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Trial record 1 of 1 for:    NCT01244061
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A Multi-National Study To Assess How Effective And Safe The Smoking Cessation Medicine Varenicline Is In Smokers Who Have Already Tried Varenicline In The Past As A Prescription Medicine From Their Usual Healthcare Provider

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ClinicalTrials.gov Identifier: NCT01244061
Recruitment Status : Completed
First Posted : November 19, 2010
Results First Posted : June 9, 2014
Last Update Posted : June 9, 2014
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Smoking Cessation
Interventions Drug: Varenicline
Drug: Placebo
Enrollment 498
Recruitment Details This was a Phase 4, randomized, double-blind, placebo-controlled, parallel group, 2-arm, multicenter study. A total of 498 participants were randomized into the study at 36 investigator sites.
Pre-assignment Details  
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description Participants received 0.5 mg per day of varenicline on Days 1 to 3, 1.0 mg per day on Days 4 to 7, and 2.0 mg per day (1.0 mg twice daily, ie, 2 x 0.5 mg tablets in the morning and 2 x 0.5 mg tablets in the evening) from Weeks 1 to 12. Participants received 1 tablet per day of placebo from Days 1 to 3, which was titrated up to 2 tablets per day from Days 4 to 7, and then to 4 tablets per day (2 tablets in the morning and 2 tablets in the evening) from Week 1 to Week 12.
Period Title: Overall Study
Started 251 247
Completed 169 144
Not Completed 82 103
Reason Not Completed
Death             1             0
Did not meet entrance criteria             1             0
Lack of Efficacy             1             3
Lost to Follow-up             34             30
Withdrawal by Subject             29             46
Other             8             19
Protocol Violation             1             1
Adverse Event             5             2
Randomized but not treated             2             2
Arm/Group Title Varenicline Placebo Total
Hide Arm/Group Description Participants received 0.5 mg per day of varenicline on Days 1 to 3, 1.0 mg per day on Days 4 to 7, and 2.0 mg per day (1.0 mg twice daily, ie, 2 x 0.5 mg tablets in the morning and 2 x 0.5 mg tablets in the evening) from Weeks 1 to 12. Participants received 1 tablet per day of placebo from Days 1 to 3, which was titrated up to 2 tablets per day from Days 4 to 7, and then to 4 tablets per day (2 tablets in the morning and 2 tablets in the evening) from Week 1 to Week 12. Total of all reporting groups
Overall Number of Baseline Participants 249 245 494
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Number of participants
Number Analyzed 249 participants 245 participants 494 participants
< 18 years 0 0 0
18-44 years 94 94 188
45-64 years 135 139 274
>= 65 years 20 12 32
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 249 participants 245 participants 494 participants
Female
125
  50.2%
124
  50.6%
249
  50.4%
Male
124
  49.8%
121
  49.4%
245
  49.6%
1.Primary Outcome
Title Continuous Abstinence Rate (CAR) From Week 9 Through Week 12
Hide Description The percentage of participants who, from Week 9 through Week 12, reported no smoking and no use of other nicotine-containing products since the last study visit/last contact (on the Nicotine Use Inventory) and who did not have carbon monoxide (CO)> 10ppm at any visits during this time frame.
Time Frame Week 9 through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) included all participants as the primary participant population for efficacy analyses in this study and was defined as all participants who had received ≥1 dose, including partial doses, of randomized study drug.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Participants received 0.5 mg per day of varenicline on Days 1 to 3, 1.0 mg per day on Days 4 to 7, and 2.0 mg per day (1.0 mg twice daily, ie, 2 x 0.5 mg tablets in the morning and 2 x 0.5 mg tablets in the evening) from Weeks 1 to 12.
Participants received 1 tablet per day of placebo from Days 1 to 3, which was titrated up to 2 tablets per day from Days 4 to 7, and then to 4 tablets per day (2 tablets in the morning and 2 tablets in the evening) from Week 1 to Week 12.
Overall Number of Participants Analyzed 249 245
Measure Type: Number
Unit of Measure: Percentage of participants
45.0 11.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments The study was conducted on a sample size to achieve at least 90% power for the treatment comparison in the primary efficacy endpoint assuming an odds ratio of 3.36 with a placebo abstinence rate of 12% and varenicline abstinence rate of 31%. The intent of the primary efficacy analysis was to evaluate the hypothesis that varenicline is superior to placebo for smoking cessation after 12 weeks of treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The statistical significance was declared for each hypothesis firstly for CAR Weeks 9-12, and then secondly for CAR Weeks 9-52 until a p-value > 0.05 was obtained, at which point the hypothesis would be declared to be not statistically significant.
