A Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of Vonoprazan in Adolescents With Symptomatic Gastroesophageal Reflux Disease

Gastroesophageal Reflux 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 Adolescents With Symptomatic Gastroesophageal Reflux Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05343364
• Other study ID #: VPED-102
• Status: Completed
• Phase: Phase 1
• Start date: May 9, 2022
• Est. completion date: June 13, 2023

Study information

• Verified date: December 2023
• Source: Phathom Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the pharmacokinetic profile of vonoprazan in adolescent participants with symptomatic gastroesophageal reflux disease (GERD).

Description:

This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 13, 2023
• Est. primary completion date: May 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

Inclusion Criteria:

• The participant is 12 to 17 years of age, inclusive, at the time of informed consent signing and throughout study participation.

• 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 has a medical history of 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.

• The participant has symptoms of at least moderate heartburn severity based on the GERD Symptom Assessment-Investigator scale performed at screening.

• The participant must be able to swallow study drug.

• Parent or legal guardian (ie, legally authorized representative [LAR]) is willing and able to complete the informed consent process and comply with study procedures and visit schedule. The participant will provide assent as applicable.

• A female participant of childbearing potential who is or may be sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from the signing of informed consent until 2 weeks after the last dose of study drug.

Exclusion Criteria:

• The participant has used prescription or non-prescription proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) within 7 days prior to randomization or requires their 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 who 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 such as fundoplication.

• The participant has any abnormal laboratory test values at the start of the Screening Period.

• The participant has a history of hypersensitivity or allergies to vonoprazan (including the formulation excipients: D-mannitol, microcrystalline cellulose, hydroxypropyl cellulose, fumaric acid, croscarmellose sodium, magnesium stearate, hypromellose, macrogol 8000, and titanium oxide, or red or yellow ferric oxide).

• The participant used any prescription (excluding hormonal birth control) or over-the-counter medications (including CYP3A4 inducers), including herbal or nutritional supplements, within 14 days (or 5 half-lives) before the first dose of study drug or throughout the study. NOTE: Acid suppressive therapies are considered separately under exclusion criteria 1 and 2.

• 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.

• Female participant has a positive pregnancy test at screening or check in or is lactating.

• The participant has a positive urine drug or alcohol result at screening.

• The participant has positive results at screening for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus.

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

Related Conditions & MeSH terms

• Esophagitis, Peptic
• Gastroesophageal Reflux

Intervention

Drug:
• Vonoprazan
Oral Tablet

Locations

Country	Name	City	State
United States	Advanced Research Center - Elligo	Anaheim	California
United States	ARC Clinical Research at Four Points	Austin	Texas
United States	Boston Specialists	Boston	Massachusetts
United States	PriMED Clinical Research	Dayton	Ohio
United States	Pediatric Gastro	El Paso	Texas
United States	Preferred Research Partners, Inc.	Little Rock	Arkansas
United States	Legacy Clinical Solutions: Tandem Clinical Research, LLC	Marrero	Louisiana
United States	University of South Alabama (USA) Physicians Group	Mobile	Alabama
United States	Infinite Clinical Trials	Morrow	Georgia
United States	University of Rochester Medical Center	Rochester	New York

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 Observed Drug Concentration at Steady State (Cmax-ss) of Vonoprazan	Plasma pharmacokinetic (PK) parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time.	Blood samples were collected predose, once between 0.5 and 2 hours, and once between 2.5 and 4 hours post-dose on Days 7 and 14
Primary	Area Under the Plasma Concentration-time Curve During the Dosing Interval t (AUCt) of Vonoprazan	PK parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time.	Blood samples were collected predose, once between 0.5 and 2 hours, and once between 2.5 and 4 hours post-dose on Days 7 and 14
Primary	Apparent Oral Clearance (CL) of Vonoprazan	PK parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time.	Blood samples were collected predose, once between 0.5 and 2 hours, and once between 2.5 and 4 hours post-dose on Days 7 and 14
Primary	Central Volume of Distribution (Vc) of Vonoprazan	PK parameters were estimated using a non-linear mixed effects model and were determined from the concentration-time data for all evaluable participants. Actual sampling times, rather than scheduled or nominal sampling times, were used in all computations using sampling time.	Blood samples were collected predose, once between 0.5 and 2 hours, and once between 2.5 and 4 hours post-dose on Days 7 and 14
Secondary	Number of Participants Experiencing Adverse Events (AEs)	AE: any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug.; Treatment-emergent adverse event (TEAE): any AE that occurred after the first dose of study drug or at baseline that worsens in either intensity or frequency after the first dose of study drug.; Serious AE: any AE for which the following occurred: death, was life threatening, hopsitalization or prolongation of hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or the AE was deemed an important medical event.; Related AE: any AE that follows a reasonable temporal sequence from administration of study drug, or for which possible involvement of the drug cannot be ruled out, although factors other than the study drug may also be responsible.; Clinically significant changes from baseline in laboratory test values, (hematology, serum chemistry and urinalysis), electrocardiograms and vital signs were reported as AEs.	Up to Day 28