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Trial record 6 of 8 for:    smoking cessation | ( Map: Mexico )

Randomized Study Comparing the Efficacy and Safety of Varenicline Tartrate to Placebo in Smoking Cessation When Subjects Are Allowed to Set Their Own Quit Date

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ClinicalTrials.gov Identifier: NCT00691483
Recruitment Status : Completed
First Posted : June 5, 2008
Results First Posted : September 30, 2010
Last Update Posted : November 20, 2015
Sponsor:
Information provided by:
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Smoking Cessation
Interventions Drug: placebo
Drug: varenicline
Enrollment 659
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description Varenicline 0.5 milligrams (mg) administered once daily (QD) for the first 3 days followed by 0.5 mg varenicline twice daily (BID) for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24. Placebo matched to varenicline.
Period Title: Overall Study
Started 493 166
Received Treatment 486 165
Completed 425 [1] 141
Not Completed 68 25
Reason Not Completed
Adverse Event             14             6
Lost to Follow-up             17             10
Withdrawal by Subject             24             7
Other known cause             6             1
Randomized by not treated             7             1
[1]
Completed refers to completion of the study.
Arm/Group Title Varenicline Placebo Total
Hide Arm/Group Description Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24. Placebo matched to varenicline. Total of all reporting groups
Overall Number of Baseline Participants 486 165 651
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 486 participants 165 participants 651 participants
Between 18 and 44 years 248 93 341
Between 45 and 64 years 209 64 273
>= 65 years 29 8 37
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 486 participants 165 participants 651 participants
Female
193
  39.7%
66
  40.0%
259
  39.8%
Male
293
  60.3%
99
  60.0%
392
  60.2%
1.Primary Outcome
Title Percentage of Participants With 4-week Continuous Abstinence (CA)
Hide Description The percentage of participants who reported complete abstinence from cigarette smoking and other nicotine use (on the Nicotine Use Inventory) and who did not have carbon monoxide (CO) >10 parts per million (ppm) at any visits Week 9 through Week 12. A participant was considered a responder if they met the following criterion: said they had not smoked or used nicotine products ‘since the last visit’ and did not have CO >10 ppm.
Time Frame Week 9 through Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): took at least 1 dose, including partial doses, of randomized study drug. Missing CO measurements imputed as =<10 ppm. Missing visit(s) imputed based on next available visit. Subjects who discontinued study and were lost to follow up were assumed smokers. Missing data not imputed from other weekly interview questions.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.
Placebo matched to varenicline.
Overall Number of Participants Analyzed 486 165
Measure Type: Number
Unit of Measure: Percentage of participants
53.9 19.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Sample size to be based on a continuity-corrected Chi-square 2-sided test with a 0.05 significance level and a 3:1 randomization ratio of Varenicline to placebo. 652 subjects to provide >=90% power to detect Varenicline versus placebo differences in primary and key secondary efficacy endpoints (assuming placebo CA rates of 0.24 [Weeks 9-12] and 0.18 [Weeks 9-24] and Varenicline CA rates of 0.46 [Weeks 9-12] and 0.31 [Weeks 9-24]) (odds ratio of >=2.67 [Weeks 9-12] and >=2.10 [Weeks 9-24]).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments To preserve the type I family-wise error rate of 0.05, a step-down procedure to be used for the analysis of CA for Week 9 through Week 12 and the CA for Week 9 through Week 24.
Method Regression, Logistic
Comments Model to include the main effects of treatment and pooled center.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.03
Confidence Interval (2-Sided) 95%
3.80 to 9.56
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Continuous Abstinence (CA) From Smoking Weeks 9-24
Time Frame Week 9 through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Missing CO measurements imputed as =<10 ppm. Missing visit(s) imputed based on next available visit. Subjects who discontinued study and were lost to follow up were assumed smokers. Missing data not imputed from other weekly interview questions.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.
Placebo matched to varenicline.
Overall Number of Participants Analyzed 486 165
Measure Type: Number
Unit of Measure: Percentage of participants
35.2 12.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Sample size to be based on a continuity-corrected Chi-square 2-sided test with a 0.05 significance level and a 3:1 randomization ratio of Varenicline to placebo. 652 subjects to provide >=90% power to detect Varenicline versus placebo differences in primary and key secondary efficacy endpoints (assuming placebo CA rates of 0.24 [Weeks 9-12] and 0.18 [Weeks 9-24] and Varenicline CA rates of 0.46 [Weeks 9-12] and 0.31 [Weeks 9-24]) (odds ratio of >=2.67 [Weeks 9-12] and >=2.10 [Weeks 9-24]).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments To preserve the type I family-wise error rate of 0.05, a step-down procedure to be used for the analysis of CA for Week 9 through Week 12 and the CA for Week 9 through Week 24.
