A Study to Compare the Bioavailability (BA) of Dexlansoprazole Delayed-release Capsules

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03801148
• Collaborator: (none)
• Enrollment: 122
• Location: 1
• Arms: 4
• Actual Duration (Months): 2.9
• Patients Per Site Per Month: 41.7

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the BA of 30 or 60 milligram (mg) dexlansoprazole capsule manufactured at TOB (Takeda GmbH Plant Oranienburg) to the corresponding 30 or 60 mg dexlansoprazole manufactured at TPC (Takeda Pharmaceutical Company Ltd.).

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. Dexlansoprazole is being tested in healthy participants to compare the BA of dexlansoprazole capsules manufactured by TOB relative to dexlansoprazole capsules manufactured by TPC, under fed conditions. The study consists of two parts: Part 1 participants will receive dexlansoprazole 30 mg capsules manufactured by TOB and TPC in a crossover fashion; Part 2 participants will receive dexlansoprazole 60 mg capsules manufactured by TOB and TPC in a crossover fashion.

The study will enroll approximately 120 participants. Participants will be randomly assigned (by chance, like flipping a coin) to 1 of the 4 treatment sequences as following:

• 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)

All participants will be asked to take capsule of assigned dexlansoprazole on Day 1, 30 minutes following the beginning of a high-fat/high calorie breakfast of each treatment period.

This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 86 days. Participants will be contacted by phone call approximately 10 days after the last dose of study drug for a follow-up assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 122 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 Following a High-Fat Meal
• Actual Study Start Date: Jan 10, 2019
• Actual Primary Completion Date: Feb 25, 2019
• Actual Study Completion Date: Apr 9, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1:Dexlansoprazole 30mg (TOB) + Dexlansoprazole 30mg (TPC) Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (Regimen A [test]), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5 day washout period, followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (Regimen B [reference]), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2.	Drug: 30 mg dexlansoprazole capsules manufactured at TOB; Dexlansoprazole delayed-release capsules.; Drug: 30 mg dexlansoprazole capsules manufactured at TPC; Dexlansoprazole delayed-release capsules.
Experimental: Part 1:Dexlansoprazole 30mg (TPC) + Dexlansoprazole 30mg (TOB) Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (Regimen B [reference]), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5 day washout period, followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (Regimen A [test]), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2.	Drug: 30 mg dexlansoprazole capsules manufactured at TOB; Dexlansoprazole delayed-release capsules.; Drug: 30 mg dexlansoprazole capsules manufactured at TPC; Dexlansoprazole delayed-release capsules.
Experimental: Part 2:Dexlansoprazole 60mg (TOB) + Dexlansoprazole 60mg (TPC) Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (Regimen C [test]), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5 day washout period, followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (Regimen D [reference]), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2.	Drug: 60 mg dexlansoprazole capsules manufactured at TOB; Dexlansoprazole delayed-release capsules.; Drug: 60 mg dexlansoprazole capsules manufactured at TPC; Dexlansoprazole delayed-release capsules.
Experimental: Part 2:Dexlansoprazole 60mg (TPC) + Dexlansoprazole 60mg (TOB) Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (Regimen D [reference]), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5 day washout period, followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (Regimen C [test]), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2.	Drug: 60 mg dexlansoprazole capsules manufactured at TOB; Dexlansoprazole delayed-release capsules.; Drug: 60 mg dexlansoprazole capsules manufactured at TPC; Dexlansoprazole delayed-release capsules.

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. AUC0_infobs: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for Dexlansoprazole [Day 1 pre-dose and at multiple time points (up to 24 hours) post dose]

4. AUC0_infpred: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Predicted Value of the Last Quantifiable Concentration 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. Has a body mass index (BMI) from 18 to 30 kilogram per square meter (kg/m^2), at Screening.

2. Is willing and able to consume the high-fat/high-calorie breakfast administered during the study.

Exclusion Criteria:

1. 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 equal (=) 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.

2. 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).

3. Has received any known hepatic or renal clearance altering agents (example, erythromycin, cimetidine, barbiturates, phenothiazines, fluvoxamine, etc) for a period of 28 days prior to Day 1 of Period 1.

4. Has donated blood products (such as plasma) within 30 days or has donated whole blood or lost 450 milliliter (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.

5. With the exception of acetaminophen, the subject has taken any excluded medication, supplements, or food products 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 (example, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard), and charbroiled meats. 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.

6. 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 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.

