Smoking CessationPhase 2NCT03471767
AXS-05 Phase II Trial on Smoking Behavior
A Phase 2 study testing AXS-05 and Bupropion SR in people with Smoking Cessation and Smoking, Cigarette, run by James Davis at 1 site in United States.
Trial summary
This research study is designed with the purpose of evaluating a new drug, combination Dextromethorphan-Bupropion (AXS-05), for its effects on smoking behavior. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Smoking Cessation, Smoking, Cigarette, Nicotine Dependence
- What is being tested?
- AXS-05 and Bupropion SR
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Mar 2018to 31 Mar 2019
- Phase
- Phase 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18 years or above
- Daily smoker using 10 or more cigarettes per day
- Willing to be smoke-free for 7 days
- Is able to provide written informed consent (in English) to participate in the study and able to understand the procedures and study requirements.
- Is willing to voluntarily sign and date an informed consent form that is approved by an institutional review board before the conduct of any study procedure.
Who cannot join
- Current use of a smoking cessation medication (e.g. nicotine replacement, Varenicline, bupropion)
- Current use of tobacco product other than cigarettes (e.g. e-cigarettes, smokeless tobacco)
- Not pregnant or breastfeeding
- Contraindication to the use of bupropion.
- Additional criteria may apply.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke Center for Smoking Cessation
Durham, North Carolina, 27705
About this study
Official title: A Randomized, Double-Blind 4-Week Study to Evaluate the Impact of AXS-05 on Smoking Behavior
This research study is designed with the purpose of evaluating a new drug, combination Dextromethorphan-Bupropion (AXS-05), for its effects on smoking behavior.
Read the detailed description
This study aims to investigate the potential efficacy of a combination of two FDA-approved agents, sustained release (SR) Bupropion (BUP) and immediate release (IR) Dextromethorphan (DXM), for the purpose of smoking cessation treatment. DXM, a widely used over-the-counter cough suppressant, is a nicotine receptor antagonist. In fact, studies by Duke's Center for Smoking Cessation (CSC) have shown that administration of DXM leads to a decrease in self-administration of nicotine in nicotine-dependent rats. DXM, however, has not been studied in humans. DXM, when taken alone, is not expected to be useful for treating nicotine dependence in humans given DXM rapidly metabolizes in humans via CYP2D6. As a result, therapeutic concentrations needed to bind to nicotine receptors are not obtained. Therapeutic concentrations of DXM are required, therefore, to allow DXM to bind to nicotine receptors and act as a nicotine antagonist. In order to attain therapeutic concentrations of DXM a metabolism inhibitor must be introduced. BUP is a well-known FDA approved smoking cessation medication that has been shown to inhibit the metabolism of DXM. When BUP is co-administered with DXM to healthy volunteers, a significant increase in DXM plasma levels is observed.
Currently, Axsome Therapeutics Inc. (Axsome) is developing and testing an oral fixed-dose combination of IR DXM with SR BUP to achieve therapeutic concentrations of DXM. This investigational drug has been named AXS-05. Axsome has found AXS-05 to be generally safe and well-tolerated in three Phase 1 studies. The adverse event profile of AXS-05 was similar to that of BUP alone.
Given the distinct mechanisms by which BUP and DXM interact, it is hoped that combining DXM and BUP will prove more efficacious than either drug administered alone for the purpose of tobacco use treatment in humans.
- Conditions
- Smoking Cessation, Smoking, Cigarette, Nicotine Dependence
- Being tested
- AXS-05, Bupropion SR
- Keywords
- Smoking cessation, Nicotine dependence, Bupropion, DXM, Nicotine addiction, Cigarette smoking, Dextromethorphan
- Medical subject headings
- Smoking Cessation, Cigarette Smoking, Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AXS-05Drug
Also called Bupropion/dextromethorphan
Dextromethorphan Immediate Release + Bupropion Sustained Release: Take 1 tablet two times per day, at least 8 hours apart and 1 hour prior to a meal, and 2 hours after a meal.
