EVarQuit: Extended Pre-quit Varenicline to Assist in Quitting Smoking

NCT03262662 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: STUDY00000911R01CA206193
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

Brief Summary

Varenicline is the most effective smoking cessation therapy available. Nevertheless, most smokers using varenicline relapse within the first few months after quitting. Varenicline is hypothesized to help smokers to quit in part by reducing the reinforcing effects of smoking during the standard 1-week pre-quitting treatment phase. Learning theory and previous human and animal research support the hypothesis that a longer period of varenicline treatment prior to the target quit date (TQD) will lead to greater reductions in smoking before quitting, and higher long-term cessation rates, compared to standard varenicline treatment. Building on promising preliminary clinical data, the study tests these hypotheses with a full-scale randomized clinical trial (RCT). 320 treatment-seeking smokers will be randomized to a standard run-in group (3 weeks of placebo, followed by the standard 1 week of pre-TQD varenicline) or an extended run-in group (4 weeks of pre-TQD varenicline). Both groups will receive brief individual cessation counseling and 11 weeks of post-TQD varenicline. The primary outcome measure will be bio-verified continuous abstinence at end-of-treatment (weeks 8-11 post-quit; cessation at 26-weeks post TQD will also be examined. Hypothesized mediating mechanisms (e.g., smoking reinforcement) will be evaluated by behavioral, physiological, and subjective measures assessed both in the lab and using real-world, real-time electronic momentary assessments (EMA). The investigators predict that long-term, bio-verified smoking cessation will be improved among the extended run-in group compared to the standard run-in group. The investigators further predict the improved clinical outcomes with extended run-in varenicline will be explained (or mediated) by greater pre-quit reductions in smoking reinforcement among the extended run-in group compared to the standard run-in group. The significance of this work is clear: The project aims to make best available treatment for smoking cessation even better, using a method that is ripe for dissemination and an approach that will elucidate critical mechanisms to target in the next generation of treatment enhancement.

Conditions

Tobacco Smoking

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Continuous Abstinence at End-of-Treatment (EOT) as Assessed by Self-Report and Bio-verification

  Number of participants with bio-verified (cotinine level of 15 ng/mL or less) self-reported continuous abstinence from smoking (not even a puff) during the final four weeks of treatment

  Self-report Treatment Weeks 12-15; bio-verification ~Week 16

Secondary Outcomes (2)

• Pre-quit Change in Cigarettes Smoked Per Day

  Treatment Week 1 vs. Treatment Week 4 (final week before TQD)

• Number of Participants With Continuous Abstinence at 6-Month Follow-Up as Assessed by Self-Report and Bio-verification

  Self-report Treatment Weeks 12-28; bio-verification ~Week 16 and ~Week 29

Study Arms (2)

Extended Run-In

EXPERIMENTAL

\*\* 4 weeks of varenicline prior to the target quit date (TQD) \*\* \+ 11 weeks of post-TQD varenicline Standard varenicline dosing titration in initial week of therapy (one 0.5 mg tablet orally daily x 3 days, then one 0.5 mg tablet twice daily x 4 days); then 1 mg twice daily thereafter. Brief individual counseling at clinic visits

Drug: Varenicline; Behavioral: Brief smoking cessation counseling

Standard Run-In

ACTIVE COMPARATOR

\*\* 3 weeks of placebo followed by 1 week of varenicline prior to the target quit date (TQD) \*\* \+ 11 weeks of post-TQD varenicline Standard varenicline dosing titration in initial week of therapy (one 0.5 mg tablet orally daily x 3 days, then one 0.5 mg tablet twice daily x 4 days); then 1 mg twice daily thereafter. Brief individual counseling at clinic visits

Drug: Varenicline; Behavioral: Brief smoking cessation counseling

Interventions

Varenicline DRUG

oral varenicline tablets

Also known as: Chantix

Extended Run-In; Standard Run-In

Brief smoking cessation counseling BEHAVIORAL

\~10-minute individual counseling at each of 6 clinic visits

Extended Run-In; Standard Run-In

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: Approximately equal numbers of men and women will participate.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least moderately motivated to quit smoking and intention to make a quit attempt with varenicline 1 month after treatment begins.
• Planning to remain in western New York (NY) during the study period
• Willing to use varenicline and to refrain from other cessation treatments and tobacco products during the study period.
• English speaker
• To be intent-to-treat (ITT), the participant must complete Lab Visit 1 and meet minimal completion rate for real-world (EMA) assessments.

