Bioequivalence Study of Dexlansoprazole Capsules From Two Manufacturing Plants

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03131895
• Collaborator: (none)
• Enrollment: 116
• Location: 1
• Arms: 4
• Actual Duration (Months): 3.2
• Patients Per Site Per Month: 36.4

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: 30 mg dexlansoprazole capsules manufactured at TOB; Drug: 30 mg dexlansoprazole capsules manufactured at TPC; Drug: 60 mg dexlansoprazole capsules manufactured at TOB; Drug: 60 mg dexlansoprazole capsules manufactured at TPC	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official 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
• Actual Study Start Date: Apr 25, 2017
• Actual Primary Completion Date: Jul 3, 2017
• Actual Study Completion Date: Jul 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1, Sequence 1 (Regimen A, B) 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.	Drug: 30 mg dexlansoprazole capsules manufactured at TOB; Dexlansoprazole delayed-release.; Drug: 30 mg dexlansoprazole capsules manufactured at TPC; Dexlansoprazole delayed-release.
Experimental: Part 1, Sequence 2 (Regimen B, A) 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.	Drug: 30 mg dexlansoprazole capsules manufactured at TOB; Dexlansoprazole delayed-release.; Drug: 30 mg dexlansoprazole capsules manufactured at TPC; Dexlansoprazole delayed-release.
Experimental: Part 2, Sequence 3 (Regimen C, D) 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.	Drug: 60 mg dexlansoprazole capsules manufactured at TOB; Dexlansoprazole delayed-release.; Drug: 60 mg dexlansoprazole capsules manufactured at TPC; Dexlansoprazole delayed-release.
Experimental: Part 2, Sequence 4 (Regimen D, C) 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.	Drug: 60 mg dexlansoprazole capsules manufactured at TOB; Dexlansoprazole delayed-release.; Drug: 60 mg dexlansoprazole capsules manufactured at TPC; Dexlansoprazole delayed-release.

Outcome Measures

Primary Outcome Measures

1. Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole [Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose]

2. AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Dexlansoprazole [Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose]

3. AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Dexlansoprazole [Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Healthy men and women aged 18 to 55 years old, inclusive, with a body mass index between 18 and 30 kilogram per square meter (kg/m^2), inclusive.

2. Who are capable of understanding and complying with protocol requirements.

3. Must be in good health as determined by a physician based upon medical history, vital signs, electrocardiogram (ECG), and physical examination.

4. 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.

5. Must sign a written informed consent form (ICF) prior to initiation of study procedures.

Exclusion Criteria:

1. 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 (example, a history of malabsorption, severe esophageal reflux, peptic ulcer disease or erosive esophagitis (EE) with frequent [more than once per week] occurrence of heartburn).

2. 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.

3. Have received dexlansoprazole in a previous clinical study or as a therapeutic agent within 6 months of Screening,

4. 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.

5. Any significant results from physical examination or clinical laboratory results that make the participant unsuitable for the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRAHS Phase 1 unit	Salt Lake City	Utah	United States	84106

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Jun 6, 2017
• Statistical Analysis Plan - Jun 28, 2017

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03131895
• Other Study ID Numbers: TAK-390MR-1001; U1111-1184-2186
• First Posted: Apr 27, 2017
• Last Update Posted: Jun 14, 2019
• Last Verified: Mar 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Dexlansoprazole; Lansoprazole

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 1 investigative site in the United States from 25 April 2017 to 31 July 2017.
Pre-assignment Detail	Healthy participants were enrolled in this 2 part study to receive dexlansoprazole 30 milligram (mg) capsules manufactured by Takeda GmbH Plant (Oranienburg, Germany) (TOB) or 30 mg capsules manufactured by Takeda Pharmaceutical Company Ltd. (Osaka, Japan) (TPC) in Part 1 and dexlansoprazole 60 mg capsules by TOB or 60 mg capsules by TPC in Part 2.

