AddictionPhase 1/2NCT05976646

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

A Phase 1/2 study testing Auvelity in people with Addiction and Opioid Use, run by Virginia Commonwealth University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Addiction, Opioid Use, Substance Use Disorders
What is being tested?: Auvelity
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 18 participants
Where: 1 siteUnited States
Study dates: 18 Sep 2023to 9 Jul 2025
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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).

Who cannot join

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

Show all 10Show fewer

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.
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.

Trial locations and contacts

1 site in 1 country.

United States1 site

CARI Research Clinic- VCU Institute for Drug and Alcohol Studies
Richmond, Virginia, 23219

Other trials in United States

About this study

Official title: Phase Ib/2a Drug-drug Interaction Study of a Combination of 45mg Dextromethorphan With 105 mg Bupropion (AUVELITY) as an Adjunctive Treatment for Buprenorphine/Naloxone for Opioid Use Disorder

Read the detailed description

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. The compound to be studied in this protocol will be a pre-configured combination of 45mg dextromethorphan with 105 mg Bupropion (AuvelityTM, hereafter referred as Auvelity). Notably, other NMDA receptor antagonists such as ketamine have also been shown to rapidly improve mood and reduce suicidality. OUD has also been linked to histories of trauma and syndromes of negative mood, where opioid use in many individuals was initially motivated by a desire to alleviate a negative mood state. Lastly, using the NIDA Phenotyping Battery, our group has also found negative emotionality to be part of a constellation of neurofunctional domains that are associated with SUD severity. Taken together, providing AUVELITY as an adjunctive treatment to buprenorphine could be an avenue to target crucial underlying mechanisms of OUD and improve OUD treatment outcomes.

Conditions: Addiction, Opioid Use, Substance Use Disorders, Opioid Use Disorder
Being tested: Placebo, Auvelity
Medical subject headings: Behavior, Addictive, Substance-Related Disorders, Opioid-Related Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT05976646
Study group	Role	What they receive
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. Receives: Drug: Placebo
Auvelity	Experimental	Orally-administered combination of dextromethorphan with Bupropion (trade name Auvelity) Receives: Drug: Auvelity

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
.
Measured: Baseline to Week 2 follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Sep 20239 Jul 2025

First posted4 Aug 2023
Study start18 Sep 2023
Primary completion9 Jul 2025
Study completion9 Jul 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for AddictionStudies of the same condition, open and under way.
More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05976646
Sponsor's protocol ID: HM20027635
Other IDs: 5UG1DA050207
Status last verified: Jul 2026
First submitted: 24 Jul 2023
Last updated: 19 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase Ib/2a Drug-drug Interaction Study of a Combination of 45mg Dextromethorphan With 105 mg Bupropion (AUVELITY) as an Adjunctive Treatment for Buprenorphine/Naloxone for Opioid Use Disorder
ClinicalTrials.gov ID: NCT05976646
Acronym / sponsor ID: HM20027635
Conditions: Addiction, Opioid Use, Substance Use Disorders, Opioid Use Disorder
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Virginia Commonwealth UniversityUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: 18 Sep 2023 (actual)
Primary completion: 9 Jul 2025 (actual)
Study completion: 9 Jul 2025 (actual)
First posted: 4 Aug 2023 (actual)
Results: Posted 19 Aug 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboSubjects who are randomized to placebo will receive identical capsules to the test product at the same time periods noted above, administered orally.
Auvelity	Experimental	Drug: AuvelityOrally-administered combination of dextromethorphan with Bupropion (trade name Auvelity)

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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)

Key exclusion criteria (10 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboSubjects who are randomized to placebo will receive identical capsules to the test product at the same time periods noted above, administered orally.	Drug	Placebo
AuvelityOrally-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.	Drug	Auvelity

Primary outcome

Safety- as Measured by Average Heart Rate (Pulse) at Each Testing Visit
Time frame: Baseline and Day 8 (PK testing visits)
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.
Safety- as Measured by Average Blood Pressure at Each Testing Visit
Time frame: Baseline and Day 8 (PK testing visits)
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.
Safety- as Measured by Average Pulse Oximetry at Each Testing Visit
Time frame: Baseline and Day 8 (PK testing visits)
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.
Safety- as Measured by Average Respiratory Rate at Each Testing Visit
Time frame: Baseline and Day 8 (PK testing visits)
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.
Safety- as Measured by Total Number of Adverse Events
Time frame: Baseline to Week 2 follow-up
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. .

Results and safety

Results posted to the registry on 19 Aug 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	6	6
Auvelity	12	12

Primary outcome: Safety- as Measured by Average Heart Rate (Pulse) at Each Testing Visit

Time frame: Baseline and Day 8 (PK testing visits). Mean (Standard Deviation). Unit: bpm

Measure	Placebo n = 6	Auvelity n = 12
Baseline	72.63 (16.53)	72.81 (7.90)
Day 8	67.53 (9.04)	67.9 (6.29)

Population analysed: all participants who Started the study (i.e., 6 and 12 participants in each Arm/Group, respectively) were assessed at each time point reported in the data table.

Primary outcome: Safety- as Measured by Average Blood Pressure at Each Testing Visit

Time frame: Baseline and Day 8 (PK testing visits). Mean (Standard Deviation). Unit: mmHg

Measure	Placebo n = 6	Auvelity n = 12
Systolic Baseline	125.93 (13.31)	128.71 (14.07)
Systolic Day 8	122.47 (13.20)	125.38 (15.07)
Diastolic Baseline	73.10 (5.)	77.14 (8.15)
Diastolic Day 8	75.33 (8.53)	75.57 (6.11)

Population analysed: all participants who Started the study (i.e., 6 and 12 participants in each Arm/Group, respectively) were assessed at each time point reported in the data table.

Primary outcome: Safety- as Measured by Average Pulse Oximetry at Each Testing Visit

Time frame: Baseline and Day 8 (PK testing visits). Mean (Standard Deviation). Unit: percentage of SpO2

Measure	Placebo n = 6	Auvelity n = 12
Baseline	98.07 (1.11)	97.75 (1.51)
Day 8	98.87 (.92)	97.22 (1.29)

Population analysed: all participants who Started the study (i.e., 6 and 12 participants in each Arm/Group, respectively) were assessed at each time point reported in the data table.

Primary outcome: Safety- as Measured by Average Respiratory Rate at Each Testing Visit

Time frame: Baseline and Day 8 (PK testing visits). Mean (Standard Deviation). Unit: breaths/min

Measure	Placebo n = 6	Auvelity n = 12
Baseline	16.87 (1.17)	16.33 (.63)
Day 8	16.67 (1.09)	16.40 (.98)

Population analysed: all participants who Started the study (i.e., 6 and 12 participants in each Arm/Group, respectively) were assessed at each time point reported in the data table.

Adverse events

Time frame: From Baseline to end of study participation, approximately 3 weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Auvelity	0 of 12 (0%)	9 of 12 (75%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Frederick G Moeller principal investigator

Virginia Commonwealth University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Auvelity in people with Addiction and Opioid Use, run by Virginia Commonwealth University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety- as Measured by Average Heart Rate (Pulse) at Each Testing Visit (time frame: Baseline and Day 8 (PK testing visits)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05976646.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.