Official Title: “Combination Therapy With Varenicline and Bupropion for Smoking Cessation”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: October 2012

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 450 cigarette smokers at the Mayo Clinic in Rochester, MN, and the University of Minnesota in Minneapolis, MN.

Intervention(s) in this Clinical Trial

• Drug: varenicline and bupropion
  • varenicline - 1 mg bid for 12 weeks bupropion sr - 150 mg bid for 12 weeks
• Drug: varenicline and placebo
  • varenicline (1 mg bid) for 12 weeks placebo for 12 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: varenicline and buproprion SR
  • Everyone randomized to this arm will receive varenicline (up to 1mg bid) and bupropion SR (150 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year.
• Placebo Comparator: varenicline and placebo
  • Everyone randomized to this arm will receive varenicline (up to 1mg bid) and placebo (0 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year.

Primary Measures

• To evaluate the efficacy of 12 weeks of combination therapy with varenicline and bupropion SR compared to varenicline alone for increasing the prolonged and point prevalence smoking abstinence rates at 12 weeks in cigarettes smokers.
  • Time Frame: 3 months
    Safety Issue?: No

Secondary Measures

• To evaluate the efficacy of 12 weeks of combination therapy with varenicline and bupropion SR compared to varenicline alone for increasing the prolonged and point prevalence smoking abstinence rates at 26 and 52 weeks in cigarettes smokers.
  • Time Frame: 6 and 12 months
    Safety Issue?: No
• To evaluate the efficacy of combination therapy with varenicline and bupropion SR compared to varenicline alone for decreasing tobacco craving and nicotine withdrawal symptoms among cigarette smokers trying to achieve smoking abstinence.
  • Time Frame: 3, 6, and 12 months
    Safety Issue?: No
• To evaluate the efficacy of 12 weeks of combination therapy with varenicline and bupropion SR compared to varenicline alone for attenuating weight gain after smoking cessation.
  • Time Frame: 3 months
    Safety Issue?: No

Inclusion Criteria:

• 1. at least 18 years of age;
• 2. smoking greater than or equal to 10 cigarettes per day for at least 6 months;
• 3. motivated to stop smoking.

Exclusion Criteria:

• 1. an unstable medical condition;
• 2. unstable angina, myocardial infarction, or coronary angioplasty within the past 3 months or an untreated cardiac dysrhythmia;
• 3. a personal history of seizures;
• 4. a history of closed head trauma with any loss of consciousness or amnesia in the last 5 years;
• 5. a history of closed head trauma with greater than or equal to 30 minutes of loss of consciousness or amnesia or resulting in skull fracture or subdural hematoma/brain contusion;
• 6. a history or psychosis, bipolar disorder, bulimia or anorexia nervosa);
• 7. current depression as assessed by Center for Epidemiologic Studies Depression (CES-D);
• 8. active substance abuse other than nicotine;
• 9. used an investigational drug within the last 30 days;
• 10. current use of using a behavioral or pharmacologic tobacco treatment and unwilling or unable to discontinue use;
• 11. current use of bupropion or varenicline in the previous 30 days;
• 12. current (past 14 days) use of antipsychotic or antidepressant;
• 13. an allergy to bupropion or varenicline;
• 14. untreated hypertension or baseline systolic blood pressure greater than or equal to 180 or diastolic greater than or equal to 100;
• 15. another member of their household already participating in this study.
• 16. All female subjects of childbearing potential who have a positive pregnancy test or refuse to use contraception during participation in the study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Mayo Clinic

Overall Clinical Trial Officials and Contacts

Jon Ebbet, MD Principal Investigator Mayo Clinic  

Overall Contact: Ivana T Croghan, PhD 507-266-1944 nicotineresearch@mayo.edu

Information obtained from ClinicalTrials.gov on February 04, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00935818

Study ID Number: 09-003598

ClinicalTrials.gov Identifier: NCT00935818

Health Authority: United States: Food and Drug Administration