Study to Evaluate the Pharmacokinetics and Safety of Dexlansoprazole in Pediatric Subjects With Symptomatic Gastroesophageal Reflux Disease

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01045096
• Collaborator: (none)
• Enrollment: 36
• Locations: 4
• Arms: 3
• Duration (Months): 11.1
• Patients Per Site: 9
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the pharmacokinetics and safety of dexlansoprazole, once daily (QD), in pediatric subjects with symptomatic Gastroesophageal Reflux Disease.

Condition or Disease	Intervention/Treatment	Phase
Gastroesophageal Reflux	Drug: Dexlansoprazole; Drug: Dexlansoprazole; Drug: Dexlansoprazole	Phase 1

Detailed Description

Gastroesophageal Reflux Disease (GERD) is a condition of several causes resulting in the backward flow of gastric contents into the esophagus through the lower esophageal sphincter. The prevalence of GERD in the pediatric population is increasingly becoming recognized and documented. It is a disease that may persist through adulthood, with symptoms in older children and adolescents similar to those seen in adults.

Younger children generally present with extra-esophageal manifestations, regurgitation, and epigastric pain, while older children and adolescents typically present with adult-type GERD symptoms of heartburn and regurgitation. Treatment for GERD is aimed at improving symptoms and healing esophageal inflammation.

Takeda Global Research & Development Center, Inc. (TGRD) developed dexlansoprazole delayed release capsules as a new therapy for treating acid related disorders including symptomatic non-erosive GERD, healing of erosive esophagitis (EE) and maintenance of healed EE.

Dexlansoprazole delayed release capsules have not been studied in subjects younger than 12 years of age. This study is designed to evaluate the safety of dexlansoprazole delayed release capsules in the pediatric population (1 to 11 years old) and to determine if the PK profile of dexlansoprazole in subjects 1 to 11 years of age is similar to that in adults given a similar dose.

Subjects who satisfy the screening evaluation and Inclusion/Exclusion Criteria may be enrolled in the study. Eligible subjects will be assigned to one of three treatment groups. Attempts will be made to enroll an equal number of male and female subjects in each treatment group.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Official Title: A Phase 1, Randomized, Open-Label, Parallel Design, Multicenter Study to Evaluate the Pharmacokinetics and Safety of Dexlansoprazole Delayed Release Capsules in Pediatric Subjects Ages 1 to 11 Years Old With Symptomatic Gastroesophageal Reflux Disease
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexlansoprazole 15 mg QD	Drug: Dexlansoprazole; Dexlansoprazole 15 mg, delayed release capsules, orally, once daily for up to 7 days.; Other Names: Kapidex TAK-390MR Dexilant
Experimental: Dexlansoprazole 30 mg QD	Drug: Dexlansoprazole; Dexlansoprazole 30 mg, delayed release capsules, orally, once daily for up to 7 days; Other Names: Kapidex TAK-390MR Dexilant
Experimental: Dexlansoprazole 60 mg QD	Drug: Dexlansoprazole; Dexlansoprazole 60 mg, delayed release capsules, orally, once daily for up to 7 days; Other Names: Kapidex TAK-390MR Dexilant

Outcome Measures

Primary Outcome Measures

1. Time to Reach the Peak Plasma Concentration (Tmax) [Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.]

   Time to reach the maximum plasma concentration (Cmax) of Dexlansoprazole, equal to time (hours) to Cmax, as observed on Day 7. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.

2. The Peak Plasma Concentration (Cmax) [Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.]

   Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.

3. Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUC(0-tlqc)) [Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.]

   AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (tlqc), calculated using the linear trapezoidal rule. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.

4. Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to 24 Hours Post-dose (AUC(0-24)) [Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.]

   AUC(0-24) is measure of area under the curve over the dosing interval (tau), where tau is the length of the dosing interval (24 hours), calculated using the linear trapezoidal rule. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.

Other Outcome Measures

1. Dose-normalized Peak Plasma Concentration (Cmax/Dose) [Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.]

   Maximum observed plasma concentration (the peak plasma concentration of a drug after administration), normalized by dose. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.