Method Regression, Logistic
Comments Model to include the main effects of treatment and pooled center.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.45
Confidence Interval (2-Sided) 95%
2.62 to 7.55
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Long Term Quit Through Week 24
Hide Description Responder for the primary endpoint of CA from Week 9 through Week 12 and who had no more than 6 days of smoking during the non-treatment phase of the study. For Weeks 13, 16, 20, and 24, long term quit was determined by CO-confirmed in-clinic visit.
Time Frame Week 9 through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. If the number of days smoked was missing for a subject visit, the CA responder status of the subject at that visit determined the imputation.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.
Placebo matched to varenicline.
Overall Number of Participants Analyzed 486 165
Measure Type: Number
Unit of Measure: Percentage of participants
40.7 14.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Statistical testing to be 2-sided and use a 0.05 level of significance. Confidence intervals to have a 95% confidence level. Statistical significance to be declared unless a p-value >0.05 was obtained.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A 0.05 level of significance without adjustment for multiplicity.
Method Regression, Logistic
Comments Model to include the main effects of treatment and pooled center.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.91
Confidence Interval (2-Sided) 95%
2.96 to 8.13
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With 7-day Point Prevalence of Nonsmoking (Smoking Cessation)
Hide Description Percentage of participants with complete abstinence from cigarette smoking or other nicotine-containing (treatment phase) or tobacco (non-treatment phase) products use for the 7 days prior to Week 12 and Week 24, respectively, who did not have CO >10 ppm at any visits. CO-confirmed in-clinic visit.
Time Frame Week 12 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Missing weekly interview questions of whether the subject had "smoked in the last 7 days" were not imputed; missing CO was imputed as =<10 ppm.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.
Placebo matched to varenicline.
Overall Number of Participants Analyzed 486 165
Measure Type: Number
Unit of Measure: Percentage of participants
Week 12 59.5 24.2
Week 24 43.0 17.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Week 12. Statistical testing to be 2-sided and use a 0.05 level of significance. Confidence intervals to have a 95% confidence level. Statistical significance to be declared unless a p-value >0.05 was obtained.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A 0.05 level of significance without adjustment for multiplicity.
Method Regression, Logistic
Comments Model to include the main effects of treatment and pooled center.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.66
Confidence Interval (2-Sided) 95%
3.66 to 8.75
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Week 24. Statistical testing to be 2-sided and use a 0.05 level of significance. Confidence intervals to have a 95% confidence level. Statistical significance to be declared unless a p-value >0.05 was obtained.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A 0.05 level of significance without adjustment for multiplicity.
Method Regression, Logistic
Comments Model to include the main effects of treatment and pooled center.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.12
Confidence Interval (2-Sided) 95%
2.58 to 6.58
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With 4-week Point Prevalence of Nonsmoking
Hide Description Percentage of participants with complete abstinence from cigarette smoking or use of tobacco products for the 4 weeks prior to Week 24 who did not have CO >10 ppm at any visits.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Missing inventory interview questions of whether the subject had "smoked or used any other tobacco products" in the last 4 weeks were not imputed. Missing CO was imputed as =<10 ppm.
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.
Placebo matched to varenicline.
Overall Number of Participants Analyzed 486 165
Measure Type: Number
Unit of Measure: Percentage of participants
42.0 17.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Statistical testing to be 2-sided and use a 0.05 level of significance. Confidence intervals to have a 95% confidence level. Statistical significance to be declared unless a p-value >0.05 was obtained.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A 0.05 level of significance without adjustment for multiplicity.
Method Regression, Logistic
Comments Model to include the main effects of treatment and pooled center.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.14
Confidence Interval (2-Sided) 95%
2.58 to 6.67
Estimation Comments [Not Specified]
6.Other Pre-specified Outcome
Title Change From Baseline in Fagerström Test for Nicotine Dependence (FTND) to Day of First Quit Attempt (FQA) Through Week 5 by Smoking Status at Weeks 9-12
Hide Description Change in nicotine dependence from baseline to the date of the FQA within the first 5 weeks. FTND was designed to provide an ordinal measure of nicotine dependence related to cigarette smoking. It contains items that evaluate the quantity of cigarette consumption, the compulsion to use, and dependence. The FTND contains 4 yes-no and 2 multiple choice questions and can be used in a self-report format. The items on FTND are scored 0 to 3 for multiple choice items, the items are summed to yield a total score of 0-10 (0=minimum nicotine dependence; 10=maximum nicotine dependence).
Time Frame Baseline through Week 5
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants analyzed = participants with FQA through Week 5, excluding 157 participants for whom FTND was not done at the time of FQA (1 participant also had inconsistent FQA date with first dosing date). Analysis done by smoking status at Week 12 (Responder for the primary endpoint of CA Weeks 9-12).
