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

Heartburn Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04799158
• Other study ID #: NERD-201
• Status: Completed
• Phase: Phase 2
• Start date: March 25, 2021
• Est. completion date: January 17, 2022

Study information

• Verified date: December 2022
• 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, 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 458
• Est. completion date: January 17, 2022
• Est. primary completion date: December 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

Drug:
• Vonoprazan
Orally via capsules
• Placebo
Orally via capsules

Locations

Country	Name	City	State
United States	Investigative Clinical Research	Annapolis	Maryland
United States	Pinnacle Research Group	Anniston	Alabama
United States	North Alabama Research Center LLC	Athens	Alabama
United States	Inquest Clinical Research	Baytown	Texas
United States	Treasure Valley Medical Research	Boise	Idaho
United States	Imagine Research of Palm Beach County	Boynton Beach	Florida
United States	Family Medicine Associates of Texas	Carrollton	Texas
United States	Javara Inc	Charlotte	North Carolina
United States	Care Access	Chicago	Illinois
United States	eStudySite	Chula Vista	California
United States	GW Research, Inc	Chula Vista	California
United States	Iowa Digestive Disease Center	Clive	Iowa
United States	IACT Health	Columbus	Georgia
United States	Remington Davis Inc	Columbus	Ohio
United States	Clinical Trials Management LLC	Covington	Louisiana
United States	Riverside Clinical Research	Edgewater	Florida
United States	GI Associates and Endoscopy Center	Flowood	Mississippi
United States	Paragon Rx Clinical	Garden Grove	California
United States	Medication Management LLC	Greensboro	North Carolina
United States	Carolina Research	Greenville	North Carolina
United States	Drug Trials America	Hartsdale	New York
United States	Peters Medical Research, LLC	High Point	North Carolina
United States	Biopharma Informatic, LLC	Houston	Texas
United States	Synergy Group US, LLC	Houston	Texas
United States	Medical Affiliated Research Center Inc	Huntsville	Alabama
United States	Nature Coast Clinical Research	Inverness	Florida
United States	ENCORE Borland-Groover Clinical Research	Jacksonville	Florida
United States	OM Research LLC	Lancaster	California
United States	Sierra Clinical Research - ClinEdge	Las Vegas	Nevada
United States	Site 1	Las Vegas	Nevada
United States	Site 2	Las Vegas	Nevada
United States	Preferred Research Partners - ClinEdge	Little Rock	Arkansas
United States	ClinCloud	Maitland	Florida
United States	Legacy Clinical Solutions: Tandem Clinical Research, LLC	Marrero	Louisiana
United States	Rio Grande Gastroenterology	McAllen	Texas
United States	Clinical Trials Management LLC	Metairie	Louisiana
United States	Clinical Research Associates Inc	Nashville	Tennessee
United States	Coastal Carolina Research Center	North Charleston	South Carolina
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	Advanced Research Institute	Ogden	Utah
United States	Quality Clinical Research	Omaha	Nebraska
United States	G. Medical Center	Orlando	Florida
United States	Advanced Gastroenterology Associates, LLC	Palm Harbor	Florida
United States	Elite Clinical Studies, LLC	Phoenix	Arizona
United States	Clinical Research Center of Florida	Pompano Beach	Florida
United States	Rapid City Medical Center LLP	Rapid City	South Dakota
United States	Advanced Research Institute	Reno	Nevada
United States	Gastroenterology Research of San Antonio (GERSA)	San Antonio	Texas
United States	Quality Research Inc	San Antonio	Texas
United States	Medical Associates Research Group, Inc.	San Diego	California
United States	Advanced Research Institute	Sandy	Utah
United States	Paragon Rx Clinical, Inc.	Santa Ana	California
United States	Sherman Clinical Research	Sherman	Texas
United States	Virginia Gastroenterology Institute	Suffolk	Virginia
United States	Precision Clinical Research, LLC	Sunrise	Florida
United States	In Quest Medical Research	Suwanee	Georgia
United States	Guardian Angel Research Center	Tampa	Florida
United States	Del Sol Research Management - Clinedge	Tucson	Arizona
United States	Frontier Clinical Research, LLC	Uniontown	Pennsylvania
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
United States	Florida Medical Clinic, LLC Clinical Research Division	Zephyrhills	Florida

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 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	Percentage of Evaluable Heartburn Episodes Completely Relieved Within 3 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.	On-Demand Treatment Period: Day 1 to Day 42
Secondary	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	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	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
Secondary	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	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	Percentage of Days Study Drug Was Taken Over the On-Demand Treatment Period		On-Demand Treatment Period: Day 1 to Day 42
Secondary	Percentage of 24-Hour Heartburn-Free Days Over the On-Demand Treatment Period	A 24-hour heartburn-free day was defined as a day having no heartburn among all diary entries for that day. The percentage of 24-hour heartburn-free days was calculated using all days with at least 1 evening or morning diary entry during the treatment period of this phase.	On-Demand Treatment Period: Day 1 to Day 42