Clinical trial NCT03131895
Conditions: Healthy Volunteers
Keywords: Drug therapy
Sponsor: Takeda
Start date: 2017-04-25; Completion date: 2017-07-31
Enrollment: 116 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of this study is to assess the bioavailability of dexlansoprazole from a 30 milligram (mg) or 60 mg delayed-release capsule manufactured at Takeda GmbH Plant Oranienburg, Germany (TOB) relative to that of dexlansoprazole from a 30 mg or 60 mg capsule manufactured at Takeda Pharmaceutical Company Ltd. (Osaka, Japan) (TPC).

Detailed description:
The drug being tested in this study is called dexlansoprazole. This study will compare bioavailability of dexlansoprazole from 30 mg and 60 mg dexlansoprazole delayed release capsules manufactured at TOB relative to the corresponding 30 mg and 60 mg dexlansoprazole delayed release capsules manufactured at TPC. The study will enroll approximately 104 participants. Participants will be randomly assigned (by chance, like flipping a coin) to 1 of the 4 treatment sequences:

* Dexlansoprazole 30 mg TOB followed by Dexlansoprazole 30 mg TPC
* Dexlansoprazole 30 mg TPC followed by Dexlansoprazole 30 mg TOB
* Dexlansoprazole 60 mg TOB followed by Dexlansoprazole 60 mg TPC
* Dexlansoprazole 60 mg TPC followed by Dexlansoprazole 60 mg TOB

All participants will be asked to take single oral dose of dexlansoprazole at the same time on Day 1 of each Period. This single center trial will be conducted in the United States. The overall time to participate in this study is 18 days. Participants will visit the clinic on Day -1 and remained confined until Day 2 of Period 1 and 2. A washout period of minimum 5 days will be maintained between the doses in each Period. Participants will be contacted by telephone 10 (+/-2) days after the last dose of study drug for a follow-up assessment.

Arms: arm 1: Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (Regimen A \[test\]), orally, once on Day 1 of Period 1 following a 10 hour fast, followed by minimum of 5 day washout period, followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (Regimen B \[reference\]), orally, once on Day 1 of Period 2 following a 10-hour fast. arm 2: Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (Regimen B \[reference\]), orally, once on Day 1 of Period 1 following a 10 hour fast, followed by minimum of 5 day washout period, followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (Regimen A \[test\]), orally, once on Day 1 of Period 2 following a 10-hour fast. arm 3: Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (Regimen C \[test\]), orally, once on Day 1 of Period 1 following a 10 hour fast, followed by minimum of 5 day washout period, followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (Regimen D \[reference\]), orally, once on Day 1 of Period 2 following a 10-hour fast. arm 4: Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (Regimen D \[reference\]), orally, once on Day 1 of Period 1 following a 10 hour fast, followed by minimum of 5 day washout period, followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (Regiment C \[test\]), orally, once on Day 1 of Period 2 following a 10-hour fast.
Interventions: intervention 1: 30 mg dexlansoprazole capsules manufactured at TOB intervention 2: 30 mg dexlansoprazole capsules manufactured at TPC intervention 3: 60 mg dexlansoprazole capsules manufactured at TOB intervention 4: 60 mg dexlansoprazole capsules manufactured at TPC
Intervention descriptions: intervention 1: Dexlansoprazole delayed-release. intervention 2: Dexlansoprazole delayed-release. intervention 3: Dexlansoprazole delayed-release. intervention 4: Dexlansoprazole delayed-release.

Protocol documents:
Prot_000.pdf: 
This may include, but is not limited to, redaction of the following: 


•
Title: A Phase 1, Randomized, Open-Label, Single-Center, Single-Dose, Two-Period Two-Part 
Crossover Study in Healthy Subjects to Compare the Bioavailability of Dexlansoprazole from 
Dexlansoprazole Delayed-Release Capsules 30 mg and 60 mg Manufactured by Takeda GmbH 
Plant Oranienburg Relative to Dexlansoprazole Delayed-Release Capsules 30 mg and 60 mg 
Manufactured by Takeda Pharmaceutical Company Limited Osaka Plant 
NCT Number: NCT03131895
Protocol Approve Date: 06 June 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, Randomized, Open-Label, Single-Center, Single-Dose, Two-Period Two-Part 
Crossover Study in Healthy Subjects to Compare the Bioavailability of 
Dexlansoprazole from Dexlansoprazole Delayed-Release Capsules 30 mg and 60 mg 
Manufactured by Takeda GmbH Plant Oranienburg Relative to Dexlansoprazole 
Delayed-Release Capsules 30 mg and 60 mg Manufactured by Takeda Pharmaceutical 
Company Limited Osaka Plant 
Phase 1 Bioequivalence Study of Dexlansoprazole Capsules from Two Manufacturing Plants
Sponsor:
Takeda Development Center Americas, Inc.
One Takeda Parkway, Deerfield, IL 60015
Study Number:
TAK-390MR-1001
IND Number:
069927
EudraCT Number:
Not Applicable
Compound:
Dexlansoprazole Delayed-Release Capsules
Date:
06 June 2017
Amendment Number:
02
Amendment History: 
Date
Amendment Number
Amendment Type
Region
28 October 2016
Initial Protocol
Not applicable
USA
30 March 2017
01
Nonsubstantial
USA
06 June 2017
02
Nonsubstantial
USA
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.
Takeda-sponsored investigators per individual country requirements 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
Primary Medical Monitor (primary medical 
monitor for the study providing medical advice on 
protocol and compound)
Takeda Medical Monitor (medical advice on 
protocol and compound if primary medical 
monitor not available)
Responsible Medical Officer (carries overall 
responsibility for the conduct of the study)
Personal 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.
Personal Protected Data


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INVESTIGATOR AGREEMENT
I confirm that I have read and that I understand this protocol, the package insert, 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/Province)
Location of Facility (Country)


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1.3
Protocol Amendment 02 Summary of Changes
Rationale for Amendment 02
This document describes the changes in reference to the protocol incorporating Amendment 02. 
The primary reason for this amendment is to allow the replacement of subjects who are 
discontinued or withdrawn.
For specific descriptions of the changes listed below and where these changes are located, see 
Appendix F.
Changes in Amendment 02
1. Allow the replacement of subjects who are discontinued or withdrawn.
2. Correct the dose shown in Part 2 of the crossover study design schematic.
3. Remove all reference to the subject’s legally acceptable representative.
4. Update the definitions of women of (and not of) childbearing potential.
5. Update the subject replacement information based on the allowance for replaced subjects.
6. Clarify that an 8-hour fast may not be possible at Early termination.
7. Correct the sequence numbers in Table 8.b for Part 2 of the study.


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TABLE OF CONTENTS
1.0
ADMINISTRATIVE INFORMATION ...........................................................................2
1.1
Contacts.....................................................................................................................2
1.2
Approval....................................................................................................................3
1.3
Protocol Amendment 02 Summary of Changes ..........................................................5
2.0
STUDY SUMMARY ....................................................................................................11
3.0
STUDY REFERENCE INFORMATION ......................................................................15
3.1
Study-Related Responsibilities.................................................................................15
3.2
Principal Investigator...............................................................................................15
3.3
List of Abbreviations ...............................................................................................16
3.4
Corporate Identification...........................................................................................17
4.0
INTRODUCTION.........................................................................................................18
4.1
Background .............................................................................................................18
4.2
Rationale for the Proposed Study.............................................................................18
5.0
STUDY OBJECTIVES AND ENDPOINTS..................................................................19
5.1
Objectives................................................................................................................19
5.1.1
Primary Objective(s) ...................................................................................19
5.1.2
Additional Objectives..................................................................................19
5.2
Endpoints.................................................................................................................19
5.2.1
Primary Endpoints.......................................................................................19
5.2.2
Additional Endpoints ..................................................................................19
5.2.3
Safety Endpoints.........................................................................................19
6.0
STUDY DESIGN AND DESCRIPTION.......................................................................20
6.1
Study Design ...........................................................................................................20
6.2
Justification for Study Design, Dose, and Endpoints ................................................22
6.3
Premature Termination or Suspension of Study or Investigational Site.....................23
6.3.1
Criteria for Premature Termination or Suspension of the Study...................23
6.3.2
Criteria for Premature Termination or Suspension of Investigational Sites ..23
6.3.3
Procedures for Premature Termination or Suspension of the Study or the 
Participation of Investigational Site(s).........................................................23
7.0
SELECTION AND DISCONTINUATION/WITHDRAWAL OF SUBJECTS..............24
7.1
Inclusion Criteria .....................................................................................................24
7.2
Exclusion Criteria ....................................................................................................24
7.3
Excluded Medications and Dietary Products ............................................................26
7.4
Diet, Fluid and Activity Control...............................................................................27


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7.4.1
Confinement ...............................................................................................27
7.4.2
Diet and Fluid .............................................................................................27
7.4.3
Activity Control..........................................................................................28
7.5
Criteria for Discontinuation or Withdrawal of a Subject...........................................28
7.6
Procedures for Discontinuation or Withdrawal of a Subject......................................29
8.0
CLINICAL TRIAL MATERIAL MANAGEMENT ......................................................30
8.1
Study Medication.....................................................................................................30
8.1.1
Dosage Form, Manufacturing, Packaging, and Labeling..............................30
8.1.2
Storage........................................................................................................30
8.1.3
Dose and Regimen ......................................................................................30
8.1.4
Overdose.....................................................................................................31
8.2
Investigational Drug Assignment and Dispensing Procedures ..................................32
8.3
Randomization Code Creation and Storage..............................................................32
8.4
Accountability and Destruction of Sponsor-Supplied Drugs.....................................32
8.5
Reserve Study Medication Samples for Retention....................................................34
9.0
STUDY PLAN ..............................................................................................................35
9.1
Study Procedures.....................................................................................................35
9.1.1
Informed Consent Procedure.......................................................................35
9.1.1.1
Pharmacogenomic Informed Consent Procedure.....................................35
9.1.2
Demographics, Medical History, and Medication History Procedure...........35
9.1.3
Physical Examination Procedure .................................................................35
9.1.4
Weight, Height and BMI.............................................................................36
9.1.5
Vital Sign Procedure ...................................................................................36
9.1.6
Documentation of Concomitant Medications...............................................37
9.1.7
Documentation of Concurrent Medical Conditions......................................37
9.1.8
Procedures for Clinical Laboratory Samples................................................37
9.1.9
Contraception and Pregnancy Avoidance Procedure....................................39
9.1.10
Pregnancy ...................................................................................................40
9.1.11
ECG Procedure ...........................................................................................40
9.1.12
Pharmacogenomic Sample Collection .........................................................40
9.1.13
PK Sample Collection.................................................................................41
9.1.13.1
Collection of Blood for PK Sampling .....................................................41
9.1.14
PK Parameters.............................................................................................42
9.1.15
Documentation of Screen Failure ................................................................42
9.1.16
Documentation of Randomization ...............................................................43


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9.2
Monitoring Subject Treatment Compliance..............................................................43
9.3
Schedule of Observations and Procedures................................................................43
9.3.1
Screening ....................................................................................................43
9.3.2
Check-in (Day -1) .......................................................................................44
9.3.3
Treatment Phase (Day 1).............................................................................44
9.3.4
Day 2 (Period 1)..........................................................................................45
9.3.5
Day 2 (Period 2)/Study Exit ........................................................................45
9.3.6
Early Termination .......................................................................................45
9.3.7
Follow-up ...................................................................................................46
9.3.8
Unscheduled Visit.......................................................................................46
9.4
Biological Sample Retention and Destruction ..........................................................46
9.5
Blood Volume .........................................................................................................47
10.0
PRETREATMENT EVENTS AND ADVERSE EVENTS ............................................48
10.1
Definitions...............................................................................................................48
10.1.1
Pretreatment Events ....................................................................................48
10.1.2
AEs.............................................................................................................48
10.1.3
Additional Points to Consider for PTEs and AEs.........................................48
10.1.4
SAEs...........................................................................................................50
10.1.5
Severity of PTEs and AEs ...........................................................................51
10.1.6
Causality of AEs .........................................................................................51
10.1.7
Relationship to Study Procedures................................................................51
10.1.8
Start Date....................................................................................................52
10.1.9
Stop Date ....................................................................................................52
10.1.10
Frequency ...................................................................................................52
10.1.11
Action Concerning Study Medication..........................................................52
10.1.12
Outcome .....................................................................................................52
10.2
Procedures...............................................................................................................53
10.2.1
Collection and Reporting of AEs.................................................................53
10.2.1.1
PTEs and AEs Collection Period ............................................................53
10.2.1.2
PTEs and AEs Reporting ........................................................................53
10.2.2
Collection and Reporting of SAEs...............................................................54
10.2.3
Reporting of Abnormal LFTs......................................................................54
10.3
Follow-up of SAEs ..................................................................................................54
10.3.1
Safety Reporting to Investigators, IRBs and Regulatory Authorities............55
11.0
STUDY-SPECIFIC COMMITTEES .............................................................................56


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12.0
DATA HANDLING AND RECORDKEEPING............................................................57
12.1
CRFs (Electronic)....................................................................................................57
12.2
Record Retention .....................................................................................................57
13.0
STATISTICAL METHODS..........................................................................................59
13.1
Statistical and Analytical Plans ................................................................................59
13.1.1
Analysis Sets...............................................................................................59
13.1.2
Analysis of Demographics and Other Baseline Characteristics ....................59
13.1.3
PK Analysis ................................................................................................59
13.1.4
Safety Analysis ...........................................................................................60
13.2
Interim Analysis and Criteria for Early Termination ................................................60
13.3
Determination of Sample Size..................................................................................60
14.0
QUALITY CONTROL AND QUALITY ASSURANCE...............................................61
14.1
Study-Site Monitoring Visits ...................................................................................61
14.2
Protocol Deviations..................................................................................................61
14.3
Quality Assurance Audits and Regulatory Agency Inspections ................................62
15.0
ETHICAL ASPECTS OF THE STUDY........................................................................63
15.1
IRB Approval ..........................................................................................................63
15.2
Subject Information, Informed Consent, and Subject Authorization .........................64
15.3
Subject Confidentiality ............................................................................................65
15.4
Publication, Disclosure, and Clinical Trial Registration Policy.................................65
15.4.1
Publication and Disclosure..........................................................................65
15.4.2
Clinical Trial Registration...........................................................................66
15.4.3
Clinical Trial Results Disclosure .................................................................66
15.5
Insurance and Compensation for Injury....................................................................66
16.0
REFERENCES..............................................................................................................67
LIST OF IN-TEXT TABLES
Table 6.a
Part 1 Sequences................................................................................................20
Table 6.b
Part 2 Sequences................................................................................................21
Table 7.a
Prohibited Medications, Supplements, and Dietary Products ..............................27
Table 8.a
Study Medication – Sponsor Supplied................................................................30
Table 8.b
Dose and Regimen .............................................................................................31
Table 9.a
Clinical Laboratory Tests...................................................................................38
Table 9.b
Collection of Blood Samples for PK Analysis ....................................................41
Table 9.c
Approximate Blood Volume ..............................................................................47


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Table 10.a
Takeda Medically Significant AE List................................................................51
Table 14.a
Windows for PK Sample Collection...................................................................61
LIST OF IN-TEXT FIGURES
Figure 6.a
Schematic of Study Design ................................................................................22
Figure 6.b
Schematic of Crossover Design..........................................................................22
LIST OF APPENDICES
Appendix A
Schedule of Study Procedures............................................................................68
Appendix B
Responsibilities of the Investigator.....................................................................70
Appendix C
Elements of the Subject Informed Consent.........................................................72
Appendix D
Investigator Consent to Use of Personal Information..........................................75
Appendix E
Collection, Storage, and Shipment of Bioanalytical Samples..............................76
Appendix F
Detailed Description of Amendments to Text.....................................................79


