Lemborexant + Naltrexone for Alcoholism

Overseen By Nadine Obeid, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Baylor College of Medicine

Must not be taking: Opioids, Benzodiazepines, Hypnotics

Disqualifiers: Unstable medical conditions, Drug use disorder, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well a combination of two drugs, lemborexant (a sleep aid) and naltrexone (used to treat alcohol dependence), reduces alcohol cravings in individuals with both alcohol use disorder and insomnia. The study will also assess the combination's effects on sleep quality, depression, anxiety, and any thoughts of self-harm. Participants will receive either lemborexant with naltrexone or a placebo with naltrexone for four weeks. Suitable candidates include individuals with alcohol use disorder and insomnia who have been admitted to The Menninger Clinic. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use naltrexone, lemborexant, opioid medications, scheduled benzodiazepines, or hypnotics before joining. Other stable medications might be allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that lemborexant is generally safe and well-tolerated as an additional treatment for insomnia. The FDA has already approved it for treating insomnia in adults, supporting its safety profile. In past studies, participants using lemborexant did not experience significant balance issues, even when consuming alcohol.

Naltrexone is a common treatment for alcohol use disorder (AUD) and helps reduce alcohol cravings. It has been safely used in many individuals with AUD.

When used together, lemborexant and naltrexone do not appear to cause serious side effects. However, one study found that taking lemborexant with alcohol might affect thinking or memory.

Overall, the combination of lemborexant and naltrexone seems safe, but prospective participants should consider these findings when deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcoholism?

Researchers are excited about the combination of Lemborexant and Naltrexone for treating alcoholism because it introduces a fresh approach. While Naltrexone is already a standard treatment that helps reduce the craving for alcohol, Lemborexant, a medication typically used for insomnia, may enhance the effectiveness by improving sleep quality, which is often disrupted in individuals with alcoholism. This dual approach could address both alcohol cravings and sleep issues simultaneously, potentially offering a more comprehensive treatment option compared to current therapies.

What evidence suggests that this trial's treatments could be effective for alcohol use disorder and insomnia?

Research has shown that naltrexone, which participants in this trial will receive, helps reduce heavy drinking and improve outcomes for people with alcohol use disorder (AUD). It blocks the "high" feeling from alcohol, reducing cravings. Studies have demonstrated that naltrexone can significantly decrease heavy drinking episodes. In this trial, some participants will also receive lemborexant, as researchers are studying its potential to improve sleep, a common issue for people with AUD. Combining lemborexant with naltrexone could enhance the overall treatment by addressing both alcohol cravings and sleep problems. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with alcohol use disorder and insomnia, as diagnosed by DSM-5 criteria. Participants must not have used opioids or certain sedatives recently, be free from acute alcohol withdrawal, and cannot have liver issues or other drug disorders (except nicotine/cannabis). Pregnant/breastfeeding individuals or those with a known sensitivity to the study drugs are excluded.

Inclusion Criteria

diagnosis of alcohol use disorder using the DSM-5 criteria confirmed with SCID-5 and

You have a history of alcohol use disorder and meet the criteria for alcohol use disorder as specified in the DSM-5.

Admission to The Menninger clinic

Exclusion Criteria

My liver function tests are not more than 3 times the normal limit.

You have a substance use disorder, except for nicotine and cannabis.

I have been diagnosed with narcolepsy and may have other stable health conditions or use psychiatric medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either Lemborexant plus Naltrexone or Placebo plus Naltrexone for alcohol craving and sleep issues

4 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Lemborexant
• Naltrexone

Trial Overview The study aims to see if adding Lemborexant to Naltrexone helps reduce alcohol cravings more than just Naltrexone alone in people with both alcoholism and sleep problems. It also looks at how this combination affects sleep quality, mood, and thoughts of self-harm.

How Is the Trial Designed?

