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.
- gastro-oesophageal reflux disease
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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.