search
Back to results

AXS-05 Phase II Trial on Smoking Behavior

Primary Purpose

Smoking Cessation, Smoking, Cigarette, Nicotine Dependence

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AXS-05
Bupropion SR
Sponsored by
James Davis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Smoking Cessation focused on measuring Smoking cessation, Nicotine dependence, Bupropion, DXM, Nicotine addiction, Cigarette smoking, Dextromethorphan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Duke Center for Smoking Cessation

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

AXS-05

Bupropion SR

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change in Smoking Intensity
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
A biochemical marker of smoking intensity.

Secondary Outcome Measures

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.
Medication Adherence
Medication adherence is measured by composite self-reported diaries.
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).
Medication Tolerance by Serious Adverse Events
Measured by FDA reporting guidelines on adverse event or serious adverse event designation.
Urinary Levels of Dextromethorphan
Measured via Urinary Dextromethorphan testing.

Full Information

First Posted
March 19, 2018
Last Updated
December 15, 2022
Sponsor
James Davis
Collaborators
Axsome Therapeutics, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT03471767
Brief Title
AXS-05 Phase II Trial on Smoking Behavior
Official Title
A Randomized, Double-Blind 4-Week Study to Evaluate the Impact of AXS-05 on Smoking Behavior
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
March 25, 2018 (Actual)
Primary Completion Date
March 31, 2019 (Actual)
Study Completion Date
March 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
James Davis
Collaborators
Axsome Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Smoking Cessation, Smoking, Cigarette, Nicotine Dependence
Keywords
Smoking cessation, Nicotine dependence, Bupropion, DXM, Nicotine addiction, Cigarette smoking, Dextromethorphan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Participants are randomized to either take AXS-05 or BUP SR in parallel for the duration of the study.
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AXS-05
Arm Type
Experimental
Arm Description
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.
Arm Title
Bupropion SR
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AXS-05
Other Intervention Name(s)
Bupropion/dextromethorphan
Intervention Description
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
Intervention Name(s)
Bupropion SR
Other Intervention Name(s)
Wellbutrin SR, Zyban SR
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Smoking Intensity
Description
Smoking intensity refers to the number of cigarettes smoked per day.
Time Frame
Baseline (V1), 3-Week Follow-Up Visit (V4)
Title
Percentage of Participants Who Experienced a More Than 50% Reduction in Expired Carbon Monoxide (CO) Levels
Description
A biochemical marker of smoking intensity.
Time Frame
Baseline (V1), 3-Week Follow-Up Visit (V4)
Secondary Outcome Measure Information:
Title
Change in Smoking Behavior
Description
7-day point prevalence smoking abstinence. Measured by composite self-report diaries and biochemically confirmed via expired CO and salivary cotinine.
Time Frame
3-Week Follow-Up Visit (V4), 4-Week Follow-Up Visit (V5)
Title
Medication Adherence
Description
Medication adherence is measured by composite self-reported diaries.
Time Frame
Baseline (V1), 3-Week Follow-Up Visit (V4)
Title
Medication Tolerance by Self-Reported Side Effects
Description
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).
Time Frame
Baseline (V1), 3-Week Follow-Up Visit (V4)
Title
Medication Tolerance by Serious Adverse Events
Description
Measured by FDA reporting guidelines on adverse event or serious adverse event designation.
Time Frame
Baseline (V1), 4-Week Follow-Up Visit (V5)
Title
Urinary Levels of Dextromethorphan
Description
Measured via Urinary Dextromethorphan testing.
Time Frame
3-Week Follow-Up Visit (V4)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Key Inclusion Criteria: Age 18 years or above Daily smoker using 10 or more cigarettes per day Willing to be smoke-free for 7 days Is able to provide written informed consent (in English) to participate in the study and able to understand the procedures and study requirements. 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: Current use of a smoking cessation medication (e.g. nicotine replacement, Varenicline, bupropion) Current use of tobacco product other than cigarettes (e.g. e-cigarettes, smokeless tobacco) Not pregnant or breastfeeding Contraindication to the use of bupropion. Additional criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James M Davis, MD
Organizational Affiliation
Duke Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke Center for Smoking Cessation
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States

12. IPD Sharing Statement

Learn more about this trial

AXS-05 Phase II Trial on Smoking Behavior

We'll reach out to this number within 24 hrs