2. Dose-normalized Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUC(0-tlqc)/Dose) [Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.]

   AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (tlqc), calculated using the linear trapezoidal rule, and normalized by dose. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.

3. Dose-normalized Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to 24 Hours Post-dose (AUC(0-24)/Dose) [Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.]

   AUC(0-24) is measure of area under the curve over the dosing interval (tau), where tau is the length of the dosing interval (24 hours), calculated using the linear trapezoidal rule and normalized by dose. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must have a body weight within the 5th through 95th percentile by age, inclusive, as determined by the National Center for Health Statistics .

• Females of childbearing potential must not be nursing, must have a negative serum pregnancy test at the Screening Visit and on Day -1, and if sexually active agree to routinely use adequate contraception from Screening and throughout the duration of the study.

• Subjects who take prescription or non-prescription proton pump inhibitors (PPI), histamine receptor antagonists (except cimetidine), sucralfate, or antacids on a regular or as required basis must agree to discontinue usage on Day -1 and agree to discontinue use throughout the study.

• Must have a history of GERD symptoms for at least 2 months prior to Screening or is currently symptomatic, as determined by the investigator.

• Must be able to swallow study drug capsule or must be able to ingest study drug granules sprinkled on 1 tablespoon of applesauce.

Exclusion Criteria:

• Has evidence of current cardiovascular, central nervous system, pulmonary, endocrine disease, hepatic, hematopoietic, renal, or metabolic dysfunction, serious allergy, asthma, or allergic skin rash.

• Has a known hypersensitivity to any PPI or any component of the formulation of dexlansoprazole capsules.

• Is taking any other prescription (except birth control) or nonprescription medication (including cimetidine), vitamins, or dietary supplements within 10 days prior to Day 1, or has taken herbal over-the-counter medications within 28 days prior to Day 1.

• Has a positive test result for hepatitis B surface antigen or hepatitis C virus antibody.

• Has donated or lost greater than 10% of the total blood volume, undergone plasmapheresis, or has had a transfusion of any blood product within 90 days prior to the first dose of study drug.

• Has a history of alcohol abuse or illegal drug use or drug abuse in the past, or tests positive for alcohol or drugs of abuse at the initial Screening Visit or Day -1 or is unwilling to agree to abstain from alcohol and drugs throughout the study.

• Has used a product containing nicotine within 90 days prior to the first dose of study drug or has a positive cotinine screen at the initial Screening Visit or Day -1 or is unwilling to agree to abstain throughout the study.

• Is determined to be a Cytochrome P450 2C19 poor metabolizer (ie, genotyped homozygous non-wild-type).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Anaheim	California	United States
2		Miami Garden	Florida	United States
3		Kansas City	Missouri	United States
4		Cincinnati	Ohio	United States

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Clinical Science, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Dexilant Package Insert

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT01045096
• Other Study ID Numbers: T-P107-174; U1111-1112-1684
• First Posted: Jan 8, 2010
• Last Update Posted: Apr 5, 2012
• Last Verified: Mar 1, 2012

• Keywords provided by Takeda: Gastroesophageal Reflux; Erosive Esophagitis; Pharmacokinetics; Pediatrics; Drug Therapy
• Additional relevant MeSH terms: Gastroesophageal Reflux; Esophagitis, Peptic; Dexlansoprazole; Lansoprazole

Study Results

Participant Flow

Recruitment Details	Participants took part in this study at 3 investigative sites in the United States from 04 March 2010 to 09 February 2011.
Pre-assignment Detail	36 participants with gastroesophageal reflux disease were assigned to 1 of 3 once daily (QD) treatment regimens (15 mg, 30 mg or 60 mg dexlansoprazole) based on baseline body weight.

