contraceptives:

Cap (plus spermicidal cream or 
jelly) PLUS male condom and 
spermicide.

Diaphragm (plus spermicidal 
cream or jelly) PLUS male 
condom and spermicide.

Copper T PLUS 
condom or spermicide.

Progesterone T PLUS 
condom or spermicide.

Implants.

Hormone shot/injection.

Combined pill.

Minipill.

Patch.

Vaginal ring PLUS male 
condom and spermicide.
Subjects will be provided with information on acceptable 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, donation of ova, and sperm donation
during the course of the study.
During the course of the study, regular serum hCG pregnancy tests will be performed only for 
women of childbearing potential and subjects will receive continued guidance with respect to the 
avoidance of pregnancy and sperm donation as part of the study procedures. In addition to a 
negative serum hCG pregnancy test at Screening, subjects also must have a negative serum hCG 
pregnancy test Check-in (Day-1) prior to receiving any dose of study medication. Women will also 
be given a serum hCG pregnancy test upon Study Exit (Day 2) or Early Termination.
9.1.10 Pregnancy
If any subject is found to be pregnant during the study she should be withdrawn and any 
sponsor-supplied drug should be immediately discontinued. In addition, any pregnancies in the 
partner of a man during the study or for up to 30 days after the last dose should also be recorded 
following authorization from the subject’s partner.
If the pregnancy occurs during administration of active study medication, eg, after Day 1 or within 
30 days of the last dose of active study medication, the pregnancy should be reported immediately, 
using a pregnancy notification form, to the contact listed in Section 1.0.
If the woman or female partner of a man subject agrees to the primary care physician being 
informed, the investigator should notify the primary care physician that the subject/female partner 
of the subject was participating in a clinical study at the time she became pregnant and provide 
details of treatment the subject received.
All reported pregnancies will be followed up to final outcome, using the pregnancy form. The 
outcome, including any premature termination, must be reported to the sponsor. An evaluation 
after the birth of the child will also be conducted.


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9.1.11 ECG Procedure
A standard 12-lead ECG will be recorded at the time points stipulated in Appendix A. The 
investigator (or a qualified observer at the investigational site) will interpret the ECG using 1 of the 
following categories: within normal limits, abnormal but not clinically significant, or abnormal 
and clinically significant.
The results of the ECG will be captured on the source documents and appropriate eCRF and the 
original hard copies should be kept as source documentation. ECGs on thermal paper must be 
photocopied and the copy should be kept in the subjects’ source documents.
All stationary 12-lead ECG machines will be supplied by the site. The ECGs should be collected 
following an approximate 5-minute rest period. Should technical difficulties occur during 
collection of the ECG, a reasonable attempt should be made to repeat the ECG shortly after the 
failed attempt.
9.1.12 Sample Collection for Genotype Analysis
Genotyping and phenotyping analysis for CYP2C19 will be required for all subjects because 
dexlansoprazole is metabolized by the polymorphic isozyme CYP2C19. On Day 1, one blood 
sample (approximately 2 mL) for genotype analysis will be collected into vacutainers containing 
anticoagulant K2EDTA according to the schedule in Appendix A. Instructions for sample 
processing and shipment are provided in Appendix E.
9.1.13 Pharmacokinetic Sample Collection
9.1.13.1 Collection of Blood for Pharmacokinetic Sampling
On Day 1, blood samples (one 6-mL sample per scheduled time) for the determination of 
dexlansoprazole plasma concentrations will be collected into chilled vacutainers containing 
anticoagulant K2EDTA according to the schedule in Appendix A.
Instructions for sample processing and shipment are provided in Appendix E.
Blood samples will be collected according to Table 9.b.
Table 9.b
Collection of Blood Samples for Pharmacokinetic Analysis
Day
Blood Sample Collection Time (hours)
Day 1
One 6 mL sample at predose (no earlier than 30 min predose) (0 hour) and, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 
10, 12, 16, and 24 hours postdose
The actual time of sample collection will be recorded on the source document and eCRF. The PK 
sample should not be collected at the Early Termination Visit if a PK collection is not scheduled. 


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9.1.14 Pharmacokinetic Parameters
The PK parameters of dexlansoprazole will be determined from the concentration-time profiles for 
all evaluable subjects. Actual sampling times, rather than scheduled sampling times, will be used 
in all computations involving sampling times. The following PK parameters will be calculated 
from plasma concentration values:
Symbol/Term
Definition
Plasma
AUClast
Area under the plasma concentration-time curve from time 0 to time of the last quantifiable 
concentration.
AUC∞
Area under the plasma concentration-time curve from time 0 to infinity. 
Cmax
Maximum observed concentration.
CL/F
Apparent clearance after extravascular administration. 
λz
Terminal disposition phase rate constant.
t1/2z
Terminal disposition phase half-life. 
tmax
Time of first occurrence of Cmax.
Vz/F
Apparent volume of distribution during the terminal disposition phase after extravascular 
administration.
Other parameters may be calculated, if appropriate.
9.1.15 Documentation of Screen Failure
Investigators must account for all subjects who sign informed consent. If the subject is found to be 
not eligible at this visit, the investigator should complete the relevant eCRF.
The primary reason for screen failure is recorded in the eCRF using the following categories:

PTE/AE.

Did not meet inclusion criteria or did meet exclusion criteria.

Significant protocol deviation.

Lost to follow-up.

Voluntary withdrawal <specify reason>.

Study termination.

Other <specify reason>.
Subject numbers assigned to subjects who fail screening should not be reused.
9.1.16 Documentation of Study Entrance
Only subjects who meet all of the inclusion criteria and none of the exclusion criteria are eligible 
for entrance into the study.


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If the subject is found to be not eligible for entrance, the investigator should record the primary 
reason for failure on the applicable eCRF.
9.2
Monitoring Subject Treatment Compliance
Study medication will be administered while subjects are under observation in the clinical research 
unit. Following administration of the study medication, appropriate mouth and/or hand checks will 
be performed to ensure that the dose is swallowed and noted in the source document. The date and 
time of each dose will be recorded in the source documents and on the eCRFs. An inventory of the 
study medication supplies dispensed will be performed by the site pharmacist or authorized study 
designee and recorded onto the Drug Accountability Log in the subject’s source document records 
or equivalent. The exact dose time of consecutive subjects may be staggered to facilitate logistics 
at the site.
9.3
Schedule of Observations and Procedures
The schedule for all study-related procedures for all evaluations is shown in Appendix A. 
Assessments should be completed at the designated visit/time point(s).
9.4
Blood Volume
Total blood sampling volume for an individual subject is shown in Table 9.c.
Table 9.c
Approximate Blood Volume
Sample Type
Sample 
Volume 
(mL)
Estimated Blood Collection
Total 
Volume 
(mL)
Number of 
Samples
Treatment Days
Clinical laboratory tests
20 mL
3
Screening, Check-in (Day -1), Study Exit
60
Genotyping
2 mL
1
Day 1
2
PK blood collection
6 mL
15
Day 1 to 2
90
Total Approximate Blood Sampling Volume
152
The maximum volume of blood at any single day is approximately 84 mL, and the approximate 
total volume of blood for the study is 152 mL.
Direct venipuncture is the preferred method of blood collection. 


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10.0
PRETREATMENT EVENTS AND ADVERSE EVENTS
10.1
Definitions
10.1.1 PTEs
A PTE is defined as any untoward medical occurrence in a clinical investigation subject who has 
signed informed consent to participate in a study but prior to administration of any study drug; it 
does not necessarily have to have a causal relationship with study participation.
10.1.2 AEs
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a drug; it does not necessarily have to have a causal relationship with this 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.
10.1.3 Additional Points to Consider for PTEs and AEs
An untoward finding generally may:

Indicate a new diagnosis or unexpected worsening of a pre-existing condition. (Intermittent 
events for pre-existing conditions underlying disease should not be considered PTEs or 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. 

