A Study to Evaluate the Efficacy and Safety of Arbaclofen Placarbil (XP19986) as Adjunctive Therapy in Subjects With Gastroesophageal Reflux Disease (GERD)

Study Overview
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Brief Summary
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The purpose of the study is to evaluate efficacy and safety of arbaclofen placarbil (XP19986) versus placebo as adjunctive therapy in subjects with troublesome GERD symptoms despite therapy with approved doses of a Proton Pump Inhibitor (PPI).

Official Title
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A Dose-Response Efficacy and Safety Study of Arbaclofen Placarbil (XP19986) as Adjunctive Therapy in Subjects With Gastroesophageal Reflux Disease (GERD) Who Are Incomplete Responders to a Proton Pump Inhibitor (PPI)

Conditions
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Gastroesophageal Reflux Disease

Intervention / Treatment
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* Drug: arbaclofen placarbil-Cohort 1
* Drug: Placebo-Cohort 5
* Drug: arbaclofen placarbil-Cohort 2
* Drug: arbaclofen placarbil-Cohort 3
* Drug: arbaclofen placarbil-Cohort 4
* Drug: PPI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: confirmed diagnosis of GERD by a gastroenterologist minimum of 3 months of GERD symptoms prior to screening. currently taking an FDA approved dose of PPI therapy for symptomatic GERD for at least 4 weeks prior to screening experienced partial relief of GERD symptoms while receiving approved dose and regimen of PPI therapy experienced GERD symptoms, defined as heartburn (with or without regurgitation or other GERD symptoms) on ≥ 3 days during the week prior to screening Exclusion Criteria: evidence of erosive esophagitis or erosive gastritis on upper gastrointestinal endoscopy during screening has not experienced any GERD symptom improvement after an adequate course of PPI treatment (at least 2 weeks) unstable or severe medical condition

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: arbaclofen placarbil-Cohort 1<br>arbaclofen placarbil 20 mg QD with PPI* * Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD | Drug: arbaclofen placarbil-Cohort 1<br>* After the 4 week screening period, eligible subjects will be randomized to adjunctive study treatment (arbaclofen placarbil 20 mg QD) for 7 weeks including titration and taper periods<br>* Other names: XP19986;Drug: PPI<br>* Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD<br>* Other names: Proton Pump Inhibitor;|
| Experimental: arbaclofen placarbil-Cohort 2<br>arbaclofen placarbil 40 mg QD with PPI* * Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD | Drug: arbaclofen placarbil-Cohort 2<br>* After the 4 week screening period, eligible subjects will be randomized to adjunctive study treatment (arbaclofen placarbil 40 mg QD) with for 7 weeks including titration and taper periods<br>* Other names: XP19986;Drug: PPI<br>* Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD<br>* Other names: Proton Pump Inhibitor;|
| Experimental: arbaclofen placarbil-Cohort 3<br>arbaclofen placarbil 20 mg BID with PPI* * Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD | Drug: arbaclofen placarbil-Cohort 3<br>* After the 4 week screening period, eligible subjects will be randomized to adjunctive study treatment (arbaclofen placarbil 20 mg BID) for 7 weeks including titration and taper periods<br>* Other names: XP19986;Drug: PPI<br>* Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD<br>* Other names: Proton Pump Inhibitor;|
| Experimental: arbaclofen placarbil-Cohort 4<br>arbaclofen placarbil 30 mg BID with PPI* * Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD | Drug: arbaclofen placarbil-Cohort 4<br>* After the 4 week screening period, eligible subjects will be randomized to adjunctive study treatment (arbaclofen placarbil 30 mg BID) for 7 weeks including titration and taper periods<br>* Other names: XP19986;Drug: PPI<br>* Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD<br>* Other names: Proton Pump Inhibitor;|
| Placebo Comparator: Placebo-Cohort 5<br>Placebo dose with PPI* * Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD | Drug: Placebo-Cohort 5<br>* After the 4 week screening period, eligible subjects will be randomized to adjunctive study treatment (placebo) for 7 weeks including titration and taper periods<br>* Other names: XP19986 matching placebo;Drug: PPI<br>* Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD<br>* Other names: Proton Pump Inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heartburn Episodes | number of episodes | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regurgitation Episodes | number of episodes | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GERD