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2.0
STUDY SUMMARY
Name of Sponsor(s):
Takeda Development Center Americas, Inc.
Compound:
Dexlansoprazole Delayed-Release Capsules
Title of Protocol: A Phase 1, Randomized, Open-Label, 
Single-Center, Single-Dose, Two-Period Two Part 
Crossover Study in Healthy Subjects to Compare the 
Bioavailability of Dexlansoprazole from Dexlansoprazole 
Delayed-Release Capsules 30 mg and 60 mg Manufactured 
by Takeda GmbH Plant Oranienburg Relative to 
Dexlansoprazole Delayed-Release Capsules 30 mg and 60 
mg Manufactured by Takeda Pharmaceutical Company 
Limited Osaka Plant
IND No.: 
069927
EudraCT No.:
Not applicable
Study Number: TAK-390MR-1001
Phase: 1
Study Design:
This is a phase 1, randomized, open-label, single-center, single-dose, 2-part, 2-way crossover bioavailability (BA) 
study to compare the BA of 30 or 60 mg dexlansoprazole capsules manufactured at Takeda GmbH Plant Oranienburg 
(TOB) to the corresponding 30 or 60 mg dexlansoprazole capsules manufactured at Takeda Pharmaceutical Company 
Ltd. (TPC) plant in Osaka, Japan. The study will be conducted in 2 parts. In Part 1, 52 healthy subjects will receive 
dexlansoprazole 30 mg capsules manufactured by TOB and TPC in a crossover fashion. In Part 2, an additional 
52 healthy subjects will receive dexlansoprazole 60 mg capsules manufactured by TOB and TPC in a crossover 
fashion. Due to the difference between the Granules-L used in the 30 mg (Granules-LL) and 60 mg (Granules-LS) 
capsules, the relative BA of both dosage strengths will be assessed. If bioequivalence (BE) is not achieved with the 
first TOB formulation, the study may be repeated for one or both dose strengths in new subjects who will receive the 
same TOB formulation or a different TOB formulation. The same study design will be used if additional formulation 
assessments are needed.
Subjects who satisfy the Screening evaluation and selection criteria may be enrolled in the study. For each part, 
eligible subjects will be randomized on Day 1 of Period 1 in a 1:1 ratio to 1 of 2 sequences, which defines the order in 
which they will receive dexlansoprazole regimens in Periods 1 and 2. The dosing between Periods will be separated by 
a minimum 5-day washout interval. During Periods 1 and 2, blood samples will be collected over 24 hours postdose to 
measure dexlansoprazole plasma concentrations. The treatment sequences are outlined in the following tables for 
Part 1 and for Part 2.
Part 1 Sequences
Sequences
Number of Subjects
Period 1
Period 2
1
26
A
B
2
26
B
A
Regimen A (test): A single dexlansoprazole 30 mg capsule manufactured at TOB administered orally on Day 1 
following a 10-hour fast.
Regimen B (reference): A single dexlansoprazole 30 mg capsule manufactured at TPC administered orally on Day 1 
following a 10-hour fast. 


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Part 2 Sequences
Sequences
Number of Subjects
Period 1
Period 2
3
26
C
D
4
26
D
C
Regimen C (test): A single dexlansoprazole 60 mg capsule manufactured at TOB administered orally on Day 1 
following a 10-hour fast.
Regimen D (reference): A single dexlansoprazole 60 mg capsule manufactured at TPC administered orally on Day 1 
following a 10-hour fast. 
In each period of each part, subjects will be confined from Check-in Day -1 until all study procedures have been 
completed on Day 2. Study drug will be administered on Day 1 of each period at approximately 0800 hours, following 
a 10-hour fast. Dosing may be staggered to help facilitate logistics at the site. Subjects will be instructed to swallow the 
intact capsule with 240 mL of water. On Day 1 of each period, breakfast will not be served. During Periods 1 and 2 of 
each part, blood samples will be collected over 24 hours postdose to measure dexlansoprazole plasma concentrations.
A blood sample for pharmacogenomics (PGx) will also be collected on Day 1 of Period 1 of each part. The 
cytochrome P-450 (CYP)2C19 isozyme is a polymorphic enzyme that is involved in the metabolism of 
dexlansoprazole. A genotype test for CYP2C19 will determine the subject’s metabolizer status.
Subjects will be discharged from the study site on Day 2 of each period (subjects will exit the study on Day 2 of 
Period 2 within each part), and the dosing between periods within each part will be separated by a minimum 5-day 
washout interval.
A follow-up phone call will be made 10 (±2) days post last dose of study drug to inquire for any ongoing adverse 
events (AEs) or serious adverse events (SAEs), new AEs or SAEs, and concomitant medications taken since final 
dose. Subjects who withdraw their consent will still be contacted for a safety follow-up call. The contact will only be 
recorded in their source documents and the electronic case report forms (eCRFs), according to data protection 
regulations.
Primary completion date will be based on the final data collection for the primary endpoint, Day 2 of Period 2. End of 
trial (study completion date) will be based on the final data collection date for the entire study, which is the follow-up 
phone call.
A schematic of the study design is shown below.
Schematic of Study Design
Screening 
Period
Check-in
(Periods 1 
and 2)
Treatment Periods 1 and 2
Study Exit 
(Period 2)
Follow-up
Phone Call
Dexlansoprazole 30 
and 60 mg capsule 
Single Dose PK
Discharge
(Period 1)
Days -28 to -2
Day -1
Day 1
Day 2 Period 1
Day 2
Day 10 (±2 days)
Confinement 
PK=Pharmacokinetic.
Note: There is a minimum 5-day washout period between the dose in Period 1 and the dose in Period 2. A follow-up 
phone call will be made for collection of AEs, SAEs, and concomitant medications taken since the final dose.
Primary Objectives:

To assess the BA of dexlansoprazole from a 30 mg capsule manufactured at TOB relative to that of 
dexlansoprazole from a 30 mg capsule manufactured at TPC.

To assess the BA of dexlansoprazole from a 60 mg capsule manufactured at TOB relative to that of 
dexlansoprazole from a 60 mg capsule manufactured at TPC.
Additional Objectives:

To evaluate the safety and tolerability of dexlansoprazole following oral administration of a single 


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dexlansoprazole 30 or 60 mg capsule.
Subject Population: Healthy subjects aged 18 to 55 years, inclusive, who have a body mass index between 18 and 
30 kg/m2.
Number of Subjects:
Per dose level: 52
Estimated Total: 104
If additional formulation assessments are required, up to an 
additional 104 subjects will be enrolled.
Number of Sites:
Estimated total: 1 in the United States
Dose Level(s):
30 mg dexlansoprazole
60 mg dexlansoprazole
Route of Administration:
Oral
Duration of Treatment:
Part 1: Dexlansoprazole 30 mg capsule (manufactured at 
TOB or TPC) administered on Day 1 of Periods 1 and 2.
Part 2: Dexlansoprazole 60 mg capsule (manufactured at 
TOB or TPC) administered on Day 1 of Periods 1 and 2.
Total number of dosing days: 2 per Part.
Period of Evaluation:
Screening: 27 days.
Check-in (Day -1) for each Period: 2 days total.
Treatment Period (Days 1 to 2) for each Period: 4 days 
total.
Washout between periods: 5 days.
Follow-up phone call: 10 days (±2) after last dose.
Total Study Duration including Screening: 
Approximately 48 days
Main Criteria for Inclusion:
Healthy men and women aged 18 to 55 years old, inclusive, with a body mass index between 18 and 30 kg/m2, 
inclusive, who are capable of understanding and complying with protocol requirements. Subjects must be in good 
health as determined by a physician based upon medical history, vital signs, electrocardiogram (ECG), and physical 
examination. Subjects must have clinical chemistry, hematology, and complete urinalysis (after fasting for at least 
8 hours) at Screening and Check-in (Day -1 of Period 1) results within the reference range for the testing laboratory 
unless the out-of-range results are deemed not clinically significant by the investigator. Subjects must sign a written 
informed consent form (ICF) prior to initiation of study procedures.
Main Criteria for Exclusion:
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 (EE) with frequent [more than once per week] occurrence of heartburn); or has consumed medications, 
certain foods, and supplements, including prescription and over-the-counter medications, within the 
protocol-specified time periods prior to Check-in (Day -1 of Period 1), or is unwilling to agree to abstain from these 
products. The subject must not have received dexlansoprazole in a previous clinical study or as a therapeutic agent 
within 6 months of Screening, or have a known hypersensitivity to any component of the formulation of 
dexlansoprazole capsules or other drugs with the same mechanism of action (including lansoprazole, omeprazole, 
rabeprazole, pantoprazole, or esomeprazole), or related compounds; or any significant results from physical 
examination or clinical laboratory results that make the subject unsuitable for the study.


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Main Criteria for Evaluation and Analyses:
Primary Endpoints
The primary endpoints for this study are the following plasma PK parameters of dexlansoprazole derived on Day 1 of 
each period:

Maximum observed concentration (Cmax).

Area under the concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast).

Area under the concentration-time curve from time 0 to infinity (AUC∞).
Additional Endpoints
In addition, the following plasma PK parameters for dexlansoprazole: time to first occurrence of Cmax (tmax), terminal 
disposition phase half-life (t1/2z), terminal disposition phase rate constant (λz), apparent clearance after extravascular 
administration (CL/F), apparent volume of distribution during the terminal disposition phase after extravascular 
administration (Vz/F).
Safety Endpoints
Safety will be assessed by summarizing the incidence of AEs, clinical laboratory values, physical examinations, 
ECGs, and vital signs.
Statistical Considerations:
For each regimen of each part, dexlansoprazole plasma concentrations and PK parameter estimates will be tabulated 
and descriptive statistics computed.
For each part, analysis of variance (ANOVA) will be performed on natural logarithms of dexlansoprazole Cmax and 
area under the plasma concentration-time curve (AUC) with factors for sequence, subject nested within sequence, 
period, and regimen. The factor of the subject nested within sequence will be the error term for testing the sequence 
effect. Other factors will be tested with the residual as the error term. For the relative BA determination, pairwise 
comparisons will be performed to assess the relative BA of dexlansoprazole via point estimates and 90% confidence 
intervals (CI) for the ratio of Cmax and AUC central values of the dexlansoprazole 30 or 60 mg capsules manufactured 
at TOB compared to the respective 30 or 60 mg capsules manufactured at TPC. A conclusion of BE in the PK of 
dexlansoprazole between test regimen (dexlansoprazole capsule - TOB) and the reference regimen (dexlansoprazole 
capsule - TPC) will be reached if the 90% CIs for Cmax and AUC are within the (0.80–1.25) interval. 
Statistical analyses of other plasma PK parameters will be performed, if appropriate.
Sample Size Justification:
For each part, a sample size of 52 (26 per sequence) will be used in this study. This sample size will allow for up to 
6 dropouts (11.5% dropout rate) and provide 90% probability of concluding equivalence on dexlansoprazole Cmax
between the 2 regimens if the true difference between dexlansoprazole Cmax central values from 2 regimens is no more 
than 5%. The power for concluding equivalence on dexlansoprazole AUC between 2 regimens would be over 90%. 
This sample size was based on the intrasubject variance of 0.075 for log(Cmax) and 0.024 for log(AUC) from the 
TAK-390MR_107 study.
If BE is not achieved with the first TOB formulation assessed, the study may be repeated for one or both dose strengths
in new subjects who will receive the same TOB formulation or a different TOB formulation. The same study design 
will be used if additional formulation assessments are needed.


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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 vendors identified 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
AE
adverse event
ALT
alanine aminotransferase
ANOVA
analysis of variance
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
AUC∞
AUC from time 0 to infinity
AUClast
AUC from time 0 to time of the last quantifiable concentration
BA
bioavailability
BE
bioequivalence
BMI
body mass index
CI
confidence interval
CL/F
apparent clearance after extravascular administration
Cmax
maximum observed concentration
CRO
contract research organization
CS
clinically significant
CYP
cytochrome P-450
DNA
deoxyribonucleic acid
ECG
electrocardiogram
EDTA
ethylenediamine tetraacetic acid
eCRF
electronic case report form
EE
erosive esophagitis
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GERD
gastroesophageal reflux disease
GI
gastrointestinal
HBsAg
hepatitis B surface antigen
hCG
human chorionic gonadotropin
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
IBD
international birth date
ICF
informed consent form
ICH
International Conference on Harmonisation
IEC
independent ethics committee
IND
Investigational New Drug
INR
international normalized ratio
IRB
institutional review board


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IUD
intrauterine device
LFT
liver function test
MAV
markedly abnormal value
MedDRA
Medical Dictionary for Regulatory Activities
MHRA
United Kingdom Medicines and Healthcare products Regulatory Agency
NCS
not clinically significant
NDA
New Drug Application
PGx
pharmacogenomics
PK
pharmacokinetic(s)
PMDA
Pharmaceuticals and Medical Devices Agency (of Japan)
PPI
proton-pump inhibitor
PTE
pretreatment event
SAE
serious adverse event
SAP
statistical analysis plan
SOP
standard operating procedure
SUSAR
suspected unexpected serious adverse reaction
t1/2z
terminal disposition phase half-life
TEAE
treatment-emergent adverse event
tmax
time to first occurrence of Cmax
ULN
upper limit of normal
US
United States
Vz/F
apparent volume of distribution during the terminal disposition phase after extravascular 
administration, calculated using the observed value of the last quantifiable concentration.
WHODRUG
World Health Organization Drug Dictionary
3.4
Corporate Identification 
Takeda
TDC Japan, TDC Asia, TDC Europe and/or TDC Americas, as applicable
TDC Americas
Takeda Development Center Americas, Inc.
TOB
Takeda GmbH Plant Oranienburg, Germany
TPC
Takeda Pharmaceutical Company Ltd. (Osaka, Japan)


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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, is 
currently marketed in over 90 countries and has a well-established safety profile. 
Takeda Development Center Americas, Inc. (TDC Americas) 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) and 
adolescents (12 to 17 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 (US) in January 2009. The international birth date (IBD) is 30 January 2009.
The dual delayed-release capsule formulation of dexlansoprazole consists of 2 types of 
enteric-coated granules contained within a single capsule. Each type of granule has a different 
pH-dependent release profile. The formulation has been designed to have drug released within 1 to 
2 hours of administration, followed by a second release phase within 4 to 5 hours of the dose. This 
dual delayed-release formulation is designed to extend the duration of drug exposure and maintain 
pharmacologically active levels of drug over a longer period of time, resulting in prolonged 
elevation of intragastric pH. 
The pharmacokinetic (PK), pharmacodynamic, efficacy, and safety profiles of dexlansoprazole 
capsules following administration of dexlansoprazole 30, 60, and 90 mg capsules in adults have 
been extensively studied. Dexlansoprazole 60 mg capsules are approved for the healing of EE and 
dexlansoprazole 30 mg capsules are approved for the treatment of symptomatic nonerosive 
GERD, and the maintenance of healed EE. Currently, dexlansoprazole granules (Granules-LL and 
Granules-H for 30 mg and Granules-LS and Granules-H for 60 mg) are manufactured and 
encapsulated into capsule product at Takeda Pharmaceutical Company, Ltd. (TPC) located in 
Osaka, Japan.
4.2
Rationale for the Proposed Study
The rationale for conducting this study is to qualify an additional production site (Takeda GmbH 
Plant Oranienburg [TOB]) for the manufacture of dexlansoprazole capsules by establishing the 
bioequivalence (BE) of dexlansoprazole 30 and 60 mg capsules manufactured by TOB with 
dexlansoprazole 30 and 60 mg capsules manufactured by the TPC plant in Osaka.


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5.0
STUDY OBJECTIVES AND ENDPOINTS
5.1
Objectives
5.1.1
Primary Objective(s)

To assess the bioavailability (BA) of dexlansoprazole from a 30 mg capsule manufactured at 
TOB relative to that of dexlansoprazole from a 30 mg capsule manufactured at TPC.

To assess the BA of dexlansoprazole from a 60 mg capsule manufactured at TOB relative to 
that of dexlansoprazole from a 60 mg capsule manufactured at TPC.
5.1.2
Additional Objectives

To evaluate the safety and tolerability of dexlansoprazole following oral administration of a 
single 30 mg or 60 mg dexlansoprazole capsule. 
5.2
Endpoints
5.2.1
Primary Endpoints
The following plasma PK parameters of dexlansoprazole derived on Day 1 of each period:

Maximum observed concentration (Cmax).

Area under the concentration-time curve from time 0 to time of the last quantifiable 
concentration (AUClast).

Area under the concentration-time curve from time 0 to infinity (AUC∞).
5.2.2
Additional Endpoints

Time to first occurrence of Cmax (tmax).

Terminal disposition phase half-life (t1/2z).

Terminal disposition phase rate constant (λz).

Apparent clearance after extravascular administration (CL/F).

