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

NCT04799158 | Completed Phase 2 Results FDA Drug

• 1 other identifier: NERD-201
• Study Type: interventional
• Target: 458
• Locations: 1 country
• Sites: 63

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

Keywords

Symptomatic Non-Erosive Gastroesophageal Reflux Disease; NERD; Vonoprazan; Heartburn

Outcome Measures

Primary Outcomes (1)

• Percentage of Evaluable Heartburn Episodes Completely Relieved Within 3 Hours and With No Further Heartburn Reported for 24 Hours After Taking Study Drug

  An evaluable heartburn episode was an episode for which study drug was taken and for which the participant completed at least one entry in the heartburn episode diary. For a heartburn episode to be considered completely relieved, a participant must not have taken rescue antacid within 3 hours of taking study drug. For sustained relief, complete relief must have been accompanied by 24 hours without another heartburn episode after taking study drug.

  On-Demand Treatment Period: Day 1 to Day 42

Secondary Outcomes (6)

• Percentage of Evaluable Heartburn Episodes Completely Relieved Within 3 Hours After Taking Study Drug

  On-Demand Treatment Period: Day 1 to Day 42

• Percentage of Evaluable Heartburn Episodes for Each Participant That Are Completely Relieved Within 3 Hours and With No Further Heartburn Reported for 24 Hours After Taking Study Drug

  On-Demand Treatment Period: Day 1 to Day 42

• Mean Number of Tablets of Rescue Antacid Taken Per Day Over the On-Demand Treatment Period

  On-Demand Treatment Period: Day 1 to Day 42

• Percentage of Participants With Complete Relief of Heartburn Within 3 Hours After the First Episode and With No Further Heartburn Reported for 24 Hours After Taking Study Drug

  On-Demand Treatment Period: Day 1 to Day 42

• Percentage of Days Study Drug Was Taken Over the On-Demand Treatment Period

  On-Demand Treatment Period: Day 1 to Day 42

Study Arms (5)

Run-In Period

EXPERIMENTAL

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

Drug: Vonoprazan

Vonoprazan 10 mg: On-Demand Treatment Period

EXPERIMENTAL

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.

Drug: Vonoprazan

Vonoprazan 20 mg: On-Demand Treatment Period

EXPERIMENTAL

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.

Drug: Vonoprazan

Vonoprazan 40 mg: On-Demand Treatment Period

EXPERIMENTAL

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.

Drug: Vonoprazan

Placebo: On-Demand Treatment Period

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Vonoprazan DRUG

Orally via capsules

Run-In Period; Vonoprazan 10 mg: On-Demand Treatment Period; Vonoprazan 20 mg: On-Demand Treatment Period; Vonoprazan 40 mg: On-Demand Treatment Period

Placebo DRUG

Orally via capsules

Placebo: On-Demand Treatment Period

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant is ≥18 years of age at the time of informed consent signing.
• In the opinion of the investigator or sub investigators, the participant is capable of understanding and complying with protocol requirements.
• 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.
• The participant identified their main symptom as heartburn, a burning sensation in the retrosternal area (behind the breastbone).
• History of episodes of heartburn for 6 months or longer prior to screening.
• Heartburn reported on 4 or more days during any 7 consecutive days in the Screening Period as recorded in the electronic diary.
• 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.
• The participant completes the Run-In Period, during which the participant was at least 80% compliant with open-label study drug.
• The participant has stable disease, ie, no heartburn the last 7 days of the Run-In Period.
• Participant completes at least 80% of diary entries during Run-In Period, including 80% of diary entries over the last 7 days.

You may not qualify if:

• The participant has active irritable bowel syndrome (IBS) or had a flare of IBS requiring therapy within the prior 6 months.
• The participant has a history of or is suspected of having functional heartburn diagnosed by the Rome IV criteria.
• The participant has a history of or is suspected of having functional dyspepsia diagnosed by the Rome IV criteria.
• The participant has endoscopic Barrett's esophagus (\>1 cm of columnar-lined esophagus) and/or definite dysplastic changes in the esophagus.
• 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.
• The participant has scleroderma (systemic sclerosis).
• 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).
• The participant has an active gastric or duodenal ulcer within 4 weeks before the first dose of study drug.
• Use of prescription or non-prescription proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) throughout the study.
• 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.
• 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.
• The participant has cutaneous lupus erythematosus or systemic lupus erythematosus.
• The participant has had clinically significant upper or lower gastrointestinal bleeding within 4 weeks prior to screening.
• The participant has Zollinger-Ellison syndrome or other gastric acid hypersecretory conditions.
• 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.

Sponsors & Collaborators

• Phathom Pharmaceuticals, Inc.: lead

Study Sites (63)

Pinnacle Research Group

Anniston, Alabama, 36207, United States

Location

North Alabama Research Center LLC

Athens, Alabama, 35611-2456, United States

Location

Medical Affiliated Research Center Inc

Huntsville, Alabama, 35801, United States

Location

Elite Clinical Studies, LLC

Phoenix, Arizona, 85018, United States

Location

Del Sol Research Management - Clinedge

Tucson, Arizona, 85712-5637, United States

Location

Preferred Research Partners - ClinEdge

Little Rock, Arkansas, 72211-3868, United States

Location

Arkansas Gastroenterology

North Little Rock, Arkansas, 72117-2924, United States

Location

GW Research, Inc

Chula Vista, California, 91910-3906, United States

Location

eStudySite

Chula Vista, California, 91911-6660, United States

Location

Paragon Rx Clinical

Garden Grove, California, 92840-3103, United States

Location

OM Research LLC

Lancaster, California, 93534-5504, United States

Location

Medical Associates Research Group, Inc.

