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
- Guy E Boeckxstaens1,2,
- Hanneke Beaumont2,
- Jan G Hatlebakk3,
- Debra G Silberg4,
- Karin Björck5,
- Maria Karlsson5,
- Hans Denison5
- 1Department of Gastroenterology, University Hospital Leuven, Catholic University of Leuven, Belgium
- 2Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
- 3Institute of Medicine, Haukeland University Hospital, University of Bergen, Norway
- 4AstraZeneca Pharmaceuticals LP, Wilmington, Delaware, USA
- 5AstraZeneca R&D, Mölndal, Sweden
- Correspondence to Professor Dr Guy E Boeckxstaens, Department of Gastroenterology, University Hospital Leuven, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium;
Contributors This study was planned by AstraZeneca, with input on the study design by the authors. The collection and analysis of data was done by AstraZeneca. The authors have had access to the study data, participated in the interpretation of data and provided content for the manuscript. Both AstraZeneca and the authors approved the final version of the manuscript for submission. Medical writing and editing support funded by AstraZeneca was provided by Andrew Stead and Simon Lancaster, from in Science Communications, a Wolters Kluwer business.
- Accepted 2 February 2011
- Published Online First 14 March 2011
Objective To 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 A 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 A 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 Lesogaberan add-on therapy to PPIs significantly improved heartburn and regurgitation symptoms; however, the proportion of responders was small.
Clinical trial number NCT00394472.
Funding This study was supported by AstraZeneca.
Competing interests GEB was supported by a grant (Odysseus programme, G.0905.07) of the Flemish ‘Fonds voor Wetenschappelijk Onderzoek’ (FWO) and has received financial support in the form of consultation fees and grant/research funding from AstraZeneca, and in the form of consultation fees from Movetis. HB has no competing interests to declare. JGH has received financial support in the form of speaker's fees and grant/research funding from AstraZeneca. DGS, KB, MK and HD are employees of AstraZeneca.
Ethics approval This study was conducted with the approval of an independent Institutional Review Board/Research Ethics Committee within each country.
Provenance and peer review Not commissioned; externally peer reviewed.