Concurrent Bupropion / Varenicline for Smoking Cessation (ConNic4)

This study has been completed.
Sponsor:
Collaborators:
Philip Morris USA, Inc.
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01303861
First received: February 23, 2011
Last updated: August 4, 2014
Last verified: May 2014
Results First Received: July 5, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver);   Primary Purpose: Treatment
Condition: Nicotine Dependence
Interventions: Drug: Varenicline
Drug: Bupropion
Drug: Nicotine patches
Drug: Nicotine Inhaler

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment began on 3/07/11 and ended on 11/30/12. Of the 702 subjects consented during this period, 218 were in our Charlotte, NC office, 157 were in our Durham, NC office, 151 were in our Raleigh, NC office and 176 were in our Winston-Salem, NC office. Only 349 subjects met all study criteria, and 22 discontinued prior to being assigned.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Varenicline

This group will consist of smokers who, based on smoking behavior, Do NOT respond favorably to pre-cessation nicotine patches (assessed at Session P2). They will receive varenicline.

Varenicline: For the first 3 days after being switched from nicotine patches (occurring at one week before the target quit date), smokers in this group will receive varenicline 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 weeks.

Nicotine Patches Only

This group will consist of smokers who, based on smoking behavior, respond favorably to pre-cessation nicotine patches(assessed at Session P2). They will continue to receive only nicotine patches.

Nicotine patches: Nicotine Replacement Therapy Groups:

  1. For smokers with high baseline CO: 42 mg/24 h for 2 weeks before the quit date and 3 weeks after the quit date, 21 mg/24 h for 4 weeks, 14 mg/24 h for 2 weeks, and 7 mg/24 h for 2 weeks; or
  2. For smokers with low baseline CO: 21 mg/24 h for 2 weeks before the quit date and 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks.

Varenicline and varenicline in combination with bupropion groups:

  1. For smokers with high baseline CO: 42 mg/24 h for 1 week
  2. For smokers with low baseline CO: 21 mg/24 h for 1 week
Nicotine Patches With Nicotine Inhaler

This group will consist of smokers who, based on smoking behavior, respond favorably to pre-cessation nicotine patches (assessed at Session P2). They will continue to receive nicotine patches and will receive a nicotine inhaler to use as needed after their quit date.

Nicotine patches: Nicotine Replacement Therapy Groups:

  1. For smokers with high baseline CO: 42 mg/24 h for 2 weeks before the quit date and 3 weeks after the quit date, 21 mg/24 h for 4 weeks, 14 mg/24 h for 2 weeks, and 7 mg/24 h for 2 weeks; or
  2. For smokers with low baseline CO: 21 mg/24 h for 2 weeks before the quit date and 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks.

Varenicline and varenicline in combination with bupropion groups:

  1. For smokers with high baseline CO: 42 mg/24 h for 1 week
  2. For smokers with low baseline CO: 21 mg/24 h for 1 week

Nicotine Inhaler: Nicotine inhaler to use as needed after quit date

Varenicline With Bupropion

This group will consist of smokers who, based on smoking behavior, DO NOT respond favorably to pre-cessation nicotine patches (assessed at Session P2). They will receive varenicline in combination with bupropion.

Varenicline: For the first 3 days after being switched from nicotine patches (occurring at one week before the target quit date), smokers in this group will receive varenicline 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 weeks.

Bupropion: For the first 3 days after being switched from nicotine patches (occurring at one week before the target quit date), smokers in this group will receive bupropion at a dose of 150mg once per day. Subsequently, the dose will be 150mg twice per day, and will remain at that dose for the remainder of the 12 weeks.


Participant Flow:   Overall Study
    Varenicline     Nicotine Patches Only     Nicotine Patches With Nicotine Inhaler     Varenicline With Bupropion  
STARTED     109     50     55     113  
Finished Treatment Phase     71     34     39     72  
COMPLETED     51     25     19     54  
NOT COMPLETED     58     25     36     59  
Lost to Follow-up                 34                 14                 27                 31  
Lack of Efficacy                 3                 2                 1                 0  
Withdrawal by Subject                 16                 8                 8                 23  
Adverse Event                 4                 1                 0                 5  
Pregnancy                 1                 0                 0                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subjects who failed to respond to pre-cessation nicotine patch treatment were randomized to receive varenicline, or varenicline + bupropion. Subjects who showed reductions in ad lib smoking were randomly assigned to nicotine patch only or patch + nicotine inhaler. 22 Subjects discontinued study participation prior to being assigned to a condition.

Reporting Groups
  Description
Varenicline

This group will consist of smokers who, based on smoking behavior, DO NOT respond favorably to pre-cessation nicotine patches (assessed at Session P2). They will receive varenicline.

Varenicline: For the first 3 days after being switched from nicotine patches (occurring at one week before the target quit date), smokers in this group will receive varenicline 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 weeks.

