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: Completed

Administrative data

• NCT number: NCT03471767
• Other study ID #: Pro00089413
• Status: Completed
• Phase: Phase 2
• Start date: March 25, 2018
• Est. completion date: March 31, 2019

Study information

• Verified date: December 2022
• Source: Duke University
• Contact: n/a
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: March 31, 2019
• Est. primary completion date: March 31, 2019
• 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 + 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 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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
James Davis	Axsome Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Smoking Intensity	Smoking intensity refers to the number of cigarettes smoked per day.	Baseline (V1), 3-Week Follow-Up Visit (V4)
Primary	Percentage of Participants Who Experienced a More Than 50% Reduction in Expired Carbon Monoxide (CO) Levels	A biochemical marker of smoking intensity.	Baseline (V1), 3-Week Follow-Up Visit (V4)
Secondary	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.	3-Week Follow-Up Visit (V4), 4-Week Follow-Up Visit (V5)
Secondary	Medication Adherence	Medication adherence is measured by composite self-reported diaries.	Baseline (V1), 3-Week Follow-Up Visit (V4)
Secondary	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).	Baseline (V1), 3-Week Follow-Up Visit (V4)
Secondary	Medication Tolerance by Serious Adverse Events	Measured by FDA reporting guidelines on adverse event or serious adverse event designation.	Baseline (V1), 4-Week Follow-Up Visit (V5)
Secondary	Urinary Levels of Dextromethorphan	Measured via Urinary Dextromethorphan testing.	3-Week Follow-Up Visit (V4)