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

Sponsor

Phathom Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT04799158

Collaborator

(none)

458

Enrollment

Locations

Arms

8.9

Actual Duration (Months)

7.5

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Erosive Gastro-Esophageal Reflux Disease Heartburn	Drug: Vonoprazan Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

458 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

During the Run-In Period, participants will receive open-label vonoprazan.

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 25, 2021

Actual Primary Completion Date :

Dec 16, 2021

Actual Study Completion Date :

Dec 20, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Run-In Period Participants will receive vonoprazan 20 mg once daily for up to 4 weeks.	Drug: Vonoprazan Orally via capsules
Experimental: Vonoprazan 10 mg: On-Demand Treatment Period 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 Orally via capsules
Experimental: Vonoprazan 20 mg: On-Demand Treatment Period 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 Orally via capsules
Experimental: Vonoprazan 40 mg: On-Demand Treatment Period 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 Orally via capsules
Placebo Comparator: Placebo: On-Demand Treatment Period 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 Orally via capsules

Outcome Measures

Primary Outcome Measures

Percentage of Evaluable Heartburn Episodes 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]
An evaluable heartburn episode is an episode for which study drug is taken and for which the participant completes at least one entry in the heartburn episode diary. For a heartburn episode to be considered completely relieved, a participant must not take rescue antacid within 3 hours of taking study drug.

Secondary Outcome Measures

Percentage of Evaluable Heartburn Episodes Completely Relieved Within 3 Hours After Taking Study Drug [On-Demand Treatment Period Day 1 to Day 42]
An evaluable heartburn episode is an episode for which study drug is taken and for which the participant completes at least one entry in the heartburn episode diary. For a heartburn episode to be considered completely relieved, a participant must not take rescue antacid within 3 hours of taking study drug.
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]
An evaluable heartburn episode is an episode for which study drug is taken and for which the participant completes at least one entry in the heartburn episode diary. For a heartburn episode to be considered completely relieved, a participant must not take rescue antacid within 3 hours of taking study drug.
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]
Percentage of 24-Hour Heartburn-Free Days Over the On-Demand Treatment Period [On-Demand Treatment Period Day 1 to Day 42]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria for Run-In Period

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.

Inclusion Criteria for On-Demand Treatment Period

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.
The participant continues to fulfill all eligibility criteria for the Run-In Period (except Inclusion Criteria 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

