Comparison of Vonoprazan to Esomeprazole in Participants With Symptomatic GERD Who Responded Partially to a High Dose of Proton Pump Inhibitor (PPI)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02743949
• Date of registration: 14/04/2016
• Prospective Registration: Yes
• Primary sponsor: Takeda
• Public title: Comparison of Vonoprazan to Esomeprazole in Participants With Symptomatic GERD Who Responded Partially to a High Dose of Proton Pump Inhibitor (PPI)
• Scientific title: A Randomized, Double-Blind, Proof-of-Concept, Phase 2 Study to Evaluate the Efficacy and Safety of Once Daily Oral Vonoprazan 20 mg or Vonoprazan 40 mg Compared to Esomeprazole 40 mg for the Treatment of Subjects With Symptomatic Gastro-Esophageal Reflux Disease Who Have a Partial Response Following Treatment With a High Dose of Proton Pump Inhibitor
• Date of first enrolment: July 14, 2016
• Target sample size: 256
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02743949
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Belgium, Bulgaria, Czech Republic, Czechia, Estonia, Poland, United Kingdom

Contacts

• Name: Medical Director Clinical Science
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding and
complying with protocol requirements.

2. The participant or, when applicable, the participant's legally acceptable
representative signs and dates a written, informed consent form and any required
privacy authorization prior to the initiation of any study procedures.

3. Is a man or a woman and =18 years of age, at the time of the Screening visit.

4. Has a documented history of symptoms of both heartburn (burning pain) and acid
regurgitation prior to entry into the study.

5. The subject has a medical history of = 8 weeks of persistent heartburn symptoms in the
presence of regurgitation symptoms (persistent heartburn symptoms defined as heartburn
symptoms on = 2 days a week) that are troublesome despite appropriate and correctly
performed treatment with a PPI at standard doses.

6. Is =85% compliant at taking their Run-in medication and completing their e-Diary.
Compliance for taking the Run-in medication is defined as the medication provided
(esomeprazole and placebo) taken for 85% of the 6 weeks Run-in Period (or on 36 of 42
days of the Run-in Period).Compliance for the e-Diary is defined as the percentage of
scheduled assessments that are completed based on 2 assessments per day (daytime and
nighttime). For randomization, 85% compliance is required and is defined as 12 of 14
assessments completed over the 7-day period (Day -21 to Day-14) prior to the single
blind Placebo Run-in Period.

7. Has a partial response to a PPI defined as having heartburn on 2 to 5 days and
regurgitation on at least one day of the last week (Week 4) of a 4 week PPI Run-In
Period with esomeprazole 40 mg and an increase of at least 2 symptom days of heartburn
in the last week of a 2 week Placebo Run-In Period (4 to 7 symptom days) and at least
one symptom day with regurgitation compared with the last week of the PPI Run-In
Period.

8. A female participant of childbearing potential who is sexually active with a
nonsterilized male partner agrees to use routinely adequate contraception from signing
of informed consent throughout the duration of the study and for 4 weeks after last
dose of the study medication.

Exclusion Criteria:

1. Has received any investigational compound within 30 days prior to the Screening Visit.

2. Has received vonoprazan in a previous clinical study.

3. Is an immediate family member, study site employee, is in a dependent relationship
with a study site employee who is involved in conduct of this study (eg, spouse,
parent, child, sibling), or may have consented under duress.

4. Has, in the judgment of the investigator, clinically significant abnormal
hematological parameters of hemoglobin, hematocrit, or erythrocytes at Screening.

5. Has a history of erosive esophagitis of Los Angeles (LA) Classification Grade B
severity or worse prior to screening or at Screening endoscopy.

6. Has a history of or any coexisting diseases affecting the esophagus (eg, Barrett's
esophagus, eosinophilic esophagitis, esophageal varices, scleroderma, viral or fungal
infection, or esophageal stricture), history of radiation therapy or cryotherapy to
the esophagus, caustic trauma, or physiochemical trauma such as sclerotherapy to the
esophagus.

7. Has "alarm features" in symptomatology, including odynophagia, severe dysphagia,
bleeding, weight loss, anemia, and blood in stool, pointing to a possible malignant
disease of the gastrointestinal (GI) tract. Participants displaying "alarm symptoms"
in addition to the "typical" gastroesophageal reflux disease (GERD) symptoms may be
included based on endoscopic exclusion of malignancy.

8. Has current or historical chest pain due to cardiac diseases (eg, within one year).

9. Has had surgical treatment for GERD (eg, cardiaplasty), dilation of an esophageal
stricture (other than Schatzki ring) or gastric or duodenal surgery, except simple
oversew of an ulcer or endoscopic polypectomy of benign polyps.

10. Has active gastric or duodenal ulcers which have been confirmed by endoscopy within 30
days prior to Screening. Gastric or duodenal erosions are not exclusionary, unless
considered severe and symptomatic by the investigator.

11. Has had an acute upper gastrointestinal hemorrhage within 30 days prior to Screening.

12. Has current or historical evidence of Zollinger-Ellison syndrome or other
hypersecretory condition.

13. Has current or historical evidence of eosinophilic esophagitis (evidence may be based
on the following: missing response to acid suppressive therapy, the presence of
eosinophilia in histological probes of the esophageal mucosa, a normal pH profile of
the distal esophagus, symptoms of dysphagia and food impaction). The exclusion of
participants based on a predominance of the "typical" eosinophilic esophagitis
symptoms only (as above) is considered acceptable. However, in participants with a
predominance of "typical" symptoms and co-existing significant dysphagia and food
impaction, the syndrome should be excluded by endoscopy with biopsy.

14. Has a documented history (within 6 months prior to screening) of functional dyspepsia
(suggested by the presence of one or more of the following symptoms: epigastric pain,
postprandial fullness or early satiety), or irritable bowel syndrome or other
gastrointestinal diseases which are not acid-related, and therefore, are nonresponsive
to gastric acid-blocking treatment.

15. Has a documented history of familial adenomatous polyposis.

16. Has known intolerance, hypersensitivity or allergies to any PPI or their components
(including lansoprazole, dexlansoprazole, omeprazole, rabeprazole, pantoprazole, or
esomeprazole), any component of vonoprazan, or antacid(s) selected as rescue
medication for this study.

17. Has a history of alcohol abuse, illegal drug use, or drug addiction within the 12
months prior to Screening, 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.
Participants must have a negative drug screen at Screening.

18. Has evidence of a serious uncontrolled concomitant disease including: clinically
significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic,
gastrointestinal, systemic, or endocrine disease or other abnormality (other than the
disease being studied), which may impact the ability of the participant to participate
or potentially confound the study results.


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Gastroesophageal Reflux

Intervention(s)

Drug: Esomeprazole Placebo

Drug: Esomeprazole

Drug: Vonoprazan

Primary Outcome(s)

Percentage of Heartburn-Free 24-Hour Periods (Day and Night) During 4 Weeks of Treatment [Time Frame: 4 Weeks]

Secondary Outcome(s)

Percentage of Participants With =1 Sustained Resolution of Heartburn During the 4-Week Treatment Period [Time Frame: 4 Weeks]

Secondary ID(s)

2015-001154-14

U1111-1172-2373

16/LO/0285

Vonoprazan-2001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 18/02/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02743949