Arbaclofen placarbil in GERD: a randomized, double-blind, placebo-controlled study.

Abstract

OBJECTIVES:

It has been shown that arbaclofen placarbil (AP) inhibits reflux in gastroesophageal reflux disease (GERD) following single oral dosing. This study evaluated the efficacy and safety of AP over 4 weeks in subjects with symptomatic GERD.

METHODS:

One hundred fifty-six subjects with heartburn and/or regurgitation ≥3 days/week and either no history of taking proton pump inhibitors (PPIs naive, n=58) or at least partial symptom response to PPI therapy (PPI responsive, n=98) were enrolled in this randomized, double-blind, placebo-controlled trial. All GERD therapies including PPIs were discontinued 2 weeks before randomization to AP 20, 40, or 60 mg daily, 30 mg twice daily, or placebo for 4 weeks. Randomization was stratified by prior PPI use.

RESULTS:

In the primary analysis, change from baseline in weekly heartburn events between AP and placebo for the entire study group was not statistically significant. However, a significant interaction was observed between prior PPI use and response to AP treatment. In pre-planned secondary analyses of the PPI-responsive subgroup, percent reductions from baseline in weekly heartburn events were greater for each AP dose vs. placebo (P<0.05) and the percentage of subjects who reported complete resolution of heartburn during week 4 was higher in each AP treatment group (21, 28, 30, and 50% for AP 20, 40, 60 mg daily, and 30 mg twice daily, respectively) compared with placebo (6%) (P<0.05 for 30 mg twice daily). Corresponding analyses of the PPI-naive subgroup showed no significant differences. AP was well tolerated; withdrawals due to adverse events were infrequent.

CONCLUSIONS:

AP was not superior to placebo in reducing the number of weekly heartburn events over 4 weeks in the primary analysis of the entire study population. Exploratory subgroup analyses suggest that response to PPI treatment before the study was associated with a response to AP treatment.

• Authors: Nimish B Vakil, F Jacob Huff, Amy Bian, Drew S Jones, David Stamler
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 106 Issue 8 Pg. 1427-38 (Aug 2011) ISSN: 1572-0241 [Electronic] United States
• PMID: 21519360 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Muscle Relaxants, Central
• Prodrugs
• Proton Pump Inhibitors
• Baclofen
• arbaclofen placarbil

Topics

• Adult
• Aged
• Baclofen (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Dizziness (chemically induced)
• Double-Blind Method
• Drug Administration Schedule
• Fatigue (chemically induced)
• Female
• Gastroesophageal Reflux (complications, drug therapy, physiopathology)
• Headache (chemically induced)
• Heartburn (etiology, physiopathology, prevention & control)
• Humans
• Male
• Middle Aged
• Muscle Relaxants, Central (administration & dosage, adverse effects, therapeutic use)
• Nausea (chemically induced)
• Prodrugs (therapeutic use)
• Proton Pump Inhibitors (therapeutic use)
• Treatment Failure