You may not qualify if:

• Use of other tobacco products, including e-cigarettes, in past 7 days
• Use of smoking cessation medication, including nicotine replacement therapy, in the past 14 days
• Prior allergy/hypersensitivity to varenicline
• Pregnant or breast-feeding
• Substance use:
• Alcohol: AUDIT score \> 15 at intake, suggestive of alcohol dependence and warranting treatment; for those with scores between 8 and 15, the investigators will advise reducing drinking).
• Medical treatment for substance use (SU) in past 3 months, including Suboxone (buprenorphine) and methadone (at phone screen)
• Using a combination of the National Institute on Drug Abuse (NIDA) modified ASSIST (4-26 = moderate risk; 27+ = high risk) and urine toxicology screen (both at intake):
• Cannabis: ASSIST=27+ (tox screen not used)
• Cocaine: ASSIST=7+ OR positive tox screen
• Methamphetamine: ASSIST=7+ OR positive tox screen
• Inhalants, hallucinogens, sedatives, or sleeping pills: ASSIST score = 7+
• Prescription stimulants: With prescription, ASSIST 27+; Without prescription, ASSIST 7+
• Opioids: With prescription, ASSIST 27+ (note ineligible if prescription is for buprenorphine or methadone); Without prescription, ASSIST 7+ OR positive tox screen
• (Note: ASSIST 4+ modified to 7+ in 2018 to avoid excluding people with past SU problems. clinicaltrials.gov edited 12/18/18)

Sponsors & Collaborators

• State University of New York at Buffalo: lead
• National Cancer Institute (NCI): collaborator
• Pfizer: collaborator

Study Sites (1)

State University of New York at Buffalo

Buffalo, New York, 14260, United States

Location

Related Publications (6)

• Cooper RK, Gass J, Mahoney MC, Tiffany ST, Colder CR, Maguin E, Schlienz NJ, Lawson SC, Tyndale RF, Sandhur B, Hawk LW. Do lab-based assessments of pretreatment smoking reinforcement and cue-specific craving predict smoking cessation with varenicline? Psychol Addict Behav. 2025 Dec;39(8):713-722. doi: 10.1037/adb0001081. Epub 2025 Jul 28.

  PMID: 40720285 DERIVED

• Tonkin S, Gass J, Wray J, Maguin E, Mahoney M, Colder C, Tiffany S, Hawk LW Jr. Evaluating Declines in Compliance With Ecological Momentary Assessment in Longitudinal Health Behavior Research: Analyses From a Clinical Trial. J Med Internet Res. 2023 Jun 22;25:e43826. doi: 10.2196/43826.

  PMID: 37347538 DERIVED

• Hawk LW Jr, Tiffany ST, Colder CR, Ashare RL, Wray JM, Tyndale RF, Brandon TH, Mahoney MC. Effect of Extending the Duration of Prequit Treatment With Varenicline on Smoking Abstinence: A Randomized Clinical Trial. JAMA Netw Open. 2022 Nov 1;5(11):e2241731. doi: 10.1001/jamanetworkopen.2022.41731.

  PMID: 36367720 DERIVED

• Ferkin AC, Tonkin SS, Maguin E, Mahoney MC, Colder CR, Tiffany ST, Hawk LW. A Psychometric Evaluation of the Stanford Expectations of Treatment Scale (SETS) in the Context of a Smoking Cessation Trial. Nicotine Tob Res. 2022 Nov 12;24(12):1914-1920. doi: 10.1093/ntr/ntac187.

  PMID: 35906990 DERIVED

• Mahoney MC, Park E, Schlienz NJ, Duerr C, Hawk LW. Transitioning to Remote Clinic Visits in a Smoking Cessation Trial During the COVID-19 Pandemic: Mixed Methods Evaluation. JMIR Form Res. 2021 Apr 30;5(4):e25541. doi: 10.2196/25541.

  PMID: 33878020 DERIVED

• Lawson SC, Gass JC, Cooper RK Jr, Tonkin SS, Colder CR, Mahoney MC, Tiffany ST, Hawk LW Jr. The impact of three weeks of pre-quit varenicline on reinforcing value and craving for cigarettes in a laboratory choice procedure. Psychopharmacology (Berl). 2021 Feb;238(2):599-609. doi: 10.1007/s00213-020-05713-7. Epub 2020 Nov 21.

  PMID: 33219852 DERIVED

MeSH Terms

Conditions

Tobacco Smoking

Interventions

Varenicline

Condition Hierarchy (Ancestors)

Smoking; Behavior; Tobacco Use

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines

Results Point of Contact

• Title: Larry Hawk, PhD
• Organization: University at Buffalo

lhawk@buffalo.edu

716-829-2323

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Psychology

Study Record Dates

• First Submitted: August 22, 2017
• First Posted: August 25, 2017
• Study Start: October 1, 2017
• Primary Completion: April 5, 2021
• Study Completion: July 8, 2021
• Last Updated: September 26, 2025
• Results First Posted: July 11, 2023

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 2023\. We are currently awaiting confirmation from NAHDAP that our archival plan fits their expectations. Data will be available indefinitely (as long as NAHDAP is supported).
• Access Criteria: Public release; anyone who registers on the website.

Locations

US (1)