Nicotine Patches Only

This group will consist of smokers who, based on smoking behavior, respond favorably to pre-cessation nicotine patches(assessed at Session P2). They will continue to receive only nicotine patches.

Nicotine patches: Nicotine Replacement Therapy Groups:

  1. For smokers with high baseline carbon monoxide (CO): 42 mg/24 h for 2 weeks before the quit date and 3 weeks after the quit date, 21 mg/24 h for 4 weeks, 14 mg/24 h for 2 weeks, and 7 mg/24 h for 2 weeks; or
  2. For smokers with low baseline CO: 21 mg/24 h for 2 weeks before the quit date and 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks.

Varenicline and varenicline in combination with bupropion groups:

  1. For smokers with high baseline CO: 42 mg/24 h for 1 week
  2. For smokers with low baseline CO: 21 mg/24 h for 1 week
Nicotine Patches With Nicotine Inhaler

This group will consist of smokers who, based on smoking behavior, respond favorably to pre-cessation nicotine patches (assessed at Session P2). They will continue to receive nicotine patches and will receive a nicotine inhaler to use as needed after their quit date.

Nicotine patches: Nicotine Replacement Therapy Groups:

  1. For smokers with high baseline CO: 42 mg/24 h for 2 weeks before the quit date and 3 weeks after the quit date, 21 mg/24 h for 4 weeks, 14 mg/24 h for 2 weeks, and 7 mg/24 h for 2 weeks; or
  2. For smokers with low baseline CO: 21 mg/24 h for 2 weeks before the quit date and 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks.

Varenicline and varenicline in combination with bupropion groups:

  1. For smokers with high baseline CO: 42 mg/24 h for 1 week
  2. For smokers with low baseline CO: 21 mg/24 h for 1 week

Nicotine Inhaler: Nicotine inhaler to use as needed after quit date

Varenicline With Bupropion

This group will consist of smokers who, based on smoking behavior, DO NOT respond favorably to pre-cessation nicotine patches (assessed at Session P2). They will receive varenicline in combination with bupropion.

Varenicline: For the first 3 days after being switched from nicotine patches (occurring at one week before the target quit date), smokers in this group will receive varenicline 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 weeks.

Bupropion: For the first 3 days after being switched from nicotine patches (occurring at one week before the target quit date), smokers in this group will receive bupropion at a dose of 150mg once per day. Subsequently, the dose will be 150mg twice per day, and will remain at that dose for the remainder of the 12 weeks.

Dropped Prior to Condition Assignment These subjects discontinued study participation prior to being assigned to a condition.
Total Total of all reporting groups

Baseline Measures
    Varenicline     Nicotine Patches Only     Nicotine Patches With Nicotine Inhaler     Varenicline With Bupropion     Dropped Prior to Condition Assignment     Total  
Number of Participants  
[units: participants]
  109     50     55     113     22     349  
Age  
[units: participants]
           
<=18 years     0     0     0     0     0     0  
Between 18 and 65 years     109     49     54     113     22     347  
>=65 years     0     1     1     0     0     2  
Age  
[units: years]
Mean ± Standard Deviation
  45.58  ± 11.39     45.20  ± 10.56     42.09  ± 12.22     44.22  ± 10.47     44.77  ± 11.28     44.42  ± 11.20  
Gender  
[units: participants]
           
Female     63     30     34     58     10     195  
Male     46     20     21     55     12     154  
Ethnicity (NIH/OMB)  
[units: participants]
           
Hispanic or Latino     4     1     1     2     1     9  
Not Hispanic or Latino     105     49     54     111     21     340  
Unknown or Not Reported     0     0     0     0     0     0  
Race (NIH/OMB)  
[units: participants]
           
American Indian or Alaska Native     0     0     1     0     0     1  
Asian     2     0     0     0     0     2  
Native Hawaiian or Other Pacific Islander     0     0     1     0     0     1  
Black or African American     32     20     19     41     9     121  
White     71     29     31     68     11     210  
More than one race     1     1     3     3     2     10  
Unknown or Not Reported     3     0     0     1     0     4  
Region of Enrollment  
[units: participants]
           
United States     109     50     55     113     22     349  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Four-week Continuous Abstinence From Cigarette Smoking   [ Time Frame: Study week 8 thru week 11 ]

2.  Secondary:   Seven Day Point Abstinence From Cigarette Smoking   [ Time Frame: Six months post quit date ]

3.  Secondary:   Continuous Cigarette Abstinence From Quit Date   [ Time Frame: From Quit date to end of treatment (week 11) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Jed E. Rose
Organization: Duke University Medical Center - Duke Center for Smoking Cessation
phone: 919-668-5055
e-mail: jed.rose@dm.duke.edu


No publications provided


Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01303861     History of Changes
Other Study ID Numbers: Pro00027351, 1P50DA027840-01A1
Study First Received: February 23, 2011
Results First Received: July 5, 2014
Last Updated: August 4, 2014
Health Authority: United States: Institutional Review Board