Method Regression, Logistic
Comments The analysis model included main effect of treatment and pooled center.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 7.08
Confidence Interval (2-Sided) 95%
4.34 to 11.55
Estimation Comments [Not Specified]
2.Secondary Outcome
Title CAR From Week 9 Through Week 52
Hide Description The percentage of participants who, from Week 9 through Week 52, reported no smoking (Weeks 9 through 52) and no use of other nicotine-containing products (Weeks 9 through 12), or no use of other tobacco products (Weeks 13 through 52), since the last study visit/last contact (on the Nicotine Use Inventory) and who did not have CO >10 ppm at any of these visits during this time frame.
Time Frame Week 9 through Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all participants as the primary participant population for efficacy analyses in this study and was defined as all participants who had received ≥1 dose, including partial doses, of randomized study drug.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Participants received 0.5 mg per day of varenicline on Days 1 to 3, 1.0 mg per day on Days 4 to 7, and 2.0 mg per day (1.0 mg twice daily, ie, 2 x 0.5 mg tablets in the morning and 2 x 0.5 mg tablets in the evening) from Weeks 1 to 12.
Participants received 1 tablet per day of placebo from Days 1 to 3, which was titrated up to 2 tablets per day from Days 4 to 7, and then to 4 tablets per day (2 tablets in the morning and 2 tablets in the evening) from Week 1 to Week 12.
Overall Number of Participants Analyzed 249 245
Measure Type: Number
Unit of Measure: Percentage of participants
20.1 3.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments The sample size was sufficient to achieve 80% power for the treatment comparison in the key secondary end point for an odds ratio of 2.55 with a placebo abstinence rate of 6% and varenicline abstinence rate of 14%. The intent of the key secondary efficacy analysis was to evaluate the hypothesis that varenicline is superior to placebo for smoking cessation from Week 9 to the end of non-treatment follow up period at Week 52.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical significance was declared for each hypothesis in the order above until a p-value >0.05 was obtained, at which point the hypothesis was declared to be not statistically significant.
Method Regression, Logistic
Comments The analysis model included main effect of treatment and pooled center.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 9.00
Confidence Interval (2-Sided) 95%
3.97 to 20.41
Estimation Comments [Not Specified]
3.Secondary Outcome
Title CAR From Week 9 Through Week 24
Hide Description The percentage of participants who, from Week 9 through Week 24, reported no smoking (Weeks 9 through 24) and no use of other nicotine-containing products (Weeks 9 through 12), or no use of other tobacco products (Weeks 13 through 24), since the last study visit/last contact (on the Nicotine Use Inventory) and who did not have CO >10 ppm at any of these visits during this time frame.
Time Frame Week 9 through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all participants as the primary participant population for efficacy analyses in this study and was defined as all participants who had received ≥1 dose, including partial doses, of randomized study drug.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Participants received 0.5 mg per day of varenicline on Days 1 to 3, 1.0 mg per day on Days 4 to 7, and 2.0 mg per day (1.0 mg twice daily, ie, 2 x 0.5 mg tablets in the morning and 2 x 0.5 mg tablets in the evening) from Weeks 1 to 12.
Participants received 1 tablet per day of placebo from Days 1 to 3, which was titrated up to 2 tablets per day from Days 4 to 7, and then to 4 tablets per day (2 tablets in the morning and 2 tablets in the evening) from Week 1 to Week 12.
Overall Number of Participants Analyzed 249 245
Measure Type: Number
Unit of Measure: Percentage of participants
28.9 7.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The statistical test was two-sided and at a 0.05 level of significance. No adjustment was made for the analysis of multiple secondary endpoints.
Method Regression, Logistic
Comments The analysis model included main effect of treatment and pooled center.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.83
Confidence Interval (2-Sided) 95%
3.25 to 10.44
Estimation Comments [Not Specified]
4.Secondary Outcome
Title 7-day Point Prevalence (PP) of Abstinence at Weeks 12, 24, and 52
Hide Description The secondary endpoint of 7-day point prevalence of smoking cessation was determined by evaluating a participant's cigarette smoking status, and other nicotine (and/or other tobacco) use, based on the "last 7 days" questions in the Nicotine Use Inventory. Additionally, a participant was not considered a responder if the expired CO was >10 ppm at the time point being summarized. Participants were considered responders independently at each visit.
Time Frame Weeks 12, 24 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all participants as the primary participant population for efficacy analyses in this study and was defined as all participants who had received ≥1 dose, including partial doses, of randomized study drug.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Participants received 0.5 mg per day of varenicline on Days 1 to 3, 1.0 mg per day on Days 4 to 7, and 2.0 mg per day (1.0 mg twice daily, ie, 2 x 0.5 mg tablets in the morning and 2 x 0.5 mg tablets in the evening) from Weeks 1 to 12.