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.
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.
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.
The participant is taking any excluded medications or treatments listed in the protocol.
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.
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.
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.
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).
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.
The participant has any of the following abnormal laboratory test values at the start of the Screening Period:
Creatinine levels: >2 mg/dL (>177 μmol/L)
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × the upper limit of normal (ULN) or total bilirubin >2 × ULN (except participants with Gilbert Syndrome)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Research Group	Anniston	Alabama	United States	36207
2	North Alabama Research Center LLC	Athens	Alabama	United States	35611-2456
3	Medical Affiliated Research Center Inc	Huntsville	Alabama	United States	36305
4	Elite Clinical Studies, LLC	Phoenix	Arizona	United States	85018
5	Del Sol Research Management - Clinedge	Tucson	Arizona	United States	85712-5637
6	Preferred Research Partners - ClinEdge	Little Rock	Arkansas	United States	72211-3868
7	Arkansas Gastroenterology	North Little Rock	Arkansas	United States	72117-2924
8	GW Research, Inc	Chula Vista	California	United States	91910-3906
9	Velocity Clinical Research	Chula Vista	California	United States	91911-6660
10	Paragon Rx Clinical	Garden Grove	California	United States	92840-3103
11	OM Research LLC	Lancaster	California	United States	93534-5504
12	Medical Associates Research Group, Inc.	San Diego	California	United States	92123-4207
13	Paragon Rx Clinical, Inc.	Santa Ana	California	United States	92703-1811
14	Western States Clinical Research Inc	Wheat Ridge	Colorado	United States	80033-6800
15	Imagine Research of Palm Beach County	Boynton Beach	Florida	United States	33435-5610
16	Riverside Clinical Research	Edgewater	Florida	United States	32132
17	Nature Coast Clinical Research	Inverness	Florida	United States	34452-4717
18	ENCORE Borland-Groover Clinical Research	Jacksonville	Florida	United States	32256-6004
19	ClinCloud	Maitland	Florida	United States	32751-3320
20	G. Medical Center	Orlando	Florida	United States	32807-4346
21	Advanced Gastroenterology Associates, LLC	Palm Harbor	Florida	United States	34684
22	Clinical Research Center of Florida	Pompano Beach	Florida	United States	33060-6934
23	Precision Clinical Research, LLC	Sunrise	Florida	United States	33351-7311
24	Guardian Angel Research Center	Tampa	Florida	United States	33614
25	IACT Health	Columbus	Georgia	United States	31904-8946
26	In Quest Medical Research	Suwanee	Georgia	United States	30024-9134
27	Treasure Valley Medical Research	Boise	Idaho	United States	83706-1345
28	Summit Center of Clinical Research	Chicago	Illinois	United States	60616-2311
29	Iowa Digestive Disease Center	Clive	Iowa	United States	50325-8151
30	Clinical Trials Management LLC	Covington	Louisiana	United States	70433-4966
31	Legacy Clinical Solutions: Tandem Clinical Research, LLC	Marrero	Louisiana	United States	70072-3156
32	Clinical Trials Management LLC	Metairie	Louisiana	United States	70006-4165
33	Investigative Clinical Research	Annapolis	Maryland	United States	21401-1091
34	Gastroenterology Associates of Western Michigan, PLC	Wyoming	Michigan	United States	49519-9691
35	Quality Clinical Research	Omaha	Nebraska	United States	68114
36	Sierra Clinical Research - ClinEdge	Las Vegas	Nevada	United States	89106-4159
37	Site 2	Las Vegas	Nevada	United States	89119
38	Site 1	Las Vegas	Nevada	United States	89128
39	Advanced Research Institute	Reno	Nevada	United States	89511
40	Drug Trials America	Hartsdale	New York	United States	10530-1837
41	Tryon Medical Partners	Charlotte	North Carolina	United States	28287-3884
42	Medication Management LLC	Greensboro	North Carolina	United States	27408-7099
43	Carolina Digestive Diseases	Greenville	North Carolina	United States	27834-3761
44	Peters Medical Research, LLC	High Point	North Carolina	United States	27262-4800
45	Trial Management Associates LLC	Wilmington	North Carolina	United States	28403-7018
46	Remington Davis Inc	Columbus	Ohio	United States	43215-7098
47	Frontier Clinical Research, LLC	Uniontown	Pennsylvania	United States	15401-9069
48	Coastal Carolina Research Center	North Charleston	South Carolina	United States	29405
49	Rapid City Medical Center LLP	Rapid City	South Dakota	United States	57701-5462
50	Clinical Research Associates Inc	Nashville	Tennessee	United States	37203-2066
51	Inquest Clinical Research	Baytown	Texas	United States	77521-2416
52	Family Medicine Associates of Texas	Carrollton	Texas	United States	75010
53	Synergy Group US, LLC	Houston	Texas	United States	77036
54	Biopharma Informatic, LLC	Houston	Texas	United States	77084
55	Rio Grande Gastroenterology	McAllen	Texas	United States	78530
56	Quality Research Inc	San Antonio	Texas	United States	78209-1744
57	Gastroenterology Research of San Antonio (GERSA)	San Antonio	Texas	United States	78229-3270
58	Sherman Clinical Research	Sherman	Texas	United States	75092
59	Advanced Research Institute	Ogden	Utah	United States	84405
60	Advanced Research Institute	Sandy	Utah	United States	84092-4350
61	Virginia Gastroenterology Institute	Suffolk	Virginia	United States	23435