Combination Bupropion / Varenicline for Smoking Cessation in Male Smokers (ConNic5)

Previous results from the investigators' Center have shown that combination treatment with Chantix and Zyban is more successful in helping men quit smoking. The investigators hope to replicate these findings with this study.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence
• Intervention / Treatment: Drug: Chantix; Drug: Nicotine patches; Drug: Zyban

• Study Type: Interventional
• Enrollment (Actual): 376
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Duke Center for Smoking Cessation
    • Durham, North Carolina, United States, 27705
      • Duke Center for Smoking Cessation
    • Raleigh, North Carolina, United States, 27609
      • Duke Center for Smoking Cessation
    • Winston-Salem, North Carolina, United States, 27103
      • Duke Center for Smoking Cessation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Have no known serious medical conditions;
• Male;
• Are 18-65 years old;
• Smoke an average of at least 10 cigarettes per day;
• Have smoked at least one cumulative year;
• Have an expired air carbon monoxide (CO) reading of at least 10ppm;
• Able to read and understand English;
• Express a desire to quit smoking in the next thirty days.

Potential subjects must agree to use acceptable contraception.

Potential subjects must agree to avoid the following:

• participation in any other nicotine-related modification strategy outside of this protocol;
• use of tobacco products other than cigarettes, including pipe tobacco, cigars, e-cigarettes, snuff, and chewing tobacco;
• use of experimental (investigational) drugs or devices;
• use of illegal drugs;
• use of opiate medications.

Exclusion Criteria:

• Hypertension;
• Hypotension with symptoms;
• Coronary heart disease;
• Lifetime history of heart attack;
• Cardiac rhythm disorder (irregular heart rhythm);
• Chest pains (unless history, exam, and electrocardiogram (ECG) clearly indicate a non-cardiac source);
• Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure);
• History of skin allergy;
• Active skin disorder (e.g., psoriasis) within the last five years;
• Liver or kidney disorder (except kidney stones, gallstones);
• Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn;
• Active ulcers in the past 30 days;
• Currently symptomatic lung disorder/disease (including but not limited to Chronic obstructive pulmonary disease (COPD), emphysema, and asthma);
• Brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder);
• Migraine headaches that occur more frequently than once per week;
• Recent, unexplained fainting spells;
• Problems giving blood samples;
• Diabetes treated with insulin; non-insulin treated diabetes (unless glucose is less than 180mg/dcl and HbA1c is less than 7%);
• Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer);
• Other major medical condition;
• Current psychiatric disease (with the exception of anxiety disorders, Obsessive Compulsive Disorder (OCD) and ADHD);
• Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide;
• Current depression;
• Bulimia or anorexia;
• Use of opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed) within the past 14 days;
• Smoking more than one cigar a month.
• Alcohol abuse;
• Significant adverse reaction to nicotine patches, bupropion / Wellbutrin / Zyban or Chantix / varenicline in the past.
• Current participation or recent participation (in the past 30 days) in another smoking study at our Center or another research facility.
• Current participation in another research study.

Use (within the past 30 days) of:

• Illegal drugs (or if the urine drug screen is positive for tetrahydrocannabinol (THC), Cocaine, Amphetamine, Opiates, Methamphetamines, phencyclidine (PCP), Benzodiazepines, or Barbiturates),
• Experimental (investigational) drugs;
• Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine);
• Smokeless tobacco (chewing tobacco, snuff), pipes or e-cigarettes;
• Wellbutrin, bupropion, Zyban, Chantix, varenicline, nicotine replacement therapy or any other smoking cessation aid.

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: Chantix; For the first 3 days after being switched from Nicotine Replacement Therapy (NRT) (occurring at one week after initiation of nicotine patch treatment, one week before the target Quit Day), smokers in this group will receive treatment with Chantix at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week. Subsequently, the dose will be 1 mg twice per day, and will remain at that dose for the remainder of the 12-week active treatment duration.	Drug: Chantix; Other Names: Varenicline; Drug: Nicotine patches; All participants will receive 21 mg/24 h dose nicotine (nic.) patches for 1 week.; Other Names: NRT
Experimental: Chantix + Zyban; For the first 3 days after being switched from NRT (occurring at one week after initiation of nicotine patch treatment, one week before the target Quit Day), smokers in this group will receive treatment with Chantix at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week plus Zyban at a dose of 150mg once per day. Subsequently, the dose of Chantix will be 1 mg twice per day and the dose of Zyban will be 150 mg twice per day for the remainder of the 12-week active treatment duration.	Drug: Chantix; Other Names: Varenicline; Drug: Nicotine patches; All participants will receive 21 mg/24 h dose nicotine (nic.) patches for 1 week.; Other Names: NRT; Drug: Zyban; Other Names: Bupropion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Completing Continuous Four-week Abstinence From Smoking Between the 8-week and 11-week Post Quit Day Visits	This will be determined by a composite of self-report at the 11-week study visit of no smoking between the 8-week and 11-week visits and expired air carbon monoxide (CO) <10 ppm (measured at the 11-week study visit). An intent-to-treat criterion will be used, whereby drop-outs are considered to be non-abstinent.	Period between 8-week and 11-week visits post target Quit Day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Completing Seven-day Point Abstinence From Smoking at 6 Months Post Quit Day	This will be determined by a self-report of no smoking for the previous seven days when called for 6-month follow-up confirmed by expired air CO.	6 months post Quit Day
Number of Participants Completing Continuous Abstinence From Smoking Between Quit Day and 11-week Post Quit Day Visit	This will be determined by a composite of self-report of no smoking between study visits at the 1-week, 3-week, 7-week and 11-week post Quit Day study visits and expired air carbon monoxide (CO) <10 ppm (measured at those study visits). An intent-to-treat criterion will be used, whereby drop-outs are considered to be non-abstinent.	Quit Day to 11-week post Quit Day study visit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Smoking Withdrawal Symptoms	Withdrawal symptoms will be assessed by questionnaire on Quit Day, Week 1, Week 3, Week 7 and Week 11 post target quit date and 6 months post quit Follow-Up (if applicable) using the Shiffman-Jarvik questionnaire, which consists of 33-items rated from 1 to 7, where 1= not at all, 2= very little, 3= a little, 4= moderately, 5= a lot, 6= quite a lot, and 7= extremely. The 33 items are grouped into 8 subscales: Craving, Negative Affect, Appetite, Arousal, Somatic - Anxiety, Somatic - G.I., Somatic - Respiratory Tract, and Habit Withdrawal. The range of scores for each subscale will be 1-7, with higher scores indicating more of the withdrawal symptom having been experienced.	Quit Day and 1 week, 3 weeks, 7 Weeks, 11 Weeks and 6 months post Quit Day

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute on Drug Abuse (NIDA); Philip Morris USA, Inc.

Publications and helpful links

General Publications

• Rose JE, Behm FM. Combination Varenicline/Bupropion Treatment Benefits Highly Dependent Smokers in an Adaptive Smoking Cessation Paradigm. Nicotine Tob Res. 2017 Aug 1;19(8):999-1002. doi: 10.1093/ntr/ntw283.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: March 6, 2013
• First Submitted That Met QC Criteria: March 6, 2013
• First Posted (Estimate): March 7, 2013

Study Record Updates

• Last Update Posted (Estimate): January 18, 2016
• Last Update Submitted That Met QC Criteria: December 14, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Smoking cessation; varenicline; bupropion; Nicotine addiction; Cigarette smoking; Zyban; Chantix; Nicotine patches
• 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; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Cytochrome P-450 Enzyme Inhibitors; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Dopamine Uptake Inhibitors; Nicotine; Bupropion; Varenicline
• Other Study ID Numbers: Pro00042699; 1P50DA027840-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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