Bupropion SRDrug
Also called Wellbutrin SR, Zyban SR
Bupropion Sustained Release: Take 1 tablet two times per day, at least 8 hours apart and 1 hour prior to a meal, and 2 hours after a meal.
| Study group | Role | What they receive |
|---|---|---|
| AXS-05 | Experimental | Participants will receive AXS-05 (Dextromethorphan Immediate Release + Bupropion Sustained Release) for 4 weeks and will be instructed to take 1 tablet two times per day, at least 8 hours apart and 1 hour prior to a meal, and 2 hours after a meal. Receives: Drug: AXS-05 |
| Bupropion SR | Active comparator | Participants will receive Bupropion SR (Bupropion Sustained Release) for 4 weeks and will be instructed to take 1 tablet two times per day, at least 8 hours apart and 1 hour prior to a meal, and 2 hours after a meal. Receives: Drug: Bupropion SR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Smoking Intensity
Smoking intensity refers to the number of cigarettes smoked per day.
Measured: Baseline (V1), 3-Week Follow-Up Visit (V4)
Percentage of Participants Who Experienced a More Than 50% Reduction in Expired Carbon Monoxide (CO) Levels
A biochemical marker of smoking intensity.
Measured: Baseline (V1), 3-Week Follow-Up Visit (V4)
Secondary outcomes (5)
Change in Smoking Behavior
7-day point prevalence smoking abstinence. Measured by composite self-report diaries and biochemically confirmed via expired CO and salivary cotinine.
Measured: 3-Week Follow-Up Visit (V4), 4-Week Follow-Up Visit (V5)
Medication Adherence
Medication adherence is measured by composite self-reported diaries.
Measured: Baseline (V1), 3-Week Follow-Up Visit (V4)
Medication Tolerance by Self-Reported Side Effects
Number of participants who scored 3 or higher on a 7-point Likert scale ranking severity of side effects (1-2 mild; 3-5 moderate; 6-7 severe).
Measured: Baseline (V1), 3-Week Follow-Up Visit (V4)
Medication Tolerance by Serious Adverse Events
Measured by FDA reporting guidelines on adverse event or serious adverse event designation.
Measured: Baseline (V1), 4-Week Follow-Up Visit (V5)
Urinary Levels of Dextromethorphan
Measured via Urinary Dextromethorphan testing.
Measured: 3-Week Follow-Up Visit (V4)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2018
- Study start25 Mar 2018
- Primary completion31 Mar 2019
- Study completion31 Mar 2019
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 Smoking CessationStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are randomized to either take AXS-05 or BUP SR in parallel for the duration of the study.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- James Davis
- Sponsor type
- University, hospital or other
- Collaborators
- Axsome Therapeutics, Inc.
- Responsible party
- Sponsor-investigator, James Davis, Duke University
- Investigators
- James M Davis, MD, Principal investigator, Duke Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03471767
- Sponsor's protocol ID
- Pro00089413
- Status last verified
- Dec 2022
- First submitted
- 19 Mar 2018
- Last updated
- 19 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind 4-Week Study to Evaluate the Impact of AXS-05 on Smoking Behavior
- ClinicalTrials.gov ID
- NCT03471767
- Acronym / sponsor ID
- Pro00089413
- Conditions
- Smoking Cessation, Smoking, Cigarette, Nicotine Dependence
- Keywords
- Smoking cessation, Nicotine dependence, Bupropion, DXM, Nicotine addiction, Cigarette smoking, Dextromethorphan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- James DavisUniversity, hospital or other
- Collaborators
- Axsome Therapeutics, Inc.
- Study start
- 25 Mar 2018 (actual)
- Primary completion
- 31 Mar 2019 (actual)
- Study completion
- 31 Mar 2019 (actual)
- First posted
- 21 Mar 2018 (actual)
- Results
- Posted 12 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is designed with the purpose of evaluating a new drug, combination Dextromethorphan-Bupropion (AXS-05), for its effects on smoking behavior.
Detailed description
This study aims to investigate the potential efficacy of a combination of two FDA-approved agents, sustained release (SR) Bupropion (BUP) and immediate release (IR) Dextromethorphan (DXM), for the purpose of smoking cessation treatment. DXM, a widely used over-the-counter cough suppressant, is a nicotine receptor antagonist. In fact, studies by Duke's Center for Smoking Cessation (CSC) have shown that administration of DXM leads to a decrease in self-administration of nicotine in nicotine-dependent rats. DXM, however, has not been studied in humans. DXM, when taken alone, is not expected to be useful for treating nicotine dependence in humans given DXM rapidly metabolizes in humans via CYP2D6. As a result, therapeutic concentrations needed to bind to nicotine receptors are not obtained. Therapeutic concentrations of DXM are required, therefore, to allow DXM to bind to nicotine receptors and act as a nicotine antagonist. In order to attain therapeutic concentrations of DXM a metabolism inhibitor must be introduced. BUP is a well-known FDA approved smoking cessation medication that has been shown to inhibit the metabolism of DXM. When BUP is co-administered with DXM to healthy volunteers, a significant increase in DXM plasma levels is observed.
