A Study to Evaluate the Efficacy and Safety of Vonoprazan Compared to Placebo in Participants With Symptomatic Non-Erosive Gastroesophageal Reflux Disease

NCT ID: NCT04799158

Last Updated: 2023-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 458 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-25
• Study Completion Date: 2022-01-17

Brief Summary

The primary objectives of this study are to assess the efficacy of vonoprazan (10 mg, 20 mg, and 40 mg On-Demand) compared to placebo (On-Demand) in relief of episodic heartburn over 6 weeks in participants with symptomatic non-erosive gastroesophageal reflux disease (NERD), and to assess the safety of vonoprazan (10 mg, 20 mg, and 40 mg On-Demand) compared to placebo (On-Demand) in participants with symptomatic NERD.

Conditions

Non-Erosive Gastro-Esophageal Reflux Disease; Heartburn

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Run-In Period

Participants will receive vonoprazan 20 mg once daily for up to 4 weeks.

Group Type: EXPERIMENTAL

Vonoprazan

Intervention Type: DRUG

Orally via capsules

Vonoprazan 10 mg: On-Demand Treatment Period

Participants who have stable disease (no heartburn on the last 7 days of the Run-In Period) will take vonoprazan 10 mg when heartburn occurs during the 6 week On-Demand Treatment Period. Participants can take no more than one dose in a 24 hour period.

Group Type: EXPERIMENTAL

Vonoprazan

Intervention Type: DRUG

Orally via capsules

Vonoprazan 20 mg: On-Demand Treatment Period

Participants who have stable disease (no heartburn on the last 7 days of the Run-In Period) will take vonoprazan 20 mg when heartburn occurs during the 6 week On-Demand Treatment Period. Participants can take no more than one dose in a 24 hour period.

Group Type: EXPERIMENTAL

Vonoprazan

Intervention Type: DRUG

Orally via capsules

Vonoprazan 40 mg: On-Demand Treatment Period

Participants who have stable disease (no heartburn on the last 7 days of the Run-In Period) will take vonoprazan 40 mg when heartburn occurs during the 6 week On-Demand Treatment Period. Participants can take no more than one dose in a 24 hour period.

Group Type: EXPERIMENTAL

Vonoprazan

Intervention Type: DRUG

Orally via capsules

Placebo: On-Demand Treatment Period

Participants who have stable disease (no heartburn on the last 7 days of the Run-In Period) will take a placebo when heartburn occurs during the 6 week On-Demand Treatment Period. Participants can take no more than one dose in a 24 hour period.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Orally via capsules

Interventions

Vonoprazan

Orally via capsules

Intervention Type: DRUG

Placebo

Orally via capsules

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. The participant is ≥18 years of age at the time of informed consent signing.

2. In the opinion of the investigator or sub investigators, the participant is capable of understanding and complying with protocol requirements.

3. The participant signs and dates a written informed consent form (ICF) and any required privacy authorization prior to the initiation of any study procedures. The participant is informed of the full nature and purpose of the study, including possible risks and side effects. The participant has the ability to cooperate with the investigator. Ample time and opportunity should be given to read and understand verbal and/or written instructions.

4. The participant identified their main symptom as heartburn, a burning sensation in the retrosternal area (behind the breastbone).

5. History of episodes of heartburn for 6 months or longer prior to screening.

6. Heartburn reported on 4 or more days during any 7 consecutive days in the Screening Period as recorded in the electronic diary.

7. A female participant of childbearing potential who is or may be sexually active with a non sterilized male partner agrees to routinely use adequate contraception from the signing of informed consent until 4 weeks after the last dose of study drug.

1. The participant completes the Run-In Period, during which the participant was at least 80% compliant with open-label study drug.

2. The participant has stable disease, ie, no heartburn the last 7 days of the Run-In Period.

4. Participant completes at least 80% of diary entries during Run-In Period, including 80% of diary entries over the last 7 days.

2. The participant has active irritable bowel syndrome (IBS) or had a flare of IBS requiring therapy within the prior 6 months.