PTEs/AEs caused by a study procedure (eg, a bruise after blood draw) should be recorded as a 
PTE/AE.
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 a PTE(s) or as an AE(s).
Laboratory values and ECG findings:

Changes in laboratory values or ECG parameters are only considered to be PTEs or 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 


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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 a PTE or as an AE.
Pre-existing conditions:

Pre-existing conditions (present at the time of signing of informed consent) are considered 
concurrent medical conditions and should NOT be recorded as PTEs or AEs. Baseline 
evaluations (eg, laboratory tests, ECG, X-rays etc.) should NOT be recorded as PTEs unless 
related to study procedures. However, if the subject experiences a worsening or complication 
of such a concurrent condition, the worsening or complication should be recorded 
appropriately as a PTE (worsening or complication occurs before start of study drug) or an AE 
(worsening or complication occurs after start of study drug). 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 a PTE/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 in the condition from Baseline (eg “worsening of…”).

If a subject has a degenerative concurrent condition (eg, cataracts, rheumatoid arthritis), 
worsening of the condition should only be captured as a PTE/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 PTEs or AEs:

If the subject experiences a worsening or complication of a PTE after starting administration of 
the study medication, the worsening or complication should be recorded appropriately as an 
AE. Investigators should ensure that the AE term recorded captures the change in the condition 
(eg, “worsening of…”).

If the subject experiences a worsening or complication of an AE 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 /Serious PTEs:

If the subject experiences changes in severity of an AE/serious PTE, 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 PTEs or AEs. However, if a preplanned procedure is 


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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 a PTE or 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 PTEs or AEs, but should be documented in the subject’s source 
documents. Complications resulting from an elective surgery should be reported as AEs.
Overdose:

Cases of overdose with any medication without manifested side effects are NOT considered 
PTEs or AEs, but instead will be documented on an Overdose page of the eCRF. Any 
manifested side effects will be considered PTEs or AEs and will be recorded on the AE page of 
the eCRF.
10.1.4 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).


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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 seizure
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
PTEs that fulfill 1 or more of the serious criteria above are also to be considered SAEs and should 
be reported and followed up in the same manner (see Sections 10.2.2 and 10.3).
10.1.5 Severity of PTEs and AEs
The different categories of intensity (severity) are characterized as follows:
Mild:
The event is transient and easily tolerated by the subject.
Moderate:
The event causes the subject discomfort and interrupts the subject’s usual activities.
Severe:
The event causes considerable interference with the subject’s usual activities.
10.1.6 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 possible involvement of the drug 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 drugs and concurrent treatments.
10.1.7 Relationship to Study Procedures
Relationship (causality) to study procedures should be determined for all PTEs and AEs.
The relationship should be assessed as Related if the investigator considers that there is reasonable 
possibility that an event is due to a study procedure. Otherwise, the relationship should be assessed 
as Not Related.


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10.1.8 Start Date
The start date of the AE/PTE is the date that the first signs/symptoms were noted by the subject 
and/or physician.
10.1.9
Stop Date 
The stop date of the AE/PTE is the date at which the subject recovered, the event resolved but with 
sequelae or the subject died.
10.1.10
Frequency 
Episodic AEs/PTE (eg, vomiting) or those which occur repeatedly over a period of consecutive 
days are intermittent. All other events are continuous.
10.1.11
Action Concerning Study Drug 

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 was already 
stopped before the onset of the AE.

Dose Reduced – the dose was reduced due to the particular AE.

Dose Interrupted – the dose was interrupted due to the particular AE.
10.1.12
Outcome

Recovered/Resolved – Subject returned to first assessment status with respect to the AE/PTE.

Recovering/Resolving – the intensity is lowered by one or more stages: the diagnosis or 
signs/symptoms has almost disappeared; the abnormal laboratory value improved, but has not 
returned to the normal range or to baseline; the subject died from a cause other than the 
particular AE/PTE 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 
study period has got worse than when it started; is an irreversible congenital anomaly; the 
subject died from another cause with the particular AE/PTE state remaining “Not 
recovered/not resolved”.

Resolved with sequelae – the subject recovered from an acute AE/PTE but was left with 
permanent/significant impairment (eg, recovered from a cardiovascular accident but with 
some persisting paresis.

Fatal – the AEs/PTEs which are considered as the cause of death.


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
Unknown – the course of the AE/PTE cannot be followed up due to hospital change or 
residence change at the end of the subject’s participation in the study.
10.2
Procedures
10.2.1 Collection and Reporting of AEs
10.2.1.1 PTE and AE Collection Period
Collection of PTEs will commence from the time the subject signs the informed consent to 
participate in the study and continue until the subject is first administered study medication 
(Day 1) or until screen failure. For subjects who discontinue prior to study medication 
administration, PTEs are collected until the subject discontinues study participation.
Collection of AEs will commence from the time that the subject is first administered study 
medication (Day 1). Routine collection of AEs will continue until Final Visit or Early 
Termination. A follow-up site/telephone visit will be made by each subject 5 to 10 days following 
the last dose of study drug to collect any AEs that may have occurred.
10.2.1.2 PTE and AE Reporting
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 a 
serious PTE 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. 
Non-serious PTEs, related or unrelated to the study procedure, need not to 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 PTEs and AEs will be documented in the PTE/AE page of the eCRF, 
whether or not the investigator concludes that the event is related to the drug treatment. The 
following information will be documented for each event:
1. Event term.
2. Start and stop date and time.
3. Frequency.
4. Severity.
5. Investigator’s opinion of the causal relationship between the event and administration of study 
medication(s) (related or not related) (not completed for PTEs).
6. Investigator’s opinion of the causal relationship to study procedure(s), including the details of 
the suspected procedure.


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7. Action concerning study medication (not applicable for PTEs).
8. Outcome of event.
9. Seriousness.
10.2.2 Collection and Reporting of SAEs
When an SAE occurs through the AE collection period it should be reported according to the 
following procedure:
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 1.0.
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 Serious PTEs will follow the procedure described for SAEs.
10.2.3 Reporting of Abnormal Liver Function Tests
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 eCRF 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 and 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 10.2.2. 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 or medical history/concurrent medical conditions. Follow-up laboratory 
tests as described in Section 9.1.8 must also be performed. In addition, an LFT Increases eCRF 
must be completed and transmitted with the Takeda SAE form (as per Section 10.2.2).
10.3
Follow-up of SAEs
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 


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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.
10.3.1 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 to the regulatory authorities as expedited report 
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.


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11.0
STUDY-SPECIFIC COMMITTEES
No steering committee, data safety monitoring committee, or clinical endpoint committee will be 
used in this study.


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12.0
DATA HANDLING AND RECORDKEEPING
The full details of procedures for data handling will be documented in the Data Management Plan. 
AEs, PTEs, 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 (WHODRUG).
12.1
CRFs (Electronic and Paper)
Completed eCRFs are required for each subject who signs an informed consent.
The sponsor or its designee will supply investigative sites with access to eCRFs. The sponsor will 
make arrangements to train appropriate site staff in the use of the eCRF. These forms are used to 
transmit the information collected in the performance of this study to the sponsor and regulatory 
authorities. eCRFs must be completed in English. 
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. 
The principal investigator must review the eCRFs for completeness and accuracy and must e-sign 
the appropriate eCRFs as indicated. Furthermore, the investigator must retain full responsibility 
for the accuracy and authenticity of all data entered on the eCRFs.
After the lock of the clinical study database, any change of, modification of or addition to the data 
on the eCRF should be made by the investigator with use of change and modification records of 
the eCRFs. The principal investigator must review the data change for completeness and accuracy, 
and must sign and date.
eCRFs 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 eCRFs. The completed eCRFs 
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.
12.2
Record Retention
The investigator agrees to keep the records stipulated in Section 12.1 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 should be 
copied and certified, 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 eCRFs, including audit trail, and detailed records of 
drug disposition to 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, International Conference on Harmonisation (ICH) E6 Section 4.9.5 


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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 phase 1 Site Specifications document for the sponsor’s requirements on record 
retention. The investigator should contact and receive written approval from the sponsor before 
disposing of any such documents.


