Efficacy And Safety Of PF-00885706 For The Relief Of Symptoms In Subjects With Gastro-esophageal Reflux Disease (GERD)

A Parallel-Group, Randomized, Double-Blind, Multi-Center Dose Response Study To Evaluate The Efficacy And Safety Of PF-00885706, A 5-HT4 Receptor Partial Agonist, As Add-On Therapy To Esomeprazole For The Relief Of Symptoms In Subjects With Gastro-esophageal Reflux Disease (GERD) Who Have A Poor Response To Proton Pump Inhibitor (PPI) Treatment

To understand the dose-response characteristics of PF-00885706 for efficacy in terms of symptomatic relief when used as add-on treatment to esomeprazole 20mg (standard proton pump inhibitor [PPI] treatment), in subjects with gastro-esophageal reflux (GERD) who have inadequate relief with PPIs.

Study Overview

• Status: Terminated
• Conditions: Gastroesophageal Reflux Disease
• Intervention / Treatment: Drug: PF-00885706; Drug: Esomeprazole; Drug: PF-00885706; Drug: PF-00885706; Drug: PF-00885706; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Pfizer Investigational Site
• Brazil
  • BA
    • Salvador, BA, Brazil, 40420-000
      • Pfizer Investigational Site
  • RS
    • Porto Alegre, RS, Brazil, 90035-003
      • Pfizer Investigational Site
  • SP
    • Campinas, SP, Brazil, 13070-040
      • Pfizer Investigational Site
    • Sao Paulo, SP, Brazil, 01244-030
      • Pfizer Investigational Site
• France
  • Bordeaux cedex, France, 33075
    • Pfizer Investigational Site
  • Laval, France, 53000
    • Pfizer Investigational Site
  • Lyon CEDEX 03, France, 69003
    • Pfizer Investigational Site
  • Marseille, France, 13000
    • Pfizer Investigational Site
  • Nantes CEDEX 1, France, 44093
    • Pfizer Investigational Site
  • Rennes, France, 35000
    • Pfizer Investigational Site
  • Segre, France, 49500
    • Pfizer Investigational Site
  • Tours cedex 9, France, 37044
    • Pfizer Investigational Site
  • Cedex 3
    • Nice, Cedex 3, France, 06002
      • Pfizer Investigational Site
• Germany
  • Amberg, Germany, 92224
    • Pfizer Investigational Site
  • Berlin, Germany, 10117
    • Pfizer Investigational Site
  • Eisenach, Germany, 99817
    • Pfizer Investigational Site
  • Freising, Germany, 85356
    • Pfizer Investigational Site
  • Hamburg, Germany, 22143
    • Pfizer Investigational Site
  • Karlsruhe, Germany, 76199
    • Pfizer Investigational Site
  • Koenigslutter, Germany, 38154
    • Pfizer Investigational Site
  • Konstanz, Germany, 78464
    • Pfizer Investigational Site
  • Leipzig, Germany, 04109
    • Pfizer Investigational Site
  • Madgeburg, Germany, 39120
    • Pfizer Investigational Site
  • Mannheim, Germany, 68161
    • Pfizer Investigational Site
  • Muenchen, Germany, 80469
    • Pfizer Investigational Site
  • Muenster, Germany, 48159
    • Pfizer Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 137-701
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 152-703
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 133-792
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 135-720
    • Pfizer Investigational Site
• Slovakia
  • Bratislava, Slovakia, 826 06
    • Pfizer Investigational Site
  • Bratislava, Slovakia, 833 05
    • Pfizer Investigational Site
  • Bratislava, Slovakia, 851 05
    • Pfizer Investigational Site
  • Trnava, Slovakia, 917 02
    • Pfizer Investigational Site
• Spain
  • Barcelona, Spain, 08022
    • Pfizer Investigational Site
  • Sevilla, Spain, 41014
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with a diagnosis of GERD who fulfill the following criteria:

who have symptoms for least six months prior to enrollment; who are currently on daily treatment with a PPI and have been on such treatment for at least 3 months; whose symptoms are persistent, troublesome and that include heartburn and/or regurgitation as their predominant symptoms despite treatment with a PPI; who are seeking relief of persistent symptoms.

