Varenicline and Combined NRT for Smoking Cessation

NCT02271919 | Active Not Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 2014-0213NCI-2015-00610
• Study Type: interventional
• Target: 631
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized pilot phase IV trial studies the side effects and how well varenicline works compared to nicotine replacement therapy in helping patients that smoke to quit. Varenicline is a drug that acts the same way as nicotine in the brain but is not habit-forming. Nicotine replacement therapy consists of nicotine patches and lozenges. It is not yet known if varenicline is more effective than nicotine replacement therapy in helping patients quit smoking.

Conditions

Cigarette Smoker; Tobacco Use Disorder

Outcome Measures

Primary Outcomes (8)

• Seven-day point prevalence and treatment or treatment strategy

  Estimated rates of seven-day point prevalence for varenicline and nicotine patch + lozenge at week 6 derive from meta-analyses.

  At week 6

• Main effects of varenicline and nicotine patch + lozenge on smokers who remain on these medications throughout the trial as documented in questionnaires

  Participants complete questionnaires about several topics including depression, mood, smoking behavior, and any effects from the study drug.

  Up to 12 weeks

• Probability of response at week 12 conditional on response at week 6 and continuation of treatment

  The probability of response at week 12 conditional on response at week 6 and continuation based on clinical consensus, taking into account the marginal rates of response at twelve weeks reported derived from meta-analysis. Monte Carlo simulations (K = 500) determined predictive power for the planned analyses.

  At 12 weeks

• Probability of response at week 12 conditional on non-response at week 6 and continuation of treatment

  The probability of response at week 12 conditional on non-response at week 6 and continuation of treatment based on clinical consensus, taking into account the marginal rates of response at twelve weeks reported derived from meta-analysis. Monte Carlo simulations (K = 500) determined predictive power for the planned analyses.

  At 12 weeks

• Probability of response at week 12 conditional on non-response at week 6 and augmentation of treatment

  The probability of response at week 12 conditional on non-response at week 6 and augmentation of treatment based on clinical consensus, taking into account the marginal rates of response at twelve weeks reported derived from meta-analysis. Monte Carlo simulations (K = 500) determined predictive power for the planned analyses.

  At 12 weeks

• Probability of response at week 12 conditional on non-response at week 6 and treatment switching

  The probability of response at week 12 conditional on non-response at week 6 and treatment switching based on clinical consensus, taking into account the marginal rates of response at twelve weeks reported derived from meta-analysis. Monte Carlo simulations (K = 500) determined predictive power for the planned analyses.

  At 12 weeks

• Probability that treatment continuation, switching, or augmentation confers benefit conditional upon failing to quit after the initial treatment with nicotine patch + lozenge for six weeks

  Monte Carlo simulations (K = 500) determined predictive power for the planned analyses.

  12 weeks

• Probability that treatment continuation, switching, or augmentation confers benefit conditional upon failing to quit after initial treatment with varenicline for six weeks

  Monte Carlo simulations (K = 500) determined predictive power for the planned analyses.

  12 weeks

Study Arms (2)

Group I (varenicline and placebo)

EXPERIMENTAL

Patients receive varenicline orally (PO) once daily (QD) or twice daily (BID), placebo patches QD, and placebo lozenges PO QD beginning on day 9 and continue for 6 weeks. Patients who are abstinent at week 6 will continue treatment for an additional 6 weeks. Patients who fail to achieve abstinence at week 6 are re-randomized to 6 additional weeks of therapy consisting of either continuing on the same treatment, switching to CNRT, or receiving high-dose varenicline. Patients also receive behavioral smoking cessation counseling consisting of 4 in-person visits, 4 phone visits, and 4 brief supportive phone calls lasting 10-15 minutes each over the 12 weeks of treatment.

Drug: Nicotine Lozenge; Drug: Nicotine Patch; Other: Placebo; Other: Tobacco Cessation Counseling; Drug: Varenicline

Group II (placebo, nicotine patch and lozenge)

PLACEBO COMPARATOR

Patients receive placebo tablets PO QD or BID, nicotine patches QD, and nicotine lozenges PO QD beginning on day 9 and continue for 6 weeks. Patients who are abstinent at week 6 will continue treatment for an additional 6 weeks. Patients who fail to achieve abstinence at week 6 are re-randomized to 6 additional weeks of therapy consisting of either continuing on the same treatment, switching to varenicline, or receiving high-dose CNRT. Patients also receive behavioral smoking cessation counseling consisting of 4 in-person visits, 4 phone visits, and 4 brief supportive phone calls lasting 10-15 minutes each over the 12 weeks of treatment.