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13.0
STATISTICAL METHODS
13.1
Statistical and Analytical Plans
A statistical analysis plan (SAP) will be prepared and finalized prior to database lock. This 
document will provide further details regarding the definition of analysis variables and analysis 
methodology to address all study objectives. 
The targeted review plan will be conducted prior to database lock. This review will assess the 
accuracy and completeness of the study database, subject evaluability, and appropriateness of the 
planned statistical methods.
13.1.1 Analysis Sets
All subjects who are enrolled in the study and take at least 1 dose of study drug will be included in 
the safety set.
All subjects who receive at least 1 dose of study drug and have at least 1 measureable plasma 
concentration of dexlansoprazole will be included in the PK set. 
13.1.2 Analysis of Demographics and Other Baseline Characteristics
Demographic and baseline characteristics will be summarized by dose group. Summary statistics 
(number of subjects, mean, median, SD and range) will be generated for continuous variables (eg, 
age, weight, and body mass index) and the number and percentage of subjects within each category 
will be presented for categorical variables (eg, gender, race and ethnicity).
13.1.3 Pharmacokinetic Analysis
The concentration of dexlansoprazole in plasma will be summarized by scheduled sampling time 
points and dose group using descriptive statistics. Individual plasma concentration data will be 
presented in a data listing.
Descriptive statistics (number of subjects, arithmetic mean, SD, %CV, median, minimum and 
maximum) will be used to summarize the plasma PK parameters for dexlansoprazole from each 
dose group.
A more detailed analysis will be presented in the SAP.
13.1.4 Safety Analysis
All AEs will be coded by system organ class (SOC) and preferred term (PT) using the MedDRA. 
Treatment-emergent adverse events (TEAEs) with onset occurring within 30 days (onset date –
last date of dose +1≤30) after study drug administration will be included in the summary tables. 
All AEs will be in the listings. TEAEs will be summarized by SOC and PT. The following 
summary tables will be included in the report: summary of TEAEs and drug-related AEs, 
relationship of AEs to study drug (related vs not related), severity of AEs, and related AEs. Data 
listings will be provided for all AEs including PTEs, TEAEs, AEs leading to study drug 
discontinuation, and SAEs.


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Baseline, postdose, and change from baseline to postdose laboratory values will be summarized 
using descriptive statistics for each dose group. A table with predefined criteria for markedly 
abnormal values for laboratory variables will be presented. All clinical laboratory data will be 
listed.
Vital signs will be summarized for each dose group by presenting descriptive statistics for 
baseline, postdose, and change from baseline to postdose values. Vital signs that meet predefined 
markedly abnormal criteria will be presented. All vital sign data will be provided in the data 
listings.
Shift tables for ECG evaluation will be provided overall. All ECG data will be listed in the data 
listings.
13.2
Interim Analysis and Criteria for Early Termination
No interim analysis is planned.
13.3
Determination of Sample Size
No formal sample size calculations were conducted. A sample size of 40 subjects, 20 subjects per 
parallel group, will be used in this study. This sample size is deemed to be sufficient for the 
assessment of the PK of dexlansoprazole 30 and 60 mg delayed-release capsules in the Chinese 
population.


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14.0
QUALITY CONTROL AND QUALITY ASSURANCE
14.1
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 eCRFs. Source documents are defined as original documents, data, and records. 
The investigator and institution 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 designee 
(as long as blinding is not jeopardized), including but not limited to the Investigator’s Binder, 
study medication, subject medical records, informed consent documentation, documentation of 
subject authorization to use personal health information (if separate from the informed consent 
forms), and review of eCRFs 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.
14.2
Protocol Deviations
The investigator should not deviate from the protocol, except where necessary to eliminate an 
immediate hazard to study 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.
The site should document all protocol deviations in the subject’s source documents. In the event of 
a significant deviation, the site should notify the sponsor or its designee (and IRB or EC, as 
required). 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. A Protocol Deviation Form should be completed by the site and signed by the sponsor 
or designee for any significant deviation from the protocol.
Every attempt will be made to collect each PK blood sample at the designated time point, and the 
actual time of each blood sample will be recorded on the source document and eCRF. However, 
blood samples not collected within the interval specified for the scheduled sample time should be 
reported to Takeda using the Protocol Deviation Form.


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Protocol Deviation Forms are to be completed for PK samples collected outside of the following 
intervals shown in Table 14.a:
Table 14.a
Windows for Pharmacokinetic Sample Collection
Minutes
Nominal Sampling Time
no more than 30 minutes predose
0 hour
±5
immediately postdose to ≤6 hours
±10
>6 hours to 12 hours postdose
±15
>12 hours to 24 hours
14.3
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 CFDA, the Food and Drug Administration [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 and institution guarantee 
access for quality assurance auditors to all study documents as described in Section 14.1.


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15.0
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 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.
15.1
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 or package 
insert, 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 and 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 
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.


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15.2
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 or she 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.


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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.
15.3
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 15.2).
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 eCRF).
15.4
Publication, Disclosure, and Clinical Trial Registration Policy
15.4.1 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 
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.


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15.4.2 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 
interventional clinical trials it sponsors anywhere in the world on ClinicalTrials.gov 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 American investigators), country, and 
recruiting status will be registered and available for public viewing. For some registries, Takeda 
will assist callers in locating trial 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 Takeda providing this 
information to callers must provide Takeda with a written notice requesting that their information
not be listed on the registry site.
15.4.3 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.
15.5
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 clinical study subjects. 
Refer to the Clinical 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.


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16.0
REFERENCES
1. Dexilant (dexlansoprazole) Delayed Release Capsules. Full Prescribing Information. 
Deerfield, IL: Takeda Pharmaceuticals America, Inc., Revised 16 January 2016.
2. Vakily M, Zhang W, Wu J, Atkinson SN, Mulford D. Pharmacokinetics and 
pharmacodynamics of a known active PPI with a novel dual delayed release technology, 
dexlansoprazole MR: a combined analysis of randomized controlled clinical trials. Curr Med 
Res Opin 2009;25(3):627-38.
3. Yin OQ, Tomlinson B, Chow AH, Waye MM, Chow MS. Omeprazole as a CYP2C19 marker 
in Chinese subjects: assessment of its gene-dose effect and intrasubject variability. J Clin 
Pharmacol 2004;44(6):582-9.


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Appendix A
Schedule of Study Procedures
Procedure
Pretreatment Period
Treatment Period
Early 
Termination
Follow-up
Site/Telepho
ne Visit
Postdose 5-10 
days (b)
Screening 
Days -28 to -2 
(a)
Check-in
Day -1
Day 1
Day 2/
Study Exit
Confinement
X
X
X (c)
Informed consent (d)
X
Inclusion/exclusion
criteria
X
X
Demographics and
medical history
X
Medication history
X
Concurrent medical
conditions
X
Complete physical
exam
X
X
X
X
Body weight and
height
X
X (e)
X (e)
X (e)
12-Lead ECG
X
X
X
X
Vital signs (f)
X
X (f)
X (f)
X (f)
X
Fasting safety
laboratory 
evaluations (g)
X
X
X
X
Serum pregnancy test
(h)
X
X
X
X
FSH (i)
X
HIV, HBsAg, and 
anti-HCV screening
X
Urine drug screen
X
X
Alcohol breath test
X
X
Blood sampling for
PK analysis
X (j)
X (j)
Blood sample for 
CYP2C19 genotype
testing
X
Administration of
study drug (k)
X
Pretreatment 
event/Adverse
event (l)
assessment (l)
X
X
X
X
X
X
Concomitant
medication 
assessment
X
X
X
X
X
X
Footnotes are on the following page.


