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 - N/A

INTERVENTION: Product Name: N/A Product Code: PF‐00885706 Pharmaceutical Form: Capsule* INN or Proposed INN: N/A CAS Number: N/A Current Sponsor code: PF‐00885706 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use Product Name: N/A Product Code: PF‐00885706 Pharmaceutical Form: Capsule* INN or Proposed INN: N/A CAS Number: N/A Current Sponsor code: PF‐00885706 Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 300‐ Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use Product Name: N/A Product Code: PF‐00885706 Pharmaceutical Form: Capsule* INN or Proposed INN: N/A CAS Number: N/A Current Sponsor code: PF‐00885706 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1‐ Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use Product Name: N/A Product Code: PF‐00885706 Pharmaceutical Form: Capsule* INN or Proposed INN: N/A CAS Number: N/A Current Sponsor code: PF‐00885706 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 3‐ Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use CONDITION: GASTRO‐ESOPHAGEAL REFLUX DISEASE (GERD) ; MedDRA version: 9.1 Level: LLT Classification code 10018203 Term: GERD PRIMARY OUTCOME: Main Objective: 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 PPI treatment), in subjects with GERD who have inadequate relief with PPIs. Primary end point(s): Complete resolution of heartburn and regurgitation [i.e. no more than one day with either mild heartburn or regurgitation over seven days prior to the assessment time point (Visit 6 and Visit 8)]. Secondary Objective: • To evaluate the safety of PF‐00885706 in subjects in subjects who are poor responders to PPI treatment.; • To evaluate the population pharmacokinetics (POPPK) for PF‐00885706 in a population of subjects with GERD in order to support the development of a PKPD model.; • To validate a modified patient reported outcome (PRO) instrument [modified version of the Patient Assessment of Gastro‐Intestinal SYMptoms {PAGI‐SYM} instrument and in electronic formats. INCLUSION CRITERIA: 1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. 2. Subjects with a diagnosis of GERD who fulfill the following criteria • who have symptoms for at least six months prior to enrolment • 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. * persistent symptoms: Minimum of 4 days (in a week) with at least mild symptoms (i.e. symptom does not last long and is easily tolerated) or minimum of 2 days with moderate (i.e. symptom causes discomfort and interrupts usual activities including sleep) to severe symptoms (i.e. symptom causes great interference wi