A Study to Evaluate the Efficacy and Safety of Vonoprazan Compared to Placebo in Participants With Symptomatic Non-Erosive Gastroesophageal Reflux Disease (NCT04799158)

01

Study 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.

02

Conditions studied

Non-Erosive Gastro-Esophageal Reflux Disease
Heartburn

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Heartburn 154

Keywords

Symptomatic Non-Erosive Gastroesophageal Reflux Disease
NERD
Vonoprazan
Heartburn

03

In context

Heartburn

154 studies on the registry are indexed under Heartburn; 12 are open to participants now.

This study's enrollment of 458 is above the median of 100 across 127 interventional studies indexed under Heartburn.

Browse Heartburn studies →

Lead sponsor

Phathom Pharmaceuticals, Inc. is the lead sponsor of 15 studies on the registry; 2 are open to participants now.

Of its 11 completed or terminated interventional studies of FDA-regulated products, 11 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Inclusion Criteria for Run-In Period

The participant is ≥18 years of age at the time of 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 who is or may be sexually active with a non sterilized male partner agrees to routinely use adequate 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 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 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 or allergies to vonoprazan (including the formulation : 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 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 (HIV) infection, or tests positive for the surface antigen (HBsAg), 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:
1. Creatinine levels: >2 mg/dL (>177 μmol/L)
2. (ALT) or aspartate aminotransferase (AST) >2 × the (ULN) or total >2 × ULN (except participants with Gilbert Syndrome)

Terms in these criteria, in plain language(14)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

Excipients

The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

05

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 458 participants (actual)

Study arms

Experimental
Run-In Period
Participants will receive vonoprazan 20 mg once daily for up to 4 weeks.
Drug: Vonoprazan
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
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
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
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

Interventions

DrugVonoprazan
Orally via capsules
DrugPlacebo
Orally via capsules

06

What researchers measure

Primary outcomes

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.
Time frame: On-Demand Treatment Period: Day 1 to Day 42

Secondary outcomes

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.
Time frame: 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
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.
Time frame: 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
Time frame: 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
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.
Time frame: On-Demand Treatment Period: Day 1 to Day 42
Percentage of Days Study Drug Was Taken Over the On-Demand Treatment Period
Time frame: On-Demand Treatment Period: Day 1 to Day 42
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.
Time frame: On-Demand Treatment Period: Day 1 to Day 42

07

Results

Posted Jan 4, 2023

Participant flow

This study was performed at 54 sites in the United States between 25 March 2021 and 17 January 2022. Of the 1115 participants screened for the study, 458 participants were enrolled into the Run-In Period. Of these participants, 207 participants were randomized to receive study drug in the On-Demand treatment period.

Run-In Period

Participant flow — Run-In Period
Milestone	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: On-Demand Treatment Period
Started	458	0	0	0	0
Completed	207	0	0	0	0
Not completed	251	0	0	0	0
Withdrew: Adverse event	6	0	0	0	0
Withdrew: Lost to follow-up	4	0	0	0	0
Withdrew: Significant protocol deviation	1	0	0	0	0
Withdrew: Withdrawal by subject	11	0	0	0	0
Withdrew: Miscellaneous	3	0	0	0	0
Withdrew: Did not meet on-demand eligibility criteria	226	0	0	0	0

On-Demand Treatment Period

Participant flow — On-Demand Treatment Period
Milestone	Vonoprazan 10 mg: On-Demand Treatment Period	Vonoprazan 20 mg: On-Demand Treatment Period	Vonoprazan 40 mg: On-Demand Treatment Period	Placebo: On-Demand Treatment Period
Started	52	52	51	52
Completed	51	52	49	48
Not completed	1	0	2	4
Withdrew: Adverse event	1	0	0	1
Withdrew: Lost to follow-up	0	0	0	1
Withdrew: Significant protocol deviation	0	0	1	0
Withdrew: Withdrawal by subject	0	0	1	0
Withdrew: Lack of efficacy	0	0	0	1
Withdrew: Miscellaneous	0	0	0	1

Outcome measures

PrimaryPercentage 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.