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(a) Screening procedures must be performed within 28 days prior to administration of investigational product.
(b) The routine collection of AEs will continue after dosing through the Follow-up site/telephone visit which will be 
made 5-10 days postdose.
(c) Following study procedure completion on Day 2 subjects will be discharged from the study.
(d) HIPAA=Health Insurance Portability and Accountability Act, must be signed before any study-specific procedures 
are performed.
(e) Excluding height. BMI will be calculated at Screening only.
(f) Blood pressure, pulse, respiratory rate and oral or axillary temperature will be collected at Screening. Only blood 
pressure and pulse will be collected on Day -1 through Day 2. Vital signs will be obtained upon admission, morning 
rising and 8 hours postdose.
(g) Obtained after minimum 8-hour fast. 
(h) A serum pregnancy test for all women of childbearing potential will be done at Screening, Day -1, Day 2, or if a 
subject prematurely terminates from the study.
(i) For women where menopause is suspected.
(j) Blood samples obtained predose (no more than 30 minutes prior to study drug administration) (0 hr) and at 0.5, 1, 
1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 hours postdose.
(k) Study drug administered beginning at approximately 0800 hours.
(l) Pretreatment AEs will be captured immediately following the signing of the informed consent at Screening and 
prior to study drug administration. Follow-up site or telephone visit will be made 5-10 days after last dose of study 
drug to inquire about any TEAE or SAEs, and concomitant medications taken since final dose. Any TEAE/SAE 
spontaneously reported within 30 days postdose will be included within the database as a TEAE. 


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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 investigator agrees to assume the following responsibilities:
1. Conduct the study in accordance with the protocol.
2. Personally conduct or supervise the staff who will assist in the protocol.
3. 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.
4. Ensure that all colleagues and employees assisting in the conduct of the study are informed of 
these obligations.
5. Secure prior approval of the study and any changes by an appropriate IRB/IEC that conform to 
ICH and local regulatory requirements.
6. 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.
7. Ensure that requirements for informed consent, as outlined in ICH and local regulations, are 
met.
8. 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.
9. Prepare and maintain adequate case histories of all persons entered into the study, including 
eCRFs, 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 
contact and receive written approval from the sponsor before disposing of any such 
documents.
10. Allow possible inspection and copying by the regulatory authority of GCP-specified essential 
documents.
11. Maintain current records of the receipt, administration, and disposition of sponsor-supplied 
drugs, and return all unused sponsor-supplied drugs to the sponsor.


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12. Report adverse reactions to the sponsor promptly. In the event of an SAE, notify the sponsor 
within 24 hours.


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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 may discontinue 


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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 pharmacogenomic 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.


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25. Women of childbearing potential (eg, nonsterilized, premenopausal women) who are sexually 
active must use adequate contraception (as defined in the informed consent) from Screening 
and throughout the duration of the study, and for 30days weeks after last dose of study 
medication. Regular pregnancy tests will be performed throughout the study for all women of 
childbearing potential. If a subject is found to be pregnant during study, study medication will 
be discontinued and the investigator will offer the subject the choice to receive unblinded 
treatment information. 
26. Men must use adequate contraception (as defined in the informed consent) from Screening and 
throughout the duration of the study. If the partner or wife of the subject is found to be pregnant 
during the study, the investigator will offer the subject the choice to receive unblinded 
treatment information. 
27. A statement that clinical trial information from this trial will be publicly disclosed in a publicly 
accessible website, such as ClinicalTrials.gov. 


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Appendix D
Investigator Consent to 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.


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Appendix E
Collection, Storage, and Shipment of Bioanalytical Samples
Instructions for Processing of Plasma Samples for Pharmacokinetic Analysis
1. Collect 6 mL of venous blood into a chilled Becton-Dickinson Vacutainer. For all 
TAK-390MR samples, blood samples should be collected into vacutainers containing 
anticoagulant K2EDTA. 
2. Gently invert the vacutainer several times to mix the additive with the collected blood prior to 
centrifugation and place immediately on ice or keep at ambient temperature.
3. Centrifuge the vacutainers for 10 minutes at approximately 1200 relative centrifugal force 
(RCF) at approximately 4°C in a refrigerated centrifuge or at ambient temperature. Note: if 
using a collection device other than Becton-Dickinson, refer to manufacturer’s instruction for 
proper centrifugation force and time.
4. Immediately following centrifugation, gently remove plasma from the packed cells. Split the 
plasma evenly between the 2 aliquots. A minimum of approximately 1.2 mL needs to be 
obtained for each sample. Labeling may include protocol number (TAK-390MR_106), matrix 
(ie, plasma), analyte (TAK-390MR), enrollment number, nominal day and time, and either 
“SET 1” (for original sample) or “SET 2” (for duplicate sample). 
5. Cap the labeled storage tubes and freeze the plasma samples immediately at approximately 
-20°C or lower. No more than 120 minutes will elapse between blood collection and freezing 
the plasma sample.
6. Keep samples frozen at approximately -20°C or lower until shipment site. SET 1 samples will 
be shipped first on dry ice, followed by shipment of duplicate SET 2 samples after SET 1 
samples have been received by the analytical laboratory.
Shipping of Plasma Samples
Site may adhere to the site’s SOPs on shipping samples if the SOP differs from the sample 
instructions provided.
Biological samples should be shipped on sufficient dry ice to prevent thawing during transit. 
Samples should be shipped to arrive at their destination during normal business hours (local time). 
It is recommended that samples be shipped on Monday, Tuesday or Wednesday and 2 days before 
a national holiday, in order to minimize the possibility of samples arriving at their destination on a 
weekend or holiday. For shipments outside these periods, it is recommended that a premium 
carrier who will replenish dry ice during shipment as necessary be used. Other shipping 
arrangements may be allowed with the agreement of the Sponsor. If duplicate samples are to be 
shipped, send SET 1 samples and await confirmation of arrival before shipping the duplicate SET 
2 samples.
Before shipping, make sure the sample tubes are tightly sealed. Separate each subject’s samples as 
follows:
1. Separate the duplicate SET 2 samples from the SET 1 samples.


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2. Place SET 1 samples for each subject into zipper lock bag containing additional absorbent 
material.
3. Using a permanent marker, write the enrollment number, sample matrix (ie, plasma or urine), 
analyte (TAK-390MR), number of samples, and “SET 1” on each zipper lock bag.
4. Place the bags of individual subject’s samples into a larger plastic bag so that samples are 
double bagged. Duplicate SET 2 samples should be returned to the freezer for storage.
5. An inventory of individual samples should accompany each shipment and should include the 
Sponsor’s name (Takeda), study drug (TAK-390MR), protocol number (TAK-390MR_106), 
investigator’s name, sample type (ie, plasma), subject’s enrollment number, nominal 
collection day and time, and intended sample storage conditions. When duplicate SET 2 
samples are being shipped, make a copy of the original SET 1 sample inventory and mark as 
“SET 2.” Place the inventory paperwork into a large zipper lock bag. SET 1 samples will be 
shipped first on dry ice, followed by shipment of duplicate SET 2 samples after SET 1 samples 
have been received by the analytical laboratory.
6. For sample packing, use dry ice generously (eg, 20-25 pounds per day of transit) to safeguard 
against longer than expected shipping times and delays. Use newspaper or other material to 
insulate the double-bagged samples from direct contact with the dry ice. Place the sample 
bundles into a Styrofoam container (or other suitable container) and fill the excess space with 
dry ice slabs or ice pellets (preferably the latter). Make a note of the estimated weight of the dry 
ice used per shipping container.
7. Place the inventory paperwork (in a large self-sealing bag) on top of the dry ice in the 
Styrofoam container. Place the lid on the Styrofoam container and seal completely with 
strapping tape. Place the Styrofoam container in a cardboard shipping carton and seal securely 
with strapping tape.
8. Mark the outside of shipping carton(s) with a tally number (eg, 1 of 5, 2 of 5).
9. Affix an address label to each shipping carton. Complete the address label with the following 
information:
Plasma Samples for TAK-390MR_106
10. Affix a carbon dioxide label on each carton, specifically:
Carbon Dioxide Solid UN-1845
Class 9 PKG GR III
Quantity _____________________
(fill in weight to nearest lb/kg and specify unit of measure used)
Personally Protected Data


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11. Affix 2 dry ice symbol labels on opposite sides of the carton. Mark KEEP FROZEN on each 
carton. Specify a return address and contact person on the carton.
12. Obtain the airway bill number and a receipt of shipment from the carrier.
13. After shipping of the samples, contact the analytical site and CRO representative to notify 
them of next day delivery. When calling, provide the following information:
Name of courier or transport company
Time and date the shipment left the clinical site
Airway bill number
Instructions for processing and shipping of blood samples for genotyping analysis
Detailed instructions for the handling and shipping of samples will be provided in the Lab Manual.


