Lemborexant Augmentation of Naltrexone for Alcohol Craving and Sleep

NCT05458609 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: H-52091
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study to evaluate the effects of naltrexone plus lemborexant augmentation compared to naltrexone plus placebo on cue-induced and non-cued alcohol cravings in people with alcohol use disorder and insomnia. Our secondary goals are to evaluate the effects of lemborexant plus naltrexone combination on sleep quality using self-report questionnaires and actigraph data, depression, anxiety, and suicidal ideation.

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (2)

• Cue-induced Alcohol Cravings Using the Alcohol Urge Questionnaire

  Alcohol Urge Questionnaire (AUQ) total score (range 8-56; higher scores indicate greater craving) was assessed following alcohol-related virtual reality cue exposure at baseline and at multiple post-baseline time points during treatment. For this outcome, change from baseline to the last available post-baseline AUQ assessment was calculated and reported as a single summary value.

  Baseline to last available post-baseline assessment (2 to 4 weeks after randomization)

• Non-Cued Alcohol Cravings Using the Penn Alcohol Craving Scale

  Penn Alcohol Craving Scale (PACS): The Penn Alcohol Craving Scale is a 5-item self-report questionnaire assessing alcohol craving over the prior week. Total scores range from 0 to 30, with higher scores indicating greater alcohol craving. PACS assessments were obtained at baseline and weekly during the treatment period. For this outcome, change from baseline to the endpoint PACS assessment was calculated and reported as a single summary value.

  Baseline to study endpoint (2 to 4 weeks after randomization)

Secondary Outcomes (2)

• Actigraphy to Measure Total Sleep Time

  Baseline to study endpoint (2 to 4 weeks after randomization)

• Actigraphy to Measure Total Awakenings After Sleep Onset During the Study Period

  Baseline to study endpoint (2 to 4 weeks after randomization)

Study Arms (2)

Lemborexant plus Naltrexone

ACTIVE COMPARATOR

10 milligrams of Lemborexant will be given daily at nighttime and 50 milligrams of Naltrexone will be given daily for a total of 4 weeks

Drug: Lemborexant 10 mg; Drug: Naltrexone

Placebo plus Naltrexone

PLACEBO COMPARATOR

10 milligrams of placebo will be given daily at nighttime and 50 milligrams of Naltrexone will be given daily for a total of 4 weeks

Drug: Naltrexone

Interventions

Lemborexant 10 mg DRUG

10 mg of Lemborexant

Also known as: Dayvigo

Lemborexant plus Naltrexone

Naltrexone DRUG

50 mg of Naltrexone

Also known as: Vivitrol, Revia

Lemborexant plus Naltrexone; Placebo plus Naltrexone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Admission to The Menninger clinic
• Age 18-65 years
• diagnosis of alcohol use disorder using the DSM-5 criteria confirmed with SCID-5 and
• Diagnosis of insomnia using the DSM 5 criteria, confirmed with SCID-5

You may not qualify if:

• unstable medical conditions (e.g. liver enzymes (ALT and AST) more than 3 times normal)
• acute alcohol withdrawal
• another drug use disorder other than nicotine and cannabis
• use of either of the study medications, naltrexone or lemborexant, within the last 30 days
• Use of any opioid medication within the past 10 days
• Use of scheduled benzodiazepines and hypnotics
• Breathalyzer positive for alcohol
• Known sensitivity to naltrexone or lemborexant
• Pregnant or breastfeeding
• Diagnosis of narcolepsy. The presence of other psychiatric illnesses, use of other psychotropic medications, and stable medical conditions will not be excluded.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

The Menninger Clinic

Houston, Texas, 77035, United States

Location

Related Publications (8)

• Swift RM, Aston ER. Pharmacotherapy for alcohol use disorder: current and emerging therapies. Harv Rev Psychiatry. 2015 Mar-Apr;23(2):122-33. doi: 10.1097/HRP.0000000000000079.

  PMID: 25747925 BACKGROUND

• Zindel LR, Kranzler HR. Pharmacotherapy of alcohol use disorders: seventy-five years of progress. J Stud Alcohol Drugs Suppl. 2014;75(17):79-88. doi: 10.15288/jsads.2014.s17.79.

  PMID: 24565314 BACKGROUND

• Ziolkowski M, Czarnecki D, Budzynski J, Rosinska Z, Zekanowska E, Goralczyk B. Orexin in Patients with Alcohol Dependence Treated for Relapse Prevention: A Pilot Study. Alcohol Alcohol. 2016 Jul;51(4):416-21. doi: 10.1093/alcalc/agv129. Epub 2015 Nov 22.

  PMID: 26597795 BACKGROUND

• von der Goltz C, Koopmann A, Dinter C, Richter A, Rockenbach C, Grosshans M, Nakovics H, Wiedemann K, Mann K, Winterer G, Kiefer F. Orexin and leptin are associated with nicotine craving: a link between smoking, appetite and reward. Psychoneuroendocrinology. 2010 May;35(4):570-7. doi: 10.1016/j.psyneuen.2009.09.005. Epub 2009 Oct 13.

  PMID: 19828259 BACKGROUND

• Moorman DE. The hypocretin/orexin system as a target for excessive motivation in alcohol use disorders. Psychopharmacology (Berl). 2018 Jun;235(6):1663-1680. doi: 10.1007/s00213-018-4871-2. Epub 2018 Mar 6.

  PMID: 29508004 BACKGROUND

• Rosenberg R, Murphy P, Zammit G, Mayleben D, Kumar D, Dhadda S, Filippov G, LoPresti A, Moline M. Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia Disorder: A Phase 3 Randomized Clinical Trial. JAMA Netw Open. 2019 Dec 2;2(12):e1918254. doi: 10.1001/jamanetworkopen.2019.18254.

  PMID: 31880796 BACKGROUND

• Murphy P, Moline M, Mayleben D, Rosenberg R, Zammit G, Pinner K, Dhadda S, Hong Q, Giorgi L, Satlin A. Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study. J Clin Sleep Med. 2017 Nov 15;13(11):1289-1299. doi: 10.5664/jcsm.6800.

  PMID: 29065953 BACKGROUND

• Yardley J, Karppa M, Inoue Y, Pinner K, Perdomo C, Ishikawa K, Filippov G, Kubota N, Moline M. Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial. Sleep Med. 2021 Apr;80:333-342. doi: 10.1016/j.sleep.2021.01.048. Epub 2021 Feb 1.

  PMID: 33636648 BACKGROUND

MeSH Terms

Conditions

Alcoholism

Interventions

lemborexant; Naltrexone; vivitrol

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Limitations and Caveats

This pilot study was limited by a very small sample size, reducing statistical power and increasing susceptibility to baseline imbalances. One randomized participant did not initiate treatment and was excluded from efficacy analyses. Missing follow-up data required use of last-observation methods for some outcomes. Several prespecified secondary outcomes could not be analyzed due to unavailable summary measures. Findings are preliminary and not generalizable.

Results Point of Contact

• Title: Thanh Thuy Truong, MD
• Organization: Baylor College of Medicine

tt5@bcm.edu

713-275-5251

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Subjects will be randomized to two different arms: lemborexant plus naltrexone versus placebo plus naltrexone using a computer-generated randomization scheme.

Study Record Dates

• First Submitted: July 6, 2022
• First Posted: July 14, 2022
• Study Start: February 9, 2023
• Primary Completion: January 30, 2024
• Study Completion: January 30, 2024
• Last Updated: March 24, 2026
• Results First Posted: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)