Group I: Lemborexant plus Naltrexone Active Control 2 Interventions

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

Group II: Placebo plus Naltrexone Placebo Group 1 Intervention

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

Naltrexone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vivitrol for:

• Alcohol dependence
• Opioid use disorder

Approved in European Union as Naltrexone for:

• Opioid dependence
• Alcohol dependence

Approved in Canada as Vivitrol for:

• Opioid use disorder
• Alcohol dependence

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Published Research Related to This Trial

Extended-release naltrexone (XR-NTX) is being studied as a potentially more effective treatment for alcohol dependence compared to daily oral naltrexone (O-NTX), particularly due to its once-a-month injection format which may improve adherence and retention in treatment.

The study involves 237 participants over 24 weeks and aims to evaluate the effectiveness of XR-NTX in achieving abstinence or moderate drinking, while also assessing its cost-effectiveness compared to O-NTX in a primary care setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release vs. oral naltrexone for alcohol dependence treatment in primary care (XON). Malone, M., McDonald, R., Vittitow, A., et al.[2020]

The FDA-approved extended-release injectable formulation of naltrexone (Vivitrol) offers a promising alternative to daily oral medication for alcohol dependence, potentially improving adherence and treatment outcomes.

When combined with psychosocial support, long-acting naltrexone has shown significant improvements in drinking outcomes, particularly for patients who are abstinent at the start of treatment, suggesting its efficacy in managing alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting injectable naltrexone for the treatment of alcohol dependence. Mannelli, P., Peindl, K., Masand, PS., et al.[2013]

In a 1-year open-label extension study involving 114 patients, injectable extended-release naltrexone (XR-NTX) demonstrated long-term efficacy, with 50.9% of participants remaining abstinent from opioids throughout the study.

The treatment was generally safe, with only 21.1% of patients reporting adverse events and no severe adverse events noted, although 16.7% experienced elevated liver function tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy]. Krupitsky, EM., Nunes, EV., Ling, W., et al.[2016]

In a study of 149 alcohol-dependent patients, those receiving broad-spectrum treatment (BST) combined with naltrexone had significantly more days of abstinence compared to those receiving motivational-enhancement therapy (MET) with naltrexone.

The effectiveness of BST was particularly pronounced in patients with supportive social networks, indicating that BST may provide a meaningful clinical advantage over MET when used alongside naltrexone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building better cognitive-behavioral therapy: is broad-spectrum treatment more effective than motivational-enhancement therapy for alcohol-dependent patients treated with naltrexone? Davidson, D., Gulliver, SB., Longabaugh, R., et al.[2019]

A population pharmacokinetic analysis of 453 subjects showed that the clearance and distribution of naltrexone, used for alcohol dependence, are influenced by factors like weight and age, but these differences are not clinically significant enough to require dosage adjustments.

The study found that naltrexone clearance was higher in individuals with alcohol and/or opioid dependence compared to healthy subjects, indicating that while there are variations in pharmacokinetics, standard dosing of XR-NTX remains appropriate across different subpopulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of extended-release injectable naltrexone (XR-NTX) in patients with alcohol dependence. Dunbar, JL., Turncliff, RZ., Hayes, SC., et al.[2019]

A systematic review of 49 trials found that only 14% of studies on naltrexone for alcohol dependence had high adherence assurance, which may explain the variability in treatment efficacy observed.

The study revealed a significant correlation between adherence levels and treatment outcomes, suggesting that improving adherence monitoring could enhance the effectiveness of naltrexone in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review. Swift, R., Oslin, DW., Alexander, M., et al.[2022]

A pilot study involving 30 alcohol-dependent patients showed that the long-acting injectable naltrexone (Vivitrex) is generally safe and well tolerated, with mild to moderate adverse events that resolved without intervention.

The study confirmed that therapeutic levels of naltrexone were maintained throughout the 4-month treatment period, suggesting that this formulation could improve patient adherence by eliminating the need for daily dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot evaluation of the safety and tolerability of repeat dose administration of long-acting injectable naltrexone (Vivitrex) in patients with alcohol dependence. Johnson, BA., Ait-Daoud, N., Aubin, HJ., et al.[2019]

Injectable formulations of naltrexone, such as Vivitrex/Vivitrol and Naltrel, show promise in treating alcohol dependence with potentially fewer side effects compared to oral naltrexone, which has limitations like a small treatment effect size and plasma level fluctuations.

