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Original Research

Safety and tolerability of as-needed nalmefene in the treatment of alcohol dependence: results from the Phase III clinical programme

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Abstract

Objective: To investigate safety and tolerability of nalmefene for reduction of alcohol consumption in alcohol-dependent patients.

Methods: Pooled data from three randomized, placebo-controlled studies (two 6-month; one 12-month) of 18 mg nalmefene (as-needed use) in alcohol-dependent patients looking at the total population (placebo n = 824, nalmefene n = 1123) and patients with high/very high drinking risk levels at screening and randomization (target population: placebo n = 374, nalmefene n = 450).

Results: In the study, 62.7% of patients on placebo and 74.7% on nalmefene in the total population had treatment-emergent adverse events (TEAEs). Fourty-seven (5.9%) on placebo and 149 (13.0%) on nalmefene dropped out due to TEAEs. Thirty-five (4.4%) on placebo and 57 (5.0%) on nalmefene had serious adverse events. Tolerability and safety were similar in the target population and total population. Most frequent TEAEs were transient, mainly occurring at treatment initiation. There was no difference in tolerability and safety if nalmefene was taken daily or intermittently; no signal of increased risk of suicide-related behavior with nalmefene. The higher incidence of psychiatric events in the nalmefene group was mainly due to the TEAE of confusional state.

Conclusions: Although there was a higher incidence of TEAEs and TEAEs leading to dropout, nalmefene was well-tolerated and no major safety issues were identified.

Acknowledgments

We thank all patients for their participation in the studies, and all clinical research staff for their contributions. We also thank Johan Hellsten, an employee of Lundbeck, for providing medical writing assistance in the manuscript preparation, revision, and editing. Parts of this work has previously been presented at the 22nd European Congress of Psychiatry, Munich, Germany, 1-4 March 2014, and at the 37th Annual RSA Scientific Meeting, Bellevue, Washington, USA, 21-25 June 2014

Declaration of interest

Funding for this paper was received from H Lundbeck A/S, Valby, Denmark. The sponsor had a role in the study design and data analysis, but the report was mainly written by the first author. This manuscript contains an analysis of pooled safety data from the three Lundbeck-sponsored nalmefene Phase III clinical studies with the following trial registration numbers (ClinicalTrials.gov): NCT00811720, NCT 00811941, and NCT00812461.W van den Brink has received honoraria from Lundbeck, Merck Serono, Schering-Plough, Reckitt Benckiser, Pfizer, and Eli Lilly, speaker fees from Lundbeck, investigator initiated industry grants from Alkermes, Neurotech, and Eli Lilly, is a consultant to Lundbeck, Merck Serono, Schering-Plough, and Teva, and has performed paid expert testimony for Schering-Plough. J Strang has received project grant support and/or honoraria and/or consultancy payments from Department of Health, National Treatment Agency, Public Health England, Home Office, and National Institute for Health and Clinical Excellence, and has worked with the World Health Organisation and with the United Nations Office for Drug Control. He and his institution have also received research grant support and/or payment in the form of honoraria, consultancy payments and/or travelling and/or accommodation and/or conference expenses from various pharmaceutical companies who produce, or have been considering producing, new medicines for use in the addiction treatment field, including Viropharma, Martindale, Reckitt-Benckiser, Schering-Plough, Lundbeck, UCB, MundiPharma, Alkermes, iGen. Antoni Gual has received honoraria and travel grants from Lundbeck, Janssen, and Servier. P Sørensen is employed by Lundbeck and Thomas Jon Jensen was employed by Lundbeck at the time of the conduct of the research for this paper. K Mann has received research grants from Schering-Plough, Alkermes, Lundbeck, McNeil, and Merck. He has been a paid consultant to Alkermes and Desitin, is a consultant to Lundbeck and Pfizer, and has received speaker fees from Lundbeck.

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