3. The participant has a history of or is suspected of having functional heartburn diagnosed by the Rome IV criteria.

4. The participant has a history of or is suspected of having functional dyspepsia diagnosed by the Rome IV criteria.

5. The participant has endoscopic Barrett's esophagus (>1 cm of columnar-lined esophagus) and/or definite dysplastic changes in the esophagus.

6. The participant has any other clinically significant condition affecting the esophagus, including eosinophilic esophagitis; esophageal varices; viral or fungal infection; esophageal stricture; a history of radiation therapy, radiofrequency ablation, endoscopic mucosal resection, or cryotherapy to the esophagus; or any history of caustic or physiochemical trauma (including sclerotherapy or esophageal variceal band ligation). However, participants diagnosed with Schatzki's ring (mucosal tissue ring around lower esophageal sphincter) or hiatal hernia are eligible to participate.

7. The participant has scleroderma (systemic sclerosis).

8. The participant has a history of surgery or endoscopic treatment affecting gastroesophageal reflux, including fundoplication and dilation for esophageal stricture (except Schatzki's ring) or a history of gastric or duodenal surgery (except endoscopic removal of benign polyps).

9. The participant has an active gastric or duodenal ulcer within 4 weeks before the first dose of study drug.

10. Use of prescription or non-prescription proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) throughout the study.

11. The participant has received vonoprazan in a clinical trial at any time or any other investigational compound (including those in post-marketing studies) within 30 days prior to the start of the Screening Period. A participant who has been screen failed from another clinical study and who has not been dosed may be considered for enrollment in this study.

12. The participant is a study site employee, 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, spouse, parent, child, sibling) or who may have consented under duress.

13. The participant has cutaneous lupus erythematosus or systemic lupus erythematosus.

14. The participant has had clinically significant upper or lower gastrointestinal bleeding within 4 weeks prior to screening.

15. The participant has Zollinger-Ellison syndrome or other gastric acid hypersecretory conditions.

16. 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, titanium oxide, or red or yellow ferric oxide). Skin testing may be performed according to local standard practice to confirm hypersensitivity.

17. The participant has a history of alcohol abuse, illegal drug use, drug addiction, or regularly consumes >21 units of alcohol (1 unit = 12 oz/300 mL beer, 1.5 oz/25 mL hard liquor/spirits, or 5 oz/100 mL wine) per week based on self-report within the 12 months prior to screening. Participants must have a negative urine drug screen for cannabinoids/ tetrahydrocannabinol and nonprescribed medications at screening. Participants taking prescription drugs (except prescription cannabinoids/tetrahydrocannabinol) will be allowed.

18. The participant is taking any excluded medications or treatments listed in the protocol.

19. If female, the participant is pregnant, lactating, or intending to become pregnant before, during, or within 4 weeks after participating in this study, or intending to donate ova during such time period.

20. The participant has a history or clinical manifestations of significant central nervous system, cardiovascular, pulmonary, hepatic, renal, metabolic, other gastrointestinal, urological, endocrine, or hematological disease that, in the opinion of the investigator, would confound the study results or compromise participant safety.

21. 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 Visit.

22. The participant has a history of malignancy or has been treated for malignancy within 5 years prior to the start of the Screening Period (Visit 1). (The participant may be included in the study if he/she has recovered from cutaneous basal cell carcinoma or cervical carcinoma in situ).

23. The participant has acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection, or tests positive for the hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or HCV ribonucleic acid (HCV-RNA). However, participants who test positive for HCV antibody but negative for HCV-RNA are permitted to participate.

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

1. Creatinine levels: >2 mg/dL (>177 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Phathom Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Phathom Pharmaceuticals

Locations

Pinnacle Research Group

Anniston, Alabama, United States

North Alabama Research Center LLC

Athens, Alabama, United States

Medical Affiliated Research Center Inc

Huntsville, Alabama, United States

Elite Clinical Studies, LLC

Phoenix, Arizona, United States

Del Sol Research Management - Clinedge

Tucson, Arizona, United States

Preferred Research Partners - ClinEdge

Little Rock, Arkansas, United States

Arkansas Gastroenterology

North Little Rock, Arkansas, United States

GW Research, Inc

Chula Vista, California, United States

eStudySite

Chula Vista, California, United States

Paragon Rx Clinical

Garden Grove, California, United States

OM Research LLC

Lancaster, California, United States

Medical Associates Research Group, Inc.

