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)

Heartburn Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05195528
• Other study ID #: NERD-301
• Status: Completed
• Phase: Phase 3
• Start date: January 17, 2022
• Est. completion date: May 17, 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 776
• Est. completion date: May 17, 2023
• Est. primary completion date: November 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Gastroesophageal Reflux
• Heartburn
• Non-Erosive Gastro-Esophageal Reflux Disease

Intervention

Drug:
• Vonoprazan
Orally via capsule
• Placebo
Orally via capsule

Locations

Country	Name	City	State
United States	Investigative Clinical Research	Annapolis	Maryland
United States	North Alabama Research Center LLC	Athens	Alabama
United States	Washington Gastroenterology	Bellevue	Washington
United States	Treasure Valley Medical Research	Boise	Idaho
United States	Gastroenterology Associates of Fairfield County	Bridgeport	Connecticut
United States	Connecticut Clinical Research Institute	Bristol	Connecticut
United States	NY Scientific	Brooklyn	New York
United States	Gastroenterology Consultants of South Texas, PLLC	Brownsville	Texas
United States	Alliance Research Institute	Canoga Park	California
United States	Digestive Health Associates of Texas, PA	Carrollton	Texas
United States	Family Medicine Associates of Texas	Carrollton	Texas
United States	UNC Medical Center	Chapel Hill	North Carolina
United States	Charlotte Gastroenterology and Hepatology PLLC	Charlotte	North Carolina
United States	Digestive Health Specialists	Chelmsford	Massachusetts
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	eStudy Site	Chula Vista	California
United States	GW Research, Inc	Chula Vista	California
United States	Gastro Health Research	Cincinnati	Ohio
United States	Iowa Digestive Disease Center	Clive	Iowa
United States	Remington Davis Clinical Research	Columbus	Ohio
United States	Gastro One	Cordova	Tennessee
United States	Kindred Medical Institute for Clinical Trials, LLC	Corona	California
United States	Clinical Trials Management LLC	Covington	Louisiana
United States	Cullman Research Center	Cullman	Alabama
United States	Southeast Clinical Research Center	Dalton	Georgia
United States	Atlanta Center For Gastroenterology PC	Decatur	Georgia
United States	Velocity Clinical Research - Providence	East Greenwich	Rhode Island
United States	Velocity Clinical Research - New Smyrna Beach	Edgewater	Florida
United States	Texas Tech Physicians of El Paso	El Paso	Texas
United States	BG Clinical Research	Encinitas	California
United States	The Gastroenterology Group of Northern NJ LLC	Englewood	New Jersey
United States	Lillestol Research	Fargo	North Dakota
United States	Allied Health Clinical Research Organization	Freehold	New Jersey
United States	Paragon Rx Clinical	Garden Grove	California
United States	Digestive Health Associates of Texas, P.A.dba DHAT Research Institute	Garland	Texas
United States	Gastroenterology Associates, PA of Greenville	Greenville	South Carolina
United States	Medical Research Center of Connecticut, LLC	Hamden	Connecticut
United States	Susquehanna Research Group, LLC	Harrisburg	Pennsylvania
United States	Drug Trials America	Hartsdale	New York
United States	Peters Medical Research, LLC	High Point	North Carolina
United States	Galen Medical Group	Hixson	Tennessee
United States	Biopharma Informatic, LLC	Houston	Texas
United States	Primecare Medical Group	Houston	Texas
United States	Medical Affiliated Research Center Inc	Huntsville	Alabama
United States	Grand Teton Research Group, PLLC	Idaho Falls	Idaho
United States	Nature Coast Clinical Research	Inverness	Florida
United States	East Carolina Gastroenterology	Jacksonville	North Carolina
United States	ENCORE Borland-Groover Clinical Research	Jacksonville	Florida
United States	Combined Gastro Research	Lafayette	Louisiana
United States	OM Research LLC	Lancaster	California
United States	Office of Site 1	Las Vegas	Nevada
United States	Office of Site 2	Las Vegas	Nevada
United States	Sierra Clinical Research	Las Vegas	Nevada
United States	Preferred Research Partners - ClinEdge	Little Rock	Arkansas
United States	Torrance Clinical Research Institute	Lomita	California
United States	Blue Ridge Medical Research	Lynchburg	Virginia
United States	Gastroenterology Associates of Central Georgia, LLC	Macon	Georgia
United States	ClinCloud	Maitland	Florida
United States	Tandem Clinical Research, LLC	Marrero	Louisiana
United States	Rio Grande Gastroenterology	McAllen	Texas
United States	Great Lakes Medical Research LLC	Mentor	Ohio
United States	MNGI Digestive Health	Minneapolis	Minnesota
United States	East View Medical Research, LLC	Mobile	Alabama
United States	Clinical Trials of America-NC, LLC	Mount Airy	North Carolina
United States	Clinical Research Associates Inc	Nashville	Tennessee
United States	QUALITY Medical Research	Nashville	Tennessee
United States	Vanderbilt Digestive Disease Center	Nashville	Tennessee
United States	Care Access Research	New York	New York
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	Legacy Clinical Solutions: Sensible HealthCare, LLC	Ocoee	Florida
United States	Advanced Research Institute	Ogden	Utah
United States	Quality Clinical Research - HyperCore	Omaha	Nebraska
United States	Digestive Disease Consultants, PA	Orange Park	Florida
United States	Medical Center	Orlando	Florida
United States	Advanced Gastroenterology Associates, LLC	Palm Harbor	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Elite Clinical Studies - Phoenix - Clinedge	Phoenix	Arizona
United States	Minnesota Gastroenterology PA	Plymouth	Minnesota
United States	Prospective Research Innovations	Rancho Cucamonga	California
United States	Advanced Research Institute	Reno	Nevada
United States	Clinical Research Partners LLC	Richmond	Virginia
United States	Atlanta Center For Clinical Research	Roswell	Georgia
United States	Northern California Research Corp	Sacramento	California
United States	Kalo Clinical Research	Salt Lake City	Utah
United States	Gastroenterology Research of San Antonio (GERSA)	San Antonio	Texas
United States	Quality Research Inc	San Antonio	Texas
United States	Southern Star Research Institute LLC	San Antonio	Texas
United States	Digestive Care Center	San Carlos	California
United States	Clinical Applications Laboratories Inc	San Diego	California
United States	Medical Associates Research Group, Inc.	San Diego	California
United States	Advanced Research Institute	Sandy	Utah
United States	Mount Vernon Clinical Research, LLC	Sandy Springs	Georgia
United States	Paragon Rx Clinical, Inc.	Santa Ana	California
United States	Sherman Clinical Research	Sherman	Texas
United States	GI Alliance	Southlake	Texas
United States	Texas Digestive Disease Consultants	Southlake	Texas
United States	Precision Clinical Research	Sunrise	Florida
United States	In Quest Medical Research	Suwanee	Georgia
United States	Guardian Angel Research	Tampa	Florida
United States	Texas Gastro Consultants	Tomball	Texas
United States	Kansas Medical Clinic	Topeka	Kansas
United States	Del Sol Research Management - Clinedge	Tucson	Arizona
United States	Frontier Clinical Research, LLC	Uniontown	Pennsylvania
United States	Clinical Trials of America, LLC	West Monroe	Louisiana
United States	North Shore Gastroenterology	Westlake	Ohio
United States	Western States Clinical Research Inc	Wheat Ridge	Colorado
United States	Trial Management Associates LLC	Wilmington	North Carolina
United States	Gastroenterology Associates of Western Michigan, PLC	Wyoming	Michigan

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	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	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