Drug: Nicotine Lozenge; Drug: Nicotine Patch; Other: Placebo; Other: Tobacco Cessation Counseling

Interventions

Nicotine Lozenge DRUG

Given PO

Also known as: Commit

Group I (varenicline and placebo); Group II (placebo, nicotine patch and lozenge)

Nicotine Patch DRUG

Given via patch

Also known as: NicoDerm CQ, Nicotine Skin Patch, Nicotine Transdermal Patch

Group I (varenicline and placebo); Group II (placebo, nicotine patch and lozenge)

Placebo OTHER

Given PO or via patch

Also known as: placebo therapy, PLCB, sham therapy

Group I (varenicline and placebo); Group II (placebo, nicotine patch and lozenge)

Tobacco Cessation Counseling OTHER

Receive behavioral smoking cessation counseling

Group I (varenicline and placebo); Group II (placebo, nicotine patch and lozenge)

Varenicline DRUG

Given PO

Also known as: Champix, Chantix, CP-526555

Group I (varenicline and placebo)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Smoking 5 or more cigarettes, little cigars and/or cigarillos per day, on average, within the 2 months preceding the screening visit and expired carbon monoxide (CO) greater than or equal to 6 parts per million (ppm) (if less than or equal to 5, then positive cotinine test)
• Interested in treatment that might change smoking behavior
• Able to follow verbal and written instructions in English and complete all aspects of the study
• Provide informed consent and agree to all assessments and study procedures
• Have an address and telephone number where he/she may be reached
• Be the only participant in his/her household

You may not qualify if:

• Within the month immediately preceding the screening visit, use of any form of tobacco products other than cigarettes, little cigars and/or cigarillos on 3 or more days within a week if the individual refuses to refrain from such tobacco use during the course of the study
• Current enrollment or plans to enroll in another smoking cessation program in the next 12 months
• Plan to use other nicotine substitutes (i.e., over-the-counter \[OTC\] or prescription medication for smoking cessation) or smoking cessation treatments in the next 12 months
• Uncontrolled hypertension (systolic blood pressure; \[SBP\] greater than 180 or diastolic blood pressure; \[DBP\] greater than 110)
• History of severe kidney disease (e.g. chronic or acute kidney failure) with creatinine clearance below 30 and/or severe liver disease with liver tests over 4 times the upper normal level
• Laboratory evaluations (kidney and liver) outside normal limits and of potential clinical significance in the opinion of the investigator
• Serious or unstable disease within the past 3 months
• History (last 3 months) of abnormal heart rhythms, cardiovascular disease (stroke, angina, heart attack) may result in ineligibility; these conditions will be evaluated on a case by case basis by the study physician
• Individuals rated as moderate (9-16) to high (17 or greater) on suicidality as assessed by Module B of the MINI
• Psychiatric hospitalization within 1 year of screening date
• A positive urine pregnancy test during the screening period; women who are two years post-menopausal, or who have had a tubal ligation or a partial or full hysterectomy will not be subject to a urine pregnancy test
• 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; medically acceptable contraceptives include: (1) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (2) barrier methods (such as a condom or diaphragm) used with a spermicide, or (3) an intrauterine device (IUD); contraceptive measures sold for emergency use after unprotected sex are not acceptable methods for routine use
• History of hypersensitivity or allergic reaction to varenicline, NRT, or any component of these formulations
• Any medical or psychiatric condition, illness, disorder, or concomitant medication that could compromise participant safety or treatment, as determined by the principal investigator and/or study physician
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Cinciripini PM, Green CE, Shete S, Minnix JA, Robinson JD, Cui Y, Kim S, Kypriotakis G, Beneventi D, Blalock JA, Versace F, Karam-Hage M. Smoking Cessation After Initial Treatment Failure With Varenicline or Nicotine Replacement: A Randomized Clinical Trial. JAMA. 2024 May 28;331(20):1722-1731. doi: 10.1001/jama.2024.4183.

  PMID: 38696203 DERIVED

• Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.

  PMID: 37142273 DERIVED

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

Tobacco Use Cessation Devices; Nicotine; Varenicline

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Therapeutics; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinoxalines

Study Officials

• Jason Robinson

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2014
• First Posted: October 22, 2014
• Study Start: May 14, 2015
• Primary Completion: June 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

US (1)