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)

A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Vonoprazan 10 and 20 mg Compared to Placebo for Relief of Heartburn in Subjects With Symptomatic Non-Erosive Gastroesophageal Reflux Disease (NERD) After 4 Weeks and to Evaluate the Efficacy and Safety of Vonoprazan 10 and 20 mg for Relief of Heartburn in Subjects With NERD After 6 Months

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.

Study Overview

• Status: Completed
• Conditions: Heartburn; Non-Erosive Gastro-Esophageal Reflux Disease
• Intervention / Treatment: Drug: Vonoprazan; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 776
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Athens, Alabama, United States, 35611-2456
      • North Alabama Research Center LLC
    • Cullman, Alabama, United States, 35055
      • Cullman Research Center
    • Huntsville, Alabama, United States, 35801-6002
      • Medical Affiliated Research Center Inc
    • Mobile, Alabama, United States, 36606
      • East View Medical Research, LLC
  • Arizona
    • Phoenix, Arizona, United States, 85018-5434
      • Elite Clinical Studies - Phoenix - Clinedge
    • Tucson, Arizona, United States, 85715-3834
      • Del Sol Research Management - Clinedge
  • Arkansas
    • Little Rock, Arkansas, United States, 72211-3868
      • Preferred Research Partners - ClinEdge
    • North Little Rock, Arkansas, United States, 72117-2924
      • Arkansas Gastroenterology
  • California
    • Canoga Park, California, United States, 91304-3862
      • Alliance Research Institute
    • Chula Vista, California, United States, 91910-3906
      • GW Research, Inc
    • Chula Vista, California, United States, 91911-6660
      • eStudy Site
    • Corona, California, United States, 92879-3124
      • Kindred Medical Institute for Clinical Trials, LLC
    • Encinitas, California, United States, 92024
      • BG Clinical Research
    • Garden Grove, California, United States, 92840-3103
      • Paragon RX Clinical
    • Lancaster, California, United States, 93534
      • Om Research LLC
    • Lomita, California, United States, 90717-2101
      • Torrance Clinical Research Institute
    • Rancho Cucamonga, California, United States, 91730
      • Prospective Research Innovations
    • Sacramento, California, United States, 95821-2640
      • Northern California Research Corp
    • San Carlos, California, United States, 94070-3939
      • Digestive Care Center
    • San Diego, California, United States, 92103-5639
      • Clinical Applications Laboratories Inc
    • San Diego, California, United States, 92123-4207
      • Medical Associates Research Group, Inc.
    • Santa Ana, California, United States, 92703-1811
      • Paragon RX Clinical, Inc.
  • Colorado
    • Wheat Ridge, Colorado, United States, 80033-6800
      • Western States Clinical Research Inc
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606-5301
      • Gastroenterology Associates of Fairfield County
    • Bristol, Connecticut, United States, 06010-5161
      • Connecticut Clinical Research Institute
    • Hamden, Connecticut, United States, 06518
      • Medical Research Center of Connecticut, LLC
  • Florida
    • Edgewater, Florida, United States, 32132-2720
      • Velocity Clinical Research - New Smyrna Beach
    • Inverness, Florida, United States, 34452-4717
      • Nature Coast Clinical Research
    • Jacksonville, Florida, United States, 32256-6004
      • Encore Borland-Groover Clinical Research
    • Maitland, Florida, United States, 32751-5570
      • ClinCloud
    • Ocoee, Florida, United States, 34761-2964
      • Legacy Clinical Solutions: Sensible HealthCare, LLC
    • Orange Park, Florida, United States, 32073-4752
      • Digestive Disease Consultants, PA
    • Orlando, Florida, United States, 32807-4346
      • Medical Center
    • Palm Harbor, Florida, United States, 34684-2648
      • Advanced Gastroenterology Associates, LLC
    • Sunrise, Florida, United States, 33351-7311
      • Precision Clinical Research
    • Tampa, Florida, United States, 33614-2700
      • Guardian Angel Research
  • Georgia
    • Dalton, Georgia, United States, 30720