7. Has received dexlansoprazole or lansoprazole in a previous clinical study or as a therapeutic agent within 6 months of screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Celerion	Tempe	Arizona	United States	85283

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Jan 9, 2019
• Statistical Analysis Plan - Jan 29, 2019

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03801148
• Other Study ID Numbers: TAK-390MR-1002; U1111-1224-9781
• First Posted: Jan 11, 2019
• Last Update Posted: Mar 19, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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 10 January 2019 to 09 April 2019.
Pre-assignment Detail	Healthy participants were enrolled in this 2-part and 2-way crossover study to receive dexlansoprazole 30 milligram (mg) capsules manufactured by Takeda GmbH Plant Oranienburg (TOB) and 30 mg capsules manufactured by Takeda Pharmaceutical Company Ltd. (TPC) in Part 1 and dexlansoprazole 60 mg capsules by TOB and 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, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5-day washout period, followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2.	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5 day washout period, followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5 day washout period, followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5 day washout period, followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2.
Period Title: Period 1 (2 Days)
STARTED	31	31	30	30
COMPLETED	30	30	30	30
NOT COMPLETED	1	1	0	0
Period Title: Period 1 (2 Days)
STARTED	30	30	30	30
COMPLETED	30	30	29	29
NOT COMPLETED	0	0	1	1
Period Title: Period 1 (2 Days)
STARTED	30	30	29	29
COMPLETED	30	30	29	29
NOT COMPLETED	0	0	0	0
Period Title: Period 1 (2 Days)
STARTED	30	30	29	29
COMPLETED	30	29	28	29
NOT COMPLETED	0	1	1	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, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5-day washout period, followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2.	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5 day washout period, followed by dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5 day washout period, followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once, after a high fat/calorie breakfast on Day 1 of Period 1, followed by minimum of 5 day washout period, followed by dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once, after a high fat/calorie breakfast on Day 1 of Period 2.	Total of all reporting groups
Overall Participants	31	31	30	30	122
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	31 100%	31 100%	30 100%	30 100%	122 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	19 61.3%	18 58.1%	15 50%	17 56.7%	69 56.6%
Male	12 38.7%	13 41.9%	15 50%	13 43.3%	53 43.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	24 77.4%	25 80.6%	24 80%	23 76.7%	96 78.7%
Not Hispanic or Latino	7 22.6%	6 19.4%	6 20%	7 23.3%	26 21.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 3.3%	0 0%	1 0.8%
Asian	0 0%	1 3.2%	0 0%	2 6.7%	3 2.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 3.2%	0 0%	4 13.3%	1 3.3%	6 4.9%
White	30 96.8%	29 93.5%	25 83.3%	27 90%	111 91%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 3.2%	0 0%	0 0%	1 0.8%
Region of Enrollment (Count of Participants)
United States	31 100%	31 100%	30 100%	30 100%	122 100%

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) evaluable set included all participants who enrolled into study and received at least one dose of study drug, were not discontinued from study and replaced with other participants, who completed PK sampling in both periods, complied sufficiently with protocol, and displayed evaluable PK profiles.

Arm/Group Title	Part 1: Dexlansoprazole 30 mg TOB	Part 1: Dexlansoprazole 30 mg TPC	Part 2: Dexlansoprazole 60 mg TOB	Part 2: Dexlansoprazole 60 mg TPC
Arm/Group Description	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Period 1 or 2.	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Period 1 or 2.
Measure Participants	60	60	57	57
Geometric Mean (Geometric Coefficient of Variation) [nanogram/milliliter (ng/mL)]	610.1 (52.0)	622.5 (49.9)	1381 (45.3)	1302 (50.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Dexlansoprazole 30 mg TOB, Part 1: Dexlansoprazole 30 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	Natural log (ln)-transformed-Cmax, was analyzed using an analysis of variance (ANOVA) model to assess the relative bioavailability of dexlansoprazole 30 mg capsule manufactured at TOB compared with dexlansoprazole 30 mg capsule manufactured at TPC. Geometric least square mean (LSM) ratios were calculated using the exponentiation of the difference between treatment LSM from the analyses on the ln-transformed Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LSM ratio
	Estimated Value	0.9800
	Confidence Interval	(2-Sided) 90%; 0.9171 to 1.0473
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 2: Dexlansoprazole 60 mg TOB, Part 2: Dexlansoprazole 60 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	ln-transformed-Cmax, was analyzed using an ANOVA model to assess the relative bioavailability of dexlansoprazole 60 mg capsule manufactured at TOB compared with dexlansoprazole 60 mg capsule manufactured at TPC. Geometric LSM ratios were calculated using the exponentiation of the difference between treatment LSM from the analyses on the ln-transformed Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LSM ratio
	Estimated Value	1.0737
	Confidence Interval	(2-Sided) 90%; 1.0025 to 1.1501
	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 evaluable set included all participants who enrolled into study and received at least one dose of study drug, were not discontinued from study and replaced with other participants, who completed PK sampling in both periods, complied sufficiently with protocol, and displayed evaluable PK profiles.