Apparent volume of distribution during the terminal disposition phase after extravascular 
administration (Vz/F).
5.2.3
Safety Endpoints
Safety will be assessed by summarizing the incidence of adverse events (AEs), clinical laboratory 
values, physical examinations, electrocardiograms (ECGs), and vital signs.


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6.0
STUDY DESIGN AND DESCRIPTION
6.1
Study Design
This is a phase 1, randomized, open-label, single-center, single-dose, 2-part, 2-way crossover 
study in healthy subjects to assess the BA of 30 or 60 mg dexlansoprazole capsules manufactured 
at TOB relative to the corresponding 30 or 60 mg dexlansoprazole capsules manufactured at TPC. 
The study will be conducted in 2 parts. In Part 1, 52 healthy subjects will receive dexlansoprazole 
30 mg capsules manufactured by TOB and TPC in a crossover fashion. In Part 2, an additional 
52 healthy subjects will receive dexlansoprazole 60 mg capsules manufactured by TOB and TPC 
in a crossover fashion. Due to the difference between the Granules-L used in the 30 mg 
(Granules-LL) and 60 mg (Granules-LS) capsules, the relative BA of both dosage strengths will be 
assessed. If BE is not achieved with the first TOB formulation, the study may be repeated for one 
or both dose strengths in new subjects who will receive the same TOB formulation or a different 
TOB formulation. The same study design will be used if additional formulation assessments are 
needed.
At Check-in (Day -1 of Period 1), approximately 104 subjects in total (52 in Part 1, 52 in Part 2), 
including both men and women, aged 18 to 55 years, inclusive, will be selected to participate in the 
study. Subjects who satisfy the Screening evaluation and selection criteria may be enrolled in the 
study. For each part, eligible subjects will be randomized on Day 1 of Period 1 in a 1:1 ratio to 1 of 
2 sequences, which defines the order in which they will receive dexlansoprazole regimens in 
Periods 1 and 2. The dosing between periods will be separated by a minimum 5-day washout 
interval. During Periods 1 and 2, blood samples will be collected over 24 hours postdose to 
measure dexlansoprazole plasma concentrations. 
The treatment sequences are outlined in Table 6.a (Part 1) and Table 6.b (Part 2).
Table 6.a
Part 1 Sequences
Sequences
Number of 
Subjects
Period 1
Period 2
1
26
A
B
2
26
B
A
Regimen A (test): A single dexlansoprazole 30 mg capsule manufactured at TOB administered orally on Day 1 
following a 10-hour fast.
Regimen B (reference): A single dexlansoprazole 30 mg capsule manufactured at TPC administered orally on Day 1 
following a 10-hour fast. 


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Table 6.b
Part 2 Sequences
Sequences
Number of 
Subjects
Period 1
Period 2
3
26
C
D
4
26
D
C
Regimen C (test): A single dexlansoprazole 60 mg capsule manufactured at TOB administered orally on Day 1 
following a 10-hour fast.
Regimen D (reference): A single dexlansoprazole 60 mg capsule manufactured at TPC administered orally on Day 1 
following a 10-hour fast. 
In each period of each part, subjects will be confined from Check-in Day -1 until all study 
procedures have been completed on Day 2. Study drug will be administered on Day 1 of each 
period at approximately 0800 hours, following a 10-hour fast. Dosing may be staggered to help 
facilitate logistics at the site. Subjects will be instructed to swallow the intact capsule with 240 mL 
of water. On Day 1 of each period, breakfast will not be served. During Periods 1 and 2, blood 
samples will be collected over 24 hours postdose to measure dexlansoprazole plasma 
concentrations.
A blood sample for pharmacogenomics (PGx) will also be collected on Day 1 of Period 1. The 
cytochrome P-450 (CYP)2C19 isozyme is a polymorphic enzyme that is involved in the 
metabolism of dexlansoprazole. A genotype test for CYP2C19 will determine the subject’s 
metabolizer status.
Subjects will be discharged from the study site on Day 2 of each period (subjects will exit the study 
on Day 2 of Period 2 within each part), and the dosing between periods within each part will be 
separated by a minimum 5-day washout interval.
A follow-up phone call will be made 10 (±2) days post last dose of study drug to inquire for any 
ongoing AEs or serious adverse events (SAEs), new AEs or SAEs, and concomitant medications 
taken since final dose. Any spontaneously reported AEs will continue to be collected for 30 days 
after the last dose of study drug. Subjects who withdraw their consent will still be contacted for a 
safety follow-up call. The contact will only be recorded in their source documents and the 
electronic case report forms (eCRFs), according to data protection regulations.
Primary completion date will be based on the final data collection for the primary endpoint, Day 2 
of Period 2. End of trial (study completion date) will be based on the final data collection date for 
the entire study, which is the follow-up phone call.
A schematic of the study design is included as Figure 6.a and Figure 6.b. A schedule of 
assessments is listed in Appendix A.


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Figure 6.a
Schematic of Study Design
Screening 
Period
Check-in 
(Periods 1 and 2)
Treatment Periods 1 and 2
Study Exit 
(Period 2)
Follow-Up
Phone Call
Dexlansoprazole 30 and 60 mg 
capsule
Single Dose PK
Discharge 
(Period 1)
Days -28 to -2
Day -1
Day 1
Day 2 Period 1
Day 2
Day 10±2
Confinement 
Note: There is a minimum 5-day washout period between the dose in Period 1 and the dose in Period 2. A follow-up 
phone call will be made for collection of AEs, SAEs, and concomitant medications taken since the final dose.
Figure 6.b
Schematic of Crossover Design
PART 1
PART 2
6.2
Justification for Study Design, Dose, and Endpoints
This phase 1 randomized, open-label, single-dose, 2-part, 2-way crossover relative BA study is 
designed in accordance with the Bioavailability and Bioequivalence Studies Submitted in New 
Drug Applications (NDAs) or Investigational New Drug (INDs) – General Considerations 
Guidance for Industry (March 2014) [2], and The Committee for Medicinal Products for Human 
Use Guideline on the Investigation of Bioequivalence (January 2010) [3].
A single-dose study under fasting conditions for assessing the relative BA between formulations is 
recommended in the guidances referenced above and will be used for comparison of the capsule 
formulations from each manufacturing site. The crossover design is appropriate for the objectives 
of this study because each subject receives both regimens and serves as his or her own control. 
52 subjects
26 planned 
subjects
30 mg TPC
26 planned 
subjects
30 mg TOB
washout
washout
26 planned 
subjects
30 mg TOB
26 planned 
subjects
30 mg TPC
52 subjects
26 planned 
subjects
60 mg TPC
26 planned 
subjects
60 mg TOB
washout
washout
26 planned 
subjects
60 mg TOB
26 planned 
subjects
60 mg TPC


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In humans, dexlansoprazole has a mean t1/2z of approximately 1 to 2 hours. Therefore, a minimum 
5-day washout interval between the doses is sufficient to ensure that there is no drug carryover 
effect, and collection of PK blood samples for 24 hours postdose is appropriate to characterize the 
PK of dexlansoprazole. The primary PK endpoints, Cmax and area under the concentration-time 
curve (AUC) are standard parameters to assess BA. The safety endpoints, including 
treatment-emergent adverse events (TEAEs), vital signs, 12-lead ECGs, clinical laboratory tests 
and physical examination data, are standard methods for assessing safety and tolerability in 
clinical pharmacology studies.
The CYP2C19 isozyme is a polymorphic enzyme that is involved in the metabolism of 
dexlansoprazole. 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. 
As this is a crossover study and each subject will be his/her own control, inclusion of CYP2C19 
poor metabolizers is not expected to affect the overall results of the study.
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 product, such that the risk 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), 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.
7.1
Inclusion Criteria
Attempts will be made to enroll an equal number of men and women. 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 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 in good health as determined by a physician based upon medical history, vital 
signs, ECG, and physical examination findings at Screening and Check-in.
4. The subject is a man or woman aged 18 to 55 years, inclusive, at the time of informed consent 
and first study medication dose.
5. The subject has a body mass index (BMI) from 18 to 30 kg/m2, inclusive, at Screening.
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. A woman of childbearing potential* who is sexually active with a nonsterilized* male partner 
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 serum 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 (after fasting for at least 
8 hours) at Screening and Check-in (Day -1 of Period 1) results within the reference range for 
the testing laboratory unless the out-of-range results are deemed not clinically significant by 
the investigator. 
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 30 days prior to the first dose of 
study medication.


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2. 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). 
3. The subject has a history of drug abuse (defined as any illicit drug use) or drug addiction in the 
12 months prior to Screening or a history of alcohol abuse (defined as regular consumption 
exceeding 21 units per week [1 unit = 12 ounces (oz) beer, 1.5 oz hard liquor, or 5 oz wine]) 
within 1 year prior to the Screening Visit, or is unwilling to agree to abstain from alcohol and 
drugs throughout the study. 
4. The subject has a positive test result for drugs of abuse (defined as any illicit drug use) or 
alcohol at Screening or Check-in (Day -1 of Period 1). 
5. Subject has received any known hepatic or renal clearance altering agents (eg, erythromycin, 
cimetidine, barbiturates, phenothiazines, fluvoxamine, etc) for a period of 28 days prior to 
Day 1 of Period 1. 
6. Subject has had an acute, clinically significant illness within 30 days prior to Day 1 of 
Period 1.
7. Subject has a systolic blood pressure >140 mm Hg or has a diastolic blood pressure 
>90 mm Hg at Screening or Check-in (Day -1 of Period 1).
8. Subject has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus 
(HCV) antibody at Screening or a known history of human immunodeficiency virus infection 
(HIV).
9. Subject has abnormal Screening or Day -1 of Period 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) >2.5 x the upper limit of normal (ULN) or total bilirubin >2.0 mg/dL.
10. Subject has an abnormal (clinically significant) ECG at Screening or Check-in (Day -1 of 
Period 1). Entry of any subject with an abnormal (not clinically significant) ECG must be 
approved, and documented by the signature of the principal investigator.
11. Subject has donated blood products (such as plasma) within 30 days or has donated whole 
blood or lost 450 mL or more of his or her blood volume, or had a transfusion of any blood 
product within 56 days prior to Day 1 of Period 1.
12. With the exception of acetaminophen, the subject has taken any excluded medication, 
supplements, or food products listed in Section 7.3. Hormonal contraception and hormone 
replacement therapy are allowed, as long as the subject has been on a stable dose for a 
minimum of 90 days prior to Day 1 of Period 1.
13. Subject has used nicotine-containing products (including but not limited to cigarettes, pipes, 
cigars, chewing tobacco, nicotine patch nicotine gum, e-cigarettes) within 28 days prior to 


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Check-in (Day -1 of Period 1), or has a positive cotinine test at Screening or Check-in (Day -1 
of Period 1), or is unwilling to abstain from these products for the duration of the study.
14. The subject has received dexlansoprazole or lansoprazole in a previous clinical study or as a 
therapeutic agent within 6 months of screening.
15. The subject has a history (within 6 months) or clinical manifestations of clinically significant 
metabolic, hematologic, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, 
renal, urologic, immunologic, musculoskeletal or psychiatric disorder as defined by the 
investigator, which may impact the ability of the subject to participate or potentially confound 
the study results.
16. Subject has a history of cancer, except basal cell carcinoma that has been in remission for at 
least 5 years prior to Day 1 of Period 1.
17. The subject has poor peripheral venous access.
18. Subject has a known hypersensitivity to any component of the formulation of dexlansoprazole 
capsules or other drugs with the same mechanism of action (including lansoprazole, 
omeprazole, rabeprazole, pantoprazole, or esomeprazole), or related compounds.
19. If a woman, the subject is pregnant or lactating or intending to become pregnant before, during, 
or within 30 days after participating in this study, or intending to donate ova during such time 
period. 
20. If a man, the subject intends to donate sperm during the course of this study or for 30 days 
thereafter.
21. The subject is an immediate family member, study site employee, or is in a dependent 
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.
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 and for the duration of the subject’s participation in the study. 


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Table 7.a
Prohibited Medications, Supplements, and Dietary Products
28 days prior to Check-in (Day -1 of 
Period 1)
7 days prior to Check-in (Day -1 of 
Period 1)
72 hours prior to Check-in 
(Day -1 of Period 1)
Prescription medications including 
oral contraceptives (a)
OTC medications (b)
Alcohol-containing products
Nicotine-containing products
Vitamin supplements
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
Products containing caffeine 
and/or xanthine
Hepatic or renal clearance altering 
agents
Immunization/Vaccines (c)
Intake of known OTC inhibitors/inducers 
of CYPs 3A4/5, 2C9, 2C19, 2D6, 1A2, 
2B6, 2E1, and 2A6 (d)
Poppy seeds
OTC=over-the-counter.
(a) Hormonal contraception and hormone replacement therapy (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) Lansoprazole, esomeprazole, omeprazole, cimetidine, ranitidine, and chlorpheniramine.
Subjects must be instructed not to take any medications including over-the-counter products, 
without first consulting with the investigator during the Washout Period, as well as during 
confinement.
7.4
Diet, Fluid and Activity Control 
7.4.1
Confinement
Subjects enrolled in this study will be confined in the clinical research unit for 2 consecutive nights 
in each period, beginning at Check-in (Day -1) to Day 2. There will be a minimum 5-day washout 
interval between the dose in the first period and the dose in the second period. Subjects will be 
released from the clinic during the washout interval.
7.4.2
Diet and Fluid
During each day of the confinement period, subjects will receive standardized meals and an 
evening snack, each of which contains approximately 30% fat (caloric value). The clinical 
research site will ensure the same meals are served to all subjects on Day 1 of both study periods. 
All subjects may consume water ad libitum except for 1 hour before and 1 hour after drug 
administration. 


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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 10 hours prior to dosing on Day 1 of each period. On Day 1 of 
each period, breakfast will not be served. 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 additional meals will be served on Day 1 of each period. The start and stop 
times of meals on Day 1 of each period, along with whether the meal was completely consumed, 
will be recorded in the source documentation and on the eCRF. Subjects will be fasting for a 
minimum of 8 hours prior to collection of safety labs and 24 hour PK sample on Day 2 of Periods 1 
and 2.
7.4.3
Activity Control
Subjects should be instructed to refrain from strenuous exercise starting approximately 48 hours 
prior to confinement on Day -1 of Period 1 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 or study 
medication should be recorded in the eCRF using the following categories. For screen failure 
subjects, refer to Section 9.1.15.
1. Pretreatment event or AE. The subject has experienced a pretreatment event 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 pretreatment event or AE.

Liver Function Test (LFT) Abnormalities 
Study medication should be discontinued immediately with appropriate clinical follow-up 
(including repeat laboratory tests, until a subject’s laboratory profile has returned to 
normal/baseline status, see Section 9.1.8), if the following circumstances occur at any time 
during study medication treatment: 
–
ALT or AST >8 × ULN, or
–
ALT or AST >5 × ULN and persists for more than 2 weeks, or
–
ALT or AST >3 × ULN in conjunction with elevated total bilirubin >2 × ULN or 
international normalized ratio (INR) >1.5, or ALT or AST >3 × ULN with appearance 
of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash and/or 
eosinophilia (>5%).
2. Significant protocol deviation. The discovery after the first dose of study medication 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.


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4. Voluntary withdrawal. The subject 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).
5. Study termination. The sponsor, IRB, 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.
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 by 
the investigator. In addition, efforts should be made to perform all procedures scheduled for the 
Early Termination Visit. Discontinued or withdrawn subjects may be replaced.