Arm/Group Title	Part 1: Dexlansoprazole 30 mg TOB+ Dexlansoprazole 30 mg TPC	Part 1: Dexlansoprazole 30 mg TPC + Dexlansoprazole 30 mg TOB	Part 2: Dexlansoprazole 60 mg TOB+ Dexlansoprazole 60 mg TPC	Part 2: Dexlansoprazole 60 mg TPC+ Dexlansoprazole 60 mg TOB
Arm/Group Description	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Intervention Period 1 following a 10-hour fast, followed by minimum of 5-day washout period, further followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference) orally, once on Day 1 of Intervention Period 1 following a 10-hour fast.	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 following a 10-hour fast, followed by minimum of 5-day washout period, further followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test) orally, once on Day 1 of Intervention Period 1 following a 10-hour fast.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Intervention Period 1 following a 10-hour fast, followed by minimum of 5-day washout period, further followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference) orally, once on Day 1 of Intervention Period 1 following a 10-hour fast.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 following a 10-hour fast, followed by minimum of 5-day washout period, further followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test) orally, once on Day 1 of Intervention Period 1 following a 10-hour fast.
Period Title: Intervention Period 1 (2 Days)
STARTED	28	28	30	30
COMPLETED	28	28	30	30
NOT COMPLETED	0	0	0	0
Period Title: Intervention Period 1 (2 Days)
STARTED	28	28	30	30
COMPLETED	27	23	26	25
NOT COMPLETED	1	5	4	5
Period Title: Intervention Period 1 (2 Days)
STARTED	27	23	26	25
COMPLETED	26	22	26	25
NOT COMPLETED	1	1	0	0

Baseline Characteristics

Arm/Group Title	Part 1: Dexlansoprazole 30 mg TOB+ Dexlansoprazole 30 mg TPC	Part 1: Dexlansoprazole 30 mg TPC + Dexlansoprazole 30 mg TOB	Part 2: Dexlansoprazole 60 mg TOB+ Dexlansoprazole 60 mg TPC	Part 2: Dexlansoprazole 60 mg TPC+ Dexlansoprazole 60 mg TOB	Total
Arm/Group Description	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Intervention Period 1 following a 10-hour fast, followed by minimum of 5-day washout period, further followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference) orally, once on Day 1 of Intervention Period 1 following a 10-hour fast.	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 following a 10-hour fast, followed by minimum of 5-day washout period, further followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test) orally, once on Day 1 of Intervention Period 1 following a 10-hour fast.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Intervention Period 1 following a 10-hour fast, followed by minimum of 5-day washout period, further followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference) orally, once on Day 1 of Intervention Period 1 following a 10-hour fast.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 following a 10-hour fast, followed by minimum of 5-day washout period, further followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test) orally, once on Day 1 of Intervention Period 1 following a 10-hour fast.	Total of all reporting groups
Overall Participants	28	28	30	30	116
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	30.0 (7.95)	28.5 (9.98)	29.2 (7.78)	28.4 (9.71)	29.0 (8.81)
Sex: Female, Male (Count of Participants)
Female	11 39.3%	10 35.7%	14 46.7%	14 46.7%	49 42.2%
Male	17 60.7%	18 64.3%	16 53.3%	16 53.3%	67 57.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 17.9%	6 21.4%	5 16.7%	1 3.3%	17 14.7%
Not Hispanic or Latino	21 75%	22 78.6%	25 83.3%	29 96.7%	97 83.6%
Unknown or Not Reported	2 7.1%	0 0%	0 0%	0 0%	2 1.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.6%	1 3.6%	0 0%	2 6.7%	4 3.4%
Asian	0 0%	1 3.6%	1 3.3%	2 6.7%	4 3.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 3.6%	1 3.6%	1 3.3%	1 3.3%	4 3.4%
White	26 92.9%	24 85.7%	28 93.3%	25 83.3%	103 88.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 3.6%	0 0%	0 0%	1 0.9%
Region of Enrollment (Count of Participants)
United States	28 100%	28 100%	30 100%	30 100%	116 100%
Body mass index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	24.7 (2.59)	24.4 (2.75)	24.6 (2.65)	24.5 (3.33)	24.5 (2.82)
Smoking Classification (participants) [Number]
Never Smoked	24 85.7%	28 100%	27 90%	28 93.3%	107 92.2%
Former Smoker	4 14.3%	0 0%	3 10%	2 6.7%	9 7.8%
Current Smoker	0 0%	0 0%	0 0%	0 0%	0 0%
Alcohol Classification (participants) [Number]
Never Drank	19 67.9%	19 67.9%	18 60%	18 60%	74 63.8%
Former Drinker	4 14.3%	3 10.7%	4 13.3%	1 3.3%	12 10.3%
Current Drinker	5 17.9%	6 21.4%	8 26.7%	11 36.7%	30 25.9%
Caffeine Consumption (participants) [Number]
Had caffeine consumption	15 53.6%	15 53.6%	18 60%	22 73.3%	70 60.3%
Had no caffeine consumption	13 46.4%	13 46.4%	12 40%	8 26.7%	46 39.7%
Xanthine Consumption (participants) [Number]
Had xanthine consumption	15 53.6%	15 53.6%	18 60%	22 73.3%	70 60.3%
Had no xanthine consumption	13 46.4%	13 46.4%	12 40%	8 26.7%	46 39.7%

Outcome Measures

1. Primary Outcome

Title	Cmax: Maximum Observed Plasma Concentration for Dexlansoprazole
Time Frame	Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration.