Time frame:: On-Demand Treatment Period: Day 1 to Day 42
Reported as:: Number · percentage of heartburn episodes

Percentage of Evaluable Heartburn Episodes Completely Relieved Within 3 Hours and With No Further Heartburn Reported for 24 Hours After Taking Study Drug
percentage of heartburn episodes	Vonoprazan 10 mg: On-Demand Treatment Period	Vonoprazan 20 mg: On-Demand Treatment Period	Vonoprazan 40 mg: On-Demand Treatment Period	Placebo: On-Demand Treatment Period
Percentage of Evaluable Heartburn Episodes Completely Relieved Within 3 Hours and With No Further Heartburn Reported for 24 Hours After Taking Study Drug	56.0	60.6	70.0	27.3

Statistical analysis

Vonoprazan 10 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Fisher Exact · p = <0.0001 · Percentage difference: 28.7 · 95% CI 21.84 to 35.55
Vonoprazan 20 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Fisher Exact · p = <0.0001 · Percentage difference: 33.3 · 95% CI 26.28 to 40.23
Vonoprazan 40 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Fisher Exact · p = <0.0001 · Percentage difference: 42.7 · 95% CI 35.92 to 49.42

SecondaryPercentage 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.

Time frame:: On-Demand Treatment Period: Day 1 to Day 42
Reported as:: Number · percentage of heartburn episodes

Percentage of Evaluable Heartburn Episodes Completely Relieved Within 3 Hours After Taking Study Drug
percentage of heartburn episodes	Vonoprazan 10 mg: On-Demand Treatment Period	Vonoprazan 20 mg: On-Demand Treatment Period	Vonoprazan 40 mg: On-Demand Treatment Period	Placebo: On-Demand Treatment Period
Percentage of Evaluable Heartburn Episodes Completely Relieved Within 3 Hours After Taking Study Drug	72.1	65.7	79.6	41.9

Statistical analysis

Vonoprazan 10 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Fisher Exact · p = <0.0001 · Percentage difference: 30.3 · 95% CI 23.41 to 37.09
Vonoprazan 20 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Fisher Exact · p = <0.0001 · Percentage difference: 23.9 · 95% CI 16.67 to 31.05
Vonoprazan 40 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Fisher Exact · p = <0.0001 · Percentage difference: 37.7 · 95% CI 31.00 to 44.35

SecondaryPercentage 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.

Time frame:: On-Demand Treatment Period: Day 1 to Day 42
Reported as:: Mean · % of heartburn episodes per participant

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
% of heartburn episodes per participant	Vonoprazan 10 mg: On-Demand Treatment Period	Vonoprazan 20 mg: On-Demand Treatment Period	Vonoprazan 40 mg: On-Demand Treatment Period	Placebo: On-Demand Treatment Period
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	60.08 ± 38.452	60.78 ± 37.458	71.99 ± 28.894	47.77 ± 40.998

Statistical analysis

Vonoprazan 10 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Wilcoxon rank-sum test · p = 0.1771
Vonoprazan 20 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Wilcoxon rank-sum test · p = 0.1551
Vonoprazan 40 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Wilcoxon rank-sum test · p = 0.0094

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

Time frame:: On-Demand Treatment Period: Day 1 to Day 42
Reported as:: Mean · tablets of rescue antacid per day

Mean Number of Tablets of Rescue Antacid Taken Per Day Over the On-Demand Treatment Period
tablets of rescue antacid per day	Vonoprazan 10 mg: On-Demand Treatment Period	Vonoprazan 20 mg: On-Demand Treatment Period	Vonoprazan 40 mg: On-Demand Treatment Period	Placebo: On-Demand Treatment Period
Mean Number of Tablets of Rescue Antacid Taken Per Day Over the On-Demand Treatment Period	0.1 ± 0.21	0.2 ± 0.29	0.1 ± 0.26	0.5 ± 0.87

Statistical analysis

Vonoprazan 10 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Wilcoxon rank-sum test · p = 0.3395
Vonoprazan 20 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Wilcoxon rank-sum test · p = 0.4882
Vonoprazan 40 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Wilcoxon rank-sum test · p = 0.0722

SecondaryPercentage 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.