      • Southeast Clinical Research Center
    • Decatur, Georgia, United States, 30033-6146
      • Atlanta Center For Gastroenterology PC
    • Macon, Georgia, United States, 31201-3262
      • Gastroenterology Associates Of Central Georgia, LLC
    • Roswell, Georgia, United States, 30075-2456
      • Atlanta Center for Clinical Research
    • Sandy Springs, Georgia, United States, 30328-4277
      • Mount Vernon Clinical Research, LLC
    • Suwanee, Georgia, United States, 30024-9134
      • In Quest Medical Research
  • Idaho
    • Boise, Idaho, United States, 83706-1345
      • Treasure Valley Medical Research
    • Idaho Falls, Idaho, United States, 83404-7590
      • Grand Teton Research Group, PLLC
  • Iowa
    • Clive, Iowa, United States, 50325-8151
      • Iowa Digestive Disease Center
  • Kansas
    • Topeka, Kansas, United States, 66606-1707
      • Kansas Medical Clinic
  • Louisiana
    • Covington, Louisiana, United States, 70433-4966
      • Clinical Trials Management LLC
    • Lafayette, Louisiana, United States, 70503-2636
      • Combined Gastro Research
    • Marrero, Louisiana, United States, 70072-3151
      • Tandem Clinical Research, LLC
    • West Monroe, Louisiana, United States, 71291-5324
      • Clinical Trials of America, LLC
  • Maryland
    • Annapolis, Maryland, United States, 21401-1091
      • Investigative Clinical Research
  • Massachusetts
    • Chelmsford, Massachusetts, United States, 01824-2775
      • Digestive Health Specialists
  • Michigan
    • Wyoming, Michigan, United States, 49519-9691
      • Gastroenterology Associates of Western Michigan, PLC
  • Minnesota
    • Minneapolis, Minnesota, United States, 55413
      • MNGI Digestive Health
    • Plymouth, Minnesota, United States, 55446-3661
      • Minnesota Gastroenterology PA
  • Missouri
    • Chesterfield, Missouri, United States, 63005-1248
      • Clinical Research Professionals
  • Nebraska
    • Omaha, Nebraska, United States, 68114-3723
      • Quality Clinical Research - HyperCore
  • Nevada
    • Las Vegas, Nevada, United States, 89106-4159
      • Sierra Clinical Research
    • Las Vegas, Nevada, United States, 89119-5190
      • Office of Site 1
    • Las Vegas, Nevada, United States, 89128-0802
      • Office of Site 2
    • Reno, Nevada, United States, 89511-2060
      • Advanced Research Institute
  • New Jersey
    • Englewood, New Jersey, United States, 07631-4141
      • The Gastroenterology Group of Northern NJ LLC
    • Freehold, New Jersey, United States, 07728-2974
      • Allied Health Clinical Research Organization
  • New York
    • Brooklyn, New York, United States, 11235
      • NY Scientific
    • Hartsdale, New York, United States, 10530-1837
      • Drug Trials America
    • New York, New York, United States, 10065-8559
      • Care Access Research
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514-4220
      • UNC Medical Center
    • Charlotte, North Carolina, United States, 28207-1200
      • Charlotte Gastroenterology and Hepatology PLLC
    • High Point, North Carolina, United States, 27260
      • Peters Medical Research, LLC
    • Jacksonville, North Carolina, United States, 28546-7325
      • East Carolina Gastroenterology
    • Mount Airy, North Carolina, United States, 27030-4459
      • Clinical Trials of America-NC, LLC
    • Wilmington, North Carolina, United States, 28403-7018
      • Trial Management Associates LLC
  • North Dakota
    • Fargo, North Dakota, United States, 58104-4557
      • Lillestol Research
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Gastro Health Research
    • Columbus, Ohio, United States, 43215-7098
      • Remington Davis Clinical Research
    • Mentor, Ohio, United States, 44060-6211
      • Great Lakes Medical Research LLC
    • Westlake, Ohio, United States, 44145-7215
      • North Shore Gastroenterology
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17110-3673
      • Susquehanna Research Group, LLC
    • Philadelphia, Pennsylvania, United States, 19104-5127
      • University of Pennsylvania
    • Uniontown, Pennsylvania, United States, 15401-9069
      • Frontier Clinical Research, LLC
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 02818-1762
