Varenicline and Bupropion for Smoking Cessation

Smoking Clinical Trial

— CHANBAN  

Official title:

Combination Therapy With Varenicline and Bupropion for Smoking Cessation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00935818
• Other study ID #: 09-003598
• Secondary ID: 09-0024591RO1CA1
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: July 6, 2009
• Last updated: April 25, 2014
• Start date: September 2009
• Est. completion date: April 2013

Study information

• Verified date: April 2014
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study provides an opportunity to combine varenicline and bupropion SR and capitalize on the potential additive benefit. The investigators hypothesize that this will further increase long-term (≥ 6 months) smoking abstinence rates.

Description:

Cigarette smoking is the single most important preventable cause of morbidity, mortality and excess health care costs in the United States and accounts for 30% of U.S. cancer deaths. Varenicline and bupropion SR (sustained-release) are non nicotine pharmacotherapies FDA-indicated for the treatment of tobacco dependence in cigarette smokers. Although varenicline has proven greater efficacy than bupropion SR, both medications are associated with high end-of-treatment smoking abstinence rates. However, almost two-thirds of smokers treated with varenicline report smoking at 6 months. Because varenicline and bupropion SR have different mechanisms of action and different neuropharmacologic targets, combination pharmacotherapy with these agents may increase long-term smoking abstinence rates above what is observed with single-agent therapy. In our recent pilot study of combination therapy with varenicline and bupropion SR, we observed treatment to be well-tolerated with 7-day point prevalence smoking abstinence rates of 71% (95% CI: 54-85%) at 3 months and 58% (95% CI: 41-74%) at 6 months. Determining the efficacy of combination therapy compared to single-agent therapy has immediate and important clinical implications. In this study, we will conduct a randomized, multicenter, controlled clinical trial evaluating the efficacy of combination therapy with varenicline and bupropion SR compared to varenicline and placebo in 506 cigarette smokers at the Mayo Clinic in Rochester, MN, and the University of Minnesota in Minneapolis, MN.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 506
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subject is at least 18 years of age;

2. Subject has provide written informed consent;

3. Subject is smoking greater than or equal to 10 cigarettes per day for at least 6 months;

3) Subject is able to complete all study visits 4) Subject is in good health as determined by the investigator 5) Subject has the ability to participate fully in all aspects of the study and keep scheduled appointments 6) Subject is motivated to stop smoking.

Exclusion Criteria:

Female and were pregnant, lactating or likely to become pregnant during the trial and not able nor willing to use contraception or had:

1. an unstable medical condition;

2. another household member participating in the study;

3. bupropion or varenicline allergy;

4. current use (previous 30 days) of a tobacco dependence treatment and unable or unwilling to discontinue use;

5. an unstable medical condition or unstable angina, myocardial infarction, or coronary angioplasty (past 3 months) or an untreated cardiac dysrhythmia;

6. a history of renal failure or were on renal dialysis;

7. a history of seizures;

8. as defined by the C-SSRS (Columbia-Suicide Severity Rating Scale), current non-specific suicidal thoughts or lifetime history of a suicidal attempt (defined as "potentially self-injurious act committed with at least some wish to die, as a result of act");

9. a history of closed head trauma associated with > 30 minutes of loss of consciousness, amnesia, skull fracture, subdural hematoma, or brain contusion;

10. a history or psychosis, bipolar disorder, bulimia or anorexia nervosa;

11. current moderate or severe depression as assessed by a score of = 20 on the Beck Depression Inventory, Second Edition (BDI-II) 10;

12. active substance abuse other than nicotine;

13. current (past 14 days) use of an antipsychotic, monoamine oxidase inhibitors, or drugs known to interact with bupropion SR;

14. a recent dose change of their antidepressant (within last 3 months);

15. untreated hypertension or baseline systolic blood pressure > 180 or diastolic > 100;

16. current treatment with another investigational drug for tobacco dependence (previous 30 days); or

17. current use of bupropion or varenicline (previous 30 days).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Smoking

Intervention

Drug:
• Varenicline
varenicline - 1 mg bid for 12 weeks
• placebo
placebo for 12 weeks
• bupropion SR
bupropion sr - 150 mg bid for 12 weeks

Locations

Country	Name	City	State
United States	Franciscan Skemp Hospital	LaCrosse	Wisconsin
United States	University Of Minnesota	Minneapolis	Minnesota
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI), University of Minnesota - Clinical and Translational Science Institute

Country where clinical trial is conducted

United States, 

References & Publications (1)

Ebbert JO, Hatsukami DK, Croghan IT, Schroeder DR, Allen SS, Hays JT, Hurt RD. Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial. JAMA. 2014 Jan 8;311(2):155-63. doi: 10.1001/jama.2013.28318 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prolonged Smoking Abstinence Rates at 12 Weeks in Cigarettes Smokers.	Prolonged smoking abstinence is defined as no smoking, not even a puff, in the last 7 days, and a negative response to the question "Since 2 weeks after your target quit date, have you smoked any tobacco, even a puff, for 7 consecutive days or at least once each week on 2 consecutive weeks?"	3 months	No
Primary	Point Prevalence Abstinence at 3 Months.	biochemically confirmed 7-day point prevalence abstinence defined as no smoking, not even a puff, in the previous 7 days.	3 months	No
Secondary	Prolonged Smoking Abstinence Rates at 26 Weeks in Cigarettes Smokers.		6 months	No
Secondary	Weight Gain From Baseline to 3 Months	Weight change from baseline to three months in those who met criteria for prolonged abstinence at the 3 month visit	3 months	No
Secondary	Point Prevalence Abstinence at 6 Months.	Biochemically confirmed abstinence as no smoking, even a puff, for the prior 7 days.	6 months	No
Secondary	Prolonged Abstinence at 12 Months		12 months	No
Secondary	Point Prevalence Abstinence at 12 Months	Biochemically confirmed abstinence defined as no smoking, not even a puff, in the last 7 days	12 months	No