AXS-05 Phase II Trial on Smoking Behavior

Phase 2

Completed

• Conditions: Smoking Cessation; Smoking, Cigarette; Nicotine Dependence
• Interventions: Drug: Bupropion SR; Drug: AXS-05

• Registration Number: NCT03471767
• Lead Sponsor: James Davis

Brief 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.

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 Timeline

• Study First Submitted: 2018-03-19
• Study First Submitted QC: 2018-03-19
• Study First Posted: 2018-03-21
• Study Start: 2018-03-25
• Primary Completion: 2019-03-31
• Study Completion: 2019-03-31
• Disposition First Submitted: 2020-03-13
• Results First Submitted: 2022-03-30
• Results First Submitted QC: 2022-09-14
• Disposition First Submitted QC: 2022-09-14
• Results First Posted: 2022-10-12
• Disposition First Posted: 2022-10-12
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-15
• Last Update Posted: 2022-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 58

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bupropion SR	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.
AXS-05	AXS-05	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.

Primary Outcome Measures

Name	Time	Method
Change in Smoking Intensity	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	Baseline (V1), 3-Week Follow-Up Visit (V4)	A biochemical marker of smoking intensity.

Secondary Outcome Measures

Name	Time	Method
Change in Smoking Behavior	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	Baseline (V1), 3-Week Follow-Up Visit (V4)	Medication adherence is measured by composite self-reported diaries.
Medication Tolerance by Self-Reported Side Effects	Baseline (V1), 3-Week Follow-Up Visit (V4)	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).
Medication Tolerance by Serious Adverse Events	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	3-Week Follow-Up Visit (V4)	Measured via Urinary Dextromethorphan testing.

Trial Locations

Locations (1)

Duke Center for Smoking Cessation; 🇺🇸 Durham, North Carolina, United States