Time frame:: On-Demand Treatment Period: Day 1 to Day 42
Reported as:: Number · percentage of participants

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
percentage of participants	Vonoprazan 10 mg: On-Demand Treatment Period	Vonoprazan 20 mg: On-Demand Treatment Period	Vonoprazan 40 mg: On-Demand Treatment Period	Placebo: On-Demand Treatment Period
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	56.5	61.9	62.8	60.5

Statistical analysis

Vonoprazan 10 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Fisher Exact · p = 0.8300 · Percentage difference: -3.9 · 95% CI -24.41 to 16.52
Vonoprazan 20 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Fisher Exact · p = >0.9999 · Percentage difference: 1.4 · 95% CI -19.28 to 22.16
Vonoprazan 40 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Fisher Exact · p = >0.9999 · Percentage difference: 2.3 · 95% CI -18.22 to 22.88

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

Time frame:: On-Demand Treatment Period: Day 1 to Day 42
Reported as:: Mean · percentage of days

Percentage of Days Study Drug Was Taken Over the On-Demand Treatment Period
percentage of days	Vonoprazan 10 mg: On-Demand Treatment Period	Vonoprazan 20 mg: On-Demand Treatment Period	Vonoprazan 40 mg: On-Demand Treatment Period	Placebo: On-Demand Treatment Period
Percentage of Days Study Drug Was Taken Over the On-Demand Treatment Period	21.93 ± 19.241	20.75 ± 16.950	21.01 ± 17.302	22.15 ± 23.266

Statistical analysis

Vonoprazan 10 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Wilcoxon rank-sum test · p = 0.4684
Vonoprazan 20 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Wilcoxon rank-sum test · p = 0.6560
Vonoprazan 40 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Wilcoxon rank-sum test · p = 0.6324

SecondaryPercentage 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.

Time frame:: On-Demand Treatment Period: Day 1 to Day 42
Reported as:: Mean · percentage of days

Percentage of 24-Hour Heartburn-Free Days Over the On-Demand Treatment Period
percentage of days	Vonoprazan 10 mg: On-Demand Treatment Period	Vonoprazan 20 mg: On-Demand Treatment Period	Vonoprazan 40 mg: On-Demand Treatment Period	Placebo: On-Demand Treatment Period
Percentage of 24-Hour Heartburn-Free Days Over the On-Demand Treatment Period	74.95 ± 21.410	73.57 ± 21.465	74.01 ± 22.277	71.22 ± 28.867

Statistical analysis

Vonoprazan 10 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Wilcoxon rank-sum test · p = 0.9896
Vonoprazan 20 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Wilcoxon rank-sum test · p = 0.6916
Vonoprazan 40 mg: On-Demand Treatment Period vs Placebo: On-Demand Treatment Period · Wilcoxon rank-sum test · p = 0.9316

Adverse events

Collected over Run-In Period: Day 1 to Day 28; On-Demand Treatment: Day 1 to Day 49. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Run-In Period	0/457 (0%)	4/457 (0.9%)	29/457 (6.3%)
Vonoprazan 10 mg: On-Demand Treatment Period	0/49 (0%)	0/49 (0%)	8/49 (16.3%)
Vonoprazan 20 mg: On-Demand Treatment Period	0/49 (0%)	0/49 (0%)	9/49 (18.4%)
Vonoprazan 40 mg: On-Demand Treatment Period	0/48 (0%)	0/48 (0%)	8/48 (16.7%)
Placebo: On-Demand Treatment Period	0/47 (0%)	0/47 (0%)	10/47 (21.3%)

Most frequent serious events

Most frequent serious events
Event	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: On-Demand Treatment Period
Acute myocardial infarctionCardiac disorders	1/457	0/49	0/49	0/48	0/47
Myocardial infarctionCardiac disorders	1/457	0/49	0/49	0/48	0/47
Anaphylactic reactionImmune system disorders	1/457	0/49	0/49	0/48	0/47
Suicidal ideationPsychiatric disorders	1/457	0/49	0/49	0/48	0/47

