A Study to Evaluate the Efficacy and Safety of Vonoprazan Compared to Placebo for Relief of Heartburn in Participants With Symptomatic Non-Erosive Gastroesophageal Reflux Disease (NERD)

NCT ID: NCT05195528

Last Updated: 2023-12-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

776 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-01-17

Study Completion Date

2023-05-17

Brief Summary

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The primary objectives of this study are to assess the efficacy of vonoprazan (10 mg and 20 mg once daily \[QD\]) compared to placebo (QD) in relief of heartburn over 4 weeks in participants with NERD.

Detailed Description

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Conditions

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Non-Erosive Gastro-Esophageal Reflux Disease Heartburn

Keywords

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NERD Vonoprazan

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Vonoprazan 10 mg

Participants will be administered vonoprazan at a dose of 10 mg QD in the 4 week Placebo-controlled Treatment Period. Participants randomized to vonoprazan 10 mg in the Placebo-controlled Treatment Period will continue to take the same dose in the 20 week Extension Period.

Group Type EXPERIMENTAL

Vonoprazan

Intervention Type DRUG

Orally via capsule

Vonoprazan 20 mg

Participants will be administered vonoprazan at a dose of 20 mg QD in the 4 week Placebo-controlled Treatment Period. Participants randomized to vonoprazan 20 mg in the Placebo-controlled Treatment Period will continue to take the same dose in the 20 week Extension Period.

Group Type EXPERIMENTAL

Vonoprazan

Intervention Type DRUG

Orally via capsule

Placebo

Participants will be administered the placebo QD in the 4 week Placebo-controlled Treatment Period. Participants randomized to placebo in the Placebo-controlled Treatment Period will be re-randomized to receive either vonoprazan 10 mg QD or vonoprazan 20 mg QD in the 20 week Extension Period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Orally via capsule

Interventions

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Vonoprazan

Orally via capsule

Intervention Type DRUG

Placebo

Orally via capsule

Intervention Type DRUG

Eligibility Criteria

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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 subinvestigators, the participant is capable of understanding and complying with protocol requirements, including compliance with the electronic diary.
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 subject has a diagnosis of symptomatic gastroesophageal reflux disease (GERD) with heartburn as the subject's predominant symptom prior to the Screening Period, as documented in the subject's medical record.
5. History of onset of heartburn at least 6 months prior to the Screening Period.
6. Heartburn reported on 4 or more days during any consecutive 7-day period of 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.

Exclusion Criteria

1. The participant has endoscopically confirmed erosive esophagitis (EE) during the Screening Period. Endoscopy conducted during the Screening Period should be performed after participants meet Inclusion Criterion 6 (i.e., heartburn reported on 4 or more days during any consecutive 7-day period of the Screening Period as recorded in the electronic diary).
2. The participant has active irritable bowel syndrome (IBS) or has 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 upper gastrointestinal disorders, such as:

1. Functional heartburn, as described in the Rome IV Criteria.
2. Functional dyspepsia, as described in the Rome IV Criteria.
4. The participant has endoscopic Barrett's esophagus (\>1 cm of columnar-lined esophagus) and/or definite dysplastic changes in the esophagus.
5. 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.
6. The participant has scleroderma (systemic sclerosis) or systemic lupus erythematosus.
7. The participant has a history of surgery or endoscopic treatment affecting gastroesophageal reflux, including fundoplication and dilation for esophageal stricture (except dilation for a Schatzki's ring) or a history of gastric or duodenal surgery (except endoscopic removal of benign polyps).
8. The participant has an active gastric or duodenal ulcer within 4 weeks before the first dose of study drug.
9. The participant requires or is expected to require use of prescription or non-prescription proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) throughout the study.
10. The participant has received any investigational compound (including those in post-marketing studies) within 30 days prior to the start of the Screening Period or vonoprazan in a clinical trial at any time (including participation in Study NERD-201). 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.
11. 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.
12. The participant has had clinically significant upper or lower gastrointestinal bleeding within 4 weeks prior to the Screening Period.
13. The participant has Zollinger-Ellison syndrome or other gastric acid hypersecretory conditions.
14. 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). Skin testing may be performed according to local standard practice to confirm hypersensitivity.
15. The participant has a history of alcohol abuse, illegal drug use, or drug addiction within the 12 months prior to screening, 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. Participants must have a negative urine drug screen for cannabinoids/tetrahydrocannabinol (including prescription cannabinoids) and non-prescribed medications during the Screening Period.
16. The participant is taking any excluded medications or treatments listed in the protocol, including prescription cannabinoids/tetrahydrocannabinol.
17. 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.
18. 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.
19. The participant requires hospitalization or has surgery scheduled during the course of the study (from Visit 1 to end of Follow-up Period at Visit 10) or has undergone major surgical procedures within 30 days prior to the Screening Period.
20. The participant has a history of malignancy (including mucosa-associated lymphoid tissue lymphoma) 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 cured cutaneous basal cell carcinoma or cervical carcinoma in situ).
21. The participant has acquired immunodeficiency syndrome or human immunodeficiency virus infection, or tests positive for the hepatitis B surface antigen, hepatitis C virus (HCV) antibody, or HCV-ribonucleic acid (RNA). However, participants who test positive for HCV antibody but negative for HCV-RNA are permitted to participate.
22. 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 for participants with a diagnosis of Gilbert's syndrome).
23. The subject tests positive for active H pylori infection during the Screening Period, after ≥4 weeks free from antibiotics and bismuth and ≥2 weeks free from PPIs and histamine-2 receptor antagonists (H2RAs).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Phathom Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Phathom Pharmaceuticals

