Official Title: “Effectiveness of Varenicline vs. Varenicline Plus Bupropion or Placebo for Smoking Cessation”

Objectives:

1. To evaluate the efficacy of varenicline plus bupropion (VB) vs. varenicline (V)or Placebo(P)alone for smoking cessation.

2. To evaluate the effects of VB vs. V and P on measures of nicotine withdrawal, negative affect, smoking reinforcement and craving, and measures of cognitive performance.

Secondary Objectives:

1. To evaluate the effects of VB vs. V and P on lapse progression.

2. To evaluate the effects of VB vs. V and P on smoking reduction among those who fail to quit.

Study Type: Interventional

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

Study Primary Completion Date: August 2014

The Study Drugs:

Bupropion and varenicline are designed to imitate the effects that nicotine has on the body.

This may reduce cigarette cravings and help patients quit smoking.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of a dice) to 1 of 3 treatment groups. - If you are in Group 1, you will receive varenicline and bupropion. - If you are in Group 2, you will receive varenicline and a placebo. A placebo is a substance that looks like the study drug (in this case, bupropion) but that has no active ingredients. - If you are in Group 3, you will receive a placebo that looks like varenicline and a placebo that looks like bupropion.

You will have a higher chance (3 out of 4) of receiving study drug than receiving just placebo. Equal numbers of patients will be in Groups 1 and 2. Neither you nor the study doctor will know to which group you are assigned. However, if needed for your safety, the study staff will be able to find out which study drug you are receiving.

Study Drug Administration:

You will begin taking the study drugs/placebo the day after the first study visit. A dose of the study drug/placebo combination will be made up of 1 tablet of varenicline or placebo and 1 tablet of bupropion or placebo. You should take each dose of study drugs/placebo with a cup (8 oz.) of water after eating a full meal.

On Days 1-3, you will take 1 dose of the study drug/placebo combination in the morning.

Beginning on Day 4, and then every day after that, you will take 1 dose in the morning and 1 dose in the evening (for a total of 2 doses of the study drug/placebo combination each day).

You must return any study drug bottles as well as any unused study drug to a study staff member at each study visit.

You will be given a smoking diary to record how many cigarettes you smoke (if any) each day while you are on study. You must turn in this diary at each study visit.

Study Visits:

About 1 time each week while you are taking the study drugs/placebo, the following tests and procedures will be performed: - Your weight and blood pressure will be measured. - Your CO level will be measured. - You will be asked about any other drugs you may be taking and about any side effects you may be having. - You will answer 8 questionnaires about several topics, including depression, suicide, your smoking behavior, any effects from the study drugs, and any symptoms of attention-deficit hyperactivity disorder (ADHD). These should take about 30-45 minutes total to complete. - You will do tasks that will measure your logic and attention. These will take about 15 -20 minutes to complete. - You will receive counseling about quitting smoking in which you discuss possible "triggers" for smoking and strategies for dealing with quitting smoking. These sessions will take about 15 minutes each time.

During counseling at the first study visit, you will set a "quit date" for stopping smoking for about 1 week after you start taking the study drug. You should not quit smoking before the quit date. You should stay smoke-free after the quit date.

At Week 3, saliva will be collected to check your cotinine level.

At Week 4, blood (about 1 teaspoon) will be drawn for routine tests.

Lab Sessions:

You will take part in lab sessions during the study visits at Weeks 1, 2, and 6 to test your brain activity and attention span. You will be asked to watch slides and listen to a series of tones. The slides will include pictures of people, nature, and artwork. Slides showing nude people, medical procedures, and victims of car crashes will also be shown. You will be shown examples of these slides before beginning the procedure and given the opportunity to withdraw from the study.

During the lab sessions, your brain electrical activity (EEG) will be monitored. To do this, small sensors will be placed on your scalp and face. You should not drink more than 2 cups of coffee or other caffeinated drinks for at least 2.5 hours before each session. At the first lab session, you may be asked to smoke a cigarette if the doctor thinks it is needed for you to exhibit your normal smoking behavior.

Length of Study:

You will be on study for up to 12 weeks. You will be taken off study if the doctor thinks it is in your best interest.

End-of-Study Visit:

After you have finished taking the study drugs/placebo, the following tests and procedures will be performed: - Your weight and blood pressure will be measured. - Your CO level will be measured. - You will be asked about any side effects you may be having and about any other drugs you may be taking. - Blood (about 1 teaspoon) will be drawn for routine tests. - You will answer the same questionnaires you completed at the regular study visits.

These should take about 30-45 minutes total to complete. - Saliva will be collected to measure your cotinine level.

Follow-Up Visits:

About 1, 3, 6, and 12 months after you have finished taking the study drugs/placebo, the following tests and procedures will be performed: - Your weight and blood pressure will be measured. - Your CO level will be measured. - You will be asked about any side effects you may be having and about any other drugs you may be taking. - You will answer the same questionnaires you completed at the regular study visits.

These should take about 30-45 minutes total to complete. - Saliva will be collected to measure your cotinine level.

You will be called by the study staff 16, 20, 28, 32, 40, and 48 weeks after your quit date to check on your progress in quitting smoking. Each call should take about 10-15 minutes.