Currently, Axsome Therapeutics Inc. (Axsome) is developing and testing an oral fixed-dose combination of IR DXM with SR BUP to achieve therapeutic concentrations of DXM. This investigational drug has been named AXS-05. Axsome has found AXS-05 to be generally safe and well-tolerated in three Phase 1 studies. The adverse event profile of AXS-05 was similar to that of BUP alone.
Given the distinct mechanisms by which BUP and DXM interact, it is hoped that combining DXM and BUP will prove more efficacious than either drug administered alone for the purpose of tobacco use treatment in humans.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- Participants are randomized to either take AXS-05 or BUP SR in parallel for the duration of the study.
| Arm | Type | Receives |
|---|---|---|
| AXS-05 | Experimental | Drug: AXS-05Participants will receive AXS-05 (Dextromethorphan Immediate Release + Bupropion Sustained Release) for 4 weeks and will be instructed to take 1 tablet two times per day, at least 8 hours apart and 1 hour prior to a meal, and 2 hours after a meal. |
| Bupropion SR | Active comparator | Drug: Bupropion SRParticipants will receive Bupropion SR (Bupropion Sustained Release) for 4 weeks and will be instructed to take 1 tablet two times per day, at least 8 hours apart and 1 hour prior to a meal, and 2 hours after a meal. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18 years or above
- Daily smoker using 10 or more cigarettes per day
- Willing to be smoke-free for 7 days
- Is able to provide written informed consent (in English) to participate in the study and able to understand the procedures and study requirements.
- Is willing to voluntarily sign and date an informed consent form that is approved by an institutional review board before the conduct of any study procedure.
Key exclusion criteria (5 listed)
- Current use of a smoking cessation medication (e.g. nicotine replacement, Varenicline, bupropion)
- Current use of tobacco product other than cigarettes (e.g. e-cigarettes, smokeless tobacco)
- Not pregnant or breastfeeding
- Contraindication to the use of bupropion.
- Additional criteria may apply.
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 |
|---|---|---|
| AXS-05Also: Bupropion/dextromethorphanDextromethorphan Immediate Release + Bupropion Sustained Release: Take 1 tablet two times per day, at least 8 hours apart and 1 hour prior to a meal, and 2 hours after a meal. | Drug | AXS-05 |
| Bupropion SRAlso: Wellbutrin SR, Zyban SRBupropion Sustained Release: Take 1 tablet two times per day, at least 8 hours apart and 1 hour prior to a meal, and 2 hours after a meal. | Drug | Bupropion SR |
Primary outcome
Change in Smoking Intensity
Time frame: Baseline (V1), 3-Week Follow-Up Visit (V4)
Smoking intensity refers to the number of cigarettes smoked per day.
Percentage of Participants Who Experienced a More Than 50% Reduction in Expired Carbon Monoxide (CO) Levels
Time frame: Baseline (V1), 3-Week Follow-Up Visit (V4)
A biochemical marker of smoking intensity.
5 secondary outcomes
Change in Smoking Behavior
Time frame: 3-Week Follow-Up Visit (V4), 4-Week Follow-Up Visit (V5)
Medication Adherence
Time frame: Baseline (V1), 3-Week Follow-Up Visit (V4)
Medication Tolerance by Self-Reported Side Effects
Time frame: Baseline (V1), 3-Week Follow-Up Visit (V4)
Medication Tolerance by Serious Adverse Events
Time frame: Baseline (V1), 4-Week Follow-Up Visit (V5)
Urinary Levels of Dextromethorphan
Time frame: 3-Week Follow-Up Visit (V4)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
James M Davis, MD principal investigator
Duke Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AXS-05 and Bupropion SR in people with Smoking Cessation and Smoking, Cigarette, run by James Davis 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 5 inclusion and 5 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 Dec 2022. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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 12 Oct 2022). 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?
Change in Smoking Intensity (time frame: Baseline (V1), 3-Week Follow-Up Visit (V4)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Dec 2022.