Varenicline OTC Trial on Efficacy and Safety (VOTC)

The primary goal of the proposed research is to test whether varenicline (Chantix) is safe and effective as an over-the-counter (OTC) medication.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation; Withdrawal Symptoms; Tobacco Dependence
• Intervention / Treatment: Drug: 1.0mg Varenicline b.i.d.; Drug: 0.5mg Varenicline b.i.d.; Drug: 0.0mg placebo Varenicline b.i.d.

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 307
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Arizona State University
  • California
    • Burbank, California, United States, 91505
      • Los Angeles Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria for the In-person Cohort

1. 21 years of age or older
2. Self-reported daily smoker
3. Breath CO > 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 for the In-person Cohort

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 (see site applicable SOP for Evaluating and Reporting Blood Pressure and Appendices 5 and 6 for participant handouts)
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.

Inclusion Criteria for the Remote Cohort

1. 21 years of age or older
2. Self-reported daily smoker
3. Positive cotinine from urine sample
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

10. Must own study compatible smart-phone (iPhone or Android) 11. Must be a current resident of the United States

Exclusion Criteria for the Remote Cohort

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. History of renal disease
5. Allergy to any of the ingredients in varenicline
6. Participation in another smoking cessation program or any type of clinical trial in the past 3 months
7. Use of any smoking cessation medication in the past three months
8. Any other medical condition(s) which the licensed study physician deems unacceptable for participation in this study
9. Consume greater than 21 alcohol drinks per week.
10. No two members of the same household may participate in this study
11. No study staff or their immediate family may participate in the study
12. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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 α4β2 nicotinic receptor subtype.
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	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 α4β2 nicotinic receptor subtype.
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.	Drug: 0.0mg placebo Varenicline b.i.d.; Product that looks like active varenicline, but contains no active ingredient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breath carbon monoxide verified abstinence from smoking cigarettes	Participants will provide self reported smoking status that has been verified by breath carbon monoxide	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Participants will be asked to report adverse events	Week 2 visit
Adverse events	Participants will be asked to report adverse events	Week 4 visit
Adverse events	Participants will be asked to report adverse events	Week 8 visit
Adverse events	Participants will be asked to report adverse events	Week 12 visit
Adverse events	Participants will be asked to report adverse events	Week 13 visit
Adverse events	A subset of participants will be asked to report adverse events via ecological momentary assessment (EMA). EMA asks questions via the participant mobile phone on multiple occasions, primarily at random	Change in adverse events from baseline to week 2 as measured by 5 daily EMA prompts
Withdrawal symptoms and craving	Participants will be asked to report withdrawal symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). Scores can be between 0 (absent) - 4 (severe), and the average scores will be assessed.	week 2 visit
Withdrawal symptoms and craving	Participants will be asked to report withdrawal symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). Scores can be between 0 (absent) - 4 (severe), and the average scores will be assessed.	week 4 visit
Withdrawal symptoms and craving	Participants will be asked to report withdrawal symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). Scores can be between 0 (absent) - 4 (severe), and the average scores will be assessed.	week 8 visit
Withdrawal symptoms and craving	Participants will be asked to report withdrawal symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). Scores can be between 0 (absent) - 4 (severe), and the average scores will be assessed.	week 12 visit
Withdrawal symptoms and craving	Participants will be asked to report withdrawal symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). Scores can be between 0 (absent) - 4 (severe), and the average scores will be assessed.	week 13 visit
Craving	Participants will be asked to report craving via ecological momentary assessment (EMA). EMA asks questions via the participant mobile phone on multiple occasions, primarily at random	change in craving from baseline to week 2 as measured by 5 daily EMA prompts
Breath carbon monoxide verified abstinence from smoking cigarettes	Participants who self report not smoking will be asked to have smoking status verified by breath carbon monoxide	Week 26

Collaborators and Investigators

• Sponsor: Arizona State University
• Collaborators: National Institute on Drug Abuse (NIDA); Pfizer; University of Nevada, Reno; Los Angeles Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2018
• Primary Completion (Actual): April 16, 2022
• Study Completion (Actual): April 16, 2022

Study Registration Dates

• First Submitted: May 15, 2018
• First Submitted That Met QC Criteria: June 4, 2018
• First Posted (Actual): June 15, 2018

Study Record Updates

• Last Update Posted (Actual): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Substance Withdrawal Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: 1R01DA044125 (U.S. NIH Grant/Contract); R01DA044125 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: While the exact process is unclear, when all data have been locked and investigators have published what they choose, de-identified data will be made available for the duration that we are required by NIH to maintain the data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No