Clinical trial NCT01472939: Selective 5-HT4 Receptor Agonist and Proton Pump Inhibitor (PPI) in Subjects With Gastroesophageal Reflux Disease (GERD)
Official title: A Phase 2b, Double-blind, Randomized, Placebo-controlled, Dose-finding Study to Evaluate Efficacy of a Selective 5-HT4 Receptor Agonist and Proton Pump Inhibitor (PPI) in Subjects With Gastroesophageal Reflux Disease (GERD) With Persistent Regurgitation With or Without Heartburn
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastroesophageal Reflux Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-11-17
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to establish a dose-related effect of a selective 5-HT4 receptor agonist compared to placebo on residual symptoms (regurgitation with or without heartburn) in subjects with GERD who have persistent symptoms while on PPI therapy.


Eligibility criteria: Inclusion Criteria:

1. Written Informed Consent Form signed voluntarily before the first study-related activity.
2. Aged between 18 and 70 years, inclusive.
3. Subjects with a history of the cardinal symptoms of GERD (both heartburn and regurgitation) prior to PPI therapy.
4. Subjects with symptoms of GERD for at least 6 months prior to the Screening Visit.
5. Subjects who have persistent symptoms of regurgitation for 3 or more days over the past week with or without heartburn while on PPI.
6. Subjects have at least some improvement to the symptom of heartburn while on PPI therapy.
7. Subjects on PPI therapy for at least 8 weeks prior to the Screening Visit of which the last 4 weeks are on a stable labeled dose for any GERD indication according to the country label, where a change of PPI therapy would not impact the symptoms (twice-daily dosing of PPI is not allowed in the last 4 weeks)

Exclusion Criteria:

1. Subjects who show no response to heartburn while on PPI therapy.
2. Subjects with dyspepsia symptoms that are more predominant than their GERD symptoms (heartburn and/or regurgitation).
3. Subjects with prior endoscopic anti-reflux procedure or major GI surgery or subjects with major GI disorders.
4. Presence of severe and clinically uncontrolled cardiovascular, liver, lung or neurologic disease, cancer or AIDS.
5. Alarm symptoms suggestive of malignancies or organic disease.

