A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial.

Abstract

OBJECTIVE:

o evaluate the efficacy and tolerability of add-on treatment with lesogaberan (AZD3355), a novel reflux inhibitor, in patients with persistent gastro-oesophageal reflux disease (GORD) symptoms despite proton pump inhibitor (PPI) therapy.

METHODS:

double-blind, placebo-controlled, randomised, parallel-group, multicentre phase IIA study was carried out in outpatient clinics. The study group comprised 244 adult patients with persistent GORD symptoms (heartburn and/or regurgitation) of at least mild intensity and for 3 days of 7 days before enrolment, despite ≥6 weeks of continuous PPI therapy. Patients received either lesogaberan (65 mg twice daily) or placebo in addition to PPI therapy for a period of 4 weeks. Symptom intensity, based on the Reflux Disease Questionnaire, was recorded twice daily. Treatment response (defined as at most one 24 h period with heartburn or regurgitation of not more than mild intensity during the last 7 days of treatment). Time to response, proportion of symptom-free days and measures of tolerability were also analysed.

RESULTS:

total of 232 (114 lesogaberan- and 118 placebo-treated patients) of the 244 randomised patients were analysed for efficacy. Treatment with lesogaberan, compared with placebo, resulted in a significantly larger proportion of responders to treatment (16% vs 8% of patients; p=0.026) and cumulative proportion of responders over time (log-rank p=0.0195). Lesogaberan was well tolerated: adverse events of mostly mild to moderate intensity were reported in 45% of patients on lesogaberan and in 37% on placebo.

CONCLUSIONS:

esogaberan add-on therapy to PPIs significantly improved heartburn and regurgitation symptoms; however, the proportion of responders was small. Clinical trial number NCT00394472.

• Authors: Guy E Boeckxstaens, Hanneke Beaumont, Jan G Hatlebakk, Debra G Silberg, Karin Björck, Maria Karlsson, Hans Denison
• Journal: Gut (Gut) Vol. 60 Issue 9 Pg. 1182-8 (Sep 2011) ISSN: 1468-3288 [Electronic] England
• PMID: 21402616 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• GABA-A Receptor Agonists
• Gastrointestinal Agents
• Phosphinic Acids
• Propylamines
• Proton Pump Inhibitors
• lesogaberan

Topics

• Adolescent
• Adult
• Aged
• Drug Administration Schedule
• Drug Therapy, Combination
• Epidemiologic Methods
• Female
• GABA-A Receptor Agonists (administration & dosage, therapeutic use)
• Gastroesophageal Reflux (drug therapy)
• Gastrointestinal Agents (administration & dosage, adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Phosphinic Acids (administration & dosage, adverse effects, therapeutic use)
• Propylamines (administration & dosage, adverse effects, therapeutic use)
• Proton Pump Inhibitors (therapeutic use)
• Time Factors
• Treatment Outcome
• Young Adult