Arm/Group Title	Part 1: Dexlansoprazole 30 mg TOB	Part 1: Dexlansoprazole 30 mg TPC	Part 2: Dexlansoprazole 60 mg TOB	Part 2: Dexlansoprazole 60 mg TPC
Arm/Group Description	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Period 1 or 2.	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Period 1 or 2.
Measure Participants	60	60	57	57
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter(ng*hour/mL)]	2881 (66.8)	2756 (62.8)	6608 (58.5)	6278 (59.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Dexlansoprazole 30 mg TOB, Part 1: Dexlansoprazole 30 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	ln-transformed- AUClast, was analyzed using an ANOVA model to assess the relative bioavailability of dexlansoprazole 30 mg capsule manufactured at TOB compared with dexlansoprazole 30 mg capsule manufactured at TPC. Geometric LSM ratios were calculated using the exponentiation of the difference between treatment LSM from the analyses on the ln-transformed AUClast.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LSM ratio
	Estimated Value	1.0455
	Confidence Interval	(2-Sided) 90%; 1.0070 to 1.0855
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 2: Dexlansoprazole 60 mg TOB, Part 2: Dexlansoprazole 60 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	ln-transformed- AUClast, was analyzed using an ANOVA model to assess the relative bioavailability of dexlansoprazole 60 mg capsule manufactured at TOB compared with dexlansoprazole 60 mg capsule manufactured at TPC. Geometric LSM ratios were calculated using the exponentiation of the difference between treatment LSM from the analyses on the ln-transformed AUClast.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LSM ratio
	Estimated Value	1.0610
	Confidence Interval	(2-Sided) 90%; 1.0192 to 1.1046
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	AUC0_infobs: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Observed Value 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

PK evaluable set: participants enrolled into study, received at least one dose of study drug, were not discontinued from study and replaced with other participants, completed PK sampling in both periods, complied sufficiently with protocol, displayed evaluable PK profiles. PK analysis population where data at specified time points was available.

Arm/Group Title	Part 1: Dexlansoprazole 30 mg TOB	Part 1: Dexlansoprazole 30 mg TPC	Part 2: Dexlansoprazole 60 mg TOB	Part 2: Dexlansoprazole 60 mg TPC
Arm/Group Description	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Period 1 or 2.	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Period 1 or 2.
Measure Participants	58	54	57	53
Geometric Mean (Geometric Coefficient of Variation) [ng*hour/mL]	2927 (66.2)	2885 (63.9)	6734 (60.3)	6220 (56.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Dexlansoprazole 30 mg TOB, Part 1: Dexlansoprazole 30 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	ln-transformed- AUC0_infobs, was analyzed using an ANOVA model to assess the relative bioavailability of dexlansoprazole 30 mg capsule manufactured at TOB compared with dexlansoprazole 30 mg capsule manufactured at TPC. Geometric LSM ratios were calculated using the exponentiation of the difference between treatment LSM from the analyses on the ln-transformed AUC0_infobs.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LSM ratio
	Estimated Value	1.0553
	Confidence Interval	(2-Sided) 90%; 1.0186 to 1.0933
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 2: Dexlansoprazole 60 mg TOB, Part 2: Dexlansoprazole 60 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	ln-transformed- AUC0_infobs, was analyzed using an ANOVA model to assess the relative bioavailability of dexlansoprazole 60 mg capsule manufactured at TOB compared with dexlansoprazole 60 mg capsule manufactured at TPC. Geometric LSM ratios were calculated using the exponentiation of the difference between treatment LSM from the analyses on the ln-transformed AUC0_infobs.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMR
	Estimated Value	1.0468
	Confidence Interval	(2-Sided) 90%; 1.0027 to 1.0929
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	AUC0_infpred: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity Calculated Using the Predicted Value 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

PK evaluable set: participants enrolled into study, received at least one dose of study drug, were not discontinued from study and replaced with other participants, completed PK sampling in both periods, complied sufficiently with protocol, displayed evaluable PK profiles. PK analysis population where data at specified time points was available.