Vivitrex/Vivitrol has been effective in reducing heavy drinking in alcohol-dependent males, while Naltrel has been shown to promote abstinence and reduce relapse rates, indicating that these depot formulations may offer improved therapeutic options for alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone long-acting formulation in the treatment of alcohol dependence. Johnson, BA.[2021]

A study involving 250 opioid-dependent patients, many of whom had chronic hepatitis C virus (HCV) and HIV, found that intramuscular extended-release naltrexone (XR-NTX) did not significantly increase liver enzyme levels compared to a placebo, indicating its safety in this population.

Even though some patients experienced elevated liver enzymes, these levels improved over time, and no specific symptoms were linked to these elevations, suggesting that XR-NTX can be safely administered to patients with mild to moderate chronic HCV and/or HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. Mitchell, MC., Memisoglu, A., Silverman, BL.[2019]

A systematic review of 29 randomized placebo-controlled trials involving 5997 alcohol-dependent patients found that naltrexone significantly reduces heavy drinking in 70% of the studies, highlighting its efficacy in this area.

However, naltrexone showed less effectiveness in promoting abstinence, with only 36% of trials demonstrating an advantage over placebo, suggesting that its primary benefit lies in reducing excessive drinking rather than achieving complete sobriety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking. Pettinati, HM., O'Brien, CP., Rabinowitz, AR., et al.[2013]

In a 12-week clinical trial with 202 alcohol-dependent patients, naltrexone significantly reduced the relapse rate to heavy drinking (7.9% for naltrexone vs. 18.8% for placebo), indicating its efficacy in treating alcoholism.

Naltrexone was well-tolerated with low rates of adverse events, such as abdominal pain and headache, and it did not negatively affect liver function or biochemical markers of heavy drinking, demonstrating its safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol-dependence disorder: results from a multicenter clinical trial. Guardia, J., Caso, C., Arias, F., et al.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05458609

NCT05458609 | Lemborexant Augmentation of Naltrexone ... Standard treatment for AUD with naltrexone improves cravings and other AUD outcomes, but does not improve sleep. In some cases, naltrexone may have a ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2376083/

Naltrexone long-acting formulation in the treatment of alcohol ... Vivitrex® has demonstrated efficacy at significantly decreasing heavy drinking among alcohol-dependent men; however, more data are needed to determine whether ...

3. withpower.com withpower.com/trial/phase-3-alcohol-use-disorders-aud-7-2022-1a2c7

Lemborexant + Naltrexone for Alcoholism Research shows that naltrexone, one of the drugs in the treatment, has been effective in reducing heavy drinking and improving outcomes when combined with ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0074774224000229

Repurposing drugs for treatment of alcohol use disorder Currently approved medications for alcohol use disorder (AUD) include acamprosate, disulfiram, naltrexone, nalmefene, baclofen, and sodium oxybate.

5. go.drugbank.com go.drugbank.com/conditions/DBCOND0074737

Alcohol Use Disorders (AUD) (DBCOND0074737) Lemborexant Augmentation of Naltrexone for Alcohol Craving and Sleep. Lemborexant · Naltrexone. treatment, 3, completed. NCT01362309. D-Cycloserine to Enhance ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11728975/

Phase 1b/2a safety study of lemborexant as an adjunctive ... Lemborexant, a dual orexin receptor antagonist FDA approved for insomnia in adults, was found to be safe and well-tolerated as an adjunct to ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9150140/

A randomized, placebo-controlled crossover study - PMC Coadministration of lemborexant with alcohol showed additive negative effects on cognitive measures, but not on postural stability, compared with alcohol alone.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1043661824000227

New strategies for medications to treat substance use ... This review provides a general description of these new research strategies for the development of medications to treat SUDs with emphasis on the gaps and ...