Arm/Group Title	Dexlansoprazole 15 mg QD	Dexlansoprazole 30 mg QD	Dexlansoprazole 60 mg QD
Arm/Group Description	Dexlansoprazole 15 mg, delayed release capsules, orally, once daily for up to 7 days.	Dexlansoprazole 30 mg, delayed release capsules, orally, once daily for up to 7 days	Dexlansoprazole 60 mg, delayed release capsules, orally, once daily for up to 7 days
Period Title: Overall Study
STARTED	12	12	12
Pharmacokinetic Set	9	11	11
COMPLETED	9	12	12
NOT COMPLETED	3	0	0

Baseline Characteristics

Arm/Group Title	Dexlansoprazole 15 mg QD	Dexlansoprazole 30 mg QD	Dexlansoprazole 60 mg QD	Total
Arm/Group Description	Dexlansoprazole 15 mg, delayed release capsules, orally, once daily for up to 7 days.	Dexlansoprazole 30 mg, delayed release capsules, orally, once daily for up to 7 days	Dexlansoprazole 60 mg, delayed release capsules, orally, once daily for up to 7 days	Total of all reporting groups
Overall Participants	12	12	12	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.3 (1.97)	7.8 (2.89)	10.2 (0.72)	7.1 (3.50)
Sex: Female, Male (Count of Participants)
Female	5 41.7%	2 16.7%	5 41.7%	12 33.3%
Male	7 58.3%	10 83.3%	7 58.3%	24 66.7%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	6 50%	8 66.7%	8 66.7%	22 61.1%
Non-Hispanic or Latino	6 50%	4 33.3%	4 33.3%	14 38.9%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	2 16.7%	0 0%	0 0%	2 5.6%
White	8 66.7%	12 100%	12 100%	32 88.9%
Multiracial	2 16.7%	0 0%	0 0%	2 5.6%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	12 100%	36 100%
Mean height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	92.5 (24.16)	131.9 (18.80)	146.3 (8.73)	123.6 (29.17)
Overall Mean Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	15.7 (5.43)	29.7 (11.86)	41.0 (8.50)	28.8 (13.64)
Number of Participants per Weight Group (participants) [Number]
8.6 kg - < 12.7 kg	5 41.7%	0 0%	0 0%	5 13.9%
12.7 kg - < 25.4 kg	7 58.3%	6 50%	0 0%	13 36.1%
≥ 25.4 kg	0 0%	6 50%	12 100%	18 50%
Mean Weight per Weight Group (kg) [Mean (Standard Deviation) ]
8.6 kg - < 12.7 kg	11.1 (1.05)	NA (NA)	NA (NA)	11.1 (1.05)
12.7 kg - < 25.4 kg	19.0 (4.76)	20.3 (3.67)	NA (NA)	19.6 (4.17)
≥ 25.4 kg	NA (NA)	39.1 (9.19)	41.0 (8.50)	40.3 (8.51)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	22.3 (20.08)	16.4 (3.09)	19.0 (2.56)	19.2 (11.73)

Outcome Measures

1. Primary Outcome

Title	Time to Reach the Peak Plasma Concentration (Tmax)
Description	Time to reach the maximum plasma concentration (Cmax) of Dexlansoprazole, equal to time (hours) to Cmax, as observed on Day 7. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.
Time Frame	Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) set included all participants with at least one estimable PK parameter for dexlansoprazole on Day 7.

Arm/Group Title	Dexlansoprazole 15 mg QD	Dexlansoprazole 30 mg QD	Dexlansoprazole 60 mg QD
Arm/Group Description	Dexlansoprazole 15 mg, delayed release capsules, orally, once daily for up to 7 days.	Dexlansoprazole 30 mg, delayed release capsules, orally, once daily for up to 7 days	Dexlansoprazole 60 mg, delayed release capsules, orally, once daily for up to 7 days
Measure Participants	9	11	11
Mean (Standard Deviation) [hours]	4.4 (3.18)	4.1 (2.34)	4.1 (3.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 15 mg QD, Dexlansoprazole 30 mg QD, Dexlansoprazole 60 mg QD
	Comments	Sample size of 12 participants per dose group, along with the intense PK sampling in each regimen was needed for characterization of the PK profile. An analysis of variance with covariates (ANCOVA) model with weight as a covariate and regimen as a factor were fitted to Tmax. Pairwise comparisons between regimens were conducted.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.809
	Comments
	Method	ANCOVA
	Comments

2. Other Pre-specified Outcome

Title	Dose-normalized Peak Plasma Concentration (Cmax/Dose)
Description	Maximum observed plasma concentration (the peak plasma concentration of a drug after administration), normalized by dose. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.
Time Frame	Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic set included all participants with at least one estimable PK parameter for dexlansoprazole on Day 7.