Locations

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North Alabama Research Center LLC

Athens, Alabama, United States

Site Status

Cullman Research Center

Cullman, Alabama, United States

Site Status

Medical Affiliated Research Center Inc

Huntsville, Alabama, United States

Site Status

East View Medical Research, LLC

Mobile, Alabama, United States

Site Status

Elite Clinical Studies - Phoenix - Clinedge

Phoenix, Arizona, United States

Site Status

Del Sol Research Management - Clinedge

Tucson, Arizona, United States

Site Status

Preferred Research Partners - ClinEdge

Little Rock, Arkansas, United States

Site Status

Arkansas Gastroenterology

North Little Rock, Arkansas, United States

Site Status

Alliance Research Institute

Canoga Park, California, United States

Site Status

GW Research, Inc

Chula Vista, California, United States

Site Status

eStudy Site

Chula Vista, California, United States

Site Status

Kindred Medical Institute for Clinical Trials, LLC

Corona, California, United States

Site Status

BG Clinical Research

Encinitas, California, United States

Site Status

Paragon Rx Clinical

Garden Grove, California, United States

Site Status

OM Research LLC

Lancaster, California, United States

Site Status

Torrance Clinical Research Institute

Lomita, California, United States

Site Status

Prospective Research Innovations

Rancho Cucamonga, California, United States

Site Status

Northern California Research Corp

Sacramento, California, United States

Site Status

Digestive Care Center

San Carlos, California, United States

Site Status

Clinical Applications Laboratories Inc

San Diego, California, United States

Site Status

Medical Associates Research Group, Inc.

San Diego, California, United States

Site Status

Paragon Rx Clinical, Inc.