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8.0
CLINICAL TRIAL MATERIAL MANAGEMENT
This section contains information regarding all medication 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
8.1.1
Dosage Form, Manufacturing, Packaging, and Labeling
In this protocol, the term study medication refers to all or any of the drugs defined below.
The study site will be supplied with 30-count bottles of dexlansoprazole delayed-release capsules 
30 mg manufactured at TOB (containing Granules-LL and Granules-H), and 30 mg capsules 
manufactured at TPC (containing Granules-LL and Granules-H). Also supplied will be 30-count 
bottles of dexlansoprazole delayed-release capsules 60 mg manufactured at TOB (containing 
Granules-LS and Granules-H), and 60 mg capsules manufactured at TPC (containing Granules-LS 
and Granules-H). The bottles will be packaged in an open label manner. The bottles will bear a 
single-panel computer-generated label containing the required information, including the Federal 
caution statement “CAUTION: New Drug-Limited by Federal (or United States) Law to 
Investigational Use.” 
The sponsor will supply the site with study drug as shown in Table 8.a.
Table 8.a
Study Medication – Sponsor Supplied
Formulation
Investigational Product
Dosage
Manufacturer and Location
A (test)
Dexlansoprazole capsule
30 mg
Capsules manufactured at TOB
B (reference)
Dexlansoprazole capsule
30 mg
Capsules manufactured at TPC
C (test)
Dexlansoprazole capsule
60 mg
Capsules manufactured at TOB
D (reference)
Dexlansoprazole capsule
60 mg
Capsules manufactured at TPC
8.1.2
Storage
All drug supplies used to conduct this study must be kept in an appropriate, limited-access, secure 
place until it is used or returned to the sponsor or designee for destruction. Drug supplies must be 
stored at controlled room temperature 20°C to 25°C (68°F to 77°F; see US Pharmacopeia); 
excursions allowed between 15°C and 30°C (59°F to 86°F), protected from moisture and in a 
secure location until dispensed to study subjects or returned to Takeda or its designee. Drug 
supplies will be counted and reconciled at the site before disposition or return to Takeda or 
designee. Each drug supply must be returned in its original container.
8.1.3
Dose and Regimen
Subjects will fast for a minimum of 10 hours prior to dosing in Periods 1 and 2. On Day 1 at 
approximately 0800 hours, subjects will be instructed to swallow the intact capsule with 240 mL of 


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water. Dosing may be staggered to help facilitate logistics at the site. All subjects may consume 
water ad libitum, except for 1 hour prior to and 1 hour post drug administration. Subjects must 
drink all of the water provided with the dose.
Following the administration of the study drug, hand and mouth checks will be performed to 
ensure the dose was swallowed. Although the timing of events requires that each subject will be 
consistently administered the appropriate dose 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.
On each dosing day (Day 1 of Periods 1 and 2) subjects will be administered dosing regimens 
according to the sequence group they are assigned to (See Table 8.b).
The 4 dosing regimens are:
Regimen A: A single 30 mg dexlansoprazole capsule manufactured at TOB.
Regimen B: A single 30 mg dexlansoprazole capsule manufactured at TPC.
Regimen C: A single 60 mg dexlansoprazole capsule manufactured at TOB.
Regimen D: A single 60 mg dexlansoprazole capsule manufactured at TPC.
On Day 2 of Period 1, subjects will be discharged from the study site for a minimum washout 
interval of 5 days between the dose in the first period and the dose in the second period. 
Table 8.b
Dose and Regimen
Study Part
Sequence
Number of Subjects
Period 1
Regimen
Period 2
Regimen
Part 1
30 mg
1
26
A
B
2
26
B
A
Part 2
60 mg
3
26
C
D
4
26
D
C
Regimen A: A single 30 mg dexlansoprazole capsule manufactured at TOB administered orally on Day 1 following a 
10-hour fast.
Regimen B: A single 30 mg dexlansoprazole capsule manufactured at TPC administered orally on Day 1 following a 
10-hour fast. 
Regimen C: A single 60 mg dexlansoprazole capsule manufactured at TOB administered orally on Day 1 following a 
10-hour fast.
Regimen D: A single 60 mg dexlansoprazole capsule manufactured at TPC administered orally on Day 1 following a 
10-hour fast. 
Note: If the study is repeated in the same or new formulations, the regimens will be labeled AA, BB, CC, and DD, as 
needed.
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.


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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.
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
Subjects will be assigned, in the order in which they are randomized into the study, to receive their 
treatment according to the randomization schedule allocated to the site. The Randomization 
Sequence Number will be entered onto the eCRF.
Subjects will be assigned to receive a 4-digit randomization sequence number by the clinic site 
personnel in sequential order. For Part 1, men will be assigned in ascending order starting from 
1001 and women will be assigned in descending order starting from 1052. For Part 2, men will be 
assigned in ascending order starting from 2001 and women will be assigned in descending order 
starting from 2052. Additional schedules will be generated if the second formulations are assessed. 
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 PK 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 number which is assigned at the time the 
informed consent is obtained and which is used for all other procedures to identify the subjects 
throughout the study.
8.3
Randomization Code Creation and Storage 
The randomization schedule will be generated prior to the start of the study, and will be provided 
to the site pharmacist prior to the start of this study. All randomization information will be stored 
in a secured area, accessible only by authorized personnel.
8.4
Accountability and Destruction of Sponsor-Supplied Drugs
Drug supplies will be counted and reconciled at the site before being returned to the sponsor or 
designee.
The investigator or designee must ensure that the sponsor-supplied drug is used in accordance with 
the protocol and is dispensed only to subjects enrolled in the study. To document appropriate use 
of sponsor-supplied drug, the investigator or designee must maintain records of all 
sponsor-supplied drug delivery to the site, site inventory, dispensation, use by each subject, and 
return to the sponsor or designee.


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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 the 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.
The investigator or designee must maintain 100% accountability for all sponsor-supplied drugs 
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 or 
designee.

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 or designee must record the current inventory of all sponsor-supplied drugs 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 sponsor-supplied drugs, expiry date and amount dispensed, including initials of the person 
dispensing the drug, and the date and amount returned to the site by the subject, including the 
initials of the person receiving the sponsor-supplied drug. The log should include all required 
information as a separate entry for each subject to whom sponsor-supplied drug is dispensed.
All study drug that was not returned to the site by a subject must be investigated by the site and 
appropriately documented on the drug accountability log.
Prior to site closure or at appropriate intervals, a representative from the sponsor or its designee 
will perform sponsor-supplied drug accountability and reconciliation before sponsor-supplied 
drugs are returned to the sponsor or its designee for destruction. The investigator or designee will 
retain the original documentation regarding sponsor-supplied drug accountability, return, and/or 
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 sponsor-supplied 
drug 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 
sponsor-supplied drug 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 study material
may be relabeled with the new expiry date at that site. In such cases, Takeda or its designee will 


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prepare additional labels, and all necessary documentation for completion of the procedure at the 
sites.
8.5
Reserve Study Medication Samples for Retention
The investigator will retain a reserve sample of dexlansoprazole capsules in accordance with Food 
and Drug Administration (FDA) regulations. The investigator or the investigator’s designee will 
select the appropriate number of containers of study medication for retention, as specified in the 
bioretention letter to be provided by Takeda Clinical Supplies. Reserve samples will be stored 
under conditions consistent with the product’s labeling and in a segregated area with access 
limited to authorized personnel. Each reserve sample will be retained for a period of at least 5 years 
following the date the application or supplemental application is approved by the FDA. If the 
application is not approved, regulations specify that these samples must be stored for at least 5 
years following the date of completion of this BA study. The clinical site should not dispose of the 
reserve samples without written authorization from Takeda. If at any time the investigator is 
unable to comply with these requirements, the investigator should immediately notify Takeda 
regarding arrangements for storing reserve samples and associated study records on the 
investigator’s behalf.


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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 (subject ID = site + subject number) will be assigned to 
each subject at the time that informed consent is obtained; this subject number will be used 
throughout the study.
9.1.1.1
Pharmacogenomic Informed Consent Procedure
PGx informed consent is a component of the overall study informed consent. The requirements are 
described in Section 15.2. The PGx sample collection is mandatory.
9.1.2
Demographics, Medical History, and Medication History Procedure
Demographic information to be obtained will include date of birth, gender, Hispanic ethnicity, 
race as described by the subject, height, weight, caffeine consumption, xanthine consumption, 
alcohol use, reproductive status (including last menstrual period) and smoking status of the subject 
at Screening.
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.
Medical history to be obtained will include determining whether the subject has any significant 
conditions or diseases relevant to the disease under study that resolved at or prior to signing of 
informed consent. Ongoing conditions are considered concurrent medical conditions (see 
Section 9.1.7).
9.1.3
Physical Examination Procedure
Physical exams will be performed at Screening, Check-in (Day -1 of Periods 1 and 2), Day 2 Study 
Exit for Period 2 only, Early Termination, and during Unscheduled Visits. A baseline physical 
examination (defined as the pretreatment assessment immediately prior to the start of study drug) 
will be performed at Check-in (Day -1) of Period 1. The exams 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; (11) genitourinary system; and (12) other. The 


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genitourinary examination will not be required for this protocol but will be listed on the eCRF page 
for physical examination and hard-coded as “not done.”
All physical examinations subsequent to Check-in (Day -1) of Period 1 should assess clinically 
significant changes from the Baseline Check-in (Day -1) of Period 1 examination. If a body system 
is not examined, “not done” should be indicated.
Any abnormal finding on a pretreatment physical examination assessment 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 pretreatment event 
(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 study drug must be assessed as NCS or 
CS by the investigator and recorded in the source document and eCRF. Any 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. The Takeda 
standard for collecting height is centimeters without decimal places and for weight it is kilograms 
(kg) with 1 decimal place. BMI should be derived as:
Metric:
BMI = weight (kg)/[height (m)]2
Note that although height is reported in centimeters, the formula uses meters for height; meters can 
be determined from centimeters by dividing by 100. For example, if weight=79.2 kg and 
height=176 cm (1.76 meters), then BMI=79.2/1.762=25.56818 kg/m2.
The values should be reported to 1 decimal place by rounding. Thus, in the above example BMI 
would be reported as 25.6 kg/m2. However, if the BMI is used as entry criteria based on 30 kg/m2
cut-off point, then this determination must be made after rounding.
9.1.5
Vital Sign Procedure
Vital signs will include oral body temperature, sitting blood pressure (resting 5 minutes), and pulse 
(beats per minute). Only blood pressure and pulse will be taken on Check-in (Day -1) through 
Day 2. Vital signs will be obtained at the time points stipulated in Schedule of Study Procedures 
(Appendix A). 
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.


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9.1.6
Documentation of Concomitant Medications
Subjects will be instructed not to take any medications during the study, including 
over-the-counter products, without first consulting with the investigator. Use of concomitant 
medications will not be allowed during the study unless deemed necessary in cases of medical 
emergency or approved by the sponsor on a case-by-case basis. Occasional use of acetaminophen 
(up to 2 g/day) is allowed. Acetaminophen is not allowed on Day 1 of each period. Hormonal 
contraception and HRT are allowed, as long as a subject has been on a stable dose for a minimum 
of 90 days prior to Day 1.
All medications used within 28 days prior to Screening will be recorded in the source document 
and Medication History eCRF. All medications taken from Screening through to the end of the 
study will be recorded in the source document and Concomitant Medication eCRF.
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 the Screening examination. 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. Laboratory 
samples will be taken following a minimum 8-hour overnight fast at the time points stipulated in 
the Schedule of Study Procedures (Appendix A).
Table 9.a lists the tests that will be obtained for each laboratory specimen.


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Table 9.a
Clinical Laboratory Tests
Hematology
Serum Chemistry
Urinalysis
RBC
WBC with differential 
Hemoglobin
Hematocrit
Platelets
Alanine aminotransferase 
Albumin
Alkaline phosphatase
Aspartate aminotransferase
Glucose
Total bilirubin
Total protein
Total cholesterol
Triglycerides
Serum creatinine
Blood urea nitrogen
Uric acid
gamma-glutamyl transferase
Calcium
Phosphorus
Potassium
Sodium
Chloride
Bicarbonate or carbon dioxide
Specific gravity
pH
Protein
Ketones
Glucose
Bilirubin
Red blood cells and white 
blood cells
Microscopic battery 
(RBCs, WBCs, epithelial 
cells, casts) if significant 
findings on dipstick 
urinalysis
Diagnostic Screenings:
Serum
Urine/Blood
Breath
Hepatitis panel, including HBsAg
and anti-HCV
Drug screen, including amphetamines, barbiturates, 
benzodiazepines, cannabinoids, cocaine, cotinine 
and opiates.
Alcohol
Women subjects only:
Serum hCG for pregnancy
Serum FSH If postmenopausal women 
defined as amenorrhea >1 year
FSH=follicle stimulating hormone, hCG= human chorionic gonadotropin, RBC=red blood cells, WBC=white blood 
cells.
The local laboratory will perform laboratory tests for hematology, serum chemistries, and 
urinalysis as referenced in Appendix A. The results of laboratory tests will be returned to the 
investigator, who is responsible for filing and reviewing these results for clinical significance 
together with the data in the eCRF. 
Laboratory reports must be signed and dated by the principal investigator or subinvestigator 
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 an AE in the 
subject’s source documents and on the appropriate eCRF unless they are the result of pathology for 
which there is an overall diagnosis. The investigator will maintain a copy of the laboratory 
accreditation and the reference ranges for the laboratory used. 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. 


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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 women 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.
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.
*Women of childbearing potential are defined as any female who has experienced menarche and 
who are NOT permanently sterile or postmenopausal. Women NOT of childbearing potential are 
defined as those who have been surgically sterilized (hysterectomy, bilateral oophorectomy or 
tubal ligation) or who are postmenopausal (eg, defined as 12 consecutive months with no menses 
without an alternative medical cause).**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, the only 
acceptable methods of contraception are:
Barrier methods (each time the 
subject has intercourse):
Intrauterine devices 
(IUDs):
Hormonal contraceptives:

Male condom PLUS 
spermicide.

Cap (plus spermicidal cream or 
jelly) PLUS male condom.

Diaphragm (plus spermicidal 
cream or jelly) PLUS male 
condom.

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 and donation of ova and sperm during the 
course of the study.
At Screening, 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 ova and sperm donation as part of the study procedures (Appendix A). In addition, subjects 


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must also have a negative serum hCG pregnancy test 1 day prior to receiving first dose of study 
medication.
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 male subject during the study or for 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 Check-in 
(Day -1 of Period 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 agrees to the primary care physician being informed, the investigator should notify 
the primary care physician that the subject was participating in a clinical study at the time she 
became pregnant and provide details of treatment the subject received (blinded or unblinded, as 
applicable).
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.
9.1.11 ECG Procedure
A standard 12-lead ECG will be recorded at Screening, Check-in (Day -1) of Period 1, and Day 2 
Study Exit of Periods 1 and 2 or if a subject terminates early from the study. 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. The 
following parameters will be recorded on the eCRF from the subject’s ECG trace: heart rate, QT
interval, and QRS interval.
9.1.12 Pharmacogenomic Sample Collection
When sampling of whole blood for PGx analysis occurs, every subject must sign an informed 
consent/be consented in order to participate in the study.
Deoxyribonucleic acid (DNA) form the basis for the genes that make the body produce proteins 
such as enzymes, drug transporters or drug targets, and may be evaluated for the genetic 
contribution how the drug is broken down, or how the drug affects the body. This is called a “PGx 
research study.” Specific purposes of this study include:

Identifying genetic reasons certain people respond differently to dexlansoprazole.


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
Finding out more information about how dexlansoprazole works.

Generating information needed for research, development, and regulatory approval of tests to 
predict response to dexlansoprazole.

Identifying variations in genes related to the biological target of dexlansoprazole.
This information may be used to develop a better understanding of the safety and efficacy of 
dexlansoprazole and other study medications, and for improving the efficiency, design, and study 
methods of future research studies.
One 6 mL whole blood sample for DNA isolation will be collected before dosing on Day 1 of 
Period 1 from each subject in the study, into plastic K2 ethylenediamine tetraacetic acid (EDTA) 
spray-coated tubes, and stored under frozen conditions. If necessary and feasible, a second aliquot 
of blood may be taken at any time after randomization if isolation of DNA from the first sample 
was not successful or possible.
The samples will be stored for no longer than 15 years after completion of the dexlansoprazole
study and/or until the drug development of dexlansoprazole is no longer actively pursued by 
Takeda or its collaborators. No samples will be stored for longer than permitted by the applicable 
law and samples will be destroyed upon notification from Takeda. “Stored samples” are defined as 
samples that are key-coded (the samples are stripped of all personal identifying information but a 
key links the samples to the clinical data collected from the sample donor) and are used in the 
analysis of investigational drug or related drugs.
The CYP2C19 isozyme is a polymorphic enzyme that is involved in the metabolism of 
dexlansoprazole. Therefore, the CYP2C19 metabolizer status of the subjects will be determined.
Detailed instructions for the handling and shipping of samples are provided in the Lab Manual.
9.1.13 PK Sample Collection
9.1.13.1 Collection of Blood for PK Sampling
Blood samples (4 mL) for dexlansoprazole plasma concentrations will be collected beginning on 
Day 1 of each period of each part, as shown in Table 9.b.
Instructions for sample processing and shipment are provided in Appendix E.
Table 9.b
Collection of Blood Samples for PK Analysis
Sample 
Type
Dosing Day
Time (hours)
(Periods 1 and 2)
Plasma
1
Predose (within 15 minutes prior to dose) and at 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 PK Parameters
Plasma PK parameters of dexlansoprazole will be derived using noncompartmental analysis 
methods. The PK parameters of dexlansoprazole 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 PK computations involving blood sampling times. The following PK parameters for 
dexlansoprazole will be determined. Additional PK parameters may be calculated as appropriate.
Symbol/Term
Definition
Plasma
AUClast
Area under the concentration-time curve from time 0 to time of the last quantifiable 
concentration.
AUC∞
Area under the concentration-time curve from time 0 to infinity, calculated using the observed 
value of the last quantifiable concentration.
Cmax
Maximum observed concentration.
CL/F
Apparent clearance after extravascular administration, calculated using the observed value of 
the last quantifiable concentration.
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, calculated using the observed value of the last quantifiable concentration.
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 eCRF screen failure form.
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 (specify reason).

