Varenicline OTC Trial on Efficacy and Safety

Given the recent research on varenicline showing that it is more effective than nicotine patch and bupropion, and with the removal of the box warning, research is needed to assess whether smokers can use varenicline without a prescription and formal behavioral support. To test this, the primary goal of the proposed research is to test whether varenicline is a candidate for switching from prescription (Rx) to OTC, and whether a dose lower than that currently approved is as effective in an OTC environment. To understand the within-person mechanisms explaining how and when OTC varenicline might improve cessation outcomes, the investigators also propose to assess experience with OTC varenicline via (a) ecological momentary assessment (EMA).

Primary Objectives:

1. To assess the safety and effectiveness of the current FDA-approved 1 mg b.i.d. varenicline for smoking cessation in comparison with placebo when used in a simulated OTC study condition.
2. To assess the safety and effectiveness of .5mg b.i.d. varenicline in comparison with 1mg b.i.d. varenicline and placebo when used in a simulated OTC study condition.

• Tobacco Dependence
• Withdrawal Symptoms
• Smoking Cessation

• Drug: 1.0mg Varenicline b.i.d.
  Varenicline is classified as a selective nicotine receptor partial agonist (SNRPA) that works both to stimulate the nicotine receptor and block smoking reward at the ?4?2 nicotinic receptor subtype.
• Drug: 0.5mg Varenicline b.i.d.
  Varenicline is classified as a selective nicotine receptor partial agonist (SNRPA) that works both to stimulate the nicotine receptor and block smoking reward at the ?4?2 nicotinic receptor subtype.
• Drug: 0.0mg placebo Varenicline b.i.d.
  Product that looks like active varenicline, but contains no active ingredient

• Experimental: 1.0mg varenicline b.i.d.
  Days 1 through 3: 0.5mg, once daily; days 4 through 7: 0.5mg, twice daily; days 8 through end of treatment: 1mg, twice daily.
  Intervention: Drug: 1.0mg Varenicline b.i.d.
• Experimental: 0.5mg varenicline b.i.d.
  Days 1 through 3: 0.5mg, once daily; 0.5 mg b.i.d. dose starting at day 4 through the end of the study
  Intervention: Drug: 0.5mg Varenicline b.i.d.
• Placebo Comparator: 0.0mg placebo varenicline b.i.d.
  Days 1 through 3: 0.0mg placebo once daily; days 4 through 7: 0.0mg placebo twice daily; days 8 through end of treatment: 0.0 mg placebo twice daily.
  Intervention: Drug: 0.0mg placebo Varenicline b.i.d.

Inclusion Criteria:

1. 21 years of age or older
2. Self-reported daily smoker
3. Breath Carbon monoxide > 10ppm
4. Motivated to quit smoking completely within five weeks of the Screening Visit (>5 on reported motivation)
5. Capable of and agree to complete study requirements
6. Literate in English, self-report
7. Must be available for the duration of study
8. Informed consent obtained
9. Willing and able to provide additional data between visits using ecological momentary assessment (EMA)
10. Must own study compatible smart-phone (iPhone or Android)

Exclusion Criteria:

1. Any self-report, diagnosis or treatment of heart attack, unstable angina, angioedema, seizures, cerebrovascular accident (CVA) within the last six months.
2. Any self-report, diagnosis or treatment of bipolar, schizophrenia or suicidal ideation within the last six months. (For suicidal ideation a score of ?7 on the Suicidal Behavior Questionnaire, see Appendix 15)
3. Self-report of diagnosis or treatment for depression within the past six months, unless participant has written permission by their healthcare provider to participate
4. Systolic blood pressure 160 or higher and/or diastolic blood pressure 100 or higher
5. History of renal disease
6. Allergy to any of the ingredients in varenicline
7. Participation in another smoking cessation program or any type of clinical trial in the past 3 months
8. Use of any smoking cessation medication in the past three months
9. Any other medical condition(s) which the licensed study physician deems unacceptable for participation in this study
10. Positive drug screen indicating possible substance abuse (eg opiates, amphetamines, benzodiazepines, cocaine or other substances), unless participant can show that the medication has been prescribed by licensed clinical provider.
11. Consume greater than 21 alcohol drinks per week.
12. No two members of the same household may participate in this study
13. No study staff or their immediate family may participate in the study
14. Females who are pregnant, breast feeding, or not currently using a medically approved form of birth control and unwilling to do so.

Acceptable methods of birth control include abstinence, oral contraceptives, the contraceptive patch, the contraceptive ring, and condoms.

• National Institute on Drug Abuse (NIDA)
• Los Angeles Clinical Trials
• University of Nevada, Reno
• Pfizer