NCT03970109

HLAB-002 of ANS-6637 for Alcohol Use Disorder

Human Laboratory Study of ANS-6637 for Alcohol Use Disorder

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA) · NIH
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

Primary: The primary objective of this study was to evaluate the effects of 2 different doses of ANS-6637, 200 mg (given as 2 x 100 mg tablets) and 600 mg (given as 2 x 300 mg tablets) once a day, and matched placebo, on alcohol cue-elicited alcohol craving during a human laboratory paradigm after 1 week of daily dosing among subjects with moderate to severe alcohol use disorder (AUD) as confirmed by the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5™). Secondary: Secondary objectives included evaluation of ANS-6637 200 mg, ANS-6637 600 mg, and matched placebo on reduction of alcohol consumption, alcohol craving, cigarette smoking (among smokers) and nicotine use (among nicotine users), mood, sleep, alcohol use negative consequences, study retention, and safety and tolerability throughout the last 4 weeks of the treatment phase of the study.

Detailed description

Methodology: This study was a 3-arm, double-blind, randomized, placebo-controlled, parallel group, 3-site study designed to assess the effects of ANS-6637 as compared with placebo on responses to in vivo alcohol cue exposure in the human laboratory setting. After signing informed consent, subjects were screened for eligibility and had other baseline assessments. Screening was permitted over a 14-day period and most baseline assessments were performed on the day of randomization. If eligible for the study, 81 subjects were to be randomized using a stratified permuted block randomization procedure in an approximate 1:1:1 ratio (targeting 27 subjects per group and 27 subjects per each of 3 clinical sites) to receive either ANS-6637 200 mg once daily, ANS-6637 600 mg once daily, or matched placebo for 5 weeks. Clinical site was used as the stratification variable. Subjects were seen in the clinic at screening, at randomization and 5 other times during the study. A final followup telephone interview was conducted 2 weeks after the end of study in-clinic visit. After the first week of investigational product (IP) administration at Study Week 2, subjects underwent a cue reactivity session including 4 individual visual analog scale (VAS) items assessing alcohol craving and one item assessing beverage liking. Number of Subjects (planned and analyzed): 81 planned; 43 analyzed. The study was put on clinical hold and then stopped early due to clinically significant AEs. Investigational Product, Dosage, and Mode of Administration: The target doses were 200 mg (2 x 100 mg tablets) and 600 mg (2 x 300 mg tablets) of ANS-6637 by oral administration once daily for 5 weeks. Subjects in the placebo group took an equivalent number of identically matched placebo tablets (2 per day) by oral administration once daily for 5 weeks. Duration of Treatment: Each subject participated in the study for up to 10 weeks, including up to 2 weeks of screening, 5 weeks of treatment, one end-of-study visit during the week following the last treatment dose, and a final telephone contact 2 weeks after completing treatment for a safety follow-up. Statistical Methods (Data Analysis): The original analytical plan was revised slightly due to early stopping of the study as only approximately half of the subjects were randomized to the study at that time. Analysis Populations: Modified intention-to-treat (mITT) Analysis Set: The mITT set was defined as subjects randomized to participate in the study that took at least one dose of IP and had a non-missing VAS craving primary endpoint. Safety Analysis Set: The safety analysis set includes all subjects who took at least one dose of IP. As the study closed prematurely, only the mITT and Safety Analysis sets were evaluated. Analysis of the Primary Efficacy Endpoint: Each mITT subject had an initial alcohol cue for "strength" of alcohol craving score from the VAS that was the primary endpoint. Analysis of covariance (ANCOVA) with the "strength" of alcohol craving value as the dependent variable and the pretreatment "strength' of alcohol craving score from the first alcohol cue were an independent fixed effect. Clinical site was included as an independent factor. There were 3 comparisons (ANS-6637 600 mg vs placebo; ANS-6637 200 mg vs. placebo; and ANS-6637 600 mg vs. ANS-6637 200 mg). The Tukey's method was used to adjust for multiple comparisons. No imputation for missing endpoint data was performed. Analysis of the Secondary Endpoints: There were 3 additional questions asked during the cue session for each beverage cue. Each of these questions was analyzed in the same manner as the primary endpoint. Continuous secondary endpoints during the last 4 weeks of treatment period were analyzed using a mixed-effects model with site, assessment time, and baseline drinking as fixed factors. Models also included time by treatment group interaction term. Analysis of the dichotomous secondary endpoints during the last 4 weeks of treatment period were conducted via logistic regression. No imputation for missing endpoint data was performed for secondary endpoints.

Conditions

• Alcohol Use Disorder

Interventions

Type	Name	Description
DRUG	ANS-6637	200 mg (given as 2 x 100 mg tablet) and 600 mg (given as 2 x 300 mg tablet) once a day
DRUG	Placebo oral tablet	Placebo oral tablet

Timeline

• Start date: 2019-10-08
• Primary completion: 2020-05-22
• Completion: 2020-05-22
• First posted: 2019-05-31
• Last updated: 2024-10-29
• Results posted: 2022-03-10

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study