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.


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9.1.16 Documentation of Randomization
Only subjects who meet all of the inclusion criteria and none of the exclusion criteria are eligible 
for randomization into the study. Any subjects that replace withdrawn or discontinued subjects 
will maintain the same treatment sequence as the discontinued subject.
If the subject is found to be not eligible for randomization, 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 to the nearest minute on the source document and the eCRFs. 
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 points.
9.3.1
Screening 
Subjects will be screened within 28 days prior to randomization. Subjects will be screened in 
accordance with predefined inclusion and exclusion criteria as described in Section 7.0. See 
Section 9.1.15 for procedures for documenting screening failures.
Procedures to be completed at Screening include:

Informed consent.

Demographics, medical history, and medication history.

Physical examination.

Vital signs.

Weight, height, and BMI.

Concomitant medications.

Concurrent medical conditions.

Fasting Screening clinical laboratory tests (hematology, serum chemistry, urine analysis, 
hepatitis panel, urine drug screen).

12-lead ECG procedure.

Assessment of inclusion/exclusion criteria.

Pregnancy test (women of childbearing potential).


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
FSH (only performed if menopause is suspected).

Pretreatment event assessment.
9.3.2
Check-in (Day -1)
Subjects will be admitted to the clinic on Check-in (Day -1). The following procedures will be 
performed; all results must be available prior to administration of study drug on Day 1:

Confinement.

Assessment of inclusion/exclusion criteria (Period 1 only).

Complete physical examination.

12-lead ECG.

Vital signs.

Fasting laboratory evaluations (after a minimum 8-hour fast).

Serum pregnancy test (females of childbearing potential only).

Urine drug screen, alcohol screen, and cotinine screen.

AEs: Pretreatment events are assessed on Day -1 of Period 1 and TEAEs are assessed on Day 
-1 of Period 2. 

Concomitant medication assessment.
9.3.3
Treatment Phase (Day 1)
The following procedures will be performed at Day 1:

Randomization (Period 1 only).

Confinement.

Vital signs (blood pressure and pulse only) prior to dose and 8 hours postdose.

Concomitant medication assessment.

Administration of study drug.

PK blood sampling.

Pharmacogenomic sample collection (Period 1 only).

Pretreatment event/AE assessment.
For Period 1, if the subject has satisfied all of the inclusion criteria and met none of the exclusion 
criteria for randomization, the subject should be randomized as described in Section 8.3. The 
procedure for documenting screening failures is provided in Section 9.1.15.


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9.3.4
Day 2 (Period 1) 
The following procedures will be performed at Day 2 (Period 1):

Confinement.

PK blood sampling.

AE assessment.

Concomitant medication assessment.

12-lead ECG.

Vital signs (blood pressure and pulse only).

Fasting laboratory evaluations (after a minimum 8-hour fast).
9.3.5
Day 2 (Period 2)/Study Exit 
The Final Visit will be performed on Day 2 of Period 2 or at the Early Termination Visit. The 
following procedures will be performed and documented on Day 2 of Period 2:

Confinement.

Complete physical examination (excluding genitourinary examination).

12-Lead ECG.

Vital signs (blood pressure and pulse only).

Fasting laboratory evaluations (after a minimum 8-hour fast).

Serum pregnancy test (females of childbearing potential only).

PK blood sampling.

AE assessment.

Concomitant medication assessment.
For all subjects receiving study drug, the investigator must complete the End-of-Study eCRF page.
9.3.6
Early Termination

Complete physical exam (excluding genitourinary examination).

12-Lead ECG.

Vital signs.

Fasting laboratory evaluations. (If an 8-hour fast is not possible at Early termination, 
laboratory samples will still be collected.)

Serum pregnancy test (females of childbearing potential only).


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
Pretreatment event/AE assessment.

Concomitant medication assessment.
9.3.7
Follow-up 
At 10±2 days following the last dose of study drug, a follow-up phone call will be made to inquire 
about any ongoing or new AEs, any SAEs, and concomitant medications taken since final dose. 
Any spontaneously reported AEs will continue to be collected for 30 days after the last dose of 
study drug. Subjects who withdraw their consent should still be contacted for a safety follow-up 
call. The contact should only be recorded in their source documents and the eCRFs, according to 
data protection regulations.
9.3.8
Unscheduled Visit
1. Complete physical examination.
2. Vital signs.
3. AE assessment.
4. Concomitant medication assessment.
9.4
Biological Sample Retention and Destruction
In this study, specimens for genome/gene analysis will be collected as described in Section 9.1.12. 
The genetic material will be preserved and retained at Covance Biorepository for up to, but not 
longer than, 15 years, or as required by applicable law. The sponsor has put into place a system to 
protect the subjects’ personal information to ensure optimal confidentiality and defined standard 
processes for sample and data collection, storage, analysis, and destruction.
The samples will be sent to a central laboratory that processes the blood sample and serves as a 
secure storage facility. The sponsor and researchers working with the sponsor will have access to 
the samples collected and any test results. All samples collected during the study will be stored 
securely with limited access and the sponsor will require anyone who works with the samples to 
agree to hold the research information and any results in confidence.
The sample will be labeled with a unique sample identifier similar to labeling in the main study but 
using a code that is different from the code attached to the health information and other clinical test 
results collected in the study. The sample and data are linked to personal health information with 
code numbers; the samples are stripped of all personal identifying information but a key linking 
the samples to clinical analysis data exists. This link means that the subject may be identified but 
only indirectly. The code numbers will be kept secure by, or on behalf of, the sponsor.
Subjects who consented and provided a PGx sample for DNA analysis can withdraw their consent 
and request disposal of a stored sample at any time prior to analysis. Notify sponsor of consent 
withdrawal.


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9.5
Blood Volume
Total blood sampling volume for an individual subject is shown in Table 9.c.
Table 9.c
Approximate Blood Volume
Approximate Blood Volume
Sample Type
Sample 
Volume 
(mL)
Number of Samples
Total Volume 
(mL)
Screening
Period 1
Period 2
Clinical Laboratory 
Test Samples
20
1
2
2
100
PK Samples
4
0
15
15
120
PGx DNA
6
0
1
-
6
Total Blood Sampling Volume
226
The maximum volume of blood at any single day is approximately 96 mL, and the approximate 
total volume of blood for the study is 226 mL.


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10.0
PRETREATMENT EVENTS AND ADVERSE EVENTS
10.1
Definitions
10.1.1 Pretreatment Events 
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 
medication; 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 vs 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 medication) or 
an AE (worsening or complication occurs after start of study medication). 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.


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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 
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
Torsade de pointes/ventricular fibrillation/ventricular 
tachycardia
Acute liver failure
Anaphylactic shock
Malignant hypertension
Acute renal failure
Convulsive seizure
Pulmonary hypertension
Agranulocytosis
Pulmonary fibrosis
Aplastic anemia
Confirmed or suspected endotoxin shock
Toxic epidermal necrolysis/Stevens-Johnson syndrome
Confirmed or suspected transmission of infectious agent by 
a medicinal product
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 Medication 

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 have 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 gotten 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 PTEs and AEs 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 5 to 10 days after the last dose of 
study drug is completed. Any spontaneously reported AEs will continue to be reported for 30 days 
after the last dose of study drug.
10.2.1.2 PTEs and AEs 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. 
Nonserious PTEs, related or unrelated to the study procedure, need not be followed-up for the 
purposes of the protocol.
All subjects experiencing AEs, whether considered associated with the use of the study medication 
or not, must be monitored until the symptoms subside and any clinically relevant changes in 
laboratory values have returned to Baseline or until there is a satisfactory explanation for the 
changes observed. All 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 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 LFTs
If a subject is noted to have ALT or AST elevated >3 ×ULN on 2 consecutive occasions, the 
abnormality should be recorded as an AE. In addition, an LFT Increases 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 that 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 


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and fax it immediately within 24 hours of receipt. Copies of any relevant data from the hospital 
notes (eg, ECGs, laboratory tests, discharge summary, postmortem results) should be sent to the 
addressee, if requested.
All SAEs should be followed up until resolution or permanent outcome of the event. The timelines 
and procedure for follow-up reports are the same as those for the initial report.
10.3.1 Safety Reporting to Investigators, IRBs 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, 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 an 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 study. 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)
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. Data are transcribed directly onto eCRFs.
After completion of the entry process, computer logic checks will be run to identify items, such as 
inconsistent dates, missing data, and questionable values. Queries may be issued by Takeda 
personnel (or designees) and will be answered by the site. 
Corrections to eCRFs are recorded in an audit trail that captures the old information, the new 
information, identification of the person making the correction, the date the correction was made, 
and the reason for change. Reasons for significant corrections should additionally be included. 
The principal investigator must review the eCRFs for completeness and accuracy and must sign 
and date 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 eCRFs 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, 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), 
and detailed records of drug disposition to enable evaluations or audits from regulatory authorities, 


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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 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.
A targeted data review 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
Safety Set: All subjects who enroll into the study and take at least 1 dose of study drug will be 
included in the safety set.
PK Set: All subjects in the safety set who have at least 1 valid plasma concentration of 
dexlansoprazole at scheduled sample collection time will be included in the PK set.
13.1.2 Analysis of Demographics and Other Baseline Characteristics
For each part, demographic and baseline characteristics will be summarized by sequence and 
overall. Summary statistics (number of subjects, mean, median, standard deviation and range) will 
be generated for continuous variables (eg, age, weight, and BMI) and the number and percentage 
of subjects within each category will be presented for categorical variables (eg, gender, race, and 
ethnicity).
13.1.3 PK Analysis
For each regimen of each part, dexlansoprazole plasma concentrations and PK parameter estimates 
will be tabulated and descriptive statistics computed.
For each part, analysis of variance (ANOVA) will be performed on natural logarithms of 
dexlansoprazole Cmax and AUC with factors for sequence, the subject nested within sequence, 
period and regimen. The factor of the subject nested within sequence will be the error term for 
testing the sequence effect. Other factors will be tested with the residual as the error term. For the 
relative BA determination, pairwise comparisons will be performed to assess the relative BA of 
dexlansoprazole via point estimates and 90% confidence interval (CI) for the ratio of Cmax and 
AUC central values of the dexlansoprazole 30 mg or 60 mg capsules manufactured at TOB 
compared with the respective dexlansoprazole 30 mg or 60 mg capsules manufactured at TPC. A 
conclusion of BE in the PK of dexlansoprazole between test regimen (dexlansoprazole capsule -
TOB) and the reference regimen (dexlansoprazole capsule - TPC) will be reached if the 90% CIs 
for Cmax and AUC are within the (0.80-1.25) interval. 
Statistical analyses of other plasma PK parameters will be performed if appropriate.


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13.1.4 Safety Analysis
AEs will be summarized using the safety analysis set. AEs that started or worsened in severity 
after the first dose of study drug will be summarized by regimen. AEs will be classified according 
to MedDRA system organ class, high-level term and preferred term. Summary tables for AEs will 
include numbers and percentages of subjects experiencing AEs by system organ class and 
preferred term. The following summary tables will be included in the report by intervals: summary 
of AEs, drug-related AEs, relationship of AEs to study drug, severity of AEs and related AEs. AEs 
leading to study drug discontinuation and SAEs will be listed.
Baseline, postdose, and change from Baseline to postdose laboratory, vital sign values will be 
summarized by regimen utilizing descriptive statistics. Criteria for markedly abnormal laboratory 
and vital sign values (markedly abnormal values [MAVs]) will be presented and the number and 
percentage of subjects with at least 1 markedly abnormal laboratory test result will also be 
summarized by regimen.
Shift tables for character ECG results will be provided overall to tabulate the number and 
percentage of subjects who changed status after dosing. 
13.2
Interim Analysis and Criteria for Early Termination
No interim analysis is planned.
13.3
Determination of Sample Size
For each part, a sample size of 52 (26 per sequence) will be used in this study. This sample size will 
allow for up to 6 dropouts (11.5% dropout rate) and provide 90% probability of concluding 
equivalence on dexlansoprazole Cmax between the 2 regimens if the true difference between 
dexlansoprazole Cmax central values from 2 regimens is no more than 5%. The power for 
concluding equivalence on dexlansoprazole AUC between 2 regimens would be over 90%. This 
sample size was based on the intrasubject variance of 0.075 for log(Cmax) and 0.024 for log(AUC) 
from the TAK-390MR_107 study.
If BE is not achieved with the first TOB formulation assessed, the study may be repeated in new 
subjects who will receive the same TOB formulation or a different TOB formulation. The same 
study design will be utilized if additional formulation assessments are needed.


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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 (contract research organization [CRO]) and by the IRB or independent ethics committee 
(IEC).
All aspects of the study and its documentation will be subject to review by the sponsor or designee, 
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 IEC, 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 as displayed in Table 14.a should be reported to Takeda using the 
Protocol Deviation Form. 
Table 14.a
Windows for PK 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


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Should other unexpected circumstances arise that will require deviation from protocol-specified 
procedures, the investigator should consult with the sponsor or designee (and IRB as required) to 
determine the appropriate course of action. There will be no exemptions (a prospective approved 
deviation) from the inclusion or exclusion criteria.
The sponsor or designee contact information for communicating protocol deviations is provided in 
Section 1.1. 
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 FDA, the United Kingdom Medicines and Healthcare 
products Regulatory Agency [MHRA], the Pharmaceuticals and Medical Devices Agency 
[PMDA] 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 Approval
IRBs must be constituted according to the applicable state and federal 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. If any member of the IRB 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, 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 for approval. The IRB’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 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 notify the site of drug shipment 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 study. Until the site receives 
notification to proceed with the study, no protocol activities, including screening, may occur.
Sites must adhere to all requirements stipulated by their respective IRB. This may include 
notification to the IRB 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, and submission of the investigator’s final status report to the IRB. All IRB 
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 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.
The subject 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 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 at the time of consent and prior to the subject 
entering into the study. The subject 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 the 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 the subject information sheet (if applicable) shall be given to the subject.
All revised informed consent forms must be reviewed and signed by the relevant subjects 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.


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Subjects who consented and provided a PGx sample for DNA analysis can withdraw their consent 
and request disposal of a stored sample at any time prior to analysis. Notify sponsor of consent 
withdrawal.
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, MHRA, PMDA), 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, 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 October 2016.
2. Guidance for Industry: Bioavailability and Bioequivalance Studies Submitted in NDAs or 
INDs - General Considerations. US Dept of Health and Human Services, Food and Drug 
Administration, Center for Drug Evaluation and Research (CDER). March 2014.
3. Guideline on the Investigation of Bioequivalence. European Medicines Agency, Committee 
for Medicinal Products for Human Use. 20 January 2010. Publication No. 
CPMP/EWP/QWP/1401/98 Rev. 1.