Participants received 1 tablet per day of placebo from Days 1 to 3, which was titrated up to 2 tablets per day from Days 4 to 7, and then to 4 tablets per day (2 tablets in the morning and 2 tablets in the evening) from Week 1 to Week 12.
Overall Number of Participants Analyzed 249 245
Measure Type: Number
Unit of Measure: Percentage of participants
Week 12 53.0 14.7
Week 24 32.9 15.5
Week 52 28.9 12.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Week 12 assessment
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The statistical test was two-sided and at a 0.05 level of significance. No adjustment was made for the analysis of multiple secondary endpoints.
Method Regression, Logistic
Comments The analysis model included main effect of treatment and pooled center.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 7.85
Confidence Interval (2-Sided) 95%
4.92 to 12.51
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Week 24 assessment
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The statistical test was two-sided and at a 0.05 level of significance. No adjustment was made for the analysis of multiple secondary endpoints.
Method Regression, Logistic
Comments The analysis model included main effect of treatment and pooled center.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.94
Confidence Interval (2-Sided) 95%
1.86 to 4.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Week 52 assessment
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The statistical test was two-sided and at a 0.05 level of significance. No adjustment was made for the analysis of multiple secondary endpoints.
Method Regression, Logistic
Comments The analysis model included main effect of treatment and pooled center.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.06
Confidence Interval (2-Sided) 95%
1.88 to 4.97
Estimation Comments [Not Specified]
Time Frame 2 years
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description Participants received 0.5 mg per day of varenicline on Days 1 to 3, 1.0 mg per day on Days 4 to 7, and 2.0 mg per day (1.0 mg twice daily, ie, 2 x 0.5 mg tablets in the morning and 2 x 0.5 mg tablets in the evening) from Weeks 1 to 12. Participants received 1 tablet per day of placebo from Days 1 to 3, which was titrated up to 2 tablets per day from Days 4 to 7, and then to 4 tablets per day (2 tablets in the morning and 2 tablets in the evening) from Week 1 to Week 12.
All-Cause Mortality
Varenicline Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Varenicline Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/249 (2.81%)      4/245 (1.63%)    
Cardiac disorders     
Acute coronary syndrome  1  0/249 (0.00%)  0 1/245 (0.41%)  1
General disorders     
Chest pain  1  1/249 (0.40%)  1 0/245 (0.00%)  0
Immune system disorders     
Allergy to chemicals  1  1/249 (0.40%)  1 0/245 (0.00%)  0
Hypersensitivity  1  1/249 (0.40%)  1 1/245 (0.41%)  1
Infections and infestations     
Pyelonephritis  1  1/249 (0.40%)  1 0/245 (0.00%)  0
Injury, poisoning and procedural complications     
Ankle fracture  1  1/249 (0.40%)  1 0/245 (0.00%)  0
Ligament rupture  1  0/249 (0.00%)  0 1/245 (0.41%)  1
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion  1  1/249 (0.40%)  1 0/245 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Hyperventilation  1  0/249 (0.00%)  0 1/245 (0.41%)  1
Surgical and medical procedures     
Knee arthroplasty  1  1/249 (0.40%)  1 0/245 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Varenicline Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   145/249 (58.23%)      70/245 (28.57%)    
Gastrointestinal disorders     
Constipation  1  13/249 (5.22%)  13 0/245 (0.00%)  0
Diarrhoea  1  15/249 (6.02%)  15 0/245 (0.00%)  0
Nausea  1  66/249 (26.51%)  87 22/245 (8.98%)  24
General disorders     
Fatigue  1  13/249 (5.22%)  14 0/245 (0.00%)  0
Infections and infestations     
Nasopharyngitis  1  19/249 (7.63%)  19 17/245 (6.94%)  17
Upper respiratory tract infection  1  19/249 (7.63%)  21 17/245 (6.94%)  17
Nervous system disorders     
Headache  1  26/249 (10.44%)  34 24/245 (9.80%)  32
Psychiatric disorders     
Abnormal dreams  1  36/249 (14.46%)  39 0/245 (0.00%)  0
Insomnia  1  17/249 (6.83%)  19 0/245 (0.00%)  0
Sleep disorder  1  13/249 (5.22%)  17 0/245 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
One SAE, exposure via semen, was not included under the Adverse Events since this event was considered to be experienced by a non-study participant, who was the study participant's partner. This event was coded as nonserious in the safety database.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01244061    
Other Study ID Numbers: A3051139
First Submitted: November 17, 2010
First Posted: November 19, 2010
Results First Submitted: October 30, 2013
Results First Posted: June 9, 2014
Last Update Posted: June 9, 2014