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Appendix F
Detailed Description of Amendments to Text
The primary sections of the protocol affected by the changes in Amendment No. 03 are indicated. 
The corresponding text has been revised throughout the protocol.
Change 1: Updated Appendix E Collection, Storage, and Shipment of Bioanalytical Samples.
The change occurs in Appendix E Collection, Storage, and Shipment of Bioanalytical Samples:
Initial 
wording:
Appendix E
Collection, Storage, and Shipment of Bioanalytical Samples
3. Centrifuge the vacutainers for 10 minutes at approximately 1100-1300 relative 
centrifugal force (RCF) at approximately 4°C in a refrigerated centrifuge or at ambient 
temperature. Note: if using a collection device other than Becton-Dickinson, refer to 
manufacturer’s instruction for proper centrifugation force and time.
4. Immediately following centrifugation, gently remove plasma from the packed cells. 
To ensure a more homogeneous sample, all plasma should first be transferred into 1 
aliquot. From there, split the plasma evenly between the 2 aliquots. A minimum of 
approximately 1.2 mL needs to be obtained for each sample. Labeling may include 
protocol number (TAK-390MR_106), matrix (ie, plasma), analyte (TAK-390MR), 
enrollment number, nominal day and time, and either “SET 1” (for original sample) or 
“SET 2” (for duplicate sample). 
5. Cap the labeled storage tubes and freeze the plasma samples immediately at 
approximately -20°C or lower. No more than 45 minutes will elapse between blood 
collection and freezing the plasma sample.
Instructions for processing and shipping of plasma samples for genotyping
analysis
To be determined when laboratory is selected. 


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Amended 
or new 
wording:
Appendix E
Collection, Storage, and Shipment of Bioanalytical Samples
3. Centrifuge the vacutainers for 10 minutes at approximately 1100-1300 1200
relative centrifugal force (RCF) at approximately 4°C in a refrigerated centrifuge or at 
ambient temperature. Note: if using a collection device other than Becton-Dickinson, 
refer to manufacturer’s instruction for proper centrifugation force and time
4. Immediately following centrifugation, gently remove plasma from the packed cells. 
To ensure a more homogeneous sample, all plasma should first be transferred into 1 
aliquot. From there, sSplit the plasma evenly between the 2 aliquots. A minimum of 
approximately 1.2 mL needs to be obtained for each sample. Labeling may include 
protocol number (TAK-390MR_106), matrix (ie, plasma), analyte (TAK-390MR), 
enrollment number, nominal day and time, and either “SET 1” (for original sample) or 
“SET 2” (for duplicate sample). 
5. Cap the labeled storage tubes and freeze the plasma samples immediately at 
approximately -20°C or lower. No more than 45120 minutes will elapse between 
blood collection and freezing the plasma sample. 
Instructions for processing and shipping of plasma blood samples for genotyping 
analysis
To be determined when laboratory is selected. Detailed instructions for the 
handling and shipping of samples will be provided in the Lab Manual
Rationale for Change: 
Updated to reflect the current procedures for plasma samples for pharmacokinetic analysis and to 
provide the reference to the lab manual for information regarding processing and shipment of
blood samples for genotyping analysis.


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CONFIDENTIAL
Change 2: Correct blood volume for genotype analysis and total blood volume.
The change occurs in Section 9.1.8 Procedures for Clinical Laboratory Samples, Section 9.1.12 
Sample Collection for Genotype Analysis, and Section 9.4 Blood Volume:
Initial 
wording:
Section 9.1.8 Procedures for Clinical Laboratory Samples
All samples will be collected in accordance with acceptable laboratory procedures. 
The maximum volume of blood at any single visit is approximately 84 mL, and the 
total volume of blood for the study is approximately 156 mL. Laboratory samples will 
be taken following a minimum 8-hour overnight fast on the days stipulated in the 
Schedule of Study Procedures (Appendix A).
Section 9.1.12 Sample Collection for Genotype Analysis
Genotyping and phenotyping analysis for CYP2C19 will be required for all subjects 
because dexlansoprazole is metabolized by the polymorphic isozyme CYP2C19. On 
Day 1, one blood sample (approximately 6 mL) will be collected for genotype 
analysis. Detailed instructions for the handling and shipping of samples will be 
provided in the Lab Manual.
Section 9.4 Blood Volume
Sample Type
Sample 
Volume 
(mL)
Estimated Blood Collection
Total 
Volume 
(mL)
Number 
of 
Samples
Treatment Days
Clinical laboratory 
tests
20 mL
3
Screening, Check-in (Day -1), Study 
Exit
60
Genotyping
6 mL
1
Day 1
6
PK blood collection
6 mL
15
Day 1 to 2
90
Total Approximate Blood Sampling Volume
156
The maximum volume of blood at any single day is approximately 84 mL, and the 
approximate total volume of blood for the study is 156 mL.


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Protocol Incorporating Amendment No. 03
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CONFIDENTIAL
Amended 
or new 
wording:
Section 9.1.8 Procedures for Clinical Laboratory Samples
All samples will be collected in accordance with acceptable laboratory procedures. 
The maximum volume of blood at any single visit is approximately 84 mL, and the 
total volume of blood for the study is approximately 1562 mL. Laboratory samples 
will be taken following a minimum 8-hour overnight fast on the days stipulated in the 
Schedule of Study Procedures (Appendix A).
Section 9.1.12 Sample Collection for Genotype Analysis
Genotyping and phenotyping analysis for CYP2C19 will be required for all subjects 
because dexlansoprazole is metabolized by the polymorphic isozyme CYP2C19. On 
Day 1, one blood sample (approximately 62 mL) will be collected for genotype 
analysis will be collected into vacutainers containing anticoagulant K2EDTA 
according to the schedule in Appendix A. Instructions for sample processing and 
shipment are provided in Appendix E.
Section 9.4 Blood Volume
Sample Type
Sample 
Volume 
(mL)
Estimated Blood Collection
Total 
Volume 
(mL)
Number 
of 
Samples
Treatment Days
Clinical laboratory 
tests
20 mL
3
Screening, Check-in (Day -1), Study 
Exit
60
Genotyping
62 mL
1
Day 1
62
PK blood collection
6 mL
15
Day 1 to 2
90
Total Approximate Blood Sampling Volume
1562
The maximum volume of blood at any single day is approximately 84 mL, and the 
approximate total volume of blood for the study is 1562 mL.
Rationale for Change: 
Updated current blood volume for genotype analysis and overall blood volume.


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Personally Protected Data

SAP_000.pdf: 
This may include, but is not limited to, redaction of the following: 


• 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, Single-Center, Open-Label, 2-Arm Parallel Group, Single-Dose Study to Evaluate 
the Pharmacokinetics of Dexlansoprazole 30 mg and 60 mg Delayed-Release Capsules in Healthy 
Chinese Subjects
NCT Number: NCT03316976
SAP Approve Date: 22 March 2018
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 information or company confidential information. 
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.


