Pharmacokinetic and Safety of Dexlansoprazole in Adolescents With Gastroesophageal Reflux Disease

Study Overview
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Brief Summary
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The purpose of this study is to asses the pharmacokinetics and safety of dexlansoprazole modified release (MR), once daily (QD), in adolescent subjects (age 12-17 years old) with Symptomatic Gastroesophageal Reflux Disease.

Detailed Description
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Gastroesophageal reflux disease is a condition of multifactorial etiology resulting in the reflux of gastric contents into the esophagus through the lower esophageal sphincter. The prevalence of Gastroesophageal reflux disease in the pediatric population is becoming increasingly recognized and documented. It is a chronic disease that can persist through adulthood with symptoms in older children and adolescents being similar to those seen in adults. The prevalence of gastroesophageal reflux disease increases with age, from 2.5% of children between the ages of 3 and 9 years, to 8.5% of those between the ages of 10 and 17 years. Younger children generally present with extra-esophageal manifestations, regurgitation, and epigastric pain, while older children and adolescents typically present with adult-type gastroesophageal reflux disease symptoms of heartburn and regurgitation. Treatment for gastroesophageal reflux disease is aimed at alleviating symptoms and healing the esophageal inflammation. This study evaluated the pharmacokinetics and safety of dexlansoprazole MR in the pediatric population (ages 12-17) and determined if the pharmacokinetic profile is similar to that in adults given the same dose.

Official Title
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A Phase 1, Randomized, Open-Label, Parallel Group, Multicenter Study to Evaluate the Pharmacokinetics and Safety of Dexlansoprazole Modified Release Capsules (30 mg and 60 mg) in Adolescents With Symptomatic Gastroesophageal Reflux Disease

Conditions
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Gastroesophageal Reflux

Intervention / Treatment
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* Drug: Dexlansoprazole MR
* Drug: Dexlansoprazole MR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight is greater than or equal to 30 kg. Females of childbearing potential who are sexually active must agree to use an acceptable form of contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study. Must have an estimated creatinine clearance greater than or equal to 80 mL/minute as determined from the Cockcroft-Gault formula. Participants who take prescription or non-prescription proton pump inhibitors, histamine receptor antagonists (except cimetidine), sucralfate, or antacids on a regular or as required basis must agree to discontinue usage throughout the study. Must have a history of gastroesophageal reflux disease symptoms, as documented by a physician, for at least 2 months prior to Screening or is currently symptomatic. 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, hepatic, hematopoietic, renal, or metabolic dysfunction, serious allergy, asthma, or allergic skin rash. Has any finding in his/her medical history, physical examination, or safety clinical laboratory tests giving reasonable suspicion of a disease that might interfere with the conduct of the trial or that would contraindicate taking dexlansoprazole MR or a similar drug in the same class. Has a known hypersensitivity to any proton pump inhibitors or any component of the formulation of dexlansoprazole MR (see most current version of the Investigator Brochures). Has a history of malignant disease. Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody. Has a known history of infection with the human immunodeficiency virus. Has donated or lost greater than or equal to 300 mL blood volume, undergone plasmapheresis, or has had a transfusion of any blood product within 90 days prior to the first dose of study drug. Is required to take or intends to continue taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication. Has consumed grapefruit or grapefruit juice within 14 days prior to the first dose of study drug or is unwilling to agree to abstain from grapefruit or grapefruit juice while participating in the study. 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. Has participated in a study of an investigational agent (including dosing or follow up) within 30 days prior to first dose of study drug. Has an initial Screening Visit or Day -1 laboratory value that the principal investigator considers to be clinically significant. Participant is determined to be a CYP2C19 isozyme poor metabolizer (ie, genotyped homozygous non-wild type). Is unlikely to comply with the protocol or is unsuitable for any other reason per the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) Pharmacokinetic Parameter | Tmax: Time to reach the Maximum Plasma Concentration (Cmax), equal to time (hours) to Cmax, as observed on Day 7. | After 7 days of dosing. | 
| Cmax: Maximum Observed Plasma Concentration Pharmacokinetic Parameter. | Maximum Observed Plasma Concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. | After 7 days of dosing. | 
| AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration Pharmacokinetic Parameter. | Area Under the Plasma Concentration Versus Time Curve (AUC(0-tlqc)) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]). | After 7 days of dosing. | 
| AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose Pharmacokinetic Parameter. | AUC(0-24) is measure of Area Under the Curve over the dosing interval (tau) (AUC(0-tau]), where tau is the length of the dosing interval - 24 hours in this study). | After 7 days of dosing. | 
| Terminal Phase Elimination Half-life (T1/2) Pharmacokinetic Parameter. | Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. | After 7 days of dosing. | 
| Oral Clearance (CL/F) Pharmacokinetic Parameter. | CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC(0-24), expressed in L/hr. | After 7 days of dosing. | 
| Terminal Elimination Rate Constant (λz) Pharmacokinetic Parameter. | Terminal elimination rate constant (λz) is the rate at which drugs are eliminated from the body. | After 7 days of dosing. | 
| Apparent Volume of Distribution (Vz/F) Pharmacokinetic Parameter. | Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as CL/F divided by λz. | After 7 days of dosing. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophageal Reflux, Gastro-Esophageal Reflux, Gastroesophageal Reflux Disease, GERD, Regurgitation, Gastric, Heartburn, Drug Therapy, Adolescent