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Appendix A
Schedule of Study Procedures
Study Day:
Pretreatment 
Period
Treatment Periods 1 and 2 (a)
Study Exit 
(Day 2 of 
Period 2)/ 
Early 
Termination 
Visit
Follow-up 
Phone Call 
(d)
Days 
-28 to -2 
(screening) (b)
Day -1 
(Check-in)
Day 1 (c)
Day 2
Confinement
X
X
X (e)
X (f)
Informed consent
X
Inclusion/exclusion 
criteria
X
X (g)
Demographics and 
medical history
X
Medication history
X
Physical examination
X
X
X
Height, Weight, and 
BMI (h)
X
Vital signs (i)
X
X
X
X
X
Concomitant 
medications
X
X
X
X
X
X
Concurrent medical 
conditions
X
Clinical laboratory 
tests (j)
X
X
X
X
Hepatitis panel
X
Pregnancy test (hCG) 
(k)
X
X
X
FSH (l)
X
Urine drug screen
X
X
ECG (m)
X
X
X
X
Administration of 
study drug (n) 
X
PGx DNA sample 
collection (o)
X
PK blood collection 
(p)
X
X
X (q)
AE assessment (r)
X
X
X
X
X
X
Footnotes are on last table page.


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(a) There will be at least 5 days between the dose in 1 period and the dose in a subsequent period.
(b) Screening procedures must be performed within 28 days prior to administration of investigational product.
(c) Day 1 of each treatment period.
(d) Follow-up phone call will be made 10±2 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.
(e) Following study procedure completion on Day 2 of Period 1, subjects will be discharged from the clinic to begin the washout 
period. 
(f) Following study procedure completion on Day 2 of Period 2, subjects will be discharged from the clinic. Early termination
procedures are explained in Section 9.3.6.
(g) Assessment of inclusion and exclusion criteria will be done on Day -1, Period 1 only. 
(h) The BMI is calculated using metric units as follows: Metric: BMI = weight (kg)/[height (m)]2.
(i) Vital signs: oral body temperature, sitting blood pressure (after resting 5 minutes), respiratory rate, and pulse (beats per minute) 
at Screening. Only blood pressure and pulse will be collected on Check-in (Day -1) through Day 2 of each period prior to dose and 
8 hours postdose, or if the subject terminated early from study. 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 30 minutes before or after the scheduled blood draw.
(j) Hematology, serum chemistries, and urinalysis tests. Clinical laboratory samples will be collected after a minimum of an 8 hour 
fast on Screening, Check-in (Day -1) of Periods 1 and 2; Day 2 of Period 1, and Study Exit (Day 2 of Period 2)/Early termination. If 
an 8-hour fast is not possible at Early termination, laboratory samples will still be collected.
(k) A serum pregnancy test will be done at Screening and Day -1 of each period, Study Exit (Day 2 of Period 2), or if a subject 
prematurely terminates from the study.
(l) For women where menopause is suspected (see Section 9.1.9).
(m) ECG performed at Screening, Check-in (Day -1 of Period 1), and Study Day 2 of each period, or if a subject terminates early 
from the study. 
(n) Study drug will be administered on Day 1 of each period at approximately 0800 hours, following a 10-hour fast. Dosing may be 
staggered to help facilitate logistics at the site.
(o) One 6 mL whole-blood sample will be collected for DNA analysis prior to dosing on Day 1 of Period 1 only. 
(p) Blood samples for PK obtained predose (within 15 minutes prior to dose), and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 
24 hours post Day 1 dosing in each period. 
(q) The PK sample should not be collected at the Early Termination Visit if a PK collection is not scheduled.
(r) Pretreatment AEs will be captured immediately following the signing of the informed consent at Screening until dosing on 
Day 1 of Period 1. The routine collection of AEs will continue after dosing through the follow-up phone call.


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Appendix B
Responsibilities of the Investigator
Clinical research studies sponsored by the sponsor are subject to ICH GCP and all the applicable 
local laws and regulations. The responsibilities imposed on investigators by the FDA are 
summarized in the “Statement of Investigator” (Form FDA 1572), which must be completed and 
signed before the investigator may participate in this study. 
The investigator agrees to assume the following responsibilities:
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 (non routine/non standard 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 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. 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.
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.


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11. Maintain current records of the receipt, administration, and disposition of sponsor-supplied 
drugs, and return all unused sponsor-supplied drugs to the sponsor. 
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 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, 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 will be informed in a timely manner if information becomes 
available that may be relevant to the subject’s willingness to continue participation in the 
study.
22. A statement that results of PGx analysis will not be disclosed to an individual, unless 
prevailing laws require the sponsor to do so.
23. The foreseeable circumstances or reasons under which the subject’s participation in the study 
may be terminated.
24. A written subject authorization (either contained within the informed consent form or provided 
as a separate document) describing to the subject the contemplated and permissible uses and 
disclosures of the subject’s personal information (including personal health information) for 
purposes of conducting the study. The subject authorization must contain the following 
statements regarding the uses and disclosures of the subject’s personal information:
a) that personal information (including personal health information) may be processed by or 
transferred to other parties in other countries for clinical research and safety reporting 
purposes, including, without limitation, to the following: (1) Takeda, its affiliates, and 
licensing partners; (2) business partners assisting Takeda, its affiliates, and licensing 
partners; (3) regulatory agencies and other health authorities; and (4) IRBs/IECs;
b) it is possible that personal information (including personal health information) may be 
processed and transferred to countries that do not have data protection laws that offer 
subjects the same level of protection as the data protection laws within this country; 
however, Takeda will make every effort to keep your personal information confidential, 
and your name will not be disclosed outside the clinic unless required by law;
c) that personal information (including personal health information) may be added to 
Takeda’s research databases for purposes of developing a better understanding of the 
safety and effectiveness of the study medication(s), studying other therapies for patients, 
developing a better understanding of disease, and improving the efficiency of future 
clinical studies;
d) that subjects agree not to restrict the use and disclosure of their personal information 
(including personal health information) upon withdrawal from the study to the extent that 
the restricted use or disclosure of such information may impact the scientific integrity of 
the research; and
e) that the subject’s identity will remain confidential in the event that study results are 
published.


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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 30 days 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. 
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, or for 30 days after the last dose, the pregnancy will be recorded following 
authorization from the subject’s partner.
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 
1. Collect 4 mL of venous blood into a chilled Becton-Dickinson Vacutainer. All 
dexlansoprazole blood samples should be collected into Vacutainers containing K2EDTA.
2. Gently invert the Vacutainer several times to mix the additive with the collected blood prior to 
centrifugation and place immediately on ice.
3. Centrifuge the Vacutainers for 10 minutes at a relative centrifugal force of approximately 1100 
to 1300 in a refrigerated centrifuge. Note: if using a collection device other than the 
Becton-Dickinson Vacutainer, 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 0.6 mL needs to be obtained for 
each sample. Labeling may include protocol number [TAK-390MR-1001], sample matrix (ie, 
plasma), randomization number, period, nominal day and time, analyte (dexlansoprazole), 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 until shipment to PPD Development, Middleton, WI. No more than 45 minutes 
will elapse between blood collection and freezing the plasma sample.
Shipping of Plasma Samples
The following instructions are recommended unless they differ from the site’s standard operating 
procedures (SOPs) for labeling, packaging, or shipping of PK samples.
1. Biological samples should be shipped on sufficient dry ice to prevent thawing during transit. 
Samples should be shipped to arrive at the destination during normal business hours (local 
time). For US domestic shipments, 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, and for international shipments, 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.
2. Before shipping, make sure the sample tubes are tightly sealed. Separate each subject’s 
samples as follows:
3. Separate the duplicate SET 2 samples from the SET 1 samples.
4. Place SET 1 samples for each subject into a self-sealing bag (eg, Ziploc) containing additional 
absorbent material.
5. Using a permanent marker, write the 4-digit randomization sequence number, sample matrix 
(ie, plasma), number of samples, and “SET 1” on each self-sealing bag.


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6. 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. Repeat 
steps 3 through 6 above when preparing duplicate samples for shipment, except self-sealing 
bags should be marked “SET 2.” 
7. An inventory of individual samples should accompany each shipment and should include the 
sponsor’s name (Takeda), study medication (dexlansoprazole delayed-release capsule), 
protocol number (TAK-390MR-1001), investigator’s name, sample type (ie, plasma), 
randomization number, period, nominal 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 self-sealing 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.
8. For sample packing, utilize dry ice generously (eg, 20 to 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 polystyrene plastic (eg, 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.
9. Place the inventory paperwork (in a large self-sealing bag) on top of the dry ice in the 
polystyrene plastic container. Place the lid on the polystyrene plastic container and seal 
completely with strapping tape. Place the polystyrene plastic container in a cardboard shipping 
carton and seal securely with strapping tape.
10. Mark the outside of shipping carton(s) with a tally number (eg, 1 of 5, 2 of 5).
11. Affix an address label to each shipping carton. Complete the address label with the following 
information:
Plasma Samples for dexlansoprazole delayed-release capsules:
12. 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)
Personal Protected Data


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13. 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.
14. Obtain the airway bill number and a receipt of shipment from the carrier.
15. After shipping of the samples, please contact the following to notify them of next day delivery.
16. When calling, provide the following information:
Name of courier or transport company
Time and date the shipment left the clinical site
Airway bill number
Personally Protected Data


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Appendix F
Detailed Description of Amendments to Text
The sections of the protocol affected by the changes in Amendment No. 02 are indicated.
Change 1: Allow the replacement of subjects who are discontinued or withdrawn.
The change occurs in Section 7.6 Procedures for Discontinuation or Withdrawal of a Subject.
Initial 
wording:
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 by the investigator. In addition, 
efforts should be made to perform all procedures scheduled for the Early Termination 
Visit. Discontinued or withdrawn subjects will not be replaced.
Amended 
or new 
wording:
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 by the investigator. In addition, 
efforts should be made to perform all procedures scheduled for the Early Termination 
Visit. Discontinued or withdrawn subjects will not may be replaced.
Rationale for Change:
This change was made because a greater number of subjects were discontinued or withdrawn from 
the study than was originally expected.
Change 2: Correct the dose shown in Part 2 of the crossover study design schematic.
The change occurs in Figure 6.b Schematic of Crossover Design in Section 6.1 Study Design.
Initial 
wording:
[Dose level for Part 2 was indicated to be 30 mg.]
Amended 
or new 
wording:
[Dose level for Part 2 is indicated to be 60 mg.]
Rationale for Change: 
This was corrected for consistency with the study design. 


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Change 3: Remove all reference to the subject’s legally acceptable representative.
The primary change occurs in Section 15.2 Subject Information, Informed Consent, and Subject 
Authorization.
Initial 
wording:
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.
Amended 
or new 
wording:
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.
Rationale for Change: 
This change was requested by the IRB for consistency with the language in the inclusion criterion 
regarding subject informed consent.
The following sections also reflect this change:

Section 7.5 Criteria for Discontinuation or Withdrawal of a Subject.

Appendix B Responsibilities of the Investigator.

Appendix C Elements of the Subject Informed Consent.


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Change 4: Update the definitions of women of (and not of) childbearing potential.
The change occurs in Section 9.1.9 Contraception and Pregnancy Avoidance Procedure.
Initial 
wording:
*Women NOT of childbearing potential are defined as those who have been surgically 
sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are 
postmenopausal (eg, defined as at least 1 year since last regular menses with an 
FSH>40 IU/L or at least 5 years since last regular menses, confirmed before any study 
medication is implemented).
Amended 
or new 
wording:
* Women of childbearing potential are defined as any female who has 
experienced menarche and who are NOT permanently sterile or 
postmenopausal. Women NOT of childbearing potential are defined as those who 
have been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal 
ligation) or who are postmenopausal (eg, defined as at least 1 year since last regular 
menses with an FSH>40 IU/L or at least 5 years since last regular menses, confirmed 
before any study medication is implemented 12 consecutive months with no menses 
without an alternative medical cause).
Rationale for Change: 
This was changed to reflect requested wording from the IRB during previous IRB review.
Change 5: Update the subject replacement information based on the allowance for replaced 
subjects.
The change occurs in Section 9.1.16 Documentation of Randomization.
Initial 
wording:
Only subjects who meet all of the inclusion criteria and none of the exclusion criteria 
are eligible for randomization into the study.
Amended 
or new 
wording:
Only subjects who meet all of the inclusion criteria and none of the exclusion criteria
are eligible for randomization into the study. Any subjects that replace withdrawn 
or discontinued subjects will maintain the same treatment sequence as the 
discontinued subject.
Rationale for Change: 
The new text was added to reflect the allowance for replacement subjects.


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Change 6: Clarify that an 8-hour fast may not be possible at Early termination.
The primary change occurs in Section 9.3.6 Early Termination.
Initial 
wording:
Fasting laboratory evaluations. 
Amended 
or new 
wording:
Fasting laboratory evaluations. (If an 8-hour fast is not possible at Early 
termination, laboratory samples will still be collected.)
Rationale for Change: 
This text clarifies that laboratory samples should still be collected even though subjects who 
discontinue may not have had the opportunity to fast for 8 hours prior to the visit.
This change is also reflected in footnote j of Appendix A Schedule of Study Procedures.
Change 7: Correct the sequence numbers in Table 8.b for Part 2 of the study.
The change occurs in Table 8.b Dose and Regimen.
Initial 
wording:
[Sequence numbers for Part 2 were listed as 1 and 2.]
Amended 
or new 
wording:
[Sequence numbers for Part 2 are now listed as 3 and 4.]
Rationale for Change: 
This was corrected for consistency with the information presented in Table 6.b Part 2 Sequences.


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Personal Protected Data

SAP_001.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, Randomized, Open-Label, Single-Center, Single-Dose, Two-Period Two Part 
Crossover Study in Healthy Subjects to Compare the Bioavailability of Dexlansoprazole from 
Dexlansoprazole Delayed-Release Capsules 30 mg and 60 mg Manufactured by Takeda GmbH 
Plant Oranienburg Relative to Dexlansoprazole Delayed-Release Capsules 30 mg and 60 mg 
Manufactured by Takeda Pharmaceutical Company Limited Osaka Plant 
NCT Number: NCT03131895
 SAP Approve Date: 28 June 2017
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.


1.0
TITLE PAGE
STATISTICAL ANALYSIS PLAN
STUDY NUMBER: TAK-390MR-1001
A Phase 1, Randomized, Open-Label, Single-Center, Single-Dose, Two-Period Two Part 
Crossover Study in Healthy Subjects to Compare the Bioavailability of Dexlansoprazole 
from Dexlansoprazole Delayed-Release Capsules 30 mg and 60 mg Manufactured by 
Takeda GmbH Plant Oranienburg Relative to Dexlansoprazole Delayed-Release Capsules 
30 mg and 60 mg Manufactured by Takeda Pharmaceutical Company Limited Osaka 
Plant 
Phase 1 Bioequivalence Study of Dexlansoprazole Capsules from Two Manufacturing 
Plants
Version: Final
Date: 28 June 2017
Based on:
Protocol Version: Protocol Amendment 02 
Protocol Date: 6 June 2017
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.


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1.1
Approval Signatures
Electronic signatures can be found on the last page of this document.