Most frequent other events

Showing 10 of 41

Most frequent other events
Event	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: On-Demand Treatment Period
Atrioventricular block first degreeCardiac disorders	0/457	0/49	0/49	0/48	1/47
MelaenaGastrointestinal disorders	0/457	0/49	0/49	0/48	1/47
Chest discomfortGeneral disorders	0/457	0/49	0/49	0/48	1/47
Breast abscessInfections and infestations	0/457	0/49	0/49	0/48	1/47
COVID-19Infections and infestations	2/457	1/49	1/49	1/48	1/47
CystitisInfections and infestations	0/457	0/49	0/49	0/48	1/47
Upper respiratory tract infectionInfections and infestations	0/457	0/49	0/49	1/48	1/47
Post-traumatic painInjury, poisoning and procedural complications	0/457	0/49	0/49	0/48	1/47
Gamma-glutamyltransferase increasedInvestigations	1/457	0/49	0/49	0/48	1/47
Back painMusculoskeletal and connective tissue disorders	2/457	0/49	0/49	0/48	1/47

Baseline characteristics

On-Demand Treatment Period: The Safety On-Demand Set included all participants in the Safety Run-In Set who were randomized and treated at least one heartburn episode with randomized treatment during the On-Demand Treatment period.

Age, Continuous
Age, Continuous(years)	Vonoprazan 10 mg: On-Demand Treatment Period	Vonoprazan 20 mg: On-Demand Treatment Period	Vonoprazan 40 mg: On-Demand Treatment Period	Placebo: On-Demand Treatment Period	Total
Mean	54.1 ± 11.89	55.7 ± 12.87	52.0 ± 14.60	52.7 ± 15.20	53.7 ± 13.65

Sex: Female, Male
Sex: Female, Male(Participants)	Vonoprazan 10 mg: On-Demand Treatment Period	Vonoprazan 20 mg: On-Demand Treatment Period	Vonoprazan 40 mg: On-Demand Treatment Period	Placebo: On-Demand Treatment Period	Total
Female	27	33	25	33	118
Male	22	16	23	14	75

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Vonoprazan 10 mg: On-Demand Treatment Period	Vonoprazan 20 mg: On-Demand Treatment Period	Vonoprazan 40 mg: On-Demand Treatment Period	Placebo: On-Demand Treatment Period	Total
Hispanic or Latino	16	17	15	12	60
Not Hispanic or Latino	33	32	33	35	133
Unknown or Not Reported	0	0	0	0	0

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Vonoprazan 10 mg: On-Demand Treatment Period	Vonoprazan 20 mg: On-Demand Treatment Period	Vonoprazan 40 mg: On-Demand Treatment Period	Placebo: On-Demand Treatment Period	Total
White	32	36	39	29	136
Black or African-American	7	5	6	10	28
Asian	8	6	3	7	24
American Indian or Alaska Native	0	1	0	0	1
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Other	0	0	0	0	0
Unknown	1	0	0	0	1
Not reported	1	1	0	1	3

