Varenicline and Bupropion for Smoking Cessation

Phase 2

Completed

• Conditions: Smoking
• Interventions: Drug: Varenicline; Drug: placebo; Drug: bupropion SR

• Registration Number: NCT00935818
• Lead Sponsor: Mayo Clinic

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2009-07-06
• Study First Submitted QC: 2009-07-07
• Study First Posted: 2009-07-09
• Study Start: 2009-09
• Primary Completion: 2013-04
• Study Completion: 2013-04
• Results First Submitted: 2014-03-21
• Results First Submitted QC: 2014-03-21
• Status Verified: 2014-04
• Results First Posted: 2014-04-24
• Last Update Submitted: 2014-04-25
• Last Update Posted: 2014-05-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 506

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
varenicline and buproprion SR	Varenicline	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.
varenicline and placebo	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.
varenicline and buproprion SR	bupropion 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.
varenicline and placebo	Varenicline	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 Outcome Measures

Name	Time	Method
Prolonged Smoking Abstinence Rates at 12 Weeks in Cigarettes Smokers.	3 months	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?"
Point Prevalence Abstinence at 3 Months.	3 months	biochemically confirmed 7-day point prevalence abstinence defined as no smoking, not even a puff, in the previous 7 days.

Secondary Outcome Measures

Name	Time	Method
Prolonged Smoking Abstinence Rates at 26 Weeks in Cigarettes Smokers.	6 months
Weight Gain From Baseline to 3 Months	3 months	Weight change from baseline to three months in those who met criteria for prolonged abstinence at the 3 month visit
Point Prevalence Abstinence at 6 Months.	6 months	Biochemically confirmed abstinence as no smoking, even a puff, for the prior 7 days.
Prolonged Abstinence at 12 Months	12 months
Point Prevalence Abstinence at 12 Months	12 months	Biochemically confirmed abstinence defined as no smoking, not even a puff, in the last 7 days

Trial Locations

Locations (3)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

University Of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Franciscan Skemp Hospital; 🇺🇸 LaCrosse, Wisconsin, United States