Clinical trial NCT04799158: A Study to Evaluate the Efficacy and Safety of Vonoprazan Compared to Placebo in Participants With Symptomatic Non-Erosive Gastroesophageal Reflux Disease
Official title: A Phase 2, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Vonoprazan 10 mg, 20 mg, and 40 mg Compared to Placebo for Relief of Episodic Heartburn in Subjects With Symptomatic Non-Erosive Gastroesophageal Reflux Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Erosive Gastro-Esophageal Reflux Disease
Heartburn
Keywords: Symptomatic Non-Erosive Gastroesophageal Reflux Disease
NERD
Vonoprazan
Heartburn
Lead sponsor: Phathom Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-03-16
Enrollment: 458
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria for Run-In Period

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.

Inclusion Criteria for On-Demand Treatment Period

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.
3. The participant continues to fulfill all eligibility criteria for the Run-In Period (except Inclusion Criteria 4).
4. Participant completes at least 80% of diary entries during Run-In Period, including 80% of diary entries over the last 7 days.

Exclusion Criteria for Run-In Period

1. Endoscopically confirmed erosive esophagitis (EE) during the Screening Period assessed by the investigator. Endoscopy should be performed after participants meet Inclusion Criteria 6. Any endoscopic confirmation performed in a routine clinical setting within 7 days before signing the informed consent is acceptable to use for the purpose of fulfilling the screening requirement.
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)

Primary outcomes:
measure: Percentage of Evaluable Heartburn Episodes Completely Relieved Within 3 Hours and With No Further Heartburn Reported for 24 Hours After Taking Study Drug
timeFrame: On-Demand Treatment Period: Day 1 to Day 42
Secondary outcomes:
measure: Percentage of Evaluable Heartburn Episodes Completely Relieved Within 3 Hours After Taking Study Drug
timeFrame: On-Demand Treatment Period: Day 1 to Day 42
measure: 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
timeFrame: On-Demand Treatment Period: Day 1 to Day 42
measure: Mean Number of Tablets of Rescue Antacid Taken Per Day Over the On-Demand Treatment Period
timeFrame: On-Demand Treatment Period: Day 1 to Day 42
measure: 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
timeFrame: On-Demand Treatment Period: Day 1 to Day 42
measure: Percentage of Days Study Drug Was Taken Over the On-Demand Treatment Period
timeFrame: On-Demand Treatment Period: Day 1 to Day 42
measure: Percentage of 24-Hour Heartburn-Free Days Over the On-Demand Treatment Period
timeFrame: On-Demand Treatment Period: Day 1 to Day 42
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group
state: Alabama
city: Athens
country: United States
facility: North Alabama Research Center LLC
state: Alabama
city: Huntsville
country: United States
facility: Medical Affiliated Research Center Inc
state: Alabama
city: Phoenix
country: United States
facility: Elite Clinical Studies, LLC
state: Arizona
city: Tucson
country: United States
facility: Del Sol Research Management - Clinedge
state: Arizona
city: Little Rock
country: United States
facility: Preferred Research Partners - ClinEdge
state: Arkansas
city: North Little Rock
country: United States
facility: Arkansas Gastroenterology
state: Arkansas
city: Chula Vista
country: United States
facility: GW Research, Inc
state: California
city: Chula Vista
country: United States
facility: eStudySite
state: California
city: Garden Grove
country: United States
facility: Paragon Rx Clinical
state: California
city: Lancaster
country: United States
facility: OM Research LLC
state: California
city: San Diego
country: United States
facility: Medical Associates Research Group, Inc.
state: California
city: Santa Ana
country: United States
facility: Paragon Rx Clinical, Inc.
state: California
city: Wheat Ridge
country: United States
facility: Western States Clinical Research Inc
state: Colorado
city: Boynton Beach
country: United States
facility: Imagine Research of Palm Beach County
state: Florida
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: ENCORE Borland-Groover Clinical Research
state: Florida
city: Maitland
country: United States
facility: ClinCloud
state: Florida
city: Orlando
country: United States
facility: G. Medical Center
state: Florida
city: Palm Harbor
country: United States
facility: Advanced Gastroenterology Associates, LLC
state: Florida
city: Pompano Beach
country: United States
facility: Clinical Research Center of Florida
state: Florida
city: Sunrise
country: United States
facility: Precision Clinical Research, LLC
state: Florida
city: Tampa
country: United States
facility: Guardian Angel Research Center
state: Florida
city: Zephyrhills
country: United States
facility: Florida Medical Clinic, LLC Clinical Research Division
state: Florida
city: Columbus
country: United States
facility: IACT Health
state: Georgia
city: Suwanee
country: United States
facility: In Quest Medical Research
state: Georgia
city: Boise
country: United States
facility: Treasure Valley Medical Research
state: Idaho
city: Chicago
country: United States
facility: Care Access
state: Illinois
city: Clive
country: United States
facility: Iowa Digestive Disease Center
state: Iowa
city: Covington
country: United States
facility: Clinical Trials Management LLC
state: Louisiana
city: Marrero
country: United States
facility: Legacy Clinical Solutions: Tandem Clinical Research, LLC
state: Louisiana
city: Metairie
country: United States
facility: Clinical Trials Management LLC
state: Louisiana
city: Annapolis
country: United States
facility: Investigative Clinical Research
state: Maryland
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan, PLC
state: Michigan
city: Flowood
country: United States
facility: GI Associates and Endoscopy Center
state: Mississippi
city: Omaha
country: United States
facility: Quality Clinical Research
state: Nebraska
city: Las Vegas
country: United States
facility: Sierra Clinical Research - ClinEdge
state: Nevada
city: Las Vegas
country: United States
facility: Site 2
state: Nevada
city: Las Vegas
country: United States
facility: Site 1
state: Nevada
city: Reno
country: United States
facility: Advanced Research Institute
state: Nevada
city: Hartsdale
country: United States
facility: Drug Trials America
state: New York
city: Charlotte
country: United States
facility: Javara Inc
state: North Carolina
city: Greensboro
country: United States
facility: Medication Management LLC
state: North Carolina
city: Greenville
country: United States
facility: Carolina Research
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research, LLC
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates LLC
state: North Carolina
city: Columbus
country: United States
facility: Remington Davis Inc
state: Ohio
city: Uniontown
country: United States
facility: Frontier Clinical Research, LLC
state: Pennsylvania
city: North Charleston
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Medical Center LLP
state: South Dakota
city: Nashville
country: United States
facility: Clinical Research Associates Inc
state: Tennessee
city: Baytown
country: United States
facility: Inquest Clinical Research
state: Texas
city: Carrollton
country: United States
facility: Family Medicine Associates of Texas
state: Texas
city: Houston
country: United States
facility: Synergy Group US, LLC
state: Texas
city: Houston
country: United States
facility: Biopharma Informatic, LLC
state: Texas
city: McAllen
country: United States
facility: Rio Grande Gastroenterology
state: Texas
city: San Antonio
country: United States
facility: Quality Research Inc
state: Texas
city: San Antonio
country: United States
facility: Gastroenterology Research of San Antonio (GERSA)
state: Texas
city: Sherman
country: United States
facility: Sherman Clinical Research
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Sandy
country: United States
facility: Advanced Research Institute
state: Utah
city: Suffolk
country: United States
facility: Virginia Gastroenterology Institute
state: Virginia
Study officials:
affiliation: Phathom Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: