AXS-05 Phase II Trial on Smoking Behavior

Smoking Cessation Clinical Trial

Official title:

A Randomized, Double-Blind 4-Week Study to Evaluate the Impact of AXS-05 on Smoking Behavior

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03450941
• Other study ID #: Pro00089413
• Status: Not yet recruiting
• Phase: Phase 2
• First received: February 20, 2018
• Last updated: February 23, 2018
• Start date: March 15, 2018
• Est. completion date: January 21, 2019

Study information

• Verified date: February 2018
• Source: Duke University
• Contact: Jillian EH Dirkes, MSW, LCSW
• Phone: 919-668-5055
• Email: jillian.dirkes[@]duke.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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 45 mg IR DXM with 105 mg 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: January 21, 2019
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Age 18 years or above

2. Daily smoker using 10 or more cigarettes per day

3. Willing to be smoke-free for 7 days

4. Is able to provide written informed consent (in English) to participate in the study and able to understand the procedures and study requirements.

5. 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:

1. Current use of a smoking cessation medication (e.g. nicotine replacement, Varenicline, bupropion)

2. Current use of tobacco product other than cigarettes (e.g. e-cigarettes, smokeless tobacco)

3. Not pregnant or breastfeeding

4. Contraindication to the use of bupropion.

5. Additional criteria may apply.

Related Conditions & MeSH terms

• Nicotine Dependence
• Smoking Cessation
• Smoking, Cigarette
• Tobacco Use Disorder

Intervention

Drug:
• AXS-05
Dextromethorphan Immediate Release 45mg + Bupropion Sustained Release 105 mg: 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
Bupropion Sustained Release 105 mg: 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.

Locations

Country	Name	City	State
United States	Duke Center for Smoking Cessation	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
James M. Davis, MD	Axsome Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Smoking Intensity	To evaluate the impact of AXS-05 compared to Bupropion (BUP) on smoking cessation, smoking intensity will be measured from baseline to the 3-week follow-up visit for each participant. Smoking intensity refers to the total amount of smoke inhaled by the smoker and includes the number of cigarettes smoked per day. Smoking intensity will be assessed as a latent variable modeled through three predictive factors: (1) salivary cotinine, which will be assessed at all study visits, (2) expired carbon monoxide (CO) breath testing at all study visits and (3) the number of cigarettes smoked per day assessed via daily smoking diaries.	Baseline to 3-Week Follow-Up Visit
Secondary	Change in Smoking Behavior	To compare AXS-05 to BUP on smoking abstinence within a 7-day Abstinence Test conducted between the 3-week follow-up and 4-week follow-up study visits. Smoking abstinence will be assessed by self-report diaries and biochemically confirmed via expired CO and salivary cotinine.	3-Week Follow-Up Visit to 4-Week Follow-Up Visit
Secondary	Adherence	To compare AXS-05 to BUP on adherence to self-administered drug through Medication Use diaries.	4-Week Follow-Up Visit
Secondary	Side Effects	To compare AXS-05 to BUP on tolerability through weekly, open-ended survey to assess potential side effects.	4-Week Follow-Up Visit
Secondary	Tolerance	To compare AXS-05 to BUP on the incidence of adverse events or serious adverse events utilizing FDA accepted reporting guidelines on these outcomes.	4-Week Follow-Up Visit
Secondary	Urinary Levels of DXM	To measure urine drug levels of Dextromethorphan (DXM) at weeks 1-4 and assess potential correlation of these levels with smoking behavior and side effects.	4-Week Follow-Up Visit
Secondary	Assessing Age as a Potential Covariate/Moderator	To assess age (in years) as a specific baseline variable for an association with smoking behaviors. This data will be collected using a demographic intake survey during the screening visit.	Baseline
Secondary	Assessing Gender as a Potential Covariate/Moderator	To assess gender as a specific baseline variable for an association with smoking behaviors. This data will be collected using a demographic intake survey during the screening visit.	Baseline
Secondary	Assessing Race as a Potential Covariate/Moderator	To assess race as a specific baseline variable for an association with smoking behavior outcome. This data will be collected using a demographic intake survey during the screening visit.	Baseline
Secondary	Assessing Education as a Potential Covariate/Moderator	To assess education (in years) as a specific baseline variable for an association with smoking behaviors. This data will be collected using a demographic intake survey during the screening visit.	Baseline
Secondary	Assessing Baseline Nicotine Dependence as a Potential Covariate/Moderator	To assess education (in years) as a specific baseline variable for an association with smoking behaviors. This data will be collected using the Fagerstrom Test for Nicotine Dependence (FTND) survey during the screening visit.	Baseline
Secondary	Assessing Stress as a Potential Covariate/Moderator	To assess stress as a specific baseline variable for an association with smoking behaviors. This data will be collected using the Perceived Stress Scale-4 (PSS-4) given to participants at the screening visit.	Visit 1
Secondary	Assessing Anxiety as a Potential Covariate/Moderator	To assess anxiety as a specific baseline variable for an association with smoking behaviors. This data will be collected using the State-Trait Anxiety Inventory (STAI) at the screening visit.	Visit 1
Secondary	Assessing Depression as a Potential Covariate/Moderator	To assess depression as a specific baseline variable for an association with smoking behaviors. This data will be collected using the Center for Epidemiological Studies Depression Scale (CES-D).	Visit 1
Secondary	To Compare the Change in Smoking Urges as a Potential Mediator	To compare AXS-05 to BUP on changes from baseline vs. weeks 1-4 Follow-up Visits on the following: smoking urges. Smoking urges will be assessed using self-report diaries. Assessment of smoking urges will include the following: urge frequency, urge severity, and irritability.	Baseline to 4-Week Follow-Up Visit
Secondary	To Compare the Change in Withdrawal Symptoms as a Potential Mediator	To compare AXS-05 to BUP on changes from baseline vs. weeks 1-4 Follow-up Visits on the following: withdrawal symptoms. Withdrawal symptoms will be assessed using self-report diaries.	Baseline to 4-Week Follow-Up Visit
Secondary	To Compare the Change in Smoking Reward as a Potential Mediator	To compare AXS-05 to BUP on changes from baseline vs. weeks 1-4 Follow-up Visits on the following: smoking reward. Smoking Reward will be assessed using the Modified Cigarette Evaluation Questionnaire (mCEQ).	Baseline to 4-Week Follow Up Visit
Secondary	To Compare the Change in Stress as a Potential Mediator	To compare AXS-05 to BUP on changes from baseline vs. weeks 1-4 Follow-up Visits on the following: Stress. Stress will be assessed across all study visits using the PSS-4.	Baseline to 4-Week Follow Up Visit
Secondary	To Compare the Change in Anxiety as a Potential Mediator	To compare AXS-05 to BUP on changes from baseline vs. weeks 1-4 Follow-up Visits on the following: anxiety. Anxiety will be assessed across all study visits using the STAI.	Baseline to 4-Week Follow Up Visit
Secondary	To Compare the Change in Depression as a Potential Mediator	To compare AXS-05 to BUP on changes from baseline vs. weeks 1-4 Follow-up Visits on the following: depression. Depression will be assessed across all study visits using the CES-D.	Baseline to 4-Week Follow Up Visit