Arm/Group Title	Dexlansoprazole 15 mg QD	Dexlansoprazole 30 mg QD	Dexlansoprazole 60 mg QD
Arm/Group Description	Dexlansoprazole 15 mg, delayed release capsules, orally, once daily for up to 7 days.	Dexlansoprazole 30 mg, delayed release capsules, orally, once daily for up to 7 days	Dexlansoprazole 60 mg, delayed release capsules, orally, once daily for up to 7 days
Measure Participants	9	11	11
Mean (Standard Deviation) [ng/mL/mg]	37.3 (15.02)	33.5 (24.94)	16.1 (8.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 15 mg QD, Dexlansoprazole 30 mg QD
	Comments	Sample size of 12 participants per dose group, along with the intense PK sampling in each regimen was needed for characterization of the PK profile. An ANCOVA model with weight as a covariate and regimen as a factor were fitted to dose-normalized Cmax. Pairwise comparisons between regimens were conducted.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Dose Proportionality Point Estimate
	Estimated Value	1.20
	Confidence Interval	(2-Sided) 90%; 0.660 to 2.183
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 15 mg QD, Dexlansoprazole 60 mg QD
	Comments	Sample size of 12 participants per dose group, along with the intense PK sampling in each regimen was needed for characterization of the PK profile. An ANCOVA model with weight as a covariate and regimen as a factor were fitted to dose-normalized Cmax. Pairwise comparisons between regimens were conducted.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Dose proportionality Point Estimate
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 90%; 0.463 to 2.427
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 30 mg QD, Dexlansoprazole 60 mg QD
	Comments	Sample size of 12 participants per dose group, along with the intense PK sampling in each regimen was needed for characterization of the PK profile. An ANCOVA model with weight as a covariate and regimen as a factor were fitted to dose-normalized Cmax. Pairwise comparisons between regimens were conducted.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Dose Proportionality Point Estimate
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 90%; 0.493 to 1.579
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Other Pre-specified Outcome

Title	Dose-normalized Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUC(0-tlqc)/Dose)
Description	AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (tlqc), calculated using the linear trapezoidal rule, and normalized by dose. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.
Time Frame	Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic set included all participants with at least one estimable PK parameter for dexlansoprazole on Day 7.

Arm/Group Title	Dexlansoprazole 15 mg QD	Dexlansoprazole 30 mg QD	Dexlansoprazole 60 mg QD
Arm/Group Description	Dexlansoprazole 15 mg, delayed release capsules, orally, once daily for up to 7 days.	Dexlansoprazole 30 mg, delayed release capsules, orally, once daily for up to 7 days	Dexlansoprazole 60 mg, delayed release capsules, orally, once daily for up to 7 days
Measure Participants	9	11	11
Mean (Standard Deviation) [ng*hr/mL/mg]	128 (42.1)	96 (55.6)	62 (46.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 15 mg QD, Dexlansoprazole 30 mg QD
	Comments	Sample size of 12 participants per dose group, along with the intense PK sampling in each regimen was needed for characterization of the PK profile. An ANCOVA model with weight as a covariate and regimen as a factor were fitted to dose-normalized AUC[0-tlqc]. Pairwise comparisons between regimens were conducted.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Dose Proportionality Point Estimate
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 90%; 0.693 to 1.848
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 15 mg QD, Dexlansoprazole 60 mg QD
	Comments	Sample size of 12 participants per dose group, along with the intense PK sampling in each regimen was needed for characterization of the PK profile. An ANCOVA model with weight as a covariate and regimen as a factor were fitted to dose-normalized AUC[0-tlqc]. Pairwise comparisons between regimens were conducted.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Dose Proportionality Point Estimate
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 90%; 0.584 to 2.276
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 30 mg QD, Dexlansoprazole 60 mg QD
	Comments	Sample size of 12 participants per dose group, along with the intense PK sampling in each regimen was needed for characterization of the PK profile. An ANCOVA model with weight as a covariate and regimen as a factor were fitted to dose-normalized AUC[0-tlqc]. Pairwise comparisons between regimens were conducted.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Dose Proportionality Point Estimate
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 90%; 0.632 to 1.642
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Other Pre-specified Outcome

