18 Participants Needed

Auvelity for Opioid Use Disorder

TP
KS
TP
LK
Overseen ByLori Keyser-Marcus, PhD
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Virginia Commonwealth University
Must be taking: Buprenorphine

Trial Summary

What is the purpose of this trial?

The overall goal of this project is to collect initial human data on the effects of novel compounds on safety (interactions with an opioid drug, e.g., buprenorphine) and early efficacy signals (subjective effects on negative affect, craving, and opioid withdrawal) in OUD subjects currently in MOUD treatment with buprenorphine.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as antidepressants, antiepileptics, and CNS stimulants, at least two weeks before starting the study medication. If you are on these medications, you will need to discontinue them to participate.

What data supports the effectiveness of the drug combination of dextromethorphan and bupropion for opioid use disorder?

Research in rats showed that the combination of dextromethorphan and bupropion significantly reduced self-administration of a synthetic opioid in those with high initial use, suggesting potential effectiveness for people with high-level opioid use.12345

Is Auvelity (dextromethorphan and bupropion) generally safe for humans?

There is limited safety data available for the combination of dextromethorphan and bupropion in humans, but bupropion alone has been studied for smoking cessation and methamphetamine use disorder, showing some safety in those contexts. Further studies are needed to confirm the safety of the combination specifically for opioid use disorder.13567

How does the drug Auvelity differ from other treatments for opioid use disorder?

Auvelity is unique because it includes bupropion, which is known for its role in smoking cessation and depression treatment by affecting noradrenaline and dopamine levels in the brain. This mechanism might offer a novel approach for opioid use disorder, differing from traditional treatments that often focus on opioid receptor interactions.7891011

Research Team

FG

Frederick G Moeller

Principal Investigator

Virginia Commonwealth University

Eligibility Criteria

This trial is for adults aged 18-65 with moderate to severe Opioid Use Disorder (OUD) who are currently on stable buprenorphine treatment. They must have a positive urine test for buprenorphine, mild depression symptoms or greater, and agree to use contraception if applicable. Excluded are those on certain medications like antidepressants, with serious health issues, significant heart abnormalities, or recent suicidal behavior.

Inclusion Criteria

I am currently being treated for opioid use disorder with specific medications.
Quick Inventory of Depressive Symptomatology (16-Item) (QIDS-SR16) score of mild or greater (>6)
Understand the study procedures and provide written informed consent in the English language
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Exclusion Criteria

Current severe alcohol use disorder or current benzodiazepine use or recent (within last 3 months) discontinuation of alcohol with severe alcohol use disorder or discontinuation of benzodiazepines with severe benzodiazepine use disorder
Current DSM-5 diagnosis of any psychoactive substance use disorder other than opioids, cocaine, marijuana, or nicotine, or mild or moderate alcohol use disorder. Diagnosis of mild to moderate use disorder for alcohol will not be considered exclusionary
Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
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Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Auvelity or placebo as an adjunctive treatment to buprenorphine/naloxone for opioid use disorder

8 weeks
Multiple PK study visits, each lasting up to 8 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Phase Ib/2a Drug-drug Interaction Study of a Combination of 45mg Dextromethorphan With 105 mg Bupropion
Trial OverviewThe study tests the combination of Dextromethorphan and Bupropion (Auvelity) against a placebo in people with OUD. It aims to assess drug interactions and early signs of effectiveness in reducing negative feelings, cravings, and withdrawal symptoms associated with opioid addiction.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: AuvelityExperimental Treatment1 Intervention
Orally-administered combination of dextromethorphan with Bupropion (trade name Auvelity)
Group II: PlaceboPlacebo Group1 Intervention
Subjects who are randomized to placebo will receive identical capsules to the test product at the same time periods noted above, administered orally.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials
732
Recruited
22,900,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials
2,658
Recruited
3,409,000+

Findings from Research

In a pilot study involving 49 participants with severe methamphetamine use disorder, the combination of naltrexone and bupropion showed potential efficacy, with 11 participants meeting the predefined responder criteria for treatment success.
The study's design indicated that while the combination therapy did not meet the statistical success threshold of 9 responders, the results suggest enough promise to justify further investigation into this pharmacotherapy approach.
Utilizing a Two-stage Design to Investigate the Safety and Potential Efficacy of Monthly Naltrexone Plus Once-daily Bupropion as a Treatment for Methamphetamine Use Disorder.Mooney, LJ., Hillhouse, MP., Thomas, C., et al.[2019]
In a 12-week clinical trial involving 149 methadone-maintained subjects, bupropion HCL (300 mg/day) did not show significant efficacy compared to placebo in treating cocaine dependence.
However, exploratory analyses indicated that bupropion may have a beneficial effect for individuals who were depressed at the start of the study, suggesting that targeting specific subgroups could improve treatment outcomes in future trials.
A multicenter trial of bupropion for cocaine dependence in methadone-maintained patients.Margolin, A., Kosten, TR., Avants, SK., et al.[2019]
In a 48-week study involving 588 smokers, maintenance treatment with bupropion significantly extended the time to relapse compared to a placebo, with a median of 136 days for bupropion users versus 71 days for those on double placebo.
While bupropion showed a modest benefit in preventing relapse, the advantage diminished after stopping the medication, and the use of nicotine gum was low, indicating the need for further research on its effectiveness and optimal treatment duration.
A randomized trial of bupropion and/or nicotine gum as maintenance treatment for preventing smoking relapse.Covey, LS., Glassman, AH., Jiang, H., et al.[2018]

References

Utilizing a Two-stage Design to Investigate the Safety and Potential Efficacy of Monthly Naltrexone Plus Once-daily Bupropion as a Treatment for Methamphetamine Use Disorder. [2019]
A multicenter trial of bupropion for cocaine dependence in methadone-maintained patients. [2019]
A randomized trial of bupropion and/or nicotine gum as maintenance treatment for preventing smoking relapse. [2018]
Use of pharmacotherapies for the management of addictive behaviours in Australian clinical practice. [2018]
Dextromethorphan and bupropion reduces high level remifentanil self-administration in rats. [2021]
Bupropion-varenicline interactions and nicotine self-administration behavior in rats. [2018]
Pharmacogenetic investigation of smoking cessation treatment. [2021]
Dose-Dependent Inhibition of CYP2D6 by Bupropion in Patients With Depression. [2021]
Prediction of Drug-Drug Interactions with Bupropion and Its Metabolites as CYP2D6 Inhibitors Using a Physiologically-Based Pharmacokinetic Model. [2020]
Physiologically Based Pharmacokinetic Modeling of Bupropion and Its Metabolites in a CYP2B6 Drug-Drug-Gene Interaction Network. [2023]
Examination of the metabolite hydroxybupropion in the reinforcing and aversive stimulus effects of nicotine in rats. [2018]