Exclusion Criteria:

• Subjects with erosive esophagitis - An endoscopy within the last 5 years is required to verify absence.
• Subjects with any esophageal or gastric diseases/conditions that may contribute to their GERD symptoms.
• If female; pregnant, lactating or positive serum or urine pregnancy tests.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Esomeprazole; Patients entering the run-in phase lasting 6 weeks (42 days) will be switched from their current proton pump inhibitor (PPI) treatment and maintained on a standard background PPI - open label esomeprazole 20 mg to be taken once daily 1 hour before breakfast. Subjects meeting randomization criteria at Visit 4 are randomly assigned to one of the active arms of PF-00885706 or matching placebo, in addition to esomeprazole.; Other: Placebo; Capsule, Placebo, every 12 hours (twice a day)
Experimental: 100ug	Drug: PF-00885706; Capsule, 100ug, every 12 hours (twice a day); Drug: Esomeprazole; Patients entering the run-in phase lasting 6 weeks (42 days) will be switched from their current proton pump inhibitor (PPI) treatment and maintained on a standard background PPI - open label esomeprazole 20 mg to be taken once daily 1 hour before breakfast. Subjects meeting randomization criteria at Visit 4 are randomly assigned to one of the active arms of PF-00885706 or matching placebo, in addition to esomeprazole.; Drug: PF-00885706; Capsule, 300ug, every 12 hours (twice a day); Drug: PF-00885706; Capsule, 1mg, every 12 hours (twice a day); Drug: PF-00885706; Capsule, 3mg, every 12 hours (twice a day)
Experimental: 300ug	Drug: PF-00885706; Capsule, 100ug, every 12 hours (twice a day); Drug: Esomeprazole; Patients entering the run-in phase lasting 6 weeks (42 days) will be switched from their current proton pump inhibitor (PPI) treatment and maintained on a standard background PPI - open label esomeprazole 20 mg to be taken once daily 1 hour before breakfast. Subjects meeting randomization criteria at Visit 4 are randomly assigned to one of the active arms of PF-00885706 or matching placebo, in addition to esomeprazole.; Drug: PF-00885706; Capsule, 300ug, every 12 hours (twice a day); Drug: PF-00885706; Capsule, 1mg, every 12 hours (twice a day); Drug: PF-00885706; Capsule, 3mg, every 12 hours (twice a day)
Experimental: 1mg	Drug: PF-00885706; Capsule, 100ug, every 12 hours (twice a day); Drug: Esomeprazole; Patients entering the run-in phase lasting 6 weeks (42 days) will be switched from their current proton pump inhibitor (PPI) treatment and maintained on a standard background PPI - open label esomeprazole 20 mg to be taken once daily 1 hour before breakfast. Subjects meeting randomization criteria at Visit 4 are randomly assigned to one of the active arms of PF-00885706 or matching placebo, in addition to esomeprazole.; Drug: PF-00885706; Capsule, 300ug, every 12 hours (twice a day); Drug: PF-00885706; Capsule, 1mg, every 12 hours (twice a day); Drug: PF-00885706; Capsule, 3mg, every 12 hours (twice a day)
Experimental: 3mg	Drug: PF-00885706; Capsule, 100ug, every 12 hours (twice a day); Drug: Esomeprazole; Patients entering the run-in phase lasting 6 weeks (42 days) will be switched from their current proton pump inhibitor (PPI) treatment and maintained on a standard background PPI - open label esomeprazole 20 mg to be taken once daily 1 hour before breakfast. Subjects meeting randomization criteria at Visit 4 are randomly assigned to one of the active arms of PF-00885706 or matching placebo, in addition to esomeprazole.; Drug: PF-00885706; Capsule, 300ug, every 12 hours (twice a day); Drug: PF-00885706; Capsule, 1mg, every 12 hours (twice a day); Drug: PF-00885706; Capsule, 3mg, every 12 hours (twice a day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete resolution of heartburn and regurgitation. [i.e. no more than one day with either mild heartburn or regurgitation over the seven days prior to the assessment time-point (Visit 6 and Visit 8)]	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of days with heartburn (daytime and night-time)	28 days
Number of days with regurgitation (daytime and night-time)	28 days
Number of heartburn and regurgitation-free days (24hrs)	28 days
Composite score of heartburn and regurgitation frequency and severity	28 days
Time to resolution of symptoms of heartburn/regurgitation	28 days
Number of antacid rescue medication (Gaviscon) tablets used	28 days
Severity of additional GERD symptoms	28 days
Quality of Life (assessed using PAGI-QOL to PGIC (Patient Global Impression of Change)	28 days
Complete resolution of heartburn	28 days
Complete resolution of regurgitation	28 days
Average severity of heartburn (daytime and night-time)	28 days
Average severity of regurgitation (daytime and night-time)	28 days

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: August 6, 2008
• First Submitted That Met QC Criteria: August 7, 2008
• First Posted (Estimate): August 8, 2008

Study Record Updates

• Last Update Posted (Estimate): July 14, 2011
• Last Update Submitted That Met QC Criteria: July 12, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: PPI partial responders with non-erosive GERD.
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Esomeprazole
• Other Study ID Numbers: A8311003