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Assessing Neuropsychiatric Symptoms Including Depression, Anxiety, Irritability, and Suicidal Thoughts or Behavior in Subjects Quitting Smoking on Varenicline Tartrate or Placebo

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ClinicalTrials.gov Identifier: NCT00749944
Recruitment Status : Completed
First Posted : September 10, 2008
Results First Posted : August 9, 2010
Last Update Posted : August 31, 2010
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: varenicline
Drug: placebo
Enrollment 110
Recruitment Details  
Pre-assignment Details 857 participants were screened; 110 participants met the criteria for inclusion into the study and were assigned to study treatment
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 (starting on Day 8, the first day of Week 2) Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Period Title: Overall Study
Started 55 55
Completed 50 54
Not Completed 5 1
Reason Not Completed
Lost to Follow-up             2             1
Not specified             1             0
Withdrawal by Subject             2             0
Arm/Group Title Varenicline Placebo Total
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 (starting on Day 8, the first day of Week 2) Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4) Total of all reporting groups
Overall Number of Baseline Participants 55 55 110
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 55 participants 55 participants 110 participants
Between 18 and 44 years 47 47 94
Between 45 and 64 years 7 8 15
>= 65 years 1 0 1
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants 55 participants 110 participants
Female
22
  40.0%
15
  27.3%
37
  33.6%
Male
33
  60.0%
40
  72.7%
73
  66.4%
1.Primary Outcome
Title Change From Baseline in the Profile of Mood States (POMS): Total Mood Disturbance (TMD)
Hide Description POMS TMD were responses to 65 items in 6 subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor, Fatigue, and Confusion), on ‘How you feel right now?’ (scale:0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely). All items were rated in the same direction except for Relaxed and Efficient in the Tension-Anxiety and Confusion subscales. TMD was the sum of the scores of all 6 subscales but weighting Vigor negatively. Summary results (TMD scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): All randomized subjects with at least 1 dose of study drug and at least 1 post-baseline neuropsychiatric evaluation or Minnesota Nicotine Withdrawal Scale (MNWS) obtained; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=55, 55) 0.06  (0.39) -0.66  (0.36)
Period AC (n=55, 55) 0.30  (0.35) -0.17  (0.36)
Period AD (n=55, 55) 0.95  (0.43) 0.03  (0.41)
Period AE (n=55, 55) 0.72  (0.36) 0.22  (0.37)
Period BC (n=53, 54) 0.48  (0.35) 0.91  (0.31)
Period BD (n=53, 54) 1.07  (0.47) 1.04  (0.39)
Period BE (n=54, 54) 0.59  (0.37) 0.96  (0.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
-0.33 to 1.77
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
-0.50 to 1.43
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
-0.27 to 2.11
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
-0.52 to 1.53
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.43
Confidence Interval (2-Sided) 95%
-1.35 to 0.50
Estimation Comments Mixed Models Analysis
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-1.18 to 1.24
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-1.37 to 0.63
Estimation Comments Mixed Models Analysis
2.Primary Outcome
Title Change From Baseline in the Profile of Mood States (POMS): Tension-Anxiety Subscale
Hide Description POMS Tension-Anxiety subscale data were responses to 9 items regarding ‘How you feel right now?’ on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. All items were rated in the same direction except for Relaxed. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=55, 55) 0.30  (0.30) -0.31  (0.25)
Period AC (n=55, 55) 0.15  (0.25) -0.26  (0.21)
Period AD (n=55, 55) 0.31  (0.24) -0.18  (0.27)
Period AE (n=55, 55) 0.01  (0.24) -0.43  (0.20)
Period BC (n=53, 54) -0.01  (0.24) -0.10  (0.25)
Period BD (n=53, 54) 0.06  (0.23) -0.16  (0.29)
Period BE (n=54, 54) -0.35  (0.19) -0.58  (0.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
-0.15 to 1.39
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
-0.24 to 1.07
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
-0.26 to 1.22
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
-0.18 to 1.06
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-0.58 to 0.78
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
-0.48 to 0.92
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
-0.26 to 0.72
Estimation Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in the Profile of Mood States (POMS): Depression-Dejection Subscale
Hide Description POMS Depression-Dejection subscale data responses to 15 items regarding ‘How you feel right now?’ on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=55, 55) 0.38  (0.25) -0.24  (0.18)