Primary outcomes:
measure: Change From Baseline in Percent Regurgitation-Free Days Over Weeks 5-8
timeFrame: Baseline and over weeks 5-8
Secondary outcomes:
measure: Change From Baseline in Heartburn-Free Days Over Weeks 5-8
timeFrame: Baseline and over weeks 5-8
measure: Change From Baseline in the Persistent Reflux Integrated Symptom Measurement (PRISM) Liquid and Food Domain Scores Over Weeks 5-8
timeFrame: Baseline and over weeks 5-8
measure: Area Under the Steady-state Plasma Concentration-time Curve (AUC) of SSP-002358
timeFrame: Over 8 hours post-dose (week 2 or later)
measure: Steady State Maximum Plasma Concentration (Cmax) of SSP-002358
timeFrame: Over 8 hours post-dose (week 2 or later)
measure: Time to Maximum Plasma Concentration (Tmax) of SSP-002358
timeFrame: Over 8 hours post-dose (week 2 or later)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: HOPE Research Institute
state: Arizona
city: Tucson
country: United States
facility: Genova Clinical Research
state: Arizona
city: Little Rock
country: United States
facility: Lynn Institute of the Ozarks
state: Arkansas
city: Little Rock
country: United States
facility: Preferred Research Partners, Inc
state: Arkansas
city: North Little Rock
country: United States
facility: Arkansas Gastroenterology
state: Arkansas
city: Anaheim
country: United States
facility: Anaheim Clinical Trials
state: California
city: Los Angeles
country: United States
facility: Southern California Research Institute Medical Group Inc
state: California
city: San Diego
country: United States
facility: Medical Center for Clinical Research
state: California
city: Colorado Springs
country: United States
facility: Clinicos
state: Colorado
city: Bristol
country: United States
facility: Connecticut Gastroenterology Institute
state: Connecticut
city: Stamford
country: United States
facility: Stamford Therapeutics Consortium
state: Connecticut
city: Aventura
country: United States
facility: Medical Research Unlimited, LLC
state: Florida
city: Boynton Beach
country: United States
facility: Consultants for Clinical Research of South Florida
state: Florida
city: Brandon
country: United States
facility: PAB Clinical Research
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Fort Lauderdale
country: United States
facility: S & W Clinical Research
state: Florida
city: Hialeah
country: United States
facility: Medical Research Unlimited, LLC
state: Florida
city: Jupiter
country: United States
facility: Jupiter Research
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Clinical Research, Inc.
state: Florida
city: Pinellas Park
country: United States
facility: Radiant Research
state: Florida
city: Port Orange
country: United States
facility: Accord Clinical Research, LLC
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research
state: Florida
city: Marietta
country: United States
facility: Gastrointestinal Specialists of GA, PC
state: Georgia
city: Newnan
country: United States
facility: Digestive Research Associates
state: Georgia
city: Rockford
country: United States
facility: Rockford Gastroenterology Associates, Ltd
state: Illinois
city: Wichita
country: United States
facility: Professional Research Network of Kansas, LLC
state: Kansas
city: Owensboro
country: United States
facility: Research Integrity
state: Kentucky
city: Metairie
country: United States
facility: Clinical Trials Management
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana Research Center, LLC
state: Louisiana
city: Hagerstown
country: United States
facility: Meritus Medical Center
state: Maryland
city: Brockton
country: United States
facility: Beacon Clinical Research
state: Massachusetts
city: Mexico
country: United States
facility: Center for Digestive and Liver Diseases
state: Missouri
city: Bozeman
country: United States
facility: Clinical Research Group of Montana
state: Montana
city: Omaha
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada
state: Nevada
city: Clifton
country: United States
facility: New Jersey Physicians, LLC
state: New Jersey
city: Chapel Hill
country: United States
facility: UNC Hospitals
state: North Carolina
city: Davidson
country: United States
facility: Carolinas Research Associates
state: North Carolina
city: Fayetteville
country: United States
facility: Cumberland Research Associates
state: North Carolina
city: Greensboro
country: United States
facility: Vital Research, Inc.
state: North Carolina
city: Harrisburg
country: United States
facility: Carolinas Research Associates
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Franklin
country: United States
facility: Prestige Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Foundation for Digestive Research Sciences Center
state: Oklahoma
city: Levittown
country: United States
facility: Family Medical Associates
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Clinic, Ltd.
state: Pennsylvania
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Dakota Dunes
country: United States
facility: Meridian Clinical Research
state: South Dakota
city: Chattanooga
country: United States
facility: Clinsearch, LLC
state: Tennessee
city: Dallas
country: United States
facility: Radiant Research Dallas-North
state: Texas
city: Houston
country: United States
facility: GI Consultants, P.A.
state: Texas
city: Pasadena
country: United States
facility: Pasadena Gastroenterology Assoc, dba Digestive Health Center
state: Texas
city: San Antonio
country: United States
facility: Office Based Practitioner
state: Texas
city: Clinton
country: United States
facility: Advanced Research Institute
state: Utah
city: Logan
country: United States
facility: Advanced Research Institute
state: Utah
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Sandy
country: United States
facility: Advanced Research Institute
state: Utah
city: Christiansburg
country: United States
facility: New River Valley Research Institute
state: Virginia
city: Lynchburg
country: United States
facility: Blue Ridge Medical Center
state: Virginia
city: Suffolk
country: United States
facility: Ramstad Medical Associates
state: Virginia
city: Summit
country: United States
facility: Aurora Wilkinson Medical Clinic
state: Wisconsin
city: Hradec Kralove
country: Czechia
facility: Hepato-Gastroenterology HK s.r.o.
city: Valasske Mezirici
country: Czechia
facility: Nemocnice Valasske Mezirici a.s.
city: Bohlen
country: Germany
facility: Praxis Dr. Andreas Schwittay-Facharzt fuer Innere Medizin
city: Garmisch Partenkirchen
country: Germany
facility: Zentrum fur Innere Medizin, Klinikum Garmisch Partenkirchen
city: Ludwigshafen
country: Germany
facility: Haus der Gesundheit
city: Ludwigshafen
country: Germany
facility: Praxis für Gastroenterologie und fachärztliche Innere Medizin
city: Magdeburg
country: Germany
facility: Medizinische Fakultät der Otto-von-Guericke Universität
city: Potsdam
country: Germany
facility: Gemeinschaftspraxis Dres. Brandt
city: Wallerfing
country: Germany
facility: Gemeinschaftspraxis Dres Josef und Wilma Großkopf
city: Daugavpils
country: Latvia
facility: Daugavpils Regional Hospital
city: Riga
country: Latvia
facility: Pauls Stradins Clinical University Hospital
city: Riga
country: Latvia
facility: Digestive Disease Centre "Gastro"
city: Valmiera
country: Latvia
facility: Vidzemes Hospital
city: Bialystok
country: Poland
facility: NZOZ Specjalistyczne Centrum Gastrologii Gastromed
city: Czestochowa
country: Poland
facility: Centrum Medyczne im Swietego Lukasza Sp. z o.o.
city: Katowice
country: Poland
facility: NZOZ ''Salvia''
city: Lodz
country: Poland
facility: Centrum Medyczne Szpital sw. Rodziny Sp. z o.o.
city: Lublin
country: Poland
facility: Gastromed Sp. K. NZOZ
city: Sopot
country: Poland
facility: Endoskopia Sp. z o.o.
city: Warszawa
country: Poland
facility: NZOZ Vivamed
city: Wroclaw
country: Poland
facility: Lexmedica
city: Wroclaw
country: Poland
facility: Aktywne Centrum Zdrowia NZOZ ZAWIDAWIE Sp. z o.o.
city: Brasov
country: Romania
facility: Brasov County Hospital
city: Targu-Mures
country: Romania
facility: Centrul Medical Galenus
city: Timisoara
country: Romania
facility: Cabinet Particular Policlinic Algomed SRL
city: Timisoara
country: Romania
facility: Policlinica "Dr. Citu" SRL
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Shaheen NJ, Adler J, Dedrie S, Johnson D, Malfertheiner P, Miner P, Meulemans A, Poole L, Tack J, Thielemans L, Troy S, Vakil N, Zerbib F, Ruth M. Randomised clinical trial: the 5-HT4 agonist revexepride in patients with gastro-oesophageal reflux disease who have persistent symptoms despite PPI therapy. Aliment Pharmacol Ther. 2015 Apr;41(7):649-61. doi: 10.1111/apt.13115. Epub 2015 Feb 19.