San Diego, California, United States

Paragon Rx Clinical, Inc.

Santa Ana, California, United States

Western States Clinical Research Inc

Wheat Ridge, Colorado, United States

Imagine Research of Palm Beach County

Boynton Beach, Florida, United States

Riverside Clinical Research

Edgewater, Florida, United States

Nature Coast Clinical Research

Inverness, Florida, United States

ENCORE Borland-Groover Clinical Research

Jacksonville, Florida, United States

ClinCloud

Maitland, Florida, United States

G. Medical Center

Orlando, Florida, United States

Advanced Gastroenterology Associates, LLC

Palm Harbor, Florida, United States

Clinical Research Center of Florida

Pompano Beach, Florida, United States

Precision Clinical Research, LLC

Sunrise, Florida, United States

Guardian Angel Research Center

Tampa, Florida, United States

Florida Medical Clinic, LLC Clinical Research Division

Zephyrhills, Florida, United States

IACT Health

Columbus, Georgia, United States

In Quest Medical Research

Suwanee, Georgia, United States

Treasure Valley Medical Research

Boise, Idaho, United States

Care Access

Chicago, Illinois, United States

Iowa Digestive Disease Center

Clive, Iowa, United States

Clinical Trials Management LLC

Covington, Louisiana, United States

Legacy Clinical Solutions: Tandem Clinical Research, LLC

Marrero, Louisiana, United States

Clinical Trials Management LLC

Metairie, Louisiana, United States

Investigative Clinical Research

Annapolis, Maryland, United States

Gastroenterology Associates of Western Michigan, PLC

Wyoming, Michigan, United States

GI Associates and Endoscopy Center

Flowood, Mississippi, United States

Quality Clinical Research

Omaha, Nebraska, United States

Sierra Clinical Research - ClinEdge

Las Vegas, Nevada, United States

Site 2

Las Vegas, Nevada, United States

Site 1

Las Vegas, Nevada, United States

Advanced Research Institute

Reno, Nevada, United States

Drug Trials America

Hartsdale, New York, United States

Javara Inc

Charlotte, North Carolina, United States

Medication Management LLC

Greensboro, North Carolina, United States

Carolina Research

Greenville, North Carolina, United States

Peters Medical Research, LLC

High Point, North Carolina, United States

Trial Management Associates LLC

Wilmington, North Carolina, United States

Remington Davis Inc

Columbus, Ohio, United States

Frontier Clinical Research, LLC

Uniontown, Pennsylvania, United States

Coastal Carolina Research Center

North Charleston, South Carolina, United States

Rapid City Medical Center LLP

Rapid City, South Dakota, United States

Clinical Research Associates Inc

Nashville, Tennessee, United States

Inquest Clinical Research

Baytown, Texas, United States

Family Medicine Associates of Texas

Carrollton, Texas, United States

Synergy Group US, LLC

Houston, Texas, United States

Biopharma Informatic, LLC

Houston, Texas, United States

Rio Grande Gastroenterology

McAllen, Texas, United States

Quality Research Inc

San Antonio, Texas, United States

Gastroenterology Research of San Antonio (GERSA)

San Antonio, Texas, United States

Sherman Clinical Research

Sherman, Texas, United States

Advanced Research Institute

Ogden, Utah, United States

Advanced Research Institute

Sandy City, Utah, United States

Virginia Gastroenterology Institute

Suffolk, Virginia, United States

Countries

United States

References

Fass R, Vaezi M, Sharma P, Yadlapati R, Hunt B, Harris T, Smith N, Leifke E, Armstrong D. Randomised clinical trial: Efficacy and safety of on-demand vonoprazan versus placebo for non-erosive reflux disease. Aliment Pharmacol Ther. 2023 Nov;58(10):1016-1027. doi: 10.1111/apt.17728. Epub 2023 Sep 26.

Reference Type: DERIVED

PMID: 37750406 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

NERD-201

Identifier Type: -

Identifier Source: org_study_id