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A long-term extension study for the phase 3 study of nalmefene (339-14-001) in patients with alcohol dependence

A long-term extension study for the phase 3 study of nalmefene (339-14-001) in patients with alcohol dependence

405

Overall, 405 out of 421 consenting subjects, excluding 16 screen failures, were rolled over to this trial from Trial 339-14-001 (139 subjects from the nalmefene 20-mg group, 94 from the nalmefene 10-mg group, and 172 from the placebo group; same order below). Of the 405 rolled-over subjects, 403 subjects (137, 94, and 172) received at least one dose of the investigational medicinal product (IMP) during the treatment period. Of those 403 subjects, 343 subjects (126, 84, and 133) completed the treatment period and advanced to the drug withdrawal period, with 172 subjects randomized to the 20-mg group and 171 to the placebo group. A total of 342 subjects (171 in the 20-mg group and 171 in the placebo group; same order below) completed the drug withdrawal period and advanced to the post-treatment observation period and 339 subjects (169 and 170) completed the post-treatment observation period and the trial.

- In this trial, the overall incidence of adverse events (AEs) in the treatment period was 75.4%. AEs that occurred in >=5% of all subjects were nausea (19.6%), nasopharyngitis (17.4%), dizziness (9.9%), headache (7.2%), malaise and somnolence (6.5% each), vomiting (6.2%), abdominal discomfort (5.7%), and insomnia (5.2%). The incidence of AEs in the drug withdrawal period was 17.4% in the 20-mg group and 11.7% in the placebo group. Most AEs that occurred in the trial were mild or moderate in severity. Overall, there were no AEs that showed a notable increase in incidence with extension of treatment duration throughout Trial 339-14-001 and the present trial. - No deaths were reported during the trial. The overall incidence of serious AEs (SAEs) in the treatment period of the trial was 0.7%. The overall incidence of AEs leading to treatment discontinuation in the treatment period was 10.4%. The incidence of SAEs in the drug withdrawal period was 0.6% in both the 20-mg and placebo groups, and the incidence of AEs leading to treatment discontinuation was 0.6% in the 20-mg group and none in the placebo group.

- Most AEs that occurred during the present trial were mild or moderate in severity. Overall, there were no AEs that showed a notable increase in incidence with extension of treatment duration throughout Trial 339-14-001 and the present trial. - Following nalmefene administration, neither dependency nor withdrawal symptoms developed. Nor were any concerns regarding other safety endpoints observed with extension of treatment duration.

Analysis of the efficacy of nalmefene in reducing alcohol consumption in subjects who received nalmefene for a total of 48 weeks of treatment in Trial 339-14-001 and the present trial demonstrated that both the number of HDDs and TAC decreased at Week 4 of the treatment period and that this effect lasted up until Week 48 of the treatment period. In subjects who received placebo in Trial 339-14-001, both the number of HDDs and TAC decreased after treatment with nalmefene hydrochloride 20 mg was started, and this effect lasted up until Week 48 of the treatment period.

The efficacy in reducing alcohol consumption was sustained by long-term treatment with nalmefene. Long-term treatment with nalmefene showed no notable safety concerns and was well tolerated by patients with alcohol dependence.

No

Otsuka Pharmaceutical Co., LTD.

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CL_OPCJ_RDA_Team@otsuka.jp

Otsuka Pharmaceutical Co., LTD.

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+81-3-6361-7314

completed

July. 13, 2015

Interventional

24-week treatment period: open-label, uncontrolled 4-week run-out period: double-blind, placebo-controlled

treatment purpose

3

- Patients who have completed Study 339-14-001.
- Patients who have signed the informed consent form for Study 339-14-002.

- The patient has a clinically significant unstable illness (eg, complication of New York Heart Association (NYHA) class 3 or 4 heart failure or angina pectoris, renal function disorder with estimated glomerular filtration rate (eGFR) of under 30 mL/min/1.73 m2, hepatic failure, and neoplastic disorder).
- The patient has a clinically significant abnormal electrocardiogram (ECG) which is inappropriate for the participation in the trial in the opinion of the investigator or subinvestigator.

Both

Alcohol dependent

investigational material(s)
Generic name etc : Nalmefene hydrochloride
INN of investigational material : Nalmefene Hydrochloride Hydrate
Therapeutic category code : 119 Other agents affecting central nervous system
Dosage and Administration for Investigational material : Oral administration

control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : Oral administration

safety
Adverse Events, Laboratory Parameters and Vital Signs

efficacy
The number of Heavy Drinking Days (HDDs)
Change in the number of HDDs from baseline

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Dec. 25, 2014