AXS-05 Phase II Trial on Smoking Behavior

NCT ID: NCT03471767

Last Updated: 2022-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-25
• Study Completion Date: 2019-03-31

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.

Conditions

Smoking Cessation; Smoking, Cigarette; Nicotine Dependence

Keywords

Smoking cessation; Nicotine dependence; Bupropion; DXM; Nicotine addiction; Cigarette smoking; Dextromethorphan

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

AXS-05

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Bupropion SR

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Bupropion/dextromethorphan; Wellbutrin SR; Zyban SR

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Axsome Therapeutics, Inc.

INDUSTRY

Sponsor Role: collaborator

James Davis

OTHER

Sponsor Role: lead

Responsible Party

James Davis

Medical Director, Duke Center for Smoking Cessation

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

James M Davis, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Cancer Institute

Locations

Duke Center for Smoking Cessation

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Pro00089413

Identifier Type: -

Identifier Source: org_study_id