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2.0
TABLE OF CONTENTS
1.0
TITLE PAGE ..................................................................................................................1
1.1
Approval Signatures ..................................................................................................2
2.0
TABLE OF CONTENTS.................................................................................................3
3.0
LIST OF ABBREVIATIONS..........................................................................................5
4.0
OBJECTIVES .................................................................................................................6
4.1
Primary Objectives ....................................................................................................6
4.2
Additional Objectives ................................................................................................6
4.3
Study Design .............................................................................................................6
5.0
ANALYSIS ENDPOINTS...............................................................................................9
5.1
Primary Endpoints .....................................................................................................9
5.2
Additional Endpoints .................................................................................................9
5.3
Safety Endpoints........................................................................................................9
6.0
DETERMINATION OF SAMPLE SIZE.......................................................................10
7.0
METHODS OF ANALYSIS AND PRESENTATION...................................................11
7.1
General Principles....................................................................................................11
7.1.1
Study Definitions ...............................................................................................11
7.1.2
Definition of Study Days....................................................................................11
7.1.3
Definition of Study Visit Windows ....................................................................11
7.1.4
Conventions for Missing Adverse Event Dates...................................................11
7.1.5
Conventions for Missing Concomitant Medication Dates...................................11
7.1.6
Conventions for Missing Data............................................................................12
7.2
Analysis Sets ...........................................................................................................12
7.3
Disposition of Subjects ............................................................................................12
7.4
Demographic and Other Baseline Characteristics.....................................................13
7.5
Medical History and Concurrent Medical Conditions...............................................13
7.6
Medication History and Concomitant Medications...................................................13
7.7
Study Drug Exposure and Compliance.....................................................................13
7.8
Efficacy Analysis.....................................................................................................13
7.9
Pharmacokinetic/Pharmacodynamic Analysis ..........................................................14
7.9.1
Pharmacokinetic Analysis ..................................................................................14
7.9.2
Pharmacodynamic Analysis ...............................................................................15
7.10
Other Outcomes.......................................................................................................15
7.11
Safety Analysis........................................................................................................15
7.11.1 Adverse Events ..................................................................................................16


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7.11.2 Clinical Laboratory Evaluations .........................................................................17
7.11.3 Vital Signs .........................................................................................................18
7.11.4 12-Lead ECGs ...................................................................................................18
7.11.5 Other Observations Related to Safety.................................................................18
7.12
Interim Analysis ......................................................................................................18
7.13
Changes in the Statistical Analysis Plan...................................................................18
8.0
REFERENCES..............................................................................................................19
LIST OF IN-TEXT TABLES
Table 4.a
Part 1 Sequences..................................................................................................7
Table 4.b
Part 2 Sequences..................................................................................................7
Table 7.a
Collection of Blood Samples for Pharmacokinetic Analysis ...............................14
Table 7.b
Plasma PK Parameters .......................................................................................15
Table 7.c
Clinical Laboratory Tests...................................................................................17
LIST OF IN-TEXT FIGURES
Figure 4.a
Schematic of Study Design ..................................................................................8
Figure 4.b
Schematic of Crossover Design............................................................................8
LIST OF APPENDICES
Appendix A
Schedule of Study Procedures............................................................................20
Appendix B
Criteria for Identification of Markedly Abnormal Laboratory Values .................22
Appendix C
Criteria for Abnormal Changes from Baseline of Vital Signs..............................24
Appendix D
Criteria for Markedly Abnormal Values for the 12-Lead ECG Parameters..........25


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3.0
LIST OF ABBREVIATIONS
%CV
percent coefficient of variation
λz
terminal disposition rate constant
AE
adverse event
ANOVA
analysis of variance
AUC∞
area under the plasma concentration-time curve from time 0 to infinity
AUCt
area under the plasma concentration-time curve from time 0 to the time of last 
quantifiable concentration
BMI
body mass index
Cmax
maximum observed plasma concentration
CI
confidence interval
CL/F
apparent clearance after extravascular administration
ECG
electrocardiogram
LLOQ
lower limit of quantification
MedDRA
Medical Dictionary for Drug Regulatory Activities
PK
pharmacokinetic(s)
PT
preferred term
PTE
pretreatment event
SD
standard deviation
SAE
serious adverse event
SI
International System of Units
SOC
system organ class
t1/2z
terminal elimination half-life
tmax
time to reach Cmax
TEAE
treatment-emergent adverse event
Vz/F 
apparent volume of distribution during the terminal disposition phase after 
extravascular administration, calculated using the observed value of the last 
quantifiable concentration.
WHODrug
World Health Organization Drug Dictionary


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4.0
OBJECTIVES
4.1
Primary Objectives

To assess the bioavailability (BA) of dexlansoprazole from a 30 mg capsule manufactured at
TOB relative to that of dexlansoprazole from a 30 mg capsule manufactured at TPC.

To assess the BA of dexlansoprazole from a 60 mg capsule manufactured at TOB relative to
that of dexlansoprazole from a 60 mg capsule manufactured at TPC.
4.2
Additional Objectives

To evaluate the safety and tolerability of dexlansoprazole following oral administration of a
single 30 mg or 60 mg dexlansoprazole capsule.
4.3
Study Design
This is a phase 1, randomized, open-label, single-center, single-dose, 2-part, 2-way crossover
study in healthy subjects to assess the BA of 30 or 60 mg dexlansoprazole capsules 
manufactured at TOB relative to the corresponding 30 or 60 mg dexlansoprazole capsules 
manufactured at TPC. The study will be conducted in 2 parts. In Part 1, 52 healthy subjects will 
receive dexlansoprazole 30 mg capsules manufactured by TOB and TPC in a crossover fashion. 
In Part 2, an additional 52 healthy subjects will receive dexlansoprazole 60 mg capsules 
manufactured by TOB and TPC in a crossover fashion. Due to the difference between the 
Granules-L used in the 30 mg (Granules-LL) and 60 mg (Granules-LS) capsules, the relative BA 
of both dosage strengths will be assessed. If BE is not achieved with the first TOB formulation, 
the study may be repeated for one or both dose strengths in new subjects who will receive the 
same TOB formulation or a different TOB formulation. The same study design will be used if 
additional formulation assessments are needed.
At Check-in (Day -1 of Period 1), approximately 104 subjects in total (52 in Part 1, 52 in Part 2),
including both men and women, aged 18 to 55 years, inclusive, will be selected to participate in 
the study. Subjects who satisfy the Screening evaluation and selection criteria may be enrolled in 
the study. For each part, eligible subjects will be randomized on Day 1 of Period 1 in a 1:1 ratio 
to 1 of 2 sequences, which defines the order in which they will receive dexlansoprazole regimens 
in Periods 1 and 2. The dosing between periods will be separated by a minimum 5-day washout
interval. During Periods 1 and 2, blood samples will be collected over 24 hours postdose to
measure dexlansoprazole plasma concentrations.
The treatment sequences are outlined in Table 4.a (Part 1) and Table 4.b (Part 2).


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Table 4.a
Part 1 Sequences
Sequences
Number of 
Subjects
Period 1
Period 2
1
26
A
B
2
26
B
A
Regimen A (test): A single dexlansoprazole 30 mg capsule manufactured at TOB administered orally on Day 1 
following a 10-hour fast.
Regimen B (reference): A single dexlansoprazole 30 mg capsule manufactured at TPC administered orally on Day 1 
following a 10-hour fast. 
Table 4.b
Part 2 Sequences
Sequences
Number of 
Subjects
Period 1
Period 2
3
26
C
D
4
26
D
C
Regimen C (test): A single dexlansoprazole 60 mg capsule manufactured at TOB administered orally on Day 1 
following a 10-hour fast.
Regimen D (reference): A single dexlansoprazole 60 mg capsule manufactured at TPC administered orally on Day 1 
following a 10-hour fast. 
In each period of each part, subjects will be confined from Check-in Day -1 until all study 
procedures have been completed on Day 2. Study drug will be administered on Day 1 of each 
period at approximately 0800 hours, following a 10-hour fast. Dosing may be staggered to help 
facilitate logistics at the site. Subjects will be instructed to swallow the intact capsule with 
240 mL of water. On Day 1 of each period, breakfast will not be served. During Periods 1 and 2, 
blood samples will be collected over 24 hours postdose to measure dexlansoprazole plasma 
concentrations.
A blood sample for pharmacogenomics (PGx) will also be collected on Day 1 of Period 1. The 
cytochrome P-450 (CYP)2C19 isozyme is a polymorphic enzyme that is involved in the 
metabolism of dexlansoprazole. A genotype test for CYP2C19 will determine the subject’s 
metabolizer status.
Subjects will be discharged from the study site on Day 2 of each period (subjects will exit the 
study on Day 2 of Period 2 within each part), and the dosing between periods within each part 
will be separated by a minimum 5-day washout interval.
A follow-up phone call will be made 10 (±2) days post last dose of study drug to inquire for any 
ongoing AEs or serious adverse events (SAEs), new AEs or SAEs, and concomitant medications 
taken since final dose. Any spontaneously reported AEs will continue to be collected for 30 days 
after the last dose of study drug. Subjects who withdraw their consent will still be contacted for a 
safety follow-up call. The contact will only be recorded in their source documents and the 
electronic case report forms (eCRFs), according to data protection regulations.


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Primary completion date will be based on the final data collection for the primary endpoint, Day 
2 of Period 2. End of trial (study completion date) will be based on the final data collection date 
for the entire study, which is the follow-up phone call.
A schematic of the study design is included as Figure 4.a and Figure 4.b. A schedule of 
assessments is listed in Appendix A.
Figure 4.a
Schematic of Study Design
Screening 
Period
Check-in 
(Periods 1 and 2)
Treatment Periods 1 and 2
Study Exit
(Period 2)
Follow-Up
Phone Call
Dexlansoprazole 30 and 60 
mg capsule
Single Dose PK
Discharge 
(Period 1)
Days -28 to -2
Day -1
Day 1
Day 2 Period 1
Day 2
Day 10±2
Confinement 
Note: There is a minimum 5-day washout period between the dose in Period 1 and the dose in Period 2. A follow-up 
phone call will be made for collection of AEs, SAEs, and concomitant medications taken since the final dose.
Figure 4.b
Schematic of Crossover Design


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5.0
ANALYSIS ENDPOINTS
5.1
Primary Endpoints
The following plasma PK parameters of dexlansoprazole derived on Day 1 of each period:

Maximum observed concentration (Cmax).

Area under the concentration-time curve from time 0 to time of the last quantifiable 
concentration (AUClast).

Area under the concentration-time curve from time 0 to infinity (AUC∞).
5.2
Additional Endpoints

Time to first occurrence of Cmax (tmax).

Terminal disposition phase half-life (t1/2z).

Terminal disposition phase rate constant (λz).

Apparent clearance after extravascular administration (CL/F).

Apparent volume of distribution during the terminal disposition phase after extravascular 
administration (Vz/F).
5.3
Safety Endpoints
Safety will be assessed by summarizing the incidence of adverse events (AEs), clinical 
laboratory values, physical examinations, electrocardiograms (ECGs), and vital signs.


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6.0
DETERMINATION OF SAMPLE SIZE
For each part, a sample size of 52 (26 per sequence) will be used in this study. This sample size 
will allow for up to 6 dropouts (11.5% dropout rate) and provide 90% probability of concluding
equivalence on dexlansoprazole Cmax between the 2 regimens if the true difference between
dexlansoprazole Cmax central values from 2 regimens is no more than 5%. The power for
concluding equivalence on dexlansoprazole AUC between 2 regimens would be over 90%. This
sample size was based on the intrasubject variance of 0.075 for log(Cmax) and 0.024 for 
log(AUC) from the TAK-390MR_107 study.
If BE is not achieved with the first TOB formulation assessed, the study may be repeated in new
subjects who will receive the same TOB formulation or a different TOB formulation. The same
study design will be utilized if additional formulation assessments are needed.


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7.0
METHODS OF ANALYSIS AND PRESENTATION
7.1
General Principles 
Continuous data will be summarized using descriptive statistics, including the number of 
subjects, mean, standard deviation (SD), median, minimum, and maximum. The coefficient of 
variation (%CV) and geometric mean will be included in the summary of continuous data where 
indicated. Categorical data will be summarized as the number and percentage of subjects in each 
category.
Arithmetic means, geometric means, and medians will be presented to 1 more decimal place than 
the recorded data, and SDs will be presented to 2 more decimal places than the recorded data, 
where appropriate. Where applicable, confidence intervals about a parameter estimate will be 
presented using the same number of decimal places as the parameter estimate and p-values will 
be rounded to 3 decimal places prior to assessment of statistical significance.
All study-related raw data for enrolled subjects, including derived data, will be presented in data 
listings. In addition, the actual day relative to the first dose will be presented, where applicable.
All statistical analyses will be performed using the SAS System® Version 9.4.
7.1.1
Study Definitions
There are no study-specific definitions.
7.1.2
Definition of Study Days
Study Day 1 is defined as the date of the first dose of study drug, as recorded on the electronic 
case report form (eCRF) dosing page. Other study days are defined relative to Study Day 1, with 
Day 1 being Study Day 1 and Day -1 being the day prior to Study Day 1. Study days prior to the 
first dose of study drug will be calculated as: {date of assessment/event – date of first dose of 
study drug}. Study days 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}.The calculation of day within a period 
will be similar to study day but relative to the date of administration of the first dose of study 
drug within the period.
All protocol-specified study visit dates are defined relative to Study Day 1.
7.1.3
Definition of Study Visit Windows
There will be no visit windowing.
7.1.4
Conventions for Missing Adverse Event Dates
There will be no imputation of incomplete or missing adverse event dates.
7.1.5
Conventions for Missing Concomitant Medication Dates
There will be no imputation of incomplete or missing concomitant medication dates.


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7.1.6
Conventions for Missing Data
There will be no imputation of incomplete or missing data. 
Plasma concentrations that are below the lower limit of quantification (< LLOQ) will be treated 
as zero in the summarization of concentration values and derivation of PK parameters.
7.2
Analysis Sets
The following analysis sets will be used for analysis and presentation of the study data:

Safety Analysis Set: The safety analysis set will consist of all subjects who are randomized
and received at least 1 dose of study drug. Subjects in this analysis set will be used for 
demographic, baseline characteristics, and safety summaries.

Pharmacokinetic Set: The PK set will consist of all subjects who received at least 1 dose of 
study drug and have at least 1 measurable plasma concentration.
If any subjects are found to be noncompliant in dosing schedule or with incomplete data, a 
decision will be made on a case-by-case basis as to their inclusion in the analysis but will be 
presented in the subject listings.
Number of subjects in each analysis set will be tabulated by randomization sequence and overall
for each part. 
7.3
Disposition of Subjects
Study Information, including date of first subject signing Informed Consent Form (ICF), date of 
first/last study drug, date of last subject’s last visit/contact, date of last subject’s last procedure 
for collection of data for primary endpoint, Medical Dictionary for Drug Regulatory Activities 
(MedDRA) Version, World Health Organization Drug Dictionary (WHODrug) Version, and 
SAS Version, will be tabulated for each part.
The eligibility of subjects will be summarized, along with the primary reasons of screen failure 
as recorded in eCRF.
Number of subjects randomized will be tabulated by randomization sequence (ie AB or BA, CD 
or DC) and overall for each part. 
Disposition of all enrolled subjects will be tabulated for each part. Categories will include:

Subjects who were randomized but not treated.

Subjects who completed the study.

Subjects who prematurely discontinued study.
Primary reasons for discontinuing study, as entered on the eCRF will be tabulated for each part. 


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7.4
Demographic and Other Baseline Characteristics
Demographic and study baseline characteristics, including age at informed consent, gender, 
ethnicity, race, height (cm), weight (kg), body mass index (kg/m2), smoking status, alcohol use, 
caffeine/xanthine consumption, and female reproductive status, will be summarized by sequence 
and overall for each part. 
There will be no inferential analysis of demographic and baseline characteristics.
7.5
Medical History and Concurrent Medical Conditions
Medical history is defined as significant conditions or diseases that resolved at or prior to the 
time of informed consent. Concurrent medical conditions are defined as significant conditions or 
diseases that are present at signing of informed consent.
Medical history and concurrent medical conditions will be coded using the MedDRA coding 
system.
Medical history and concurrent medical conditions will be listed by site and subject number.
There will be no summary or inferential analysis of medical history and concurrent medical 
conditions.
7.6
Medication History and Concomitant Medications
Medication history information includes any medication relevant to eligibility criteria stopped at 
or within 28 days prior to signing of informed consent. Concomitant medication is any drug 
given in addition to the study drug, taken at any time from signing of informed consent through 
the end of study.
Medication history and concomitant medications will be coded using the WHODrug.
Listings for medication history and concomitant medications will be produced by site and subject 
number. 
There will be no summary or inferential analysis of medication history and concomitant 
medications.
7.7
Study Drug Exposure and Compliance
All doses of study medication will be administered during confinement. Dosing data, including 
dosing time will be provided by subject and visit in the listings.
7.8
Efficacy Analysis
Not applicable.


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7.9
Pharmacokinetic/Pharmacodynamic Analysis
7.9.1
Pharmacokinetic Analysis
The schedule for blood samples for PK analysis of dexlansoprazole is listed in Table 7.a.
The concentration of dexlansoprazole in plasma will be summarized by regimen over each
scheduled sampling time point using descriptive statistics (arithmetic mean, SD, CV%, median,
minimum and maximum). Individual plasma concentration data versus time will be presented in 
a data listing.
In addition, the figures for mean plasma concentrations of dexlansoprazole versus time (linear 
and semi-log scale) will be generated. 
PK parameters will be estimated using non-compartmental methods with WinNonlin® (version 
6.3). Actual sampling times, rather than scheduled (nominal) sampling times, will be used in all 
computations involving sampling times. If the actual time or dose time is missing, the scheduled 
time may be substituted in order to calculate the PK parameter. Determination of points to be 
included in λz range will follow the Guideline for Defining, Calculating, and Summarizing 
Pharmacokinetic / Pharmacodynamic Parameters (EDSREP 009 R 01). All AUC values will be 
determined by the linear trapezoidal linear interpolation method of calculation.
Descriptive statistics (N, mean, SD, CV%, median, minimum and maximum) will be used to 
summarize the PK parameters for dexlansoprazole by regimen. In addition, geometric mean will 
be computed for AUCs and Cmax. The PK parameters of dexlansoprazole are listed in Table 7.b.
Box plots for Cmax and AUC∞will be generated by regimen. 
Table 7.a
Collection of Blood Samples for Pharmacokinetic Analysis
Sample 
Type
Dosing Day
Time (hours)
(Periods 1 and 2)
Plasma
1
Predose (within 15 minutes prior to dose) and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 
8, 10, 12, 16, and 24 hours postdose.


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Table 7.b
Plasma PK Parameters
Symbol/Term
Definition
Plasma
AUClast
Area under the concentration-time curve from time 0 to time of the last quantifiable 
concentration.
AUC∞
Area under the concentration-time curve from time 0 to infinity, calculated using the 
observed value of the last quantifiable concentration.
Cmax
Maximum observed concentration.
CL/F
Apparent clearance after extravascular administration, calculated using the observed value 
of the last quantifiable concentration.
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, calculated using the observed value of the last quantifiable concentration.
For each part, analysis of variance (ANOVA) will be performed on natural logarithms of 
dexlansoprazole Cmax and AUC with factors for sequence, the subject nested within sequence, 
period and regimen. The factor of the subject nested within sequence will be the error term for 
testing the sequence effect. Other factors will be tested with the residual as the error term. For 
the relative BA determination, pairwise comparisons will be performed to assess the relative BA 
of dexlansoprazole via point estimates and 90% confidence interval (CI) for the ratio of Cmax and 
AUC central values of the dexlansoprazole 30 mg or 60 mg capsules manufactured at TOB 
compared with the respective dexlansoprazole 30 mg or 60 mg capsules manufactured at TPC. A 
conclusion of BE in the PK of dexlansoprazole between test regimen (dexlansoprazole capsule -
TOB) and the reference regimen (dexlansoprazole capsule - TPC) will be reached if the 90% CIs 
for Cmax and AUC are within the (0.80-1.25) interval.
All pharmacokinetic parameters calculated will be provided in a listing.
7.9.2
Pharmacodynamic Analysis
Not applicable.
7.10
Other Outcomes
Daily meals during confinement in each period will be reported in the data listing.
7.11
Safety Analysis
Safety analyses include adverse events (AEs), clinical laboratory parameters, vital sign 
parameters, and 12-lead electrocardiogram (ECG) results.


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All summaries of safety data are based on subjects in the Safety Analysis Set. 
7.11.1 Adverse Events
A treatment-emergent adverse event (TEAE) will be defined as an AE or serious adverse event 
(SAE) that started or worsened after first study drug administration and within 30 days of last 
dose of study drug (onset date – date of last dose + 1 ≤30). A TEAE will be attributed to a 
regimen if the TEAE occurs after administration of the study drug in a period and up to just prior 
to study drug administration in the next period. A TEAE that occurs after administration of the 
study drug in the last period and up to 30 days after the last study drug dose is attributed to the 
regimen received in the last period. All AE verbatim terms will be coded by system organ class
(SOC) and preferred term using (PT) the MedDRA coding system.
TEAEs will be summarized by regimen and overall. The tables will include the number and 
percentage (N [%]) of subjects reporting any event for that term. The following TEAE tables will 
be summarized by part. 
–
Overview of TEAEs.
–
TEAEs by SOC and PT at subject and event level.
–
Subject Mappings for TEAEs.
–
TEAEs by PT.
–
Most Frequent TEAEs by PT term
–
Most Frequent Non-Serious TEAEs by PT term at subject and event level 
–
Relationship of TEAEs to Study Drug by SOC and PT.
–
Drug-Related TEAEs by SOC and PT.
–
Severity of TEAEs by SOC and PT.
–
Severity of Drug-Related TEAEs by SOC and PT.
In addition, pretreatment events (PTEs) will be summarized overall by SOC and PT.
For each regimen and overall, subjects reporting more than one occurrence for a term (SOC or 
PT) being summarized will be counted only once using the most extreme incident (most severe 
for the severity tables and related for the relationship to study drug tables).
Most frequent TEAEs are those events occurred in at least ≥5% (before any rounding) of 
subjects in a regimen. 
Data listings will be provided for all TEAEs, PTEs, TEAEs that led to study discontinuation, 
TEAEs that led to abnormal liver functions, SAEs, AEs that resulted in death, and AEs occurring 
more than 30 days after the last dose of study medication.


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7.11.2 Clinical Laboratory Evaluations
Clinical safety laboratory tests include hematology, chemistry, urinalysis, and diagnostic 
screening. Refer to Appendix A for scheduled clinical laboratory test measurements and to Table 
7.c for the list of all clinical laboratory tests.
Individual results for hematology and chemistry laboratory tests that meet the Takeda predefined 
laboratory markedly abnormal value (MAV) criteria in Appendix B will be presented in a data 
listing. If a subject has an MAV for a particular laboratory test, all visits for that subject for that 
parameter will be listed. 
All clinical laboratory data will be presented in both SI and conventional units in the data 
listings. Laboratory data outside of the normal reference range will be listed. Out of normal 
range values and MAVs will be flagged in data listings.
Table 7.c
Clinical Laboratory Tests
Hematology
Serum Chemistry
Urinalysis
RBC
WBC with differential 
Hemoglobin
Hematocrit
Platelets
Alanine aminotransferase 
Albumin
Alkaline phosphatase
Aspartate aminotransferase
Glucose
Total bilirubin
Total protein
Total cholesterol
Triglycerides
Serum creatinine
Blood urea nitrogen
Uric acid
gamma-glutamyl transferase
Calcium
Phosphorus
Potassium
Sodium
Chloride
Bicarbonate or carbon dioxide
Specific gravity
pH
Protein
Ketones
Glucose
Bilirubin
Red blood cells and white 
blood cells
Microscopic battery 
(RBCs, WBCs, epithelial 
cells, casts) if significant 
findings on dipstick 
urinalysis
Diagnostic Screenings:
Serum
Urine/Blood
Breath
Hepatitis panel, including HBsAg
and anti-HCV
Drug screen, including amphetamines, 
barbiturates, benzodiazepines, cannabinoids, 
cocaine, cotinine and opiates.
Alcohol
Women subjects only:
Serum hCG for pregnancy
Serum FSH If postmenopausal 
women defined as amenorrhea >1 
year
FSH=follicle stimulating hormone, hCG= human chorionic gonadotropin, RBC=red blood cells, WBC=white blood 
cells.


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7.11.3 Vital Signs
Refer to Appendix A for scheduled vital signs measurement visits.
Individual results for vital sign measurements that meet the Takeda predefined vital signs MAV 
criteria in Appendix C will be presented in a data listing. If a subject has an MAV for a particular 
vital sign parameter, all visits for that subject for that parameter will be listed. 
All vital sign data will be presented in the listings. Vital sign MAVs will be flagged in the 
listings.
7.11.4 12-Lead ECGs
The scheduled 12-lead ECG data will be collected according to Appendix A. The ECG 
parameters include heart rate, RR interval, PR interval, QRS interval, QT interval, and QTc 
interval (Fredericia’s and Bazett’s corrections).
Individual results for 12-lead ECG measurements that meet the Takeda predefined 12-lead ECG 
MAV criteria in Appendix D will be presented in a data listing. If a subject has an MAV for a 
particular ECG parameter, all visits for that subject for that parameter will be listed. 
All ECG data will be presented in the listings. ECG MAVs will be flagged in the listings.
7.11.5 Other Observations Related to Safety
Physical examination information will be presented in the listings. No summary tables will be 
provided.
All cases of overdose will be listed. 
Follow-up phone call information will be listed.
7.12
Interim Analysis
Not applicable.
7.13
Changes in the Statistical Analysis Plan 
None.


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8.0
REFERENCES
1. A Phase 1, Randomized, Open-Label, Single-Center, Single-Dose, Two-Period Two Part 
Crossover Study in Healthy Subjects to Compare the Bioavailability of Dexlansoprazole 
from Dexlansoprazole Delayed-Release Capsules 30 mg and 60 mg Manufactured by Takeda 
GmbH Plant Oranienburg Relative to Dexlansoprazole Delayed-Release Capsules 30 mg and 
60 mg Manufactured by Takeda Pharmaceutical Company Limited Osaka Plant. Protocol No. 
TAK-390MR-1001 Amendment 02, dated 6 June, 2017.


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Appendix A
Schedule of Study Procedures
Study Day:
Pretreatment 
Period
Treatment Periods 1 and 2 (a)
Study Exit 
(Day 2 of 
Period 2)/ 
Early 
Termination 
Visit
Follow-up 
Phone Call 
(d)
Days 
-28 to -2 
(screening) (b)
Day -1 
(Check-in)
Day 1 (c)
Day 2
Confinement
X
X
X (e)
X (f)
Informed consent
X
Inclusion/exclusion 
criteria
X
X (g)
Demographics and 
medical history
X
Medication history
X
Physical examination
X
X
X
Height, Weight, and 
BMI (h)
X
Vital signs (i)
X
X
X
X
X
Concomitant 
medications
X
X
X
X
X
X
Concurrent medical 
conditions
X
Clinical laboratory 
tests (j)
X
X
X
X
Hepatitis panel
X
Pregnancy test (hCG) 
(k)
X
X
X
FSH (l)
X
Urine drug screen
X
X
ECG (m)
X
X
X
X
Administration of 
study drug (n) 
X
PGx DNA sample 
collection (o)
X
PK blood collection 
(p)
X
X
X (q)
AE assessment (r)
X
X
X
X
X
X
Footnotes are on last table page.


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(a) There will be at least 5 days between the dose in 1 period and the dose in a subsequent period.
(b) Screening procedures must be performed within 28 days prior to administration of investigational product.
(c) Day 1 of each treatment period.
(d) Follow-up phone call will be made 10±2 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.
(e) Following study procedure completion on Day 2 of Period 1, subjects will be discharged from the clinic to begin the washout 
period. 
(f) Following study procedure completion on Day 2 of Period 2, subjects will be discharged from the clinic. Early termination
procedures are explained in Section 9.3.6.
(g) Assessment of inclusion and exclusion criteria will be done on Day -1, Period 1 only.
(h) The BMI is calculated using metric units as follows: Metric: BMI = weight (kg)/[height (m)]2.
(i) Vital signs: oral body temperature, sitting blood pressure (after resting 5 minutes), respiratory rate, and pulse (beats per 
minute) at Screening. Only blood pressure and pulse will be collected on Check-in (Day -1) through Day 2 of each period prior to 
dose and 8 hours postdose, or if the subject terminated early from study. 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 30 minutes before or after the scheduled blood 
draw.
(j) Hematology, serum chemistries, and urinalysis tests. Clinical laboratory samples will be collected after a minimum of an 8 
hour fast on Screening, Check-in (Day -1) of Periods 1 and 2; Day 2 of Period 1, and Study Exit (Day 2 of Period 2)/Early 
termination. If an 8-hour fast is not possible at Early termination, laboratory samples will still be collected.
(k) A serum pregnancy test will be done at Screening and Day -1 of each period, Study Exit (Day 2 of Period 2), or if a subject 
prematurely terminates from the study.
(l) For women where menopause is suspected (see Section 9.1.9).
(m) ECG performed at Screening, Check-in (Day -1 of Period 1), and Study Day 2 of each period, or if a subject terminates early 
from the study. 
(n) Study drug will be administered on Day 1 of each period at approximately 0800 hours, following a 10-hour fast. Dosing may 
be staggered to help facilitate logistics at the site.
(o) One 6 mL whole-blood sample will be collected for DNA analysis prior to dosing on Day 1 of Period 1 only. 
(p) Blood samples for PK obtained predose (within 15 minutes prior to dose), and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, and 
24 hours post Day 1 dosing in each period. 
(q) The PK sample should not be collected at the Early Termination Visit if a PK collection is not scheduled.
(r) Pretreatment AEs will be captured immediately following the signing of the informed consent at Screening until dosing on 
Day 1 of Period 1. The routine collection of AEs will continue after dosing through the follow-up phone call.


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Appendix B
Criteria for Identification of Markedly Abnormal Laboratory Values 
Hematology—Criteria for Markedly Abnormal Values
Parameter
Unit
Low Abnormal
High Abnormal
Hemoglobin
Both 
< 0.8 × LLN
> 1.2 × ULN
Hematocrit
Both
< 0.8 × LLN
> 1.2 × ULN
RBC count 
Both
< 0.8 × LLN 
> 1.2 × ULN
WBC count 
Both 
<0.5 x LLN
>1.5 x ULN
Platelet count
Conventional
<75 x 103/L
>600 x 103/L
SI
<75 x 109/L
>600 x 109/L
LLN=lower limit of normal, RBC=red blood cell, ULN=upper limit of normal, WBC=white blood cell. 


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Serum Chemistry—Criteria for Markedly Abnormal Values
Parameter
Unit 
Low Abnormal
High Abnormal
ALT
Both
--
≥3x ULN
AST
Both
--
≥3x ULN
GGT
Both
--
≥3x ULN
Alkaline phosphatase
Both
--
≥3x ULN
Total bilirubin
Conventional
--
>2.0 mg/dL
SI
--
>34.2 mol/L
Albumin
Conventional 
<2.5 g/dL
--
SI 
<25 g/L
--
Total protein
Both
<0.8x LLN
>1.2x ULN
Creatinine
Conventional 
--
>2.0 mg/dL
SI
>177 mol/L
Blood urea nitrogen
Conventional 
>30 mg/dL
SI
>10.7 mmol/L
Sodium
Conventional
<130 mEq/L
>150 mEq/L
SI
<130 mmol/L
>150 mmol/L
Potassium
Conventional
<3.0 mEq/L
>6.0 mEq/L
SI
<3.0 mmol/L
>6.0 mmol/L
Glucose
Conventional
< 50 mg/dL
>350 mg/dL
SI
< 2.8 mmol/L
>19.4 mmol/L
Chloride
Conventional
< 75 mEq/L
>126 mmol/L
SI
< 75 mmol/L
>126 mmol/L
Bicarbonate
Conventional 
< 8.0 mEq/L
SI
< 8.0 mmol/L
Phosphorous 
Conventional 
< 1.6 mg/dL
>6.2 mg/dL
SI 
< 0.52 mmol/L
>2.000 mmol/L
Total Cholesterol
Conventional 
--
>300 mg/dL
SI 
--
>7.72 mmol/L
Triglycerides
Both
--
>2.5x ULN
--
ALT=alanine aminotransferase, AST=aspartate aminotransferase, GGT=-glutamyl transferase, LLN=lower limit of 
normal, ULN=upper limit of normal.


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Appendix C
Criteria for Abnormal Changes from Baseline of 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
oC
< 35.6
>37.7


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Appendix D
Criteria for Markedly Abnormal Values for the 12-Lead ECG Parameters
Parameter
Lower Criteria
Upper Criteria
Heart rate
<50 beats per minute
>120 beats per minute
QT Interval
≤50 milliseconds
≥460 milliseconds
QTcB Interval
≤50 milliseconds
≥500 milliseconds OR 
≥30 milliseconds change from baseline and 
≥450 milliseconds
QTcF Interval
≤50 milliseconds
≥500 milliseconds OR 
≥30 milliseconds change from baseline and
≥450 milliseconds


 
  
 
 
 
 
 
 
 
 
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(dd-MMM-yyyy HH:mm ‘UTC’) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
090101d680634a33
TAK-390MR-1001 Statistical Analysis Plan 2017-06-28
Statistical Approval
28-Jun-2017 19:56 UTC
Pharmacovigilance Approval
28-Jun-2017 20:01 UTC
Clinical Pharmacology Approval
28-Jun-2017 20:16 UTC
Clinical Science Approval
29-Jun-2017 00:40 UTC
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