Takeda
Statistical Analysis Plan
TAK-390MR_106
Version: Final
CONFIDENTIAL
TAKEDA DEVELOPMENT CENTER
STATISTICAL ANALYSIS PLAN
STUDY NUMBER: TAK-390MR_106
A Phase 1, Single-Center, Open-Label, 2-Arm Parallel Group, Single-Dose Study to
Evaluate the Pharmacokinetics of Dexlansoprazole 30 mg and 60 mg Delayed-Release
Capsules in Healthy Chinese Subjects
Phase 1 Dexlansoprazole PK Study in Healthy Chinese Subjects
Version: Final
Date: 22 March 2018


Takeda
Statistical Analysis Plan
TAK-390MR_106
Version: Final
CONFIDENTIAL
SPONSOR APPROVAL PAGE
A Phase 1, Single-Center, Open-Label, 2-Arm Parallel Group, Single-Dose Study to
Evaluate the Pharmacokinetics of Dexlansoprazole 30 mg and 60 mg Delayed-Release
Capsules in Healthy Chinese
Phase 1 Dexlansoprazole PK Study in Healthy Chinese Subjects
Version: Final
Date: 22 March 2018
Prepared by:
Approved by:
Date: ____________
Date: ____________
Date: ____________
Date: ____________
Date: ____________
Personally Protected Data
Personally Protected Data


Takeda
Statistical Analysis Plan
TAK-390MR_106
Version: Final
CONFIDENTIAL
2.0
TABLE OF CONTENTS
1.0
TITLE PAGE ..................................................................................................................1
2.0
TABLE OF CONTENTS.................................................................................................3
3.0
LIST OF ABBREVIATIONS..........................................................................................5
4.0
OBJECTIVES .................................................................................................................6
4.1
Primary Objectives ....................................................................................................6
4.2
Secondary Objectives.................................................................................................6
4.3
Study Design .............................................................................................................6
5.0
ANALYSIS ENDPOINTS...............................................................................................7
5.1
Primary Endpoint.......................................................................................................7
5.2
Additional Endpoints .................................................................................................7
5.3
Safety Endpoints........................................................................................................7
6.0
DETERMINATION OF SAMPLE SIZE.........................................................................8
7.0
METHODS OF ANALYSIS AND PRESENTATION.....................................................9
7.1
General Considerations..............................................................................................9
7.2
Data Handling Conventions .......................................................................................9
7.2.1
Premature Withdrawal .........................................................................................9
7.2.2
Handling of Missing Data ....................................................................................9
7.2.3
Handling of Missing/Partial Date .........................................................................9
7.2.4
Definition of Baseline and Change from Baseline ................................................9
7.2.5
Definition of Study Days....................................................................................10
7.3
Analysis Sets ...........................................................................................................10
7.4
Disposition of Subjects ............................................................................................10
7.5
Protocol Deviation...................................................................................................11
7.6
Demographic and Baseline Characteristics...............................................................11
7.7
Medical History and Concurrent Medical Conditions...............................................11
7.8
Medication History and Concomitant Medications...................................................11
7.9
Study Drug Exposure and Overdose.........................................................................11
7.10
Pharmacokinetic Analysis........................................................................................12
7.11
Safety Analysis........................................................................................................12
7.11.1 Adverse Events ..................................................................................................13
7.11.2 Physical Examination.........................................................................................13
7.11.3 Clinical Laboratory Evaluations .........................................................................14
7.11.4 Vital Signs .........................................................................................................14
7.11.5 12-Lead ECGs ...................................................................................................15
7.11.6 Other Observations Related to Safety.................................................................15


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7.12
Genotype Analysis...................................................................................................15
7.13
Interim Analysis ......................................................................................................15
7.14
Changes in the Statistical Analysis Plan...................................................................15
8.0
REFERENCES..............................................................................................................16
LIST OF IN-TEXT TABLES
Table 4.a
Parallel Groups ....................................................................................................6
LIST OF IN-TEXT FIGURES
Figure 4.a
Schematic of Study Design ..................................................................................6
LIST OF APPENDICES
Appendix A
Criteria for Identification of Markedly Abnormal Laboratory Values .................17
Appendix B
Criteria for Markedly Abnormal Values for Vital Signs......................................18


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Statistical Analysis Plan
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3.0
LIST OF ABBREVIATIONS
λz
terminal disposition phase rate constant
AE
adverse event
AUC
area under the plasma concentration-time curve
AUClast
area under the plasma concentration-time curve from time 0 to time of the last 
quantifiable concentration
AUC∞
area under the plasma concentration-time curve from time 0 to infinity
BMI
body mass index
bpm
beats per minute
CL/F
apparent clearance after extravascular administration
Cmax
maximum observed concentration
CS
clinically significant
CYP
cytochrome P450
ECG
electrocardiogram
FSH
follicle stimulating hormone
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HIV
human immunodeficiency virus
MedDRA
Medical Dictionary for Regulatory Activities
NCS
not clinically significant
PK
pharmacokinetics
PT
preferred term
PTE
pretreatment event
SAE
serious adverse event
SOC
system organ class
t1/2z
terminal disposition phase half-life
TEAE
treatment-emergent adverse event
tmax
time of first occurrence of Cmax
Vz/F
volume of distribution during the terminal disposition phase after extravascular 
administration
WHO
World Health Organization


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Statistical Analysis Plan
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4.0
OBJECTIVES
4.1
Primary Objectives
The primary objective of this study is to assess the PK after a single dose of dexlansoprazole 30 
and 60 mg delayed-release capsules in healthy Chinese subjects.
4.2
Secondary Objectives
The secondary objective of this study is to evaluate the safety and tolerability of dexlansoprazole 
following oral administration of a single 30 or 60 mg dexlansoprazole delayed-release capsule. 
4.3
Study Design
This is a phase 1, open-label, single dose, 2-arm parallel study to assess the PK of a single oral 
dose of dexlansoprazole 30 and 60 mg delayed-release capsules. Forty subjects will be enrolled 
in the study, 20 subjects in Group 1 and 20 subjects in Group 2 (Table 4.a).
Table 4.a
Parallel Groups
Group
Regimen
1
A single oral dose of dexlansoprazole 30 mg delayed-release capsule
2
A single oral dose of dexlansoprazole 60 mg delayed-release capsule
A schematic of the study design is included as Figure 4.a. 
Figure 4.a
Schematic of Study Design
Pretreatment Period
Treatment Period
Follow-Up
Screening
Check-in
Dexlansoprazole Delayed-
Release Capsule
Single Dose 
(30 or 60 mg)
Discharge/Study 
Exit/Premature 
Termination
Follow-up Site/ 
Telephone Visit
Days -28 to -2
Day -1
Day 1
Day 2
5 to 10 days postdose
Confinement to Clinic
Note: A follow-up site/telephone visit will be made for collection of adverse events, serious adverse events, and 
concomitant medications taken since final dose.
Subjects will fast for a minimum of 8 hours prior to dosing. On Day 1, breakfast will be served 
1 hour postdose. Subjects may consume water ad libitum except for 1 hour before and 1 hour 
after drug administration. Dosing will commence at approximately 8:00 am on Day 1. Study 
drug will be administered with 240 mL of water. Subjects must drink all of the water provided 
with the dose.


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5.0
ANALYSIS ENDPOINTS
5.1
Primary Endpoint
The primary endpoints for this study are the PK parameters of dexlansoprazole following a 
single oral dose of dexlansoprazole 30 and 60 mg delayed-release capsules:

Cmax.

Area under the plasma concentration-time curve from time 0 to time of the last quantifiable 
concentration (AUClast).

Area under the plasma concentration-time curve from time zero to infinity (AUC∞).
5.2
Additional Endpoints

Time of first occurrence of Cmax (tmax).

Terminal disposition phase rate constant (λz).

t1/2z.

Volume of distribution during the terminal disposition phase after extravascular 
administration (Vz/F).

CL/F.
5.3
Safety Endpoints
Safety endpoints include treatment-related AEs, clinical laboratory tests (hematology, serum 
chemistry, and urinalysis), vital sign measurements, electrocardiograms (ECGs), and physical 
examinations.


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6.0
DETERMINATION OF SAMPLE SIZE
No formal sample size calculations were conducted. A sample size of 40 subjects, 20 subjects 
per parallel group, will be used in this study. This sample size is deemed to be sufficient for the 
assessment of the PK of dexlansoprazole 30 and 60 mg delayed-release capsules in the Chinese 
population.