Period AC (n=55, 55) 0.50  (0.24) -0.24  (0.13)
Period AD (n=55, 55) 0.56  (0.27) -0.10  (0.16)
Period AE (n=55, 55) 0.44  (0.24) 0.00  (0.19)
Period BC (n=53, 54) 0.51  (0.27) 0.03  (0.13)
Period BD (n=53, 54) 0.49  (0.32) 0.10  (0.14)
Period BE (n=54, 54) 0.32  (0.23) 0.23  (0.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
-0.00 to 1.24
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.18 to 1.29
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.02 to 1.30
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.43
Confidence Interval (2-Sided) 95%
-0.19 to 1.05
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
-0.09 to 1.05
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
-0.28 to 1.06
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.47 to 0.65
Estimation Comments [Not Specified]
4.Primary Outcome
Title Change From Baseline in the Profile of Mood States (POMS): Anger-Hostility Subscale
Hide Description POMS Anger-Hostility subscale data were responses to 12 items regarding ‘How you feel right now?’ on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=55, 55) 0.16  (0.36) -0.69  (0.25)
Period AC (n=55, 55) -0.04  (0.31) -0.89  (0.16)
Period AD (n=55, 55) 0.24  (0.36) -1.00  (0.22)
Period AE (n=55, 55) 0.15  (0.30) -0.68  (0.15)
Period BC (n=53, 54) -0.00  (0.29) -0.52  (0.15)
Period BD (n=53, 54) 0.22  (0.41) -0.65  (0.19)
Period BE (n=54, 54) -0.05  (0.25) -0.43  (0.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
-0.02 to 1.72
Estimation Comments Mixed Models Analysis included baseline, treatment (t; fixed), subject (random), day (d; fixed), and interaction for t-by-d.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.16 to 1.54
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 1.24
Confidence Interval (2-Sided) 95%
0.39 to 2.08
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.14 to 1.52
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
-0.06 to 1.09
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), time (fixed), d (fixed), and interactions for t-by-time, t-by-d, time-by-d and t-by-time-by-d.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.05 to 1.70
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
-0.12 to 0.88
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
5.Primary Outcome
Title Change From Baseline in the Profile of Mood States (POMS): Vigor Subscale
Hide Description POMS Vigor subscale data were responses to 8 items regarding ‘How you feel right now?’ on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=55, 55) 0.16  (0.86) 0.98  (0.75)
Period AC (n=55, 55) -1.34  (0.87) -1.15  (0.75)
Period AD (n=55, 55) -3.30  (1.18) -1.14  (0.97)
Period AE (n=55, 55) -2.80  (1.00) -1.82  (0.91)
Period BC (n=53, 54) -1.49  (0.81) -3.44  (0.83)
Period BD (n=53, 54) -3.22  (1.25) -3.22  (1.11)
Period BE (n=54, 54) -2.28  (1.02) -3.37  (1.04)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.82
Confidence Interval (2-Sided) 95%
-3.07 to 1.43
Estimation Comments Mixed Models Analysis included baseline, treatment (t; fixed), subject (random), day (d; fixed), and interaction for t-by-d.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-2.47 to 2.08
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -2.15
Confidence Interval (2-Sided) 95%
-5.19 to 0.89
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.98
Confidence Interval (2-Sided) 95%
-3.67 to 1.70
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 1.95
Confidence Interval (2-Sided) 95%
-0.36 to 4.26
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), time (fixed), d (fixed), and interactions for t-by-time, t-by-d, time-by-d and t-by-time-by-d.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-3.32 to 3.30
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
-1.80 to 3.97
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
6.Primary Outcome
Title Change From Baseline in the Profile of Mood States (POMS): Fatigue Subscale
Hide Description POMS Fatigue subscale data were responses to 7 items regarding ‘How you feel right now?’ on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. All items were rated in the same direction. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=55, 55) -0.14  (0.29) -0.65  (0.29)
Period AC (n=55, 55) -0.29  (0.28) -0.83  (0.24)
Period AD (n=55, 55) -0.58  (0.26) -0.76  (0.27)
Period AE (n=55, 55) -0.32  (0.27) -0.59  (0.24)
Period BC (n=53, 54) 0.37  (0.32) -0.22  (0.23)
Period BD (n=53, 54) -0.20  (0.29) -0.13  (0.30)
Period BE (n=54, 54) -0.16  (0.29) -0.26  (0.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
-0.29 to 1.32
Estimation Comments Mixed Models Analysis included baseline, treatment (t; fixed), subject (random), day (d; fixed), and interaction for t-by-d.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
-0.17 to 1.25
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.18
Confidence Interval (2-Sided) 95%
-0.55 to 0.92
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.26
Confidence Interval (2-Sided) 95%
-0.46 to 0.99