San Diego, California, 92123-4207, United States

Location

Paragon Rx Clinical, Inc.

Santa Ana, California, 92703-1811, United States

Location

Western States Clinical Research Inc

Wheat Ridge, Colorado, 80033-6800, United States

Location

Imagine Research of Palm Beach County

Boynton Beach, Florida, 33435-5610, United States

Location

Riverside Clinical Research

Edgewater, Florida, 32132, United States

Location

Nature Coast Clinical Research

Inverness, Florida, 34452-4717, United States

Location

ENCORE Borland-Groover Clinical Research

Jacksonville, Florida, 32256-6004, United States

Location

ClinCloud

Maitland, Florida, 32751-3320, United States

Location

G. Medical Center

Orlando, Florida, 32807-4346, United States

Location

Advanced Gastroenterology Associates, LLC

Palm Harbor, Florida, 34684, United States

Location

Clinical Research Center of Florida

Pompano Beach, Florida, 33060-6934, United States

Location

Precision Clinical Research, LLC

Sunrise, Florida, 33351-7311, United States

Location

Guardian Angel Research Center

Tampa, Florida, 33614, United States

Location

Florida Medical Clinic, LLC Clinical Research Division

Zephyrhills, Florida, 33542, United States

Location

IACT Health

Columbus, Georgia, 31904-8946, United States

Location

In Quest Medical Research

Suwanee, Georgia, 30024-9134, United States

Location

Treasure Valley Medical Research

Boise, Idaho, 83706-1345, United States

Location

Care Access

Chicago, Illinois, 60616, United States

Location

Iowa Digestive Disease Center

Clive, Iowa, 50325-8151, United States

Location

Clinical Trials Management LLC

Covington, Louisiana, 70433-4966, United States

Location

Legacy Clinical Solutions: Tandem Clinical Research, LLC

Marrero, Louisiana, 70072-3156, United States

Location

Clinical Trials Management LLC

Metairie, Louisiana, 70006-4165, United States

Location

Investigative Clinical Research

Annapolis, Maryland, 21401-1091, United States

Location

Gastroenterology Associates of Western Michigan, PLC

Wyoming, Michigan, 49519-9691, United States

Location

GI Associates and Endoscopy Center

Flowood, Mississippi, 39232, United States

Location

Quality Clinical Research

Omaha, Nebraska, 68114, United States

Location

Sierra Clinical Research - ClinEdge

Las Vegas, Nevada, 89106-4159, United States

Location

Site 2

Las Vegas, Nevada, 89119, United States

Location

Site 1

Las Vegas, Nevada, 89128, United States

Location

Advanced Research Institute

Reno, Nevada, 89511, United States

Location

Drug Trials America

Hartsdale, New York, 10530-1837, United States

Location

Javara Inc

Charlotte, North Carolina, 28287-3884, United States

Location

Medication Management LLC

Greensboro, North Carolina, 27408-7099, United States

Location

Carolina Research

Greenville, North Carolina, 27834-3761, United States

Location

Peters Medical Research, LLC

High Point, North Carolina, 27262-4800, United States

Location

Trial Management Associates LLC

Wilmington, North Carolina, 28403-7018, United States

Location

Remington Davis Inc

Columbus, Ohio, 43215-7098, United States

Location

Frontier Clinical Research, LLC

Uniontown, Pennsylvania, 15401-9069, United States

Location

Coastal Carolina Research Center

North Charleston, South Carolina, 29405, United States

Location

Rapid City Medical Center LLP

Rapid City, South Dakota, 57701-5462, United States

Location

Clinical Research Associates Inc

Nashville, Tennessee, 37203-2066, United States

Location

Inquest Clinical Research

Baytown, Texas, 77521-2416, United States

Location

Family Medicine Associates of Texas

Carrollton, Texas, 75010, United States

Location

Synergy Group US, LLC

Houston, Texas, 77036, United States

Location

Biopharma Informatic, LLC

Houston, Texas, 77084, United States

Location

Rio Grande Gastroenterology

McAllen, Texas, 78530, United States

Location

Quality Research Inc

San Antonio, Texas, 78209-1744, United States

Location

Gastroenterology Research of San Antonio (GERSA)

San Antonio, Texas, 78229-3270, United States

Location

Sherman Clinical Research

Sherman, Texas, 75092, United States

Location

Advanced Research Institute

Ogden, Utah, 84405, United States

Location

Advanced Research Institute

Sandy City, Utah, 84092-4350, United States

Location

Virginia Gastroenterology Institute

Suffolk, Virginia, 23435, United States

Location

Related Publications (1)

• 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.

  PMID: 37750406 DERIVED

MeSH Terms

Conditions

Heartburn

Interventions

1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Phathom Medical Information
• Organization: Phathom Pharmaceuticals, Inc.

medicalinformation@phathompharma.com

1-888-775-PHAT

Study Officials

• Medical Director

  Phathom Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: During the Run-In Period, participants will receive open-label vonoprazan.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: March 16, 2021
• Study Start: March 25, 2021
• Primary Completion: December 16, 2021
• Study Completion: January 17, 2022
• Last Updated: January 4, 2023
• Results First Posted: January 4, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (63)