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

Gastroesophageal Reflux Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06106022
• Other study ID #: VPED-103
• Secondary ID: 2022-003228-42
• Status: Completed
• Phase: Phase 1
• Start date: November 1, 2023
• Est. completion date: April 29, 2024

Study information

• Verified date: May 2024
• Source: Phathom Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: April 29, 2024
• Est. primary completion date: April 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 11 Years

Eligibility

Inclusion Criteria:

1. The participant has a body weight within the 5th through 95th percentile by age, inclusive, as determined by the National Center for Health Statistics.

2. 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).

3. The participant has at least one moderate GERD symptom based on the GERD Symptom Assessment-Investigator scale performed at screening.

4. The participant must be able to swallow study drug tablet with water.

5. 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.

6. Female participants who have experienced menarche must have a negative pregnancy test and will be counseled on pregnancy avoidance.

Exclusion Criteria:

1. 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.

2. The participant has used sucralfate, or antacids within 1 day prior to randomization or requires their use during the Treatment Period.

3. 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.

4. 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.

5. The participant has received any investigational compound (including vonoprazan) within 30 days prior to the start of the Screening Period.

6. 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.

7. 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.

8. The participant has undergone prior gastrointestinal surgeries.

9. The participant has any abnormal laboratory test values that are considered clinically significant in the opinion of the investigator during the Screening Period.

10. 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).

11. 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.

12. 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.

13. The participant has positive results at screening for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus (HCV).

14. The participant has severe renal impairment (estimated glomerular filtration rate < 30 mL/min).

15. The participant has moderate to severe hepatic impairment (Child-Pugh Class B and Child-Pugh Class C).

16. The participant has any of the following abnormal laboratory test values at the start of the Screening Period:

1. Creatinine levels: >1 mg/dL (>88 µmol/L ).

2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × the upper limit of normal (ULN) or total bilirubin >2 × ULN (except participants with Gilbert Syndrome).

17. In the opinion of the investigator, the participant is not suitable for entry into the study.

Related Conditions & MeSH terms

• Esophagitis, Peptic
• Gastroesophageal Reflux
• Gastroesophageal Reflux Disease

Intervention

Drug:
• Vonoprazan
Administered orally

Locations

Country	Name	City	State
United States	Children's Center for Digestive Health Care, LLC	Atlanta	Georgia
United States	Advantage Clinical Trials	Bronx	New York
United States	PriMED Clinical Research	Dayton	Ohio
United States	Maspons Pediatric Gastro	El Paso	Texas
United States	Stryde Research - NxT Step Pediatrics	Frisco	Texas
United States	Cyn3rgy Research	Gresham	Oregon
United States	Med Research Associates, Inc	Hollywood	Florida
United States	Riley Hospital for Children at IU Health	Indianapolis	Indiana
United States	Preferred Research Partners, Inc.	Little Rock	Arkansas
United States	Tandem Clinical Research GI, LLC	Marrero	Louisiana
United States	Strada Patient Care Center	Mobile	Alabama
United States	Avanza Medical Research Center	Pensacola	Florida
United States	International Center for Research	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Phathom Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Drug Concentration at Steady-state (Cmax,ss) of Vonoprazan		Days 7 and 14
Primary	Area Under the Drug Concentration-time Curve (AUCt) of Vonoprazan		Days 7 and 14
Primary	Apparent Plasma Clearance (CL/F) of Vonoprazan		Days 7 and 14
Primary	Apparent Volume of Distribution (Vz/F) of Vonoprazan		Days 7 and 14