AXS-05 Phase II Trial on Smoking Behavior
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|ClinicalTrials.gov Identifier: NCT03471767|
Recruitment Status : Completed
First Posted : March 21, 2018
Last Update Posted : March 19, 2020
|Condition or disease||Intervention/treatment||Phase|
|Smoking Cessation Smoking, Cigarette Nicotine Dependence||Drug: AXS-05 Drug: Bupropion SR||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||58 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Participants are randomized to either take AXS-05 or BUP SR in parallel for the duration of the study.|
|Masking:||Double (Participant, Care Provider)|
|Official Title:||A Randomized, Double-Blind 4-Week Study to Evaluate the Impact of AXS-05 on Smoking Behavior|
|Actual Study Start Date :||March 25, 2018|
|Actual Primary Completion Date :||March 31, 2019|
|Actual Study Completion Date :||March 31, 2019|
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.
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.
Other Name: Bupropion/dextromethorphan
Active Comparator: Bupropion SR
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.
Drug: Bupropion 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.
- Change in Smoking Intensity [ Time Frame: Baseline (V1), 3-Week Follow-Up Visit (V4) ]Smoking intensity refers to the total amount of smoke inhaled by the smoker and includes the number of cigarettes smoked per day. Measured through salivary cotinine, expired carbon monoxide (CO) breath testing, and the number of cigarettes smoked per day by composite self-report smoking diaries.
- Change in Smoking Behavior [ Time Frame: 3-Week Follow-Up Visit (V4), 4-Week Follow-Up Visit (V5) ]7-day point prevalence smoking abstinence. Measured by composite self-report diaries and biochemically confirmed via expired CO and salivary cotinine.
- Medication Adherence [ Time Frame: Baseline (V1), 3-Week Follow-Up Visit (V4) ]Medication adherence is measured by composite self-reported diaries.
- Medication Tolerance by Self-Reported Side Effects [ Time Frame: Baseline (V1), 3-Week Follow-Up Visit (V4) ]Self-reported side effects (open-ended survey questions) with a ranking scale of 1-2 (mild), 3-5 (moderate), 6-7 (severe). Any side effects of 4 or greater will be reviewed by a study medical provider.
- Medication Tolerance by Serious Adverse Events [ Time Frame: Baseline (V1), 4-Week Follow-Up Visit (V5) ]Measured by FDA reporting guidelines on adverse event or serious adverse event designation.
- Urinary Levels of Dextromethorphan [ Time Frame: Baseline (V1), 3-Week Follow-Up Visit (V4) ]Measured via Urinary Dextromethorphan testing.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03471767
|United States, North Carolina|
|Duke Center for Smoking Cessation|
|Durham, North Carolina, United States, 27705|
|Principal Investigator:||James M Davis, MD||Duke Cancer Institute|