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

Study Overview
=================
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.

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.

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

Conditions
-----------------
Gastroesophageal Reflux

Intervention / Treatment
-----------------
* Drug: Dexlansoprazole
* Drug: Dexlansoprazole
* Drug: Dexlansoprazole


Participation Criteria
=================
Eligibility Criteria
-----------------
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).

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 11 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexlansoprazole 15 mg QD<br> | Drug: Dexlansoprazole<br>* Dexlansoprazole 15 mg, delayed release capsules, orally, once daily for up to 7 days.<br>* Other names: Dexilant;|
| Experimental: Dexlansoprazole 30 mg QD<br> | Drug: Dexlansoprazole<br>* Dexlansoprazole 30 mg, delayed release capsules, orally, once daily for up to 7 days<br>* Other names: Dexilant;|
| Experimental: Dexlansoprazole 60 mg QD<br> | Drug: Dexlansoprazole<br>* Dexlansoprazole 60 mg, delayed release capsules, orally, once daily for up to 7 days<br>* Other names: Dexilant;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach the Peak Plasma Concentration (Tmax) | 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. | Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules. | 
| The Peak Plasma Concentration (Cmax) | 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. | Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules. | 
| Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUC(0-tlqc)) | 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. | Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules. | 
| Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to 24 Hours Post-dose (AUC(0-24)) | 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. | Day 7 after 7 days of dosing with dexlansoprazole delayed release capsules. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gastroesophageal Reflux, Erosive Esophagitis, Pharmacokinetics, Pediatrics, Drug Therapy