Clinical trial NCT02743949: Comparison of Vonoprazan to Esomeprazole in Participants With Symptomatic GERD Who Responded Partially to a High Dose of Proton Pump Inhibitor (PPI)
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastroesophageal Reflux
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-04-19
Enrollment: 256
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 purpose of this study is to determine the effect of vonoprazan compared to esomeprazole for preventing heartburn symptoms over a 4-week treatment period in participants who have a partial response to treatment with esomeprazole.

Detailed description: The drug being tested in this study is called vonoprazan. Vonoprazan is being tested to treat people who have symptomatic gastroesophageal reflux disease (GERD) with a partial response to treatment with a high dose of esomeprazole. This study will look at improvement in heartburn symptoms in participants who take vonoprazan compared to esomeprazole.

The study will enroll approximately 213 patients. All participants will receive esomeprazole or esomeprazole placebo-matching capsules (this is a capsule that looks like esomeprazole but has no active ingredient) during a 7-week run-in period. Participants will then be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

* Esomeprazole 40 mg
* Vonoprazan 20 mg
* Vonoprazan 40 mg

All participants will be asked to take one capsule at the same time each day throughout the study. All participants will be asked to record heartburn symptoms in a diary every morning upon waking and every evening before going to sleep.

This multi-center trial will be conducted in Europe. The overall time to participate in this study is 12 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone 1 week after the last dose of study drug for a follow-up assessment.

Eligibility 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.
19. Has planned, or is likely to require, in-patient surgery during the course of the study.
20. Has a history of cancer (except basal cell carcinoma of the skin) within 3 years prior to Screening.
21. Is known to have acquired immunodeficiency syndrome or chronic hepatitis due to any etiology.
22. Has abnormal laboratory values at Screening that suggest a clinically significant underlying disease or condition that may prevent the participant from completing the study.
23. Has an alanine aminotransferase (ALT), aspartate aminotransferase (AST) or T-bilirubin level which exceeds upper limit of normal (ULN) set by the testing laboratory at the Screening.
24. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.
25. Is required to take excluded medications or it is anticipated that the participant will require treatment with at least 1 of the disallowed concomitant medications during the study.
26. In the opinion of the investigator, is unable to comply with the requirements of the study or is unsuitable for any reason.

Primary outcomes:
measure: Percentage of Heartburn-Free 24-Hour Periods (Day and Night) During 4 Weeks of Treatment
timeFrame: 4 Weeks
Secondary outcomes:
measure: Percentage of Participants With ≥1 Sustained Resolution of Heartburn During the 4-Week Treatment Period
timeFrame: 4 Weeks
Other outcomes:
Locations:
city: Gozee
country: Belgium
facility: Medif
city: Grigomont
country: Belgium
facility: SPRL Dr Yvan CALOZET
city: Leuven
country: Belgium
facility: UZ Leuven
city: Natoye
country: Belgium
facility: SPRL MG Balthazar & Ballard
city: Oostham
country: Belgium
facility: Mortelmans, Jaak
city: Pleven
country: Bulgaria
facility: DCC 'Sv. Pantaleymon' OOD
city: Plovdiv
country: Bulgaria
facility: UMHAT "Kaspela", EOOD
city: Ruse
country: Bulgaria
facility: MHAT - Ruse, AD
city: Sliven
country: Bulgaria
facility: MHAT "Hadzhi Dimitar", OOD
city: Sofia
country: Bulgaria
facility: NMTH "Tsar Boris III"
city: Sofia
country: Bulgaria
facility: "City Clinic UMHAC" EOOD
city: Sofia
country: Bulgaria
facility: MHAT 'Tokuda Hospital Sofia', EAD
city: Sofia
country: Bulgaria
facility: UMHAT "Sv. Ivan Rilski", EAD
city: Sofia
country: Bulgaria
facility: UMHAT 'Tsaritsa Yoanna - ISUL', EAD
city: Sofia
country: Bulgaria
facility: Fourth MHAT - Sofia EAD
city: Sofia
country: Bulgaria
facility: UMHAT "SofiaMed", OOD
city: Strakonice
country: Czechia
facility: Okresni nemocniceStrakonice
city: Tallinn
country: Estonia
facility: OU Innomedica
city: Tallinn
country: Estonia
facility: Merekivi Perearstid OU
city: Tallinn
country: Estonia
facility: Merelahe Family Doctors Centre
city: Tallinn
country: Estonia
facility: West Tallinn Central Hospital
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Bialystok
country: Poland
facility: SP ZOZ Wojewodzki Szpital Zespolony im. J. Sniadeckiego
city: Czestochowa
country: Poland
facility: NZOZ Inter-Med
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
city: Krakow
country: Poland
facility: Gabinet Endoskopii Przewodu Pokarmowego
city: Rzeszow
country: Poland
facility: Centrum Medyczne Medyk
city: Sopot
country: Poland
facility: Specjalistyczna Praktyka Lekarska Dr med. Marek Horynski
city: Szczecin
country: Poland
facility: SONOMED Sp.z o.o
city: Torun
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Nasz Lekarz Praktyka Grupowa Lekarzy Rodzinnych z
city: Warszawa
country: Poland
facility: Nzoz Vivamed
city: Wroclaw
country: Poland
facility: LexMedica Osrodek Badan Klinicznych
city: Wroclaw
country: Poland
facility: EMC Instytut Medyczny S.A.
city: Plymouth
country: United Kingdom
facility: Plympton Health Centre
state: Devon
city: London
country: United Kingdom
facility: Whipps Cross University Hospital
state: Greater London
city: Watford
country: United Kingdom
facility: Sheepcot Medical Centre
state: Hertfordshire
city: Stoke on Trent
country: United Kingdom
facility: Royal Stoke University Hospital
state: Staffordshire
city: Glasgow
country: United Kingdom
facility: CPS Research
state: Strathclyde
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: