Varenicline and Combined NRT for Smoking Cessation

Varenicline and Combined NRT for Initial Smoking Cessation and Rescue Treatment in Smokers: A Randomized Pilot Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Tobacco Use Disorder; Cigarette Smoker
• Intervention / Treatment: Drug: Varenicline; Other: Tobacco Cessation Counseling; Other: Placebo; Drug: Nicotine Lozenge; Drug: Nicotine Patch

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the main effects of varenicline 2 mg (VAR) and nicotine patch + lozenge (NPL) on smokers who remain on these medications throughout the trial.

II. To estimate the probability that abstinence at twelve weeks as a function of treatment assignment at six weeks (augmentation) is moderated by initial treatment assignment (i.e. at baseline).

III. To estimate the probability that abstinence at twelve weeks as a function of treatment assignment at six weeks (switching) is moderated by initial treatment assignment (i.e. at baseline).

IV. To estimate the probability that treatment continuation, switching, or augmentation confers benefit conditional upon failing to quit after the initial treatment with nicotine patch + lozenge (NPL) for six weeks.

V. To estimate the probability that treatment continuation, switching, or augmentation confers benefit conditional upon failing to quit after initial treatment with VAR for six weeks.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: 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 that are abstinent at week 6 may continue treatment for an additional 6 weeks. 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.

GROUP II: 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 that are abstinent at week 6 may continue treatment for an additional 6 weeks. 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.

Patients who fail to achieve abstinence at week 6 are re-randomized to receive 6 additional weeks of therapy consisting of either a continuation of the same treatment; switching to the untried intervention (either NPL or varenicline); or receive NPL treatment with an additional patch (high-dose NPL) or high-dose varenicline.

After completion of study treatment, patients are followed up at 3 and 6 months.

• Study Type: Interventional
• Enrollment (Actual): 631
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Current use of certain medications: (1) smoking cessation meds (last 7 days), i.e., Wellbutrin, Bupropion, Zyban, nicotine replacement therapy (NRT), Chantix, (2) certain medications to treat depression (last 14 days), i.e. monoamine oxidase inhibitors (MAOIs) and Elavil (Amitriptyline), (3) a case by case determination will be made by study physician for medication on precautionary list, i.e. nitroglycerin, or (4) daily use of opioids for 30 days or more on phone screen or at screening is exclusionary however pro re nata (PRN) use is allowed (i.e., 3:7 days per week or less or if more frequent, use less than a month's duration)
• Meet criteria for the following psychiatric and/or substance use disorders as assessed by the MINI International Neuropsychiatric Interview (MINI): items C (current manic or hypomanic episode only), I (alcohol abuse - Alcohol Addendum - past 6 months only; current alcohol dependence), J (substance abuse - Substance Abuse Addendum - past 6 months only; current substance dependence), K (current/lifetime psychotic disorder or current/lifetime mood disorder with psychotic features); individuals who meet criteria for non-exclusionary psychiatric disorders that are considered clinically unstable and/or unsuitable to participate as determined by the principal investigator and/or 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
• Positive toxicology screen for any of the following drugs: cocaine, opiates, methadone, benzodiazepines, barbiturates, amphetamines, methamphetamines, phencyclidine (PCP), or tetrahydrocannabinol (THC); a. participants with valid prescriptions for opiates, benzodiazepines, barbiturates, amphetamines or methadone will not be excluded; b. participants failing the toxicology screen will be allowed to re-screen once; if they test positive again, they will not be allowed to return; study physician may clear participant to continue on if there is a reasonable possibility the positive drug screen is the result of cross-reactivity with the participant's concomitant medications resulting in a false positive

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I (varenicline and placebo); Patients receive varenicline PO QD or BID, placebo patches QD, and placebo lozenges PO QD beginning on day 9 and continue for 6 weeks. Patients that are abstinent at week 6 may continue treatment for an additional 6 weeks. 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: Varenicline; Given PO; Other Names: Champix; Chantix; CP-526555; Other: Tobacco Cessation Counseling; Receive behavioral smoking cessation counseling; Other: Placebo; Given PO or via patch; Other Names: placebo therapy; PLCB; sham therapy
Placebo Comparator: Group II (placebo, nicotine patch and lozenge); 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 that are abstinent at week 6 may continue treatment for an additional 6 weeks. 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.	Other: Tobacco Cessation Counseling; Receive behavioral smoking cessation counseling; Other: Placebo; Given PO or via patch; Other Names: placebo therapy; PLCB; sham therapy; Drug: Nicotine Lozenge; Given PO; Other Names: Commit; Drug: Nicotine Patch; Given via patch; Other Names: NicoDerm CQ; Nicotine Skin Patch; Nicotine Transdermal Patch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Paul Cinciripini, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• M D Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2015
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: October 17, 2014
• First Submitted That Met QC Criteria: October 20, 2014
• First Posted (Estimated): October 22, 2014

Study Record Updates

• Last Update Posted (Estimated): December 27, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine; Varenicline
• Other Study ID Numbers: 2014-0213 (Other Identifier: M D Anderson Cancer Center); NCI-2015-00610 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No