Naltrexone Injection for Alcoholism

Overseen By Rachel Weyl, BS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Pennsylvania

Must not be taking: Psychotropics, Anticonvulsants, Opioids, Anticoagulants

Disqualifiers: Planned surgery, Physical disease, Psychotic disorder, Drug use disorder, others

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

Compensation: Varies

Number of Visits: 6

Duration: 8 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a phase IV, two-arm, randomized, double-blind, placebo-controlled study to assess whether individuals identified as primarily reward drinkers are significantly more likely to reduce heavy drinking if they receive XR-NTX than a matching placebo injection. Study subjects will receive monthly injections of long-acting injectable naltrexone 380 mg (4 mL) or matching placebo. All subjects will also receive 4 sessions of Medical Management (MM). Post-treatment follow-up visits will be conducted at 4 weeks after the scheduled completion of treatment.

Will I have to stop taking my current medications?

Yes, if you are currently taking psychotropic, anticonvulsant, opioid, anticoagulant, or alcohol use disorder treatment medications, you will need to stop them to participate in this trial.

What data supports the effectiveness of the drug Naltrexone Injection for Alcoholism?

Research shows that extended-release naltrexone (XR-NTX), a once-a-month injectable drug, has been effective in reducing drinking and heavy drinking in people with alcohol dependence compared to a placebo. It has also been shown to improve the quality of life for these patients. ^{1 2 3 4 5}

How is the drug XR-NTX 380 mg unique for treating alcoholism?

XR-NTX 380 mg is unique because it is a once-a-month injection that helps reduce alcohol consumption and prolong abstinence in people with alcohol dependence, especially those who can abstain for a few days before starting treatment. This extended-release formulation provides a consistent effect over time, unlike daily oral medications. ^{2 3 4 5 6}

Research Team

Henry Kranzler, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

Adults aged 18-65 with Alcohol Use Disorder (AUD) who drink heavily and want to cut down or stop. They must be able to understand the study, have a stable address, and use reliable birth control if applicable. Excluded are those with certain mental health conditions, on conflicting medications, facing potential incarceration soon, having significant physical diseases or abnormal lab results, drug disorders other than alcohol/nicotine/cannabis, needing detoxification from alcohol or with a history of bad reactions to XR-NTX.

Inclusion Criteria

Current DSM-5 diagnosis of AUD

I am between 18 and 65 years old.

Primarily a reward drinker [i.e., with a score of >22 on the reward subscale and a score of <14 on the relief subscale of the Inventory of Drinking Situations (IDS)]

Exclusion Criteria

I don't have any major health issues that could make joining the study unsafe for me.

Current psychotic disorder (bipolar, schizophrenia, major depression with suicidal ideation, or psychotic features) identified by clinical examination or the structured interview that could interfere with study participation or make it hazardous for the subject

History of allergy or other serious adverse event due to treatment with XR-NTX

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person or virtual)

Treatment

Participants receive monthly injections of XR-NTX or placebo and complete daily IVR calls

8 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Medical Management
• Placebo intramuscular injection
• XR-NTX 380 mg, intramuscular injection

Trial Overview The trial is testing whether long-acting injectable naltrexone (XR-NTX) helps people who primarily drink for pleasure more than a placebo in reducing heavy drinking. Participants will receive either XR-NTX or placebo injections monthly along with four sessions of Medical Management counseling over eight weeks.

Participant Groups

Group I: XR-NTX 380 mg, intramuscular injection Active Control 2 Interventions

Subjects will receive an injection of XR-NTX 380 mg (4 mL) repeated once after 4 weeks.

Group II: Inactive placebo intramuscular injection Placebo Group 2 Interventions

Subjects will receive a placebo injection repeated once after 4 weeks.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Alkermes, Inc.

Industry Sponsor

Trials

118

Recruited

27,200+

Richard Pops

Alkermes, Inc.

Chief Executive Officer since 1991

BA in Economics from Stanford University

Dr. Craig Hopkinson

Alkermes, Inc.

Chief Medical Officer since 2017

MD

Findings from Research

In a 24-week study involving 250 recently detoxified opioid-dependent adults, those treated with once-monthly extended-release naltrexone (XR-NTX) had a significantly higher rate of achieving 90% abstinence from opioids compared to those receiving a placebo (51% vs 31%).

The study found that XR-NTX was effective across various demographic and clinical severity characteristics, indicating that it can be a suitable treatment option for a broad range of patients without needing specific matching factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating Opioid Dependence With Injectable Extended-Release Naltrexone (XR-NTX): Who Will Respond? Nunes, EV., Krupitsky, E., Ling, W., et al.[2022]

In a study of 624 alcohol-dependent adults over 24 weeks, those receiving the higher dose of extended-release naltrexone (XR-NTX 380 mg) showed a slightly higher participation rate in counseling and support groups compared to placebo, suggesting that XR-NTX may encourage engagement in treatment.

Participation in self-help support groups was significantly associated with reduced heavy drinking across all treatment groups, indicating that combining XR-NTX with counseling and support can be beneficial for individuals in recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of treatment with intramuscular, injectable, extended-release naltrexone on counseling and support group participation in patients with alcohol dependence. Cisler, RA., Silverman, BL., Gromov, I., et al.[2011]

Extended release naltrexone (XR-NTX) significantly reduces relapse rates in individuals with opioid use disorder, showing effectiveness across diverse demographic and psychological backgrounds, based on a study involving 308 participants.

However, individuals who reported alcohol intoxication in the 30 days prior to treatment had similar relapse rates to those receiving standard treatment, suggesting that recent alcohol use may limit the effectiveness of XR-NTX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do patient characteristics moderate the effect of extended-release naltrexone (XR-NTX) for opioid use disorder? Friedmann, PD., Wilson, D., Nunes, EV., 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]

In a 24-week study involving 624 alcohol-dependent patients, the 380 mg dose of extended-release naltrexone (XR-NTX) significantly improved quality of life in areas such as mental health, social functioning, and physical functioning compared to placebo.

Improvements in quality of life were correlated with reductions in drinking behaviors, indicating that XR-NTX not only helps reduce alcohol consumption but also enhances overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of extended-release naltrexone (XR-NTX) on quality of life in alcohol-dependent patients. Pettinati, HM., Gastfriend, DR., Dong, Q., et al.[2021]

In a study of 82 patients who had abstained from alcohol for at least 4 days, extended-release naltrexone (XR-NTX) 380 mg significantly increased the rate of abstinence compared to placebo, with a median time to first drink of 41 days versus 12 days.

XR-NTX 380 mg also led to a substantial reduction in heavy drinking days (93% decrease) and overall drinking days (90% decrease), indicating its efficacy in promoting sustained abstinence and reducing alcohol consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of extended-release naltrexone in alcohol-dependent patients who are abstinent before treatment. O'Malley, SS., Garbutt, JC., Gastfriend, DR., et al.[2013]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Treating Opioid Dependence With Injectable Extended-Release Naltrexone (XR-NTX): Who Will Respond? [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Impact of treatment with intramuscular, injectable, extended-release naltrexone on counseling and support group participation in patients with alcohol dependence. [2011]

3. United States pubmed.ncbi.nlm.nih.gov

Do patient characteristics moderate the effect of extended-release naltrexone (XR-NTX) for opioid use disorder? [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of extended-release injectable naltrexone (XR-NTX) in patients with alcohol dependence. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Effect of extended-release naltrexone (XR-NTX) on quality of life in alcohol-dependent patients. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy of extended-release naltrexone in alcohol-dependent patients who are abstinent before treatment. [2013]