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7.0
METHODS OF ANALYSIS AND PRESENTATION
7.1
General Considerations
Statistical analysis will be performed using SAS® software (SAS Institute, Inc., Cary, North 
Carolina) Version 9.2, or later.
All study-related raw data for enrolled subjects, including derived data, will be presented in data 
listings. Continuous data will be summarized using number of subjects, mean, standard 
deviation, median, minimum, and maximum. Categorical data will be summarized using the 
number and percentage of subjects for each category where appropriate.
7.2
Data Handling Conventions
7.2.1
Premature Withdrawal
The investigator may discontinue a subject’s study participation at any time during the study 
when the subject meets the study termination criteria. In addition, a subject may discontinue his 
or her 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. 
Discontinued or withdrawn subjects will not be replaced after enrollment. All available data from 
subjects who were withdrawn from the study will be listed and all available planned data will be 
included in summary.
7.2.2
Handling of Missing Data
No imputation will be used for Missing data.
7.2.3
Handling of Missing/Partial Date
Completed missing start or end dates will remain missing, with no imputation applied.
Partial dates will be imputed using below convention:

If the partial date is a start date, impute as the first day as the month (only missing day) /year 
(missing both month and day).

If the partial date is an end date, impute as the last day as the month (only missing day) /year 
(missing both month and day).

If the partial date is in the same month (only missing day) or same year (missing both month 
and day) as the study treatment, and the imputed start date of an adverse event (not 
pretreatment event) is prior to the start of study treatment, then the start date of study 
treatment will be assumed to be the start date. The AE will then be considered as start on 
treatment (worst case scenario).
The recorded partial date will be displayed in the listings.
7.2.4
Definition of Baseline and Change from Baseline
Baseline is defined as the last non-missing measurement prior to first dose of study drug.


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Statistical Analysis Plan
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Version: Final
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The change from baseline will be calculated by subtracting the baseline values from the 
individual post-baseline values. If either the baseline or post-baseline value is missing, the 
change from baseline is set to missing as well.
7.2.5
Definition of Study Days
Study day will be calculated relative to the date of the first dose of study drug in the study. The 
study day prior to the first dose of study drug will be calculated as: 
Date of assessment/event – date of first dose of study drug 
The study day on or after the first dose of study drug will be calculated as: 
Date of assessment/event – date of first dose of study drug + 1.
AEs that start more than 30 days after the last dose of study drug will be listed, but excluded 
from the summaries and analyses. 
7.3
Analysis Sets
Enrolled Subjects Set (EPS): All enrolled subjects who are enrolled will be included, which
will be used in the analysis of disposition, medical history, protocol deviation, etc.
Safety Analysis Set (SS): All subjects who are enrolled in the study and take at least 1 dose of 
study drug will be included, which will be used in the demographic summary and safety data 
analysis.
PK Analysis Set (PAS): All subjects who receive at least 1 dose of study drug and have at least 
1 measureable plasma concentration of dexlansoprazole will be included, which will be used in 
PK data analysis.
7.4
Disposition of Subjects
Disposition of all screened subjects will be tabulated (count and percent). Primary reasons for 
screen failure will be summarized and will be presented in a data listing. There will be no 
inferential analysis of subject disposition data.
Disposition of all enrolled subjects will be tabulated by dexlansoprazole dose groups and overall: 

All subjects received at least one dose of study drug.

Subjects who completed the study.

Subjects who prematurely discontinued study.
Primary reasons for discontinuation of study, as entered on the electronic case report form 
(eCRF), will be tabulated. The date of first dose, date of last dose, duration of treatment and the 
reason for premature discontinuation of study drug/study visit will be presented for each subject 
in listings.


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7.5
Protocol Deviation
A summary of the number and percentage of subjects with a significant protocol deviation by 
type of deviation will be provided using enrolled subjects set by dexlansoparzole dose groups 
and overall. Individual subject listings of significant protocol deviations will be provided.
7.6
Demographic and Baseline Characteristics
Demographic and baseline characteristics variables will be summarized by dose group and 
overall using the safety analysis set.
For continuous variables (age, weight, height, and body mass index [BMI]), summary statistics 
will be generated.
For categorical variables (gender, ethnicity, race, smoking status of the subject at Screening, 
caffeine consumption and alcohol history), the number and percentage of subjects in each 
category will be presented.
7.7
Medical History and Concurrent Medical Conditions
Medical history include any significant conditions or diseases that stopped at or prior to signing 
of informed consent. Concurrent medical conditions are those significant ongoing conditions or 
diseases that are present at signing of informed.
Medical history and concurrent medical conditions will be presented in a data listing only.
7.8
Medication History and Concomitant Medications
Medication history information to be obtained includes any medication relevant to eligibility 
criteria stopped at or within 28 days prior to signing of informed consent. Concomitant 
medications are recorded on the eCRF and include any medications, other than study drug, taken 
at any time between informed consent and the end of the study. They may be prescribed by a 
physician or obtained by the subject over the counter.
All medication history and concomitant medications will be coded by therapeutic classification, 
sub-classification, and medication using the World Health Organization Drug Dictionary (WHO 
Drug).
All medication history and concomitant medications will be listed by site (study center) and 
subject number. The listings will contain subject identifier, treatment, World Health 
Organization Drug Dictionary (WHODrug) preferred medication name, dose, unit, frequency, 
route, start date, stop date, whether the medication was ongoing, and reason for use. No summary 
or inferential statistics will be presented.
7.9
Study Drug Exposure and Overdose
Study drug administration and overdose information will be listed. Standard meal information 
will also be presented. Summaries of PK data will be provided by dose group. No other summary 
statistics for the extent of exposure to study drug or compliance calculations will be performed 
for this study.


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7.10
Pharmacokinetic Analysis
All PK summaries will be based on the PK set. PK parameters of dexlansoprazole will be 
derived using non-compartmental analysis methods. They will be determined from the 
concentration-time data for all evaluable subjects. Actual sampling times, rather than scheduled 
sampling times, will be used in all computations involving sampling times.
Serial blood samples for determination of dexlansoprazole concentrations will be collected on 
Day 1 (within 30 minutes before dosing) and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 24 
hours post dose. The concentration of dexlansoprazole in plasma will be summarized by 
scheduled sampling time points and dose group using descriptive statistics. Individual plasma 
concentration data will be presented in a data listing. Subject phenotypes will be listed with the 
concentrations.
The PK parameters of dexlansoprazole will be determined below from the concentration-time 
profiles for all evaluable subjects. Actual sampling times, rather than scheduled sampling times, 
will be used in all computations involving sampling times. The following PK parameters will be 
calculated:
Descriptive statistics (number of subjects, arithmetic mean, SD, %CV, median, minimum and 
maximum) by dose groups will be provided for dexlansoprazole plasma PK parameters. 
Geometric means will be calculated for Cmax and AUCs. Individual plasma PK parameters will 
be presented in a data listing. Subject phenotypes will be listed with the PK parameters.
No inferential statistical analysis will be performed. Additional summaries by phenotypes may 
be performed if there are sufficient number of subjects for each phenotype. More information 
please refer to separate clinical pharmacology analysis plan (CPAP).
7.11
Safety Analysis
All safety analyses will be performed using the safety analysis set. 


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7.11.1 Adverse Events
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a drug. All AEs will be coded by system organ class (SOC) and preferred term (PT) 
using the Medical Dictionary for Regulatory Agencies (MedDRA 20.0). 
A treatment-emergent adverse event (TEAE) will be defined as an AE that starts or worsens on 
or after Study Day 1 (defined as day first dosed), and no more than 30 days after the last dose of 
study drug (onset date – last date of dose +1≤30). 
In an TEAE overview table, the number and percentage of subjects who experience AEs, 
TEAEs, TEAEs by severity and relationship, SAEs, discontinued from study treatment due to an 
AEs, death will be summarized by dose groups and overall.
In addition, the number and percentage of subjects with AEs will be summarized in several 
different tables:

All TEAEs by system organ class (SOC) and preferred term (PT).