Arm/Group Title	Part 1: Dexlansoprazole 30 mg TOB	Part 1: Dexlansoprazole 30 mg TPC	Part 2: Dexlansoprazole 60 mg TOB	Part 2: Dexlansoprazole 60 mg TPC
Arm/Group Description	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Period 1 or 2.	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Period 1 or 2.	Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Period 1 or 2.
Measure Participants	58	54	57	53
Geometric Mean (Geometric Coefficient of Variation) [ng*hour/mL]	2926 (66.2)	2884 (63.9)	6733 (60.3)	6217 (56.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Dexlansoprazole 30 mg TOB, Part 1: Dexlansoprazole 30 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	ln-transformed- AUC0_infpred, was analyzed using an ANOVA model to assess the relative bioavailability of dexlansoprazole 30 mg capsule manufactured at TOB compared with dexlansoprazole 30 mg capsule manufactured at TPC. Geometric LSM ratios were calculated using the exponentiation of the difference between treatment LSM from the analyses on the ln-transformed AUC0_infpred.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LSM ratio
	Estimated Value	1.0555
	Confidence Interval	(2-Sided) 90%; 1.0188 to 1.0935
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 2: Dexlansoprazole 60 mg TOB, Part 2: Dexlansoprazole 60 mg TPC
	Comments
	Type of Statistical Test	Equivalence
	Comments	ln-transformed- AUC0_infpred, was analyzed using an ANOVA model to assess the relative bioavailability of dexlansoprazole 60 mg capsule manufactured at TOB compared with dexlansoprazole 60 mg capsule manufactured at TPC. Geometric LSM ratios were calculated using the exponentiation of the difference between treatment LSM from the analyses on the ln-transformed AUC0_infpred.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric LSM ratio
	Estimated Value	1.0472
	Confidence Interval	(2-Sided) 90%; 1.0029 to 1.0934
	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	Part 1: Dexlansoprazole 30 mg TOB		Part 1: Dexlansoprazole 30 mg TPC		Part 2: Dexlansoprazole 60 mg TOB		Part 2: Dexlansoprazole 60 mg TPC
Arm/Group Description	Dexlansoprazole 30 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Period 1 or 2.		Dexlansoprazole 30 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Period 1 or 2.		Dexlansoprazole 60 mg, delayed-release capsule manufactured by TOB (test), orally, once on Day 1 of Period 1 or 2.		Dexlansoprazole 60 mg, delayed-release capsule manufactured by TPC (reference), orally, once on Day 1 of Period 1 or 2.
All Cause Mortality
	Part 1: Dexlansoprazole 30 mg TOB		Part 1: Dexlansoprazole 30 mg TPC		Part 2: Dexlansoprazole 60 mg TOB		Part 2: Dexlansoprazole 60 mg TPC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/61 (0%)		0/59 (0%)		0/59 (0%)
Serious Adverse Events
	Part 1: Dexlansoprazole 30 mg TOB		Part 1: Dexlansoprazole 30 mg TPC		Part 2: Dexlansoprazole 60 mg TOB		Part 2: Dexlansoprazole 60 mg TPC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/61 (0%)		0/59 (0%)		0/59 (0%)
Other (Not Including Serious) Adverse Events
	Part 1: Dexlansoprazole 30 mg TOB		Part 1: Dexlansoprazole 30 mg TPC		Part 2: Dexlansoprazole 60 mg TOB		Part 2: Dexlansoprazole 60 mg TPC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/61 (6.6%)		3/61 (4.9%)		7/59 (11.9%)		5/59 (8.5%)
Gastrointestinal disorders
Abdominal distension	0/61 (0%)		1/61 (1.6%)		1/59 (1.7%)		0/59 (0%)
Abdominal pain upper	0/61 (0%)		0/61 (0%)		0/59 (0%)		1/59 (1.7%)
Diarrhoea	0/61 (0%)		0/61 (0%)		0/59 (0%)		1/59 (1.7%)
Gastrooesophageal reflux disease	0/61 (0%)		0/61 (0%)		0/59 (0%)		1/59 (1.7%)
Nausea	1/61 (1.6%)		3/61 (4.9%)		0/59 (0%)		1/59 (1.7%)
Retching	1/61 (1.6%)		0/61 (0%)		0/59 (0%)		0/59 (0%)
Vomiting	0/61 (0%)		1/61 (1.6%)		0/59 (0%)		1/59 (1.7%)
Infections and infestations
Oral herpes	0/61 (0%)		0/61 (0%)		2/59 (3.4%)		0/59 (0%)
Upper respiratory tract infection	0/61 (0%)		1/61 (1.6%)		0/59 (0%)		0/59 (0%)
Injury, poisoning and procedural complications
Ligament sprain	0/61 (0%)		0/61 (0%)		0/59 (0%)		1/59 (1.7%)
Musculoskeletal and connective tissue disorders
Back pain	0/61 (0%)		0/61 (0%)		0/59 (0%)		1/59 (1.7%)
Nervous system disorders
Headache	3/61 (4.9%)		2/61 (3.3%)		4/59 (6.8%)		3/59 (5.1%)
Respiratory, thoracic and mediastinal disorders
Nasal dryness	0/61 (0%)		0/61 (0%)		1/59 (1.7%)		0/59 (0%)
Oropharyngeal pain	0/61 (0%)		0/61 (0%)		1/59 (1.7%)		0/59 (0%)

Limitations/Caveats

[Not Specified]

More Information

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.