Arm/Group Title	Dexlansoprazole 30 mg TOB	Dexlansoprazole 30 mg TPC	Dexlansoprazole 60 mg TOB	Dexlansoprazole 60 mg TPC
Arm/Group Description	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Intervention Period 1 or 2.	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Intervention Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 or 2.
Measure Participants	51	55	55	56
Mean (Standard Deviation) [nanogram/milliliter (ng/mL)]	515.7 (257.60)	519.5 (305.66)	1027.0 (598.74)	978.6 (581.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 30 mg TOB, Dexlansoprazole 30 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	A linear mixed effect model on the natural log-transformed parameters was performed with regimen, sequence and period as a fixed effect and subject nested within sequence as a random effect. The least squares means and difference of least squares means for the log-transformed parameters were exponentiated to obtain the point estimates and 90 percent (%) confidence intervals (CIs) on the original scale.
Statistical Test of Hypothesis	p-Value	0.5535
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least square (LS) mean ratio
	Estimated Value	1.0436
	Confidence Interval	(2-Sided) 90%; 0.9453 to 1.1521
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 60 mg TOB, Dexlansoprazole 60 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	A linear mixed effect model on the natural log-transformed parameters was performed with regimen, sequence and period as a fixed effect and subject nested within sequence as a random effect. The least squares means and difference of least squares means for the log-transformed parameters were exponentiated to obtain the point estimates and 90% CIs on the original scale.
Statistical Test of Hypothesis	p-Value	0.8920
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean ratio
	Estimated Value	1.0185
	Confidence Interval	(2-Sided) 90%; 0.9334 to 1.1113
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Dexlansoprazole
Time Frame	Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration.

Arm/Group Title	Dexlansoprazole 30 mg TOB	Dexlansoprazole 30 mg TPC	Dexlansoprazole 60 mg TOB	Dexlansoprazole 60 mg TPC
Arm/Group Description	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Intervention Period 1 or 2.	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Intervention Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 or 2.
Measure Participants	51	55	55	56
Mean (Standard Deviation) [nanogram*hour per milliliter(ng*hour/mL)]	2416.3 (2280.91)	2327.6 (2052.94)	5715.5 (4521.84)	5684.7 (5361.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 30 mg TOB, Dexlansoprazole 30 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	A linear mixed effect model on the natural log-transformed parameters was performed with regimen, sequence and period as a fixed effect and subject nested within sequence as a random effect. The least squares means and difference of least squares means for the log-transformed parameters were exponentiated to obtain the point estimates and 90% CIs on the original scale.
Statistical Test of Hypothesis	p-Value	0.3209
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean ratio
	Estimated Value	1.0390
	Confidence Interval	(2-Sided) 90%; 0.9792 to 1.1024
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 60 mg TOB, Dexlansoprazole 60 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	A linear mixed effect model on the natural log-transformed parameters was performed with regimen, sequence and period as a fixed effect and subject nested within sequence as a random effect. The least squares means and difference of least squares means for the log-transformed parameters were exponentiated to obtain the point estimates and 90% CIs on the original scale.
Statistical Test of Hypothesis	p-Value	0.3896
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean ratio
	Estimated Value	1.0353
	Confidence Interval	(2-Sided) 90%; 0.9719 to 1.1029
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Dexlansoprazole
Time Frame	Day 1: pre-dose and at multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration. PK analysis set where data at specified time points was available.

