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

NCT02743949 | Completed Phase 2 Results

• 4 other identifiers: Vonoprazan-2001U1111-1172-23732015-001154-1416/LO/0285
• Study Type: interventional
• Target: 256
• Locations: 6 countries
• Sites: 39

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.

Conditions

Gastroesophageal Reflux

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Heartburn-Free 24-Hour Periods (Day and Night) During 4 Weeks of Treatment

  Participants used the Reflux Symptom Questionnaire Electronic Diary (RESQ-eD) every morning upon waking and every evening before going to sleep to document the presence of daytime and nighttime heartburn and regurgitation. The percentage of heartburn-free (HBF) 24-hour periods was calculated for each participant using the following formula: (total 24-hour periods that are heartburn free / total 24-hour periods for which both a daytime and nighttime result is marked) x 100%.

  4 Weeks

Secondary Outcomes (1)

• Percentage of Participants With ≥1 Sustained Resolution of Heartburn During the 4-Week Treatment Period

  4 Weeks

Study Arms (3)

Esomeprazole 40 mg

ACTIVE COMPARATOR

Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by esomeprazole 40 mg, over encapsulated tablets, orally, once daily for 4 weeks during the active treatment period.

Drug: Vonoprazan; Drug: Esomeprazole; Drug: Esomeprazole Placebo

Vonoprazan 20 mg

EXPERIMENTAL

Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 20 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the treatment period.

Drug: Vonoprazan; Drug: Esomeprazole; Drug: Esomeprazole Placebo

Vonoprazan 40 mg

EXPERIMENTAL

Esomeprazole 40 mg over-encapsulated tablets, orally, once daily for 4 weeks then esomeprazole placebo-matching capsules, orally, once daily for 2 weeks during the run-in period, followed by vonoprazan 40 mg, over-encapsulated capsules, orally, once daily for 4 weeks during the active treatment period.

Drug: Esomeprazole; Drug: Esomeprazole Placebo

Interventions

Vonoprazan DRUG

Vonoprazan over-encapsulated capsules

Also known as: TAK-438

Esomeprazole 40 mg; Vonoprazan 20 mg

Esomeprazole DRUG

Esomeprazole over-encapsulated tablets

Esomeprazole 40 mg; Vonoprazan 20 mg; Vonoprazan 40 mg

Esomeprazole Placebo DRUG

Esomeprazole placebo-matching capsules

Esomeprazole 40 mg; Vonoprazan 20 mg; Vonoprazan 40 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• 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.
• Is a man or a woman and ≥18 years of age, at the time of the Screening visit.
• Has a documented history of symptoms of both heartburn (burning pain) and acid regurgitation prior to entry into the study.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• Has received any investigational compound within 30 days prior to the Screening Visit.
• Has received vonoprazan in a previous clinical study.
• 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.
• Has, in the judgment of the investigator, clinically significant abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes at Screening.
• Has a history of erosive esophagitis of Los Angeles (LA) Classification Grade B severity or worse prior to screening or at Screening endoscopy.
• 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.
• Has current or historical chest pain due to cardiac diseases (eg, within one year).
• 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.
• Has had an acute upper gastrointestinal hemorrhage within 30 days prior to Screening.
• Has current or historical evidence of Zollinger-Ellison syndrome or other hypersecretory condition.
• 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.
• Has a documented history of familial adenomatous polyposis.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (39)

Medif

Gozée, 6534, Belgium

Location

SPRL Dr Yvan CALOZET

Grigomont, 6887, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

SPRL MG Balthazar & Ballard

Natoye, 5360, Belgium

Location

Mortelmans, Jaak

Oostham, 3945, Belgium

Location

DCC 'Sv. Pantaleymon' OOD

Pleven, 5800, Bulgaria

Location

UMHAT "Kaspela", EOOD

Plovdiv, 4002, Bulgaria

Location

MHAT - Ruse, AD

Rousse, 7002, Bulgaria

Location

MHAT "Hadzhi Dimitar", OOD

Sliven, 8800, Bulgaria

Location

NMTH "Tsar Boris III"

Sofia, 1233, Bulgaria

Location

"City Clinic UMHAC" EOOD

Sofia, 1407, Bulgaria

Location

MHAT 'Tokuda Hospital Sofia', EAD

Sofia, 1407, Bulgaria

Location

UMHAT "Sv. Ivan Rilski", EAD

Sofia, 1431, Bulgaria

Location

UMHAT 'Tsaritsa Yoanna - ISUL', EAD

Sofia, 1527, Bulgaria

Location

Fourth MHAT - Sofia EAD

Sofia, 1606, Bulgaria

Location

UMHAT "SofiaMed", OOD

Sofia, 1797, Bulgaria

Location

Okresni nemocniceStrakonice

Strakonice, 386 01, Czechia

Location

OU Innomedica

Tallinn, 10117, Estonia

Location

Merekivi Perearstid OU

Tallinn, 10617, Estonia

Location

Merelahe Family Doctors Centre

Tallinn, 10617, Estonia

Location

West Tallinn Central Hospital

Tallinn, 10617, Estonia

Location

North Estonia Medical Centre Foundation

Tallinn, 13419, Estonia

Location

Tartu University Hospital

Tartu, 51014, Estonia

Location

SP ZOZ Wojewodzki Szpital Zespolony im. J. Sniadeckiego

Bialystok, 15-275, Poland

Location

NZOZ Inter-Med

Częstochowa, 42-217, Poland

Location

Centrum Medyczne Plejady

Krakow, 30-349, Poland

Location

Gabinet Endoskopii Przewodu Pokarmowego

Krakow, 31-009, Poland

Location

Centrum Medyczne Medyk

Rzeszów, 35-055, Poland

Location

Specjalistyczna Praktyka Lekarska Dr med. Marek Horynski

Sopot, 81-756, Poland

Location

SONOMED Sp.z o.o

Szczecin, 71-685, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej Nasz Lekarz Praktyka Grupowa Lekarzy Rodzinnych z

Torun, 87-100, Poland

Location

Nzoz Vivamed

Warsaw, 03-580, Poland

Location

LexMedica Osrodek Badan Klinicznych

Wroclaw, 53-114, Poland

Location

EMC Instytut Medyczny S.A.

Wroclaw, 54-144, Poland

Location

Plympton Health Centre

Plymouth, Devon, PL7 1AD, United Kingdom

Location

Whipps Cross University Hospital

London, Greater London, E11 1NR, United Kingdom

Location

Sheepcot Medical Centre

Watford, Hertfordshire, WD25 0EA, United Kingdom

Location

Royal Stoke University Hospital

Stoke-on-Trent, Staffordshire, ST4 6QG, United Kingdom

Location

CPS Research

Glasgow, Strathclyde, G20 0XA, United Kingdom

Location

MeSH Terms

Conditions

Gastroesophageal Reflux

Interventions

1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; Esomeprazole

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

43 more participants enrolled due to lower screen failure rate in the 5 new sites and the long run in period limited predictability of enrolment in advance. Measures had been implemented maintaining scientific integrity and participant safety.

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2016
• First Posted: April 19, 2016
• Study Start: July 14, 2016
• Primary Completion: October 5, 2018
• Study Completion: October 12, 2018
• Last Updated: February 18, 2020
• Results First Posted: February 18, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share

Locations

BE (5); PL (11); GB (5); BU (11); ES (6); CZ (1)