Selective 5-HT4 Receptor Agonist and Proton Pump Inhibitor (PPI) in Subjects With Gastroesophageal Reflux Disease (GERD)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Gastroesophageal Reflux Disease

Intervention / Treatment
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* Drug: SSP-002358 (0.1 mg) + PPI
* Drug: SSP-002358 (0.5 mg) + PPI
* Drug: SSP-002358 (2.0 mg) + PPI
* Drug: Placebo + PPI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written Informed Consent Form signed voluntarily before the first study-related activity. Aged between 18 and 70 years, inclusive. Subjects with a history of the cardinal symptoms of GERD (both heartburn and regurgitation) prior to PPI therapy. Subjects with symptoms of GERD for at least 6 months prior to the Screening Visit. Subjects who have persistent symptoms of regurgitation for 3 or more days over the past week with or without heartburn while on PPI. Subjects have at least some improvement to the symptom of heartburn while on PPI therapy. 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: Subjects who show no response to heartburn while on PPI therapy. Subjects with dyspepsia symptoms that are more predominant than their GERD symptoms (heartburn and/or regurgitation). Subjects with prior endoscopic anti-reflux procedure or major GI surgery or subjects with major GI disorders. Presence of severe and clinically uncontrolled cardiovascular, liver, lung or neurologic disease, cancer or AIDS. Alarm symptoms suggestive of malignancies or organic disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SSP-002358 (0.1 mg) + Proton Pump Inhibitor (PPI)<br> | Drug: SSP-002358 (0.1 mg) + PPI<br>* 0.1 mg tablet three times daily (t.i.d.) taken in addition to a PPI<br>* Other names: SPD557;|
| Active Comparator: SSP-002358 (0.5 mg) + PPI<br> | Drug: SSP-002358 (0.5 mg) + PPI<br>* 0.5 mg tablet t.i.d. taken in addition to a PPI<br>|
| Active Comparator: SSP-002358 (2.0 mg) + PPI<br> | Drug: SSP-002358 (2.0 mg) + PPI<br>* 2.0 mg tablet t.i.d. taken in addition to a PPI<br>|
| Placebo Comparator: Placebo + PPI<br> | Drug: Placebo + PPI<br>* Placebo t.i.d. taken in addition to a PPI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Percent Regurgitation-Free Days Over Weeks 5-8 |  | Baseline and over weeks 5-8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Heartburn-Free Days Over Weeks 5-8 |  | Baseline and over weeks 5-8 | 
| Change From Baseline in the Persistent Reflux Integrated Symptom Measurement (PRISM) Liquid and Food Domain Scores Over Weeks 5-8 | PRISM is a 21 item patient-reported outcome instrument with 4 domains. Items are scored using various scales. Total score ranges from 0-100. Higher scores indicate more severe or frequent symptoms. | Baseline and over weeks 5-8 | 
| Area Under the Steady-state Plasma Concentration-time Curve (AUC) of SSP-002358 | Area under the plasma concentration versus time curve can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body. | Over 8 hours post-dose (week 2 or later) | 
| Steady State Maximum Plasma Concentration (Cmax) of SSP-002358 | Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administered. | Over 8 hours post-dose (week 2 or later) | 
| Time to Maximum Plasma Concentration (Tmax) of SSP-002358 |  | Over 8 hours post-dose (week 2 or later) |