Arm/Group Title	Dexlansoprazole 30 mg TOB	Dexlansoprazole 30 mg TPC	Dexlansoprazole 60 mg TOB	Dexlansoprazole 60 mg TPC
Arm/Group Description	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Intervention Period 1 or 2.	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Intervention Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 or 2.
Measure Participants	51	55	55	56
Mean (Standard Deviation) [ng*hour/mL]	2579.6 (2760.38)	2420.6 (2322.58)	5746.2 (4785.72)	5630.4 (5527.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 30 mg TOB, Dexlansoprazole 30 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	A linear mixed effect model on the natural log-transformed parameters was performed with regimen, sequence and period as a fixed effect and subject nested within sequence as a random effect. The least squares means and difference of least squares means for the log-transformed parameters were exponentiated to obtain the point estimates and 90% CIs on the original scale.
Statistical Test of Hypothesis	p-Value	0.4163
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean ratio
	Estimated Value	1.0335
	Confidence Interval	(2-Sided) 90%; 0.9733 to 1.0975
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 60 mg TOB, Dexlansoprazole 60 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	A linear mixed effect model on the natural log-transformed parameters was performed with regimen, sequence and period as a fixed effect and subject nested within sequence as a random effect. The least squares means and difference of least squares means for the log-transformed parameters were exponentiated to obtain the point estimates and 90% CIs on the original scale.
Statistical Test of Hypothesis	p-Value	0.9778
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean ratio
	Estimated Value	1.0031
	Confidence Interval	(2-Sided) 90%; 0.9458 to 1.0638
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Day 37)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Dexlansoprazole 30 mg TOB		Dexlansoprazole 30 mg TPC		Dexlansoprazole 60 mg TOB		Dexlansoprazole 60 mg TPC
Arm/Group Description	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Intervention Period 1 or 2.		Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 or 2.		Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Intervention Period 1 or 2.		Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Intervention Period 1 or 2.
All Cause Mortality
	Dexlansoprazole 30 mg TOB		Dexlansoprazole 30 mg TPC		Dexlansoprazole 60 mg TOB		Dexlansoprazole 60 mg TPC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/55 (0%)		0/55 (0%)		0/56 (0%)
Serious Adverse Events
	Dexlansoprazole 30 mg TOB		Dexlansoprazole 30 mg TPC		Dexlansoprazole 60 mg TOB		Dexlansoprazole 60 mg TPC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/55 (0%)		0/55 (0%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	Dexlansoprazole 30 mg TOB		Dexlansoprazole 30 mg TPC		Dexlansoprazole 60 mg TOB		Dexlansoprazole 60 mg TPC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/51 (15.7%)		9/55 (16.4%)		8/55 (14.5%)		11/56 (19.6%)
Blood and lymphatic system disorders
Lymphadenopathy	0/51 (0%)		0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Gastrointestinal disorders
Nausea	2/51 (3.9%)		1/55 (1.8%)		1/55 (1.8%)		0/56 (0%)
Abdominal pain	0/51 (0%)		0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Diarrhoea	0/51 (0%)		0/55 (0%)		0/55 (0%)		1/56 (1.8%)
General disorders
Injection site erosion	1/51 (2%)		0/55 (0%)		0/55 (0%)		0/56 (0%)
Injection site erythema	0/51 (0%)		1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Pyrexia	0/51 (0%)		0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Injection site haematoma	1/51 (2%)		0/55 (0%)		0/55 (0%)		0/56 (0%)
Sensation of foreign body	0/51 (0%)		1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Vessel puncture site haematoma	0/51 (0%)		1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Infections and infestations
Gastroenteritis	0/51 (0%)		0/55 (0%)		2/55 (3.6%)		0/56 (0%)
Periorbital cellulitis	0/51 (0%)		1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Viral upper respiratory tract infection	0/51 (0%)		0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Injury, poisoning and procedural complications
Procedural complication	0/51 (0%)		0/55 (0%)		1/55 (1.8%)		2/56 (3.6%)
Laceration	1/51 (2%)		0/55 (0%)		0/55 (0%)		0/56 (0%)
Procedural dizziness	0/51 (0%)		0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Sunburn	0/51 (0%)		1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/51 (2%)		1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/51 (0%)		1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Musculoskeletal pain	0/51 (0%)		1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Myalgia	1/51 (2%)		0/55 (0%)		0/55 (0%)		0/56 (0%)
Nervous system disorders
Headache	1/51 (2%)		0/55 (0%)		1/55 (1.8%)		3/56 (5.4%)
Dizziness	1/51 (2%)		0/55 (0%)		0/55 (0%)		0/56 (0%)
Presyncope	0/51 (0%)		0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Psychiatric disorders
Anxiety	0/51 (0%)		0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/51 (0%)		1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Nasal congestion	0/51 (0%)		1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Oropharyngeal pain	0/51 (0%)		0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Skin and subcutaneous tissue disorders
Dermatitis atopic	1/51 (2%)		0/55 (0%)		0/55 (0%)		0/56 (0%)
Vascular disorders
Haematoma	0/51 (0%)		0/55 (0%)		0/55 (0%)		3/56 (5.4%)
Thrombophlebitis superficial	0/51 (0%)		1/55 (1.8%)		0/55 (0%)		0/56 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.