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
-0.19 to 1.37
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), time (fixed), d (fixed), and interactions for t-by-time, t-by-d, time-by-d and t-by-time-by-d.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.91 to 0.76
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-0.65 to 0.85
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
7.Primary Outcome
Title Change From Baseline in the Profile of Mood States (POMS): Confusion Subscale
Hide Description POMS Confusion subscale data were responses to 7 items regarding ‘How you feel right now?’ on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. All items were rated in the same direction except for Efficient. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=55, 55) 0.14  (0.19) -0.09  (0.12)
Period AC (n=55, 55) 0.03  (0.17) -0.18  (0.10)
Period AD (n=55, 55) 0.10  (0.18) -0.11  (0.13)
Period AE (n=55, 55) -0.01  (0.15) -0.03  (0.13)
Period BC (n=53, 54) 0.02  (0.22) -0.07  (0.11)
Period BD (n=53, 54) 0.07  (0.22) -0.02  (0.15)
Period BE (n=54, 54) -0.14  (0.18) -0.02  (0.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
-0.20 to 0.65
Estimation Comments Mixed Models Analysis included baseline, treatment (t; fixed), subject (random), day (d; fixed), and interaction for t-by-d.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
-0.17 to 0.58
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
-0.23 to 0.65
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.37 to 0.41
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.41 to 0.59
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), time (fixed), d (fixed), and interactions for t-by-time, t-by-d, time-by-d and t-by-time-by-d.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-0.44 to 0.63
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.58 to 0.34
Estimation Comments Mixed Models Analysis included baseline, t (fixed), subject (random), d (fixed), and interaction for t-by-d.
8.Primary Outcome
Title Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS): Total Score
Hide Description The MADRS measures the overall severity of depressive symptoms and is a 10-item checklist. Each item was rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=54, 54) 1.05  (0.37) 0.83  (0.25)
Period AC (n=54, 54) 2.28  (0.35) 1.84  (0.30)
Period AD (n=54, 54) 1.19  (0.29) 1.41  (0.37)
Period AE (n=55, 54) 1.52  (0.21) 1.50  (0.28)
Period BC (n=53, 54) 2.27  (0.50) 1.69  (0.48)
Period BD (n=53, 54) -0.10  (0.35) 0.33  (0.53)
Period BE (n=53, 54) 0.40  (0.24) 0.49  (0.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
-0.66 to 1.10
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
-0.46 to 1.35
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.22
Confidence Interval (2-Sided) 95%
-1.16 to 0.71
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.68 to 0.73
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
-0.79 to 1.96
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.43
Confidence Interval (2-Sided) 95%
-1.69 to 0.82
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.86 to 0.68
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
9.Primary Outcome
Title Change From Baseline in the Hamilton Anxiety Scale (HAM-A): Total Score
Hide Description HAM-A measures treatment-related changes in generalized anxiety symptoms and is a 14-item questionnaire. Each item was scored from 0 (not present) to 4 (very severe) and a lower score indicated less affected. Total scores ranged from 0 (not affected) to 56 (very severely affected).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=54, 54) 1.01  (0.32) 0.75  (0.27)
Period AC (n=54, 54) 2.69  (0.37) 2.16  (0.28)
Period AD (n=54, 54) 1.95  (0.41) 1.86  (0.42)
Period AE (n=55, 54) 1.75  (0.28) 1.61  (0.26)
Period BC (n=53, 54) 3.15  (0.56) 2.65  (0.47)
Period BD (n=53, 54) 0.74  (0.47) 0.77  (0.62)
Period BE (n=53, 54) 0.73  (0.30) 0.81  (0.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.27
Confidence Interval (2-Sided) 95%
-0.55 to 1.08
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
-0.39 to 1.46
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-1.08 to 1.25
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
-0.62 to 0.90
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
-0.94 to 1.95
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-1.57 to 1.51
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.91 to 0.75
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
10.Primary Outcome
Title Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Aggression Total Score
Hide Description The OAS-m contains 3 scales: Aggression (Questions [Q]1 to 4), Irritability (Q5 to 6), and Suicidality (Q7 to 7b). Aggression total score was calculated by summing the weighted scores in Q1 to 4. Scores for each question ranged from 0 (no events) to 5 (very severe events). Total scores ranged from 0 (no aggression) to any number with no upper limit depending on the frequency of agressive behaviour in a week.