      • Velocity Clinical Research - Providence
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Gastroenterology Associates, PA of Greenville
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Gastro One
    • Hixson, Tennessee, United States, 37343
      • Galen Medical Group
    • Nashville, Tennessee, United States, 37203-2066
      • Clinical Research Associates Inc
    • Nashville, Tennessee, United States, 37211-4981
      • Quality Medical Research
    • Nashville, Tennessee, United States, 37232-0028
      • Vanderbilt Digestive Disease Center
  • Texas
    • Brownsville, Texas, United States, 78550
      • Gastroenterology Consultants of South Texas, PLLC
    • Carrollton, Texas, United States, 75010-4545
      • Digestive Health Associates of Texas, PA
    • Carrollton, Texas, United States, 75010
      • Family Medicine Associates of Texas
    • El Paso, Texas, United States, 79905-2707
      • Texas Tech Physicians of El Paso
    • Garland, Texas, United States, 75044-2210
      • Digestive Health Associates of Texas, P.A.dba DHAT Research Institute
    • Houston, Texas, United States, 77084
      • Biopharma Informatic, LLC
    • Houston, Texas, United States, 77024-2593
      • PrimeCare Medical Group
    • McAllen, Texas, United States, 78503
      • Rio Grande Gastroenterology
    • San Antonio, Texas, United States, 78209-1744
      • Quality Research Inc
    • San Antonio, Texas, United States, 78229-3270
      • Gastroenterology Research of San Antonio (GERSA)
    • San Antonio, Texas, United States, 78229-4894
      • Southern Star Research Institute LLC
    • Sherman, Texas, United States, 75092
      • Sherman Clinical Research
    • Southlake, Texas, United States, 76092-9167
      • Texas Digestive Disease Consultants
    • Southlake, Texas, United States, 76092
      • GI Alliance
    • Tomball, Texas, United States, 77375-3348
      • Texas Gastro Consultants
  • Utah
    • Ogden, Utah, United States, 84405-4928
      • Advanced Research Institute
    • Salt Lake City, Utah, United States, 84102
      • Kalo Clinical Research
    • Sandy, Utah, United States, 84092-4350
      • Advanced Research Institute
  • Virginia
    • Lynchburg, Virginia, United States, 24502-4272
      • Blue Ridge Medical Research
    • Richmond, Virginia, United States, 23226-3787
      • Clinical Research Partners LLC
  • Washington
    • Bellevue, Washington, United States, 98004-4631
      • Washington Gastroenterology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Vonoprazan; Orally via capsule
Experimental: 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.	Drug: Vonoprazan; Orally via capsule
Placebo Comparator: 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.	Drug: Placebo; Orally via capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Days Without Daytime or Nighttime Heartburn	Participants were assigned an electronic diary to complete twice daily, in the morning and evening. Diary day was considered heartburn-free if both morning and evening diary entries were heartburn-free and there was no reported use of rescue antacid, H2RAs, or PPIs.	Day 1 to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Days Without Rescue Antacid Use	Participants were assigned an electronic diary to complete twice daily, in the morning and evening. Participants recorded use of rescue antacid.	Day 1 to Day 28

Collaborators and Investigators

• Sponsor: Phathom Pharmaceuticals, Inc.
• Investigators: Study Director: Medical Director, Phathom Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2022
• Primary Completion (Actual): November 21, 2022
• Study Completion (Actual): May 17, 2023

Study Registration Dates

• First Submitted: January 4, 2022
• First Submitted That Met QC Criteria: January 4, 2022
• First Posted (Actual): January 19, 2022

Study Record Updates

• Last Update Posted (Actual): December 29, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: NERD; Vonoprazan
• Additional Relevant MeSH Terms: Digestive System Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux; Heartburn
• Other Study ID Numbers: NERD-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No