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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Gastroesophageal Reflux Disease

Intervention / Treatment
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* Drug: PF-00885706
* Drug: Esomeprazole
* Drug: PF-00885706
* Drug: Esomeprazole
* Drug: PF-00885706
* Drug: Esomeprazole
* Drug: PF-00885706
* Drug: Esomeprazole
* Other: Placebo
* Drug: Esomeprazole


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100ug<br> | Drug: PF-00885706<br>* Capsule, 100ug, every 12 hours (twice a day)<br>Drug: Esomeprazole<br>* 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.<br>|
| Experimental: 300ug<br> | Drug: PF-00885706<br>* Capsule, 300ug, every 12 hours (twice a day)<br>Drug: Esomeprazole<br>* 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.<br>|
| Experimental: 1mg<br> | Drug: PF-00885706<br>* Capsule, 1mg, every 12 hours (twice a day)<br>Drug: Esomeprazole<br>* 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.<br>|
| Experimental: 3mg<br> | Drug: PF-00885706<br>* Capsule, 3mg, every 12 hours (twice a day)<br>Drug: Esomeprazole<br>* 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.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Capsule, Placebo, every 12 hours (twice a day)<br>Drug: Esomeprazole<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PPI partial responders with non-erosive GERD.