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=54, 54) 0.13  (0.27) 0.48  (0.66)
Period AC (n=54, 54) 0.82  (0.37) 0.72  (0.39)
Period AD (n=54, 54) 2.24  (1.75) 0.75  (0.34)
Period AE (n=55, 54) 1.27  (0.70) 0.77  (0.48)
Period BC (n=53, 54) 0.83  (0.63) 0.22  (0.38)
Period BD (n=53, 54) 1.94  (2.27) -0.15  (0.44)
Period BE (n=53, 54) 1.00  (0.88) -0.13  (0.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-1.76 to 1.06
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
-0.96 to 1.17
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 1.49
Confidence Interval (2-Sided) 95%
-1.94 to 4.91
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
-1.18 to 2.18
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
-0.85 to 2.07
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 2.10
Confidence Interval (2-Sided) 95%
-2.60 to 6.79
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
-0.70 to 2.96
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
11.Primary Outcome
Title Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Irritability Total Score
Hide Description The OAS-m contains 3 scales: Aggression (Questions [Q]1 to 4), Irritability (Q5 to 6), and Suicidality (Q7 to 7b). Irritability total score was calculated by summing the items in Q5 to 6. Scores for each question ranged from 0 (not at all) to 5 (extreme). Total scores ranged from 0 (no irritability) to 10 (extreme irritability).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=54, 54) 0.01  (0.10) 0.01  (0.09)
Period AC (n=54, 54) 0.43  (0.10) 0.41  (0.09)
Period AD (n=54, 54) 0.46  (0.17) 0.35  (0.17)
Period AE (n=55, 54) 0.32  (0.10) 0.24  (0.08)
Period BC (n=53, 54) 0.82  (0.16) 0.78  (0.16)
Period BD (n=53, 54) 0.53  (0.19) 0.35  (0.24)
Period BE (n=53, 54) 0.38  (0.11) 0.25  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.26 to 0.27
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.25 to 0.29
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-0.37 to 0.58
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.17 to 0.34
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.40 to 0.48
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-0.44 to 0.78
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-0.14 to 0.40
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
12.Primary Outcome
Title Change From Baseline in the Overt Aggression Scale (Modified) (OAS-m): Suicidality Total Score
Hide Description The OAS-m contains 3 scales: Aggression (Questions [Q]1 to 4), Irritability (Q5 to 6), and Suicidality (Q7 to 7b). Suicidality total score was calculated by summing the items Q7 to 7b. Scores for Q7 ranged from 0 (none) to 6 (very extreme) and scores for Q7a to 7b ranged from 0 (none) to 5 (extreme). Total scores ranged from 0 (no suicidal tendency) to 16 (extreme/very extreme suicidal tendency).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
No change from baseline analysis was performed on the OAS-m Suicidality total score as the majority of observations were recorded as 0.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Primary Outcome
Title Change From Baseline in the Social Dysfunction and Aggression Scale (SDAS): Total Score
Hide Description The SDAS contains 11 items with 5 possible responses: 0=not present, 1=doubtful or very mild, 2=mild to moderate, 3=severe, and 4=extremely severe. The SDAS was collected 3 times a day during the inpatient abstinence period (BC). Total scores ranged from 0 (not present) to 44 (extremely severe).
Time Frame Baseline B (Week 2) to Week 4 (Period BC)
Hide Outcome Measure Data
Hide Analysis Population Description
No change from baseline analysis was performed on the SDAS total score as the majority of observations were recorded as 0.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
14.Primary Outcome
Title Change From Baseline in the Barratt Impulsiveness Scale – Version 11 (BIS-11): Total Score
Hide Description The BIS-11 is a 30-item self-report questionnaire designed to assess general impulsiveness taking into account the multifactorial nature of the construct. Possible responses to each item were: 1=rarely/never, 2=occasionally, 3=often, and 4=almost always/always. Scores of Items 1, 7, 8, 9, 10, 12, 13, 15, 20, 29 and 30 were reversed when calculating the total score. Total score ranged from 30 (less impulsive) to 120 (more impulsive).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=54, 54) 0.34  (0.56) -0.07  (0.50)
Period AC (n=54, 54) 0.45  (0.62) 0.37  (0.53)
Period AD (n=54, 54) 1.34  (0.74) 1.28  (1.03)
Period AE (n=55, 54) 1.19  (0.69) 0.90  (0.64)
Period BC (n=53, 54) 0.04  (0.49) 0.97  (0.43)
Period BD (n=53, 54) 1.07  (0.49) 1.81  (0.92)
Period BE (n=53, 54) 0.85  (0.52) 1.28  (0.44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
-1.09 to 1.90
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-1.54 to 1.71
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-2.47 to 2.60
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
-1.57 to 2.15
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.94
Confidence Interval (2-Sided) 95%
-2.23 to 0.36
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.74
Confidence Interval (2-Sided) 95%
-2.81 to 1.33
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.43
Confidence Interval (2-Sided) 95%
-1.78 to 0.92
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
15.Secondary Outcome
Title Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Total Score
