Phase Ib/2a Drug-drug Interaction Study of a Combination of 45mg Dextromethorphan With 105 mg Bupropion

NCT05976646 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: HM200276355UG1DA050207
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Addiction; Opioid Use; Substance Use Disorders; Opioid Use Disorder

Outcome Measures

Primary Outcomes (5)

• Safety- as measured by heart rate

  Heart rate (HR)

  During each PK study visit from visit start to end, up to approximately 8 hours

• Safety- as measured by blood pressure

  blood pressure

  During each PK study visit from visit start to end, up to approximately 8 hours

• Safety- as measured by pulse oximetry

  pulse oximetry

  During each PK study visit from visit start to end, up to approximately 8 hours

• Safety- as measured by respiratory rate

  respiratory rate

  During each PK study visit from visit start to end, up to approximately 8 hours

• Safety- as measured by Adverse events

  adverse events

  During each PK study visit from visit start to end, up to approximately 8 hours; and from baseline to end of study participation

Secondary Outcomes (1)

• Buprenorphine PK

  During each PK study visit from visit start to end, up to approximately 8 hours

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Subjects who are randomized to placebo will receive identical capsules to the test product at the same time periods noted above, administered orally.

Drug: Placebo

Auvelity

EXPERIMENTAL

Orally-administered combination of dextromethorphan with Bupropion (trade name Auvelity)

Drug: Auvelity

Interventions

Placebo DRUG

Subjects who are randomized to placebo will receive identical capsules to the test product at the same time periods noted above, administered orally.

Placebo

Auvelity DRUG

Orally-administered combination of 45 mg dextromethorphan with 105 mg Bupropion (trade name Auvelity). Auvelity will initially be administered orally once daily for three days. After 3 days on once daily AUVELITY, the participants will begin taking AUVELITY twice daily for 4 additional days as recommended in the FDA-approved prescribing information.

Auvelity

Eligibility Criteria

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

You may qualify if:

• Males and female subjects between 18 - 65 years of age;
• Understand the study procedures and provide written informed consent in the English language.
• Meet current DSM-5 criteria for OUD, of at least moderate severity, currently engaged in MOUD treatment at a buprenorphine-naloxone sublingual film total daily dose ranging from 8mg/2mg to 24mg/6mg or buprenorphine sublingual tablet 5.7mg/1.4mg to 17.1/4.3 daily for at least 2 weeks at screening. Or on a stable dose of depot injectable buprenorphine for at least four months, with at least one week since last depot buprenorphine injection.
• Have a positive urine drug screen for buprenorphine during screening and upon presenting for the first laboratory day on the clinical research unit to document buprenorphine use;
• Quick Inventory of Depressive Symptomatology (16-Item) (QIDS-SR16) score of mild or greater (\>6)
• Females must be non-pregnant and non-lactating. Additionally, for females with childbearing potential (ie., have not undergone sterilization via hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or at least 1 year post-menopausal), participants must agree to use an acceptable form of contraception during study participation and to continue its use for at least 30 days after the last dose of the study drug (e.g, abstinence, intrauterine device, hormonal implant, hormonal patch/ring/pill, condoms (male or female).

You may not qualify if:

• Contraindications for participation as determined by medical history and physical exam performed by study NP or study physician;
• Pregnant or nursing women;
• Baseline ECG with clinically significant abnormal conduction;
• Uncontrolled serious psychiatric or major medical disorder; including uncontrolled hypertension, seizure disorder, anorexia nervosa or bulimia, bipolar disorder, schizoaffective disorder, or schizophrenia;
• Taking antidepressant medications (tricyclic antidepressants, SSRIs, SNRIs, MAOIs), antibiotic linezolid, antiepileptics, or CNS stimulants (amphetamine, methylphenidate) within the two weeks prior to initiation of study medication
• History of adverse reaction or allergy to dextromethorphan or bupropion
• 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
• Significant current suicidal or homicidal ideation (C-SSRS "yes" answers on questions 4 or 5) or a history of suicide attempt within the past 6 months.
• 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.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

CARI Research Clinic- VCU Institute for Drug and Alcohol Studies

Richmond, Virginia, 23219, United States

Location

MeSH Terms

Conditions

Behavior, Addictive; Substance-Related Disorders; Opioid-Related Disorders

Condition Hierarchy (Ancestors)

Compulsive Behavior; Impulsive Behavior; Behavior; Chemically-Induced Disorders; Mental Disorders; Narcotic-Related Disorders

Study Officials

• Frederick G Moeller

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: August 4, 2023
• Study Start: September 18, 2023
• Primary Completion: July 9, 2025
• Study Completion: July 9, 2025
• Last Updated: July 23, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)