Premium
Proof‐of‐Concept Study to Assess the Nociceptin Receptor Antagonist LY 2940094 as a New Treatment for Alcohol Dependence
Author(s) -
Post Anke,
Smart Trevor S.,
Jackson Kimberley,
Mann Joanne,
Mohs Richard,
RorickKehn Linda,
Statnick Michael,
Anton Raymond,
O'Malley Stephanie S.,
Wong Conrad J.
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13147
Subject(s) - placebo , nociceptin receptor , alcohol , antagonist , medicine , clinical endpoint , alcohol dependence , anesthesia , randomized controlled trial , receptor , chemistry , opioid , opioid peptide , biochemistry , alternative medicine , pathology
Background This was a proof‐of‐concept study to evaluate the efficacy of LY 2940094, a nociceptin/orphanin FQ peptide receptor antagonist, in reducing alcohol consumption in actively alcohol‐drinking patients with alcohol dependence. Methods Eighty‐eight patients, 21 to 66 years of age, diagnosed with alcohol dependence, reporting 3 to 6 heavy drinking days per week, were randomized (1:1) to 8 weeks of treatment with once‐daily oral placebo ( N = 44) or 40 mg/d of LY 2940094 ( N = 44). The primary efficacy analysis was the change from baseline in number of drinks per day ( NDD ) utilizing mixed‐model repeated measures comparing LY 2940094 and placebo in Month 2 of the 8‐week double‐blind treatment period. The probability that the difference relative to placebo in NDD was ≤0 at endpoint was calculated, and a probability ≥80% was considered to be evidence that LY 2940094 was associated with the reduction in NDD . Results After 8 weeks of treatment, reduction in mean NDD did not differ between LY 2940094 versus placebo (−1.4 vs. −1.5, respectively, 44% probability of greater reduction relative to placebo), but there was a greater reduction in the mean percentage of heavy drinking days in a month with LY 2940094 versus placebo (−24.5 vs. −15.7%, respectively, 93% probability of a greater reduction relative to placebo), and an increase in the mean percentage of abstinent days in a month compared to placebo (9.1 vs. 1.9%, respectively, 91% probability of a greater increase relative to placebo). Patients who were treated with LY 2940094 showed decreased plasma levels of gamma‐glutamyl transferase with probabilities ≥98% for greater reduction compared with placebo at Weeks 1, 4, 6, and 8. Treatment‐emergent adverse events in ≥5% of patients treated with LY 2940094 included insomnia, vomiting, and anxiety. There were no serious adverse events or significant changes in laboratory assessments or vital signs with LY 2940094. Conclusions Although not reducing the NDD , LY 2940094, compared to placebo, did reduce heavy drinking days and increased abstinence days in patients with alcohol dependence.