Title	Dose-normalized Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to 24 Hours Post-dose (AUC(0-24)/Dose)
Description	AUC(0-24) is measure of area under the curve over the dosing interval (tau), where tau is the length of the dosing interval (24 hours), calculated using the linear trapezoidal rule and normalized by dose. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.
Time Frame	Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic set included all participants with at least one estimable PK parameter for dexlansoprazole on Day 7.

Arm/Group Title	Dexlansoprazole 15 mg QD	Dexlansoprazole 30 mg QD	Dexlansoprazole 60 mg QD
Arm/Group Description	Dexlansoprazole 15 mg, delayed release capsules, orally, once daily for up to 7 days.	Dexlansoprazole 30 mg, delayed release capsules, orally, once daily for up to 7 days	Dexlansoprazole 60 mg, delayed release capsules, orally, once daily for up to 7 days
Measure Participants	6	8	6
Mean (Standard Deviation) [ng*hr/mL/mg]	143.2 (37.58)	87.6 (46.11)	55.5 (31.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 15 mg QD, Dexlansoprazole 30 mg QD
	Comments	Sample size of 12 participants per dose group, along with the intense PK sampling in each regimen was needed for characterization of the PK profile. An ANCOVA model with weight as a covariate and regimen as a factor were fitted to dose-normalized AUC[0-24]. Pairwise comparisons between regimens were conducted.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Dose Proportionality Point Estimate
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 90%; 0.692 to 1.636
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 15 mg QD, Dexlansoprazole 60 mg QD
	Comments	Sample size of 12 participants per dose group, along with the intense PK sampling in each regimen was needed for characterization of the PK profile. An ANCOVA model with weight as a covariate and regimen as a factor were fitted to dose-normalized AUC[0-24]. Pairwise comparisons between regimens were conducted.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Dose Proportionality Point Estimate
	Estimated Value	1.26
	Confidence Interval	(2-Sided) 90%; 0.691 to 2.314
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dexlansoprazole 30 mg QD, Dexlansoprazole 60 mg QD
	Comments	Sample size of 12 participants per dose group, along with the intense PK sampling in each regimen was needed for characterization of the PK profile. An ANCOVA model with weight as a covariate and regimen as a factor were fitted to dose-normalized AUC[0-24]. Pairwise comparisons between regimens were conducted.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Dose Proportionality Point Estimate
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.777 to 1.817
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	The Peak Plasma Concentration (Cmax)
Description	Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.
Time Frame	Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic set included all participants with at least one estimable PK parameter for dexlansoprazole on Day 7.

Arm/Group Title	Dexlansoprazole 15 mg QD	Dexlansoprazole 30 mg QD	Dexlansoprazole 60 mg QD
Arm/Group Description	Dexlansoprazole 15 mg, delayed release capsules, orally, once daily for up to 7 days.	Dexlansoprazole 30 mg, delayed release capsules, orally, once daily for up to 7 days	Dexlansoprazole 60 mg, delayed release capsules, orally, once daily for up to 7 days
Measure Participants	9	11	11
Mean (Standard Deviation) [ng/mL]	559 (225.3)	1005 (748.1)	964 (519.0)

6. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUC(0-tlqc))
Description	AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (tlqc), calculated using the linear trapezoidal rule. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.
Time Frame	Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic set included all participants with at least one estimable PK parameter for dexlansoprazole on Day 7.

