A Study to Evaluate Vonoprazan in Children Who Have Symptomatic Gastroesophageal Reflux Disease

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to evaluate the pharmacokinetic (PK) profile of vonoprazan (10 or 20 mg once daily [QD]) in children ≥ 6 to < 12 years of age who have symptomatic Gastroesophageal Reflux Disease (GERD).

Official Title
-----------------
A Phase 1, Randomized, Parallel-group, Open-label, Multicenter Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of Vonoprazan (10 or 20 mg Once Daily) in Children Aged ≥ 6 to < 12 Years Who Have Symptomatic Gastroesophageal Reflux Disease

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

Intervention / Treatment
-----------------
* Drug: Vonoprazan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The participant has a body weight within the 5th through 95th percentile by age, inclusive, as determined by the National Center for Health Statistics. The participant must have a diagnosis of GERD prior to randomization and medical history of signs or symptoms of GERD for at least 3 months prior to screening, based on physical examination, current symptoms (eg, heartburn), or diagnostic tests (eg, pH or endoscopy). Notes in the medical records and/or other source documents, such as prior endoscopies, can be used to support the diagnosis and will be recorded in the electronic case report form (eCRF). The participant has at least one moderate GERD symptom based on the GERD Symptom Assessment-Investigator scale performed at screening. The participant must be able to swallow study drug tablet with water. Parent or legal guardian (ie, legally authorized representative [LAR]) is willing and able to complete the informed consent process and participants are able to comply with study procedures and visit schedule. Female participants who have experienced menarche must have a negative pregnancy test and will be counseled on pregnancy avoidance. Exclusion Criteria: The participant has used prescription or non-prescription proton pump inhibitors (PPIs) or histamine-2 receptor antagonist (H2RAs) within 7 days prior to randomization or requires use during the Treatment Period. The participant has used sucralfate, or antacids within 1 day prior to randomization or requires their use during the Treatment Period. The participant has received other agents affecting digestive organs, including muscarinic antagonists (eg, hyoscyamine), prokinetics, oral anticholinergic agents, prostaglandins, bismuth from 30 days prior to Day 1 or requires their use during the course of the study. The participant has received atazanavir sulfate or rilpivirine hydrochloride from 5 days prior to Day 1 or requires their use during the course of the study. The participant has received any investigational compound (including vonoprazan) within 30 days prior to the start of the Screening Period. The participant is an immediate family member or is in a dependent relationship with a study site employee who is involved in the conduct of this study (eg, child, sibling) or participant may have consented under duress. The participant requires hospitalization or has surgery scheduled during the course of the study or has undergone major surgical procedures within 30 days prior to the Screening Period. The participant has undergone prior gastrointestinal surgeries. The participant has any abnormal laboratory test values that are considered clinically significant in the opinion of the investigator during the Screening Period. The participant has a history of hypersensitivity or allergies to vonoprazan (including the formulation excipients: D-mannitol, microcrystalline cellulose, hydroxypropylcellulose, fumaric acid, ascorbic acid, croscarmellose sodium, magnesium stearate, hypromellose, macrogol 8000, and titanium dioxide, or red or yellow ferric oxide). The participant has used any prescription or over-the-counter medications (including herbal or nutritional supplements), other than those already excluded in criteria 1 to 5 above, within 14 days before the first dose of study drug or throughout the study. That is, unless the medication(s) is permitted by the sponsor following a review of available data which confirms concomitant administration of the medication is unlikely to affect either the safety of the participant or the pharmacokinetics of vonoprazan. The participant has consumed grapefruit or grapefruit juice, Seville orange or Seville orange-containing products (eg, marmalade), or other food products that may be CYP3A4 inhibitors (eg, vegetables from the mustard green family [kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard] and charbroiled meats) within 7 days (or 5 half-lives) before the first dose of study drug or throughout the study. The participant has positive results at screening for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus (HCV). The participant has severe renal impairment (estimated glomerular filtration rate < 30 mL/min). The participant has moderate to severe hepatic impairment (Child-Pugh Class B and Child-Pugh Class C). The participant has any of the following abnormal laboratory test values at the start of the Screening Period: Creatinine levels: >1 mg/dL (>88 μmol/L ). Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × the upper limit of normal (ULN) or total bilirubin >2 × ULN (except participants with Gilbert Syndrome). In the opinion of the investigator, the participant is not suitable for entry into the study.

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 11 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vonoprazan 10mg<br>Participants will receive vonoprazan 10mg QD for 14 days. | Drug: Vonoprazan<br>* Administered orally<br>|
| Experimental: Vonoprazan 20mg<br>Participants will receive vonoprazan 20mg QD for 14 days. | Drug: Vonoprazan<br>* Administered orally<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Drug Concentration at Steady-state (Cmax,ss) of Vonoprazan |  | Days 7 and 14 | 
| Area Under the Drug Concentration-time Curve (AUCτ) of Vonoprazan |  | Days 7 and 14 | 
| Apparent Plasma Clearance (CL/F) of Vonoprazan |  | Days 7 and 14 | 
| Apparent Volume of Distribution (Vz/F) of Vonoprazan |  | Days 7 and 14 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gastrology, Vonoprazan, Gastroesophageal Reflux Disease, Children, GERD, Pharmacokinetics