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

NCT05976646 | Completed Phase 1 Results 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 Average Heart Rate (Pulse) at Each Testing Visit

  Measuring pulse is crucial for providing real-time, objective data. It acts as a baseline indicator to detect irregularities and monitor for stress and fatigue levels. The healthy resting heart rate (RHR) for most adults is 60-100 beats per minute (bpm). A lower rate usually indicates better cardiovascular fitness. A poor score is falling above the 60-100bpm range.

  Baseline and Day 8 (PK testing visits)

• Safety- as Measured by Average Blood Pressure at Each Testing Visit

  Systolic blood pressure is the first (top/upper) number. It measures the pressure your blood is pushing against your artery walls when the heart beats. Diastolic blood pressure is the second (bottom/lower) number. It measures the pressure your blood is pushing against your artery walls while the heart muscle rests between beats. A good, healthy blood pressure for most adults is generally considered to be less than 120/80 mm Hg. It ensures participant safety by monitoring for extreme hypertension or hypotension, validating cardiovascular drug effects. Anything abovethe 130/80 mmHg is considered a high or bad reading. A high reading means that your heart is working too hard to pump blood and putting excessive strain on the arteries.

  Baseline and Day 8 (PK testing visits)

• Safety- as Measured by Average Pulse Oximetry at Each Testing Visit

  Measuring pulse oximetry (SpO2) for research safety provides real-time, noninvasive monitoring of oxygen saturation, crucial for identifying "silent hypoxia," detecting respiratory decline from interventions, and ensuring participant safety during trials. The normal range is 95%-100%. Anything below the 95% is out of normal range and cause for concern.

  Baseline and Day 8 (PK testing visits)

• Safety- as Measured by Average Respiratory Rate at Each Testing Visit

  A good, normal respiratory rate for research safety data in resting adults is 12 to 20 breaths per minute (bpm). Rates consistently under 12 or over 25 bpm are often flagged in clinical studies as potential safety concerns.

  Baseline and Day 8 (PK testing visits)

• Safety- as Measured by Total Number of Adverse Events

  Tracking adverse event (AE) rates in research is essential to ensure participant safety, determine the risk-benefit ratio of interventions, and maintain data integrity for regulatory approval. Analyzing these rates allows investigators to identify trends, detect unexpected risks early, and modify studies to prevent harm. .

  Baseline to Week 2 follow-up

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

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

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

Results Point of Contact

• Title: Dr. F. Gerard Moeller
• Organization: Virginia Commonwealth University

frederick.moeller@vcuhealth.org

(804) 828-4134

Study Officials

• Frederick G Moeller

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: August 19, 2026
• Results First Posted: August 19, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)