Santa Ana, California, United States

Site Status

Western States Clinical Research Inc

Wheat Ridge, Colorado, United States

Site Status

Gastroenterology Associates of Fairfield County

Bridgeport, Connecticut, United States

Site Status

Connecticut Clinical Research Institute

Bristol, Connecticut, United States

Site Status

Medical Research Center of Connecticut, LLC

Hamden, Connecticut, United States

Site Status

Velocity Clinical Research - New Smyrna Beach

Edgewater, Florida, United States

Site Status

Nature Coast Clinical Research

Inverness, Florida, United States

Site Status

ENCORE Borland-Groover Clinical Research

Jacksonville, Florida, United States

Site Status

ClinCloud

Maitland, Florida, United States

Site Status

Legacy Clinical Solutions: Sensible HealthCare, LLC

Ocoee, Florida, United States

Site Status

Digestive Disease Consultants, PA

Orange Park, Florida, United States

Site Status

Medical Center

Orlando, Florida, United States

Site Status

Advanced Gastroenterology Associates, LLC

Palm Harbor, Florida, United States

Site Status

Precision Clinical Research

Sunrise, Florida, United States

Site Status

Guardian Angel Research

Tampa, Florida, United States

Site Status

Southeast Clinical Research Center

Dalton, Georgia, United States

Site Status

Atlanta Center For Gastroenterology PC

Decatur, Georgia, United States

Site Status

Gastroenterology Associates of Central Georgia, LLC

Macon, Georgia, United States

Site Status

Atlanta Center For Clinical Research

Roswell, Georgia, United States

Site Status

Mount Vernon Clinical Research, LLC

Sandy Springs, Georgia, United States

Site Status

In Quest Medical Research

Suwanee, Georgia, United States

Site Status

Treasure Valley Medical Research

Boise, Idaho, United States

Site Status

Grand Teton Research Group, PLLC

Idaho Falls, Idaho, United States

Site Status

Iowa Digestive Disease Center

Clive, Iowa, United States

Site Status

Kansas Medical Clinic

Topeka, Kansas, United States

Site Status

Clinical Trials Management LLC

Covington, Louisiana, United States

Site Status

Combined Gastro Research

Lafayette, Louisiana, United States

Site Status

Tandem Clinical Research, LLC

Marrero, Louisiana, United States

Site Status

Clinical Trials of America, LLC

West Monroe, Louisiana, United States

Site Status

Investigative Clinical Research

Annapolis, Maryland, United States

Site Status

Digestive Health Specialists

Chelmsford, Massachusetts, United States

Site Status

Gastroenterology Associates of Western Michigan, PLC

Wyoming, Michigan, United States

Site Status

MNGI Digestive Health

Minneapolis, Minnesota, United States

Site Status

Minnesota Gastroenterology PA

Plymouth, Minnesota, United States

Site Status

Clinical Research Professionals

Chesterfield, Missouri, United States

Site Status

Quality Clinical Research - HyperCore

Omaha, Nebraska, United States

Site Status

Sierra Clinical Research

Las Vegas, Nevada, United States

Site Status

Office of Site 1

Las Vegas, Nevada, United States

Site Status

Office of Site 2

Las Vegas, Nevada, United States

Site Status

Advanced Research Institute

Reno, Nevada, United States

Site Status

The Gastroenterology Group of Northern NJ LLC

Englewood, New Jersey, United States

Site Status

Allied Health Clinical Research Organization

Freehold, New Jersey, United States

Site Status

NY Scientific

Brooklyn, New York, United States

Site Status

Drug Trials America

Hartsdale, New York, United States

Site Status

Care Access Research

New York, New York, United States

Site Status

UNC Medical Center

Chapel Hill, North Carolina, United States

Site Status

Charlotte Gastroenterology and Hepatology PLLC

Charlotte, North Carolina, United States

Site Status

Peters Medical Research, LLC

High Point, North Carolina, United States

Site Status

East Carolina Gastroenterology

Jacksonville, North Carolina, United States

Site Status

Clinical Trials of America-NC, LLC

Mount Airy, North Carolina, United States

Site Status

Trial Management Associates LLC

Wilmington, North Carolina, United States

Site Status

Lillestol Research

Fargo, North Dakota, United States

Site Status

Gastro Health Research

Cincinnati, Ohio, United States

Site Status

Remington Davis Clinical Research

Columbus, Ohio, United States

Site Status

Great Lakes Medical Research LLC

Mentor, Ohio, United States

Site Status

North Shore Gastroenterology

Westlake, Ohio, United States

Site Status

Susquehanna Research Group, LLC

Harrisburg, Pennsylvania, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Frontier Clinical Research, LLC

Uniontown, Pennsylvania, United States

Site Status

Velocity Clinical Research - Providence

East Greenwich, Rhode Island, United States

Site Status

Gastroenterology Associates, PA of Greenville

Greenville, South Carolina, United States

Site Status

Gastro One

Cordova, Tennessee, United States

Site Status

Galen Medical Group

Hixson, Tennessee, United States

Site Status

Clinical Research Associates Inc

Nashville, Tennessee, United States

Site Status

QUALITY Medical Research

Nashville, Tennessee, United States

Site Status

Vanderbilt Digestive Disease Center

Nashville, Tennessee, United States

Site Status

Gastroenterology Consultants of South Texas, PLLC

Brownsville, Texas, United States

Site Status

Digestive Health Associates of Texas, PA

Carrollton, Texas, United States

Site Status

Family Medicine Associates of Texas

Carrollton, Texas, United States

Site Status

Texas Tech Physicians of El Paso

El Paso, Texas, United States

Site Status

Digestive Health Associates of Texas, P.A.dba DHAT Research Institute

Garland, Texas, United States

Site Status

Primecare Medical Group

Houston, Texas, United States

Site Status

Biopharma Informatic, LLC

Houston, Texas, United States

Site Status

Rio Grande Gastroenterology

McAllen, Texas, United States

Site Status

Quality Research Inc

San Antonio, Texas, United States

Site Status

Gastroenterology Research of San Antonio (GERSA)

San Antonio, Texas, United States

Site Status

Southern Star Research Institute LLC

San Antonio, Texas, United States

Site Status

Sherman Clinical Research

Sherman, Texas, United States

Site Status

Texas Digestive Disease Consultants

Southlake, Texas, United States

Site Status

GI Alliance

Southlake, Texas, United States

Site Status

Texas Gastro Consultants

Tomball, Texas, United States

Site Status

Advanced Research Institute

Ogden, Utah, United States

Site Status

Kalo Clinical Research

Salt Lake City, Utah, United States

Site Status

Advanced Research Institute

Sandy City, Utah, United States

Site Status

Blue Ridge Medical Research

Lynchburg, Virginia, United States

Site Status

Clinical Research Partners LLC

Richmond, Virginia, United States

Site Status

Washington Gastroenterology

Bellevue, Washington, United States

Site Status

Countries

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United States

References

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Laine L, Spechler S, Yadlapati R, Schnoll-Sussman F, Smith N, Leifke E, Harris T, Hunt B, Fass R, Katz P. Vonoprazan is Efficacious for Treatment of Heartburn in Non-erosive Reflux Disease: A Randomized Trial. Clin Gastroenterol Hepatol. 2024 Nov;22(11):2211-2220.e10. doi: 10.1016/j.cgh.2024.05.004. Epub 2024 May 14.

Reference Type DERIVED
PMID: 38750866 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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NERD-301

Identifier Type: -

Identifier Source: org_study_id