TEAE by PT.

Most frequent TEAEs (>5% or >2 subjects in any dose group).

Most frequent non-serious TEAEs (>5% or >2 subjects in any dose group).

Drug-related TEAEs by SOC and PT.

Relationship to study drug for all TEAEs by SOC and PT (related vs not related).

All SAEs by SOC and PT.

Severity of all TEAEs by SOC and PT (mild, moderate, or severe).

Severity of drug-related TEAEs by SOC and PT (mild, moderate, or severe).
A subject with 2 or more AEs within the same level of the MedDRA term will be counted only 
once in that level using the most extreme incident (most severe for the severity tables and related 
for the relationship to study drug tables). 
Additionally, treatment-emergent serious adverse events, deaths, and TEAEs resulting in 
premature discontinuation from study drug will be listed. 
A pretreatment event (PTE) is defined as any untoward medical occurrence in a clinical 
investigation subject who has signed informed consent to participate in a study but prior to 
administration of any study drug. 
Data listings will be provided for all AEs including PTEs, TEAEs, AEs leading to study drug 
discontinuation, and SAEs.
7.11.2 Physical Examination
The physical examination findings will be presented in data listings.


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7.11.3 Clinical Laboratory Evaluations
All laboratory test parameters will be displayed in individual subject data listings in both SI units 
and conventional (CV) units. For test results not in SI units, the conversion to SI units will be 
done in the derived analysis datasets using the known conversion factors. If necessary, SI units 
from the central laboratory may be converted to Takeda’s preferred SI units in the derived 
analysis datasets. All summaries will be based on the values using these preferred SI units.
Clinical laboratory values (hematology, serum chemistry, and urinalysis) will be summarized (N, 
mean, SD, median, minimum, and maximum) by dose group using descriptive statistics for 
baseline, postdose, and change from baseline to postdose values. Only observations within 
7 days of the last dose of study drug will be included in the summaries. No inferential statistics 
will be presented unless otherwise stated.
A table with predefined criteria for markedly abnormal values for laboratory variables 
(Appendix A) will be presented. If a subject has a MAV for a particular laboratory test, all visits 
for that subject for that parameter will be listed. The number and percentage of subjects with at 
least 1 postdose markedly abnormal laboratory test result will be summarized. The mapping of 
the subjects who meet the MAV criteria will be listed as a table. All observations, including ones 
at unscheduled visits, will be included in the MAV evaluation and summaries.
All clinical laboratory data will be displayed in data listing. Laboratory data outside of the 
normal reference range will be indicated in the listings. In addition, MAVs will be flagged. The 
listing will include site number, subject identifier, age, gender, treatment group, study visit, and 
sample collection date and time. MAV listings will be presented in the unit specified in the MAV 
criteria in Appendix A.
7.11.4 Vital Signs
Vital signs will include weight, oral or axillary body temperature measurement, sitting blood 
pressure (after 5 minutes resting), respiration rate and pulse beats per minute (bpm). Only blood 
pressure and pulse will be taken on Check-in (Day -1) through Day 2.
Vital signs will be summarized (N, mean, SD, median, minimum, and maximum) for each dose 
group by presenting descriptive statistics for baseline, postdose, and change from baseline to 
postdose values. 
Vital signs that meet predefined markedly abnormal criteria (Appendix B) will be presented. If a 
subject has a MAV for a particular vital sign, all visits for that subject for that vital sign will be 
listed. The number and percentage of subjects with at least 1 postdose markedly abnormal vital 
signs measurement will be summarized. The mapping of the subjects who meet the MAV criteria 
will be listed as a table. All observations, including ones at unscheduled visits, will be included 
in the MAV evaluation and summaries. 
All vital sign data will be provided in the data listings. Vital sign MAVs will be flagged in the 
listings. The listing will include site number, subject identifier, age, gender, treatment group, 
study visit, and sample collection date and time.


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Statistical Analysis Plan
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Version: Final
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7.11.5 12-Lead ECGs
ECG results will be interpreted using 1 of the following categories: within normal limits, 
abnormal but not clinically significant, or abnormal and clinically significant. Shift tables for 
ECG evaluation will be provided by dose groups. All ECG data will be listed in the data listings.
7.11.6 Other Observations Related to Safety
Below information will be presented in data listing:

Child bearing potential;

Serum FSH test;

Pregnancy test results;

Hepatitis results;

HIV results;

Urine drug screen;

Alcohol test.
7.12
Genotype Analysis
Genotype test will be summarized by Genotype and phenotype, and Blood samples collected for 
genotype test will be presented in data listing.
7.13
Interim Analysis
Not applicable. 
7.14
Changes in the Statistical Analysis Plan 
None.


Takeda
Statistical Analysis Plan
TAK-390MR_106
Version: Final
CONFIDENTIAL
8.0
REFERENCES
1. Dexilant (dexlansoprazole) Delayed Release Capsules. Full Prescribing Information. 
Deerfield, IL: Takeda Pharmaceuticals America, Inc., Revised 16 January 2016.
2. Vakily M, Zhang W, Wu J, Atkinson SN, Mulford D. Pharmacokinetics and 
pharmacodynamics of a known active PPI with a novel dual delayed release technology, 
dexlansoprazole MR: a combined analysis of randomized controlled clinical trials. Curr Med 
Res Opin 2009;25(3):627-38.
3. Yin OQ, Tomlinson B, Chow AH, Waye MM, Chow MS. Omeprazole as a CYP2C19 
marker in Chinese subjects: assessment of its gene-dose effect and intrasubject variability. J 
Clin Pharmacol 2004;44(6):582-9.


Takeda
Statistical Analysis Plan
TAK-390MR_106
Version: Final
CONFIDENTIAL
Appendix A
Criteria for Identification of Markedly Abnormal Laboratory Values
Hematology—Criteria for Markedly Abnormal Values
Parameter
Low Abnormal
High Abnormal
Hemoglobin
<0.8 × LLN,
>1.2 × ULN
Hematocrit
<0.8 × LLN,
>1.2 × ULN
RBC count 
<0.8 × LLN, 
>1.2 × ULN
WBC count 
<0.5 × LLN
>1.5 × ULN
Platelet count
<75 x 103/L
>600 x 103/L
RBC=red blood cell, WBC=white blood cell.
Chemistry—Criteria for Markedly Abnormal Values
Parameter
Low Abnormal
High Abnormal
ALT
--
>3x ULN
AST
--
>3x ULN
GGT
--
>3x ULN
Alkaline phosphatase
--
>3x ULN
Total bilirubin
--
>2.0 mg/dL
Albumin
<2.5 g/dL
--
Total protein
<0.8x LLN
>1.2x ULN
Creatinine
>2.0 mg/dL
Blood Urea Nitrogen
--
>30 mg/dl
Sodium
<130 mEq/L
>150 mEq/L
Potassium
<3.0 mEq/L
>6.0 mEq/L
CPK
--
>5x ULN
ALT=alanine aminotransferase, AST=aspartate aminotransferase, GGT=-glutamyl transferase, CPK=creatine 
phosphokinase, LLN=lower limit of normal, ULN=upper limit of normal.


Takeda
Statistical Analysis Plan
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Version: Final
CONFIDENTIAL
Appendix B
Criteria for Markedly Abnormal Values for Vital Signs
Parameter
Unit
Lower Criteria 
Upper Criteria
Pulse
bpm
<50 
>120
Systolic blood pressure
mm Hg
<85 
>180
Diastolic blood pressure
mm Hg
<50 
>110
Body temperature (axillary)
oC
<35.6
>37.7


 
  
 
 
 
 
 
 
 
 
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TAK-390MR_106 Statistical Analysis Plan
Biostatistics Approval
22-Mar-2018 16:11 UTC
Clinical Operations Approval
22-Mar-2018 16:37 UTC
Pharmacovigilance Approval
23-Mar-2018 00:34 UTC
Clinical Science Approval
23-Mar-2018 09:59 UTC
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Data