08

Study locations

63 sites

Pinnacle Research Group
Anniston, Alabama 36207, United States
North Alabama Research Center LLC
Athens, Alabama 35611-2456, United States
Medical Affiliated Research Center Inc
Huntsville, Alabama 35801, United States
Elite Clinical Studies, LLC
Phoenix, Arizona 85018, United States
Del Sol Research Management - Clinedge
Tucson, Arizona 85712-5637, United States
Preferred Research Partners - ClinEdge
Little Rock, Arkansas 72211-3868, United States
Arkansas Gastroenterology
North Little Rock, Arkansas 72117-2924, United States
GW Research, Inc
Chula Vista, California 91910-3906, United States
eStudySite
Chula Vista, California 91911-6660, United States
Paragon Rx Clinical
Garden Grove, California 92840-3103, United States
OM Research LLC
Lancaster, California 93534-5504, United States
Medical Associates Research Group, Inc.
San Diego, California 92123-4207, United States
Paragon Rx Clinical, Inc.
Santa Ana, California 92703-1811, United States
Western States Clinical Research Inc
Wheat Ridge, Colorado 80033-6800, United States
Imagine Research of Palm Beach County
Boynton Beach, Florida 33435-5610, United States
Riverside Clinical Research
Edgewater, Florida 32132, United States
Nature Coast Clinical Research
Inverness, Florida 34452-4717, United States
ENCORE Borland-Groover Clinical Research
Jacksonville, Florida 32256-6004, United States
ClinCloud
Maitland, Florida 32751-3320, United States
G. Medical Center
Orlando, Florida 32807-4346, United States
Advanced Gastroenterology Associates, LLC
Palm Harbor, Florida 34684, United States
Clinical Research Center of Florida
Pompano Beach, Florida 33060-6934, United States
Precision Clinical Research, LLC
Sunrise, Florida 33351-7311, United States
Guardian Angel Research Center
Tampa, Florida 33614, United States
Florida Medical Clinic, LLC Clinical Research Division
Zephyrhills, Florida 33542, United States
IACT Health
Columbus, Georgia 31904-8946, United States
In Quest Medical Research
Suwanee, Georgia 30024-9134, United States
Treasure Valley Medical Research
Boise, Idaho 83706-1345, United States
Care Access
Chicago, Illinois 60616, United States
Iowa Digestive Disease Center
Clive, Iowa 50325-8151, United States
Clinical Trials Management LLC
Covington, Louisiana 70433-4966, United States
Legacy Clinical Solutions: Tandem Clinical Research, LLC
Marrero, Louisiana 70072-3156, United States
Clinical Trials Management LLC
Metairie, Louisiana 70006-4165, United States
Investigative Clinical Research
Annapolis, Maryland 21401-1091, United States
Gastroenterology Associates of Western Michigan, PLC
Wyoming, Michigan 49519-9691, United States
GI Associates and Endoscopy Center
Flowood, Mississippi 39232, United States
Quality Clinical Research
Omaha, Nebraska 68114, United States
Sierra Clinical Research - ClinEdge
Las Vegas, Nevada 89106-4159, United States
Site 2
Las Vegas, Nevada 89119, United States
Site 1
Las Vegas, Nevada 89128, United States
Advanced Research Institute
Reno, Nevada 89511, United States
Drug Trials America
Hartsdale, New York 10530-1837, United States
Javara Inc
Charlotte, North Carolina 28287-3884, United States
Medication Management LLC
Greensboro, North Carolina 27408-7099, United States
Carolina Research
Greenville, North Carolina 27834-3761, United States
Peters Medical Research, LLC
High Point, North Carolina 27262-4800, United States
Trial Management Associates LLC
Wilmington, North Carolina 28403-7018, United States
Remington Davis Inc
Columbus, Ohio 43215-7098, United States
Frontier Clinical Research, LLC
Uniontown, Pennsylvania 15401-9069, United States
Coastal Carolina Research Center
North Charleston, South Carolina 29405, United States
Rapid City Medical Center LLP
Rapid City, South Dakota 57701-5462, United States
Clinical Research Associates Inc
Nashville, Tennessee 37203-2066, United States
Inquest Clinical Research
Baytown, Texas 77521-2416, United States
Family Medicine Associates of Texas
Carrollton, Texas 75010, United States
Synergy Group US, LLC
Houston, Texas 77036, United States
Biopharma Informatic, LLC
Houston, Texas 77084, United States
Rio Grande Gastroenterology
McAllen, Texas 78530, United States
Quality Research Inc
San Antonio, Texas 78209-1744, United States
Gastroenterology Research of San Antonio (GERSA)
San Antonio, Texas 78229-3270, United States
Sherman Clinical Research
Sherman, Texas 75092, United States
Advanced Research Institute
Ogden, Utah 84405, United States
Advanced Research Institute
Sandy, Utah 84092-4350, United States
Virginia Gastroenterology Institute
Suffolk, Virginia 23435, United States

09

References and documents

Study documents

Study protocol ↗ · Jul 16, 2021
Statistical analysis plan ↗ · Jan 25, 2022

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No — Data from this study will be published; however, it is undecided if patient level data will be made available at this time.

10

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jan 4, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

11

Registry details

Key details

Study ID: NCT04799158
Lead sponsor: Phathom Pharmaceuticals, Inc.
Responsible party: Sponsor
First posted: Mar 16, 2021
Start date: Mar 25, 2021
Primary completion: Dec 16, 2021
Completion: Jan 17, 2022
Results posted: Jan 4, 2023
Last update: Jan 4, 2023

Study contacts

Medical Director

study director · Phathom Pharmaceuticals

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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

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