Arm/Group Title Varenicline Placebo
Hide Arm/Group Description:
Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24.
Placebo matched to varenicline.
Overall Number of Participants Analyzed 276 79
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Responders -2.3  (2.53) -1.8  (1.95)
Non-Responders -2.5  (2.55) -1.8  (2.13)
Time Frame [Not Specified]
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 Varenicline 0.5 mg administered QD for the first 3 days followed by 0.5 mg varenicline BID for the next 4 days, then 1 mg varenicline BID for the remaining 11 weeks (treatment phase). Blinded study drug was discontinued at the Week 12 visit and was followed by a non-treatment phase to Week 24. Placebo matched to varenicline.
All-Cause Mortality
Varenicline Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Varenicline Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   6/486 (1.23%)   1/165 (0.61%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrustion  1  2/486 (0.41%)  0/165 (0.00%) 
Nervous system disorders     
Carotid artery stenosis  1  1/486 (0.21%)  0/165 (0.00%) 
Syncope  1  1/486 (0.21%)  0/165 (0.00%) 
Psychiatric disorders     
Suicidal ideation  1  0/486 (0.00%)  1/165 (0.61%) 
Renal and urinary disorders     
Calculus ureteric  1  1/486 (0.21%)  0/165 (0.00%) 
Pyelocaliectasis  1  1/486 (0.21%)  0/165 (0.00%) 
Ureteric obstruction  1  1/486 (0.21%)  0/165 (0.00%) 
Vascular disorders     
Peripheral arterial occlusive disease  1  1/486 (0.21%)  0/165 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Varenicline Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   297/486 (61.11%)   79/165 (47.88%) 
Gastrointestinal disorders     
Abdominal pain  1  6/486 (1.23%)  4/165 (2.42%) 
Abdominal pain upper  1  14/486 (2.88%)  0/165 (0.00%) 
Constipation  1  23/486 (4.73%)  5/165 (3.03%) 
Diarrhoea  1  11/486 (2.26%)  3/165 (1.82%) 
Dry mouth  1  18/486 (3.70%)  3/165 (1.82%) 
Dyspepsia  1  13/486 (2.67%)  2/165 (1.21%) 
Nausea  1  142/486 (29.22%)  15/165 (9.09%) 
Toothache  1  6/486 (1.23%)  6/165 (3.64%) 
Vomiting  1  19/486 (3.91%)  1/165 (0.61%) 
General disorders     
Fatigue  1  23/486 (4.73%)  3/165 (1.82%) 
Irritability  1  14/486 (2.88%)  6/165 (3.64%) 
Infections and infestations     
Bronchitis  1  12/486 (2.47%)  1/165 (0.61%) 
Influenza  1  19/486 (3.91%)  6/165 (3.64%) 
Nasopharyngitis  1  34/486 (7.00%)  14/165 (8.48%) 
Rhinitis  1  7/486 (1.44%)  4/165 (2.42%) 
Sinusitis  1  8/486 (1.65%)  4/165 (2.42%) 
Upper respiratory tract infection  1  13/486 (2.67%)  4/165 (2.42%) 
Investigations     
Weight increased  1  17/486 (3.50%)  3/165 (1.82%) 
Metabolism and nutrition disorders     
Increased appetite  1  11/486 (2.26%)  5/165 (3.03%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  6/486 (1.23%)  4/165 (2.42%) 
Back pain  1  15/486 (3.09%)  4/165 (2.42%) 
Nervous system disorders     
Headache  1  55/486 (11.32%)  20/165 (12.12%) 
Disturbance in attention  1  11/486 (2.26%)  6/165 (3.64%) 
Dizziness  1  8/486 (1.65%)  8/165 (4.85%) 
Somnolence  1  11/486 (2.26%)  2/165 (1.21%) 
Psychiatric disorders     
Anxiety  1  4/486 (0.82%)  5/165 (3.03%) 
Depressed mood  1  5/486 (1.03%)  5/165 (3.03%) 
Depression  1  4/486 (0.82%)  5/165 (3.03%) 
Abnormal dreams  1  61/486 (12.55%)  5/165 (3.03%) 
Insomnia  1  43/486 (8.85%)  6/165 (3.64%) 
Sleep disorder  1  20/486 (4.12%)  6/165 (3.64%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  14/486 (2.88%)  5/165 (3.03%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
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: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00691483     History of Changes
Other Study ID Numbers: A3051095
First Submitted: June 3, 2008
First Posted: June 5, 2008
Results First Submitted: September 9, 2010
Results First Posted: September 30, 2010
Last Update Posted: November 20, 2015