Additional Information: - You must not take antidepressants, monoamine oxidase inhibitors, or other bupropion or varenicline product while participating in this study. - You must tell the study staff about any drugs, over-the-counter drugs, pain relievers, antacids, and/or medicinal herbs you are taking or are planning to take. - Study drugs/placebo must be kept out of the reach of children or others with limited ability to read or understand. - Do not stop taking the study drugs/placebo all at once unless instructed to do so by study staff.

This is an investigational study. Varenicline and bupropion are both FDA approved and commercially available to help people stop smoking. The use of the drugs in combination is investigational.

Up to 350 participants will take part in this study. All will be enrolled at M. D.

Anderson.

Intervention(s) in this Clinical Trial

• Drug: Varenicline
  • On Days 1-3, 1 tablet by mouth in the morning. Beginning on Day 4, and then every day after that, 1 tablet by mouth in the morning and 1 tablet by mouth in the evening (for a total of 2 doses).
• Drug: Bupropion
  • On Days 1-3, 1 tablet by mouth in the morning. Beginning on Day 4, and then every day after that, 1 tablet by mouth in the morning and 1 tablet by mouth in the evening (for a total of 2 doses).
• Other: Placebo
  • On Days 1-3, 1 tablet by mouth of placebo that looks like the study drug in the morning. Beginning on Day 4, and then every day after that, 1 tablet by mouth in the morning and 1 tablet by mouth in the evening for a total of 2 doses of the placebo each day.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Group 1
  • Varenicline and Bupropion
• Placebo Comparator: Group 2
  • Varenicline and Placebo
• Placebo Comparator: Group 3
  • Placebo that looks like varenicline and a placebo that looks like bupropion.

Primary Measures

• Quit Rate
  • Time Frame: Study visits once a week for 12 weeks, one pre-quit phone call, one support call three days after the quit date, and then phone calls by study staff 16, 20, 28, 32, 40, and 48 weeks after the quit date.
    Safety Issue?: No

Inclusion Criteria:

• 1. Age: 25-65 years old
• 2. Smoking 5 or more cigarettes per day, on average, within the two months preceding the screening visit and expired CO of 6ppm or greater.
• 3. Able to follow verbal and written instructions in English and complete all aspects of the study
• 4. Provide informed consent and agree to all assessments and study procedures
• 5. Have an address and home telephone number where they may be reached
• 6. Be the only participant in their household

Exclusion Criteria:

• 1. Within the month immediately preceding the screening visit, use of any form of tobacco products other than cigarettes on 3 or more days within a week if the individual refuses to refrain from such tobacco use during the course of the study.
• 2. Within the month immediately preceding the screening visit, use of marijuana in any form on 3 or more days within a week
• 3. Within the two weeks immediately preceding the screening visit, involvement on more than 3 days in any formal smoking cessation activities
• 4. Treatment on a continuous basis within 2 weeks before the screening visit: any contraindicated medication for Varenicline or Bupropion. Classes of contraindicated medications include, but are not limited to, antiasthmatics, antipsychotics, antidepressants, antihypertensives, antiarrhythmics, antineoplastics, antiseizures, and MAO inhibitors.
• 5. Uncontrolled hypertension (systolic blood pressure greater than 150 or diastolic blood pressure greater than 95) or other major contraindications for Bupropion or Varenicline.
• 6. Severe renal impairment (Creatinine Clearance less than 30 ml/min/1.73 m2).
• 7. Laboratory evaluations outside normal limits and of potential clinical significance in the opinion of the investigator.
• 8. Meet current criteria for psychiatric disorders or substance abuse.
• 9. Individuals rated as moderate (6 - 9) to high (10 or greater) on suicidality as assessed by Module C of the MINI.
• 10. Psychiatric hospitalization within 1 year of screening date.
• 11. A positive urine pregnancy test during the screening period. Women who are two years post menopausal or who have had a partial or full hysterectomy will not be subject to a urine pregnancy test.
• 12. Pregnant, breast-feeding or of childbearing potential and is not protected by a medically acceptable, effective method of birth control while enrolled in the study.
• 13. Use of Varenicline or Bupropion within two weeks before the screening visit.
• 14. History of hypersensitivity or allergic reaction to Varenicline, tricyclic antidepressant, Bupropion (Wellbutrin, Zyban) or similar chemical classes or any component of these formulations.
• 15. Subject considered by the investigator as unsuitable candidate for receipt of an investigational drug, or unstable to be followed up throughout the entire duration of the study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 25 Years

Maximum Age for this Clinical Trial: 65 Years

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

Lead Sponsor: M.D. Anderson Cancer Center

Overall Clinical Trial Officials and Contacts

Paul M Cinciripini, PhD Principal Investigator M.D. Anderson Cancer Center  

Overall Contact: Paul M Cinciripini, PhD 713-792-0919 

Information obtained from ClinicalTrials.gov on March 18, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00943618

Study ID Number: 2008-0850

ClinicalTrials.gov Identifier: NCT00943618

Health Authority: United States: Institutional Review Board

UT MD Anderson Cancer Center website