Arm/Group Title	Dexlansoprazole 15 mg QD	Dexlansoprazole 30 mg QD	Dexlansoprazole 60 mg QD
Arm/Group Description	Dexlansoprazole 15 mg, delayed release capsules, orally, once daily for up to 7 days.	Dexlansoprazole 30 mg, delayed release capsules, orally, once daily for up to 7 days	Dexlansoprazole 60 mg, delayed release capsules, orally, once daily for up to 7 days
Measure Participants	9	11	11
Mean (Standard Deviation) [ng*hr/mL]	1914 (631.8)	2892 (1668.6)	3747 (2795.6)

7. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to 24 Hours Post-dose (AUC(0-24))
Description	AUC(0-24) is measure of area under the curve over the dosing interval (tau), where tau is the length of the dosing interval (24 hours), calculated using the linear trapezoidal rule. Pharmacokinetic parameters were derived using noncompartmental methods from the plasma concentrations of dexlansoprazole.
Time Frame	Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic set included all participants with at least one estimable PK parameter for dexlansoprazole on Day 7.

Arm/Group Title	Dexlansoprazole 15 mg QD	Dexlansoprazole 30 mg QD	Dexlansoprazole 60 mg QD
Arm/Group Description	Dexlansoprazole 15 mg, delayed release capsules, orally, once daily for up to 7 days.	Dexlansoprazole 30 mg, delayed release capsules, orally, once daily for up to 7 days	Dexlansoprazole 60 mg, delayed release capsules, orally, once daily for up to 7 days
Measure Participants	6	8	6
Mean (Standard Deviation) [ng*hr/mL]	2149 (563.7)	2628 (1383.2)	3330 (1883.3)

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events with an onset that occurred after receiving study drug and within 30 days after the last dose of study drug.
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 15 mg QD		Dexlansoprazole 30 mg QD		Dexlansoprazole 60 mg QD
Arm/Group Description	Dexlansoprazole 15 mg, delayed release capsules, orally, once daily for up to 7 days.		Dexlansoprazole 30 mg, delayed release capsules, orally, once daily for up to 7 days		Dexlansoprazole 60 mg, delayed release capsules, orally, once daily for up to 7 days
All Cause Mortality
	Dexlansoprazole 15 mg QD		Dexlansoprazole 30 mg QD		Dexlansoprazole 60 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Dexlansoprazole 15 mg QD		Dexlansoprazole 30 mg QD		Dexlansoprazole 60 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Gastrointestinal disorders
Vomiting	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Other (Not Including Serious) Adverse Events
	Dexlansoprazole 15 mg QD		Dexlansoprazole 30 mg QD		Dexlansoprazole 60 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/12 (41.7%)		2/12 (16.7%)		3/12 (25%)
Gastrointestinal disorders
Abdominal pain	1/12 (8.3%)		1/12 (8.3%)		1/12 (8.3%)
Diarrhoea	0/12 (0%)		2/12 (16.7%)		1/12 (8.3%)
Vomiting	1/12 (8.3%)		1/12 (8.3%)		1/12 (8.3%)
Nausea	0/12 (0%)		0/12 (0%)		2/12 (16.7%)
Haematochezia	1/12 (8.3%)		0/12 (0%)		0/12 (0%)
General disorders
Irritability	1/12 (8.3%)		0/12 (0%)		0/12 (0%)
Infections and infestations
Herpes zoster	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Injury, poisoning and procedural complications
Arthropod bite	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Metabolism and nutrition disorders
Decreased appetite	1/12 (8.3%)		0/12 (0%)		0/12 (0%)
Nervous system disorders
Dizziness	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Headache	1/12 (8.3%)		0/12 (0%)		0/12 (0%)
Presyncope	0/12 (0%)		0/12 (0%)		1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Sinus congestion	1/12 (8.3%)		0/12 (0%)		0/12 (0%)
Skin and subcutaneous tissue disorders
Rash	1/12 (8.3%)		0/12 (0%)		0/12 (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 therefrom or any data, information or materials obtained or generated in the performance of it's obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.