Hide Description The MNWS total score contains 9 items (urge to smoke; depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating; restlessness; increased appetite; difficulty going to sleep; difficulty staying asleep). Each item was rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Total scores were the average score for all 9 items and ranged from 0 (no withdrawal symptoms) to 4 (extreme withdrawal symptoms).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=54, 54) 0.13  (0.04) 0.05  (0.04)
Period AC (n=54, 54) 0.10  (0.03) 0.11  (0.03)
Period AD (n=54, 54) 0.07  (0.03) 0.05  (0.03)
Period AE (n=55, 54) -0.01  (0.02) 0.04  (0.03)
Period BC (n=53, 54) -0.04  (0.04) 0.10  (0.06)
Period BD (n=53, 54) -0.08  (0.03) 0.02  (0.04)
Period BE (n=53, 54) -0.15  (0.01) -0.05  (0.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.04 to 0.19
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.11 to 0.08
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.06 to 0.09
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.11 to 0.02
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.27 to -0.01
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-0.21 to 0.01
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-0.17 to -0.03
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
16.Secondary Outcome
Title Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Negative Affect Domain Subscale
Hide Description The MNWS negative affect domain subscale contains 4 items (depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating). Each item was rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores were the average from all 4 items and ranged from 0 (no negative affect) to 4 (extreme negative affect).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=54, 54) 0.06  (0.03) 0.01  (0.02)
Period AC (n=54, 54) 0.10  (0.03) 0.09  (0.03)
Period AD (n=54, 54) 0.07  (0.03) 0.03  (0.03)
Period AE (n=55, 54) 0.05  (0.02) 0.07  (0.03)
Period BC (n=53, 54) 0.07  (0.05) 0.15  (0.05)
Period BD (n=53, 54) -0.01  (0.03) 0.02  (0.05)
Period BE (n=53, 54) -0.02  (0.02) 0.03  (0.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.03 to 0.12
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.08 to 0.09
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.04 to 0.11
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.08 to 0.05
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.22 to 0.06
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.14 to 0.09
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.11 to 0.02
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
17.Secondary Outcome
Title Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Insomnia Domain Subscale
Hide Description The MNWS insomnia domain subscale contains 2 items (difficulty going to sleep; difficulty staying asleep). Each item was rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores were the average of the 2 items and ranged from 0 (no insomnia) to 4 (extreme insomnia).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=54, 54) 0.07  (0.04) 0.12  (0.06)
Period AC (n=54, 54) 0.15  (0.04) 0.17  (0.05)
Period AD (n=54, 54) 0.04  (0.03) 0.10  (0.04)
Period AE (n=55, 54) 0.06  (0.02) 0.13  (0.06)
Period BC (n=53, 54) 0.14  (0.07) 0.09  (0.08)
Period BD (n=53, 54) -0.04  (0.05) 0.01  (0.06)
Period BE (n=53, 54) -0.06  (0.02) -0.01  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.20 to 0.09
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.15 to 0.12
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.15 to 0.04
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.20 to 0.04
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.17 to 0.27
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.21 to 0.10
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.17 to 0.07
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
18.Secondary Outcome
Title Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Urge to Smoke Subscale
Hide Description The MNWS urge to smoke subscale contains 1 item (urge to smoke) rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores ranged from 0 (no urge to smoke) to 4 (extreme urge to smoke).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=54, 54) -0.60  (0.10) -0.29  (0.09)
Period AC (n=54, 54) -1.40  (0.09) -0.97  (0.09)
Period AD (n=54, 54) -2.17  (0.12) -2.03  (0.12)
Period AE (n=55, 54) -1.90  (0.09) -1.55  (0.09)
Period BC (n=53, 54) -1.59  (0.12) -1.14  (0.14)
Period BD (n=53, 54) -1.66  (0.14) -1.58  (0.15)
Period BE (n=53, 54) -1.56  (0.10) -1.29  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.58 to -0.02
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline
Estimated Value -0.44
Confidence Interval (2-Sided) 95%
-0.69 to -0.19
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.47 to 0.20
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-0.61 to -0.09
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-0.83 to -0.07
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.50 to 0.34
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.57 to 0.02
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
19.Secondary Outcome
Title Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Restlessness Subscale
Hide Description The MNWS restlessness subscale contains 1 item (restlessness) rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores ranged from 0 (no restlessness) to 4 (extreme restlessness).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=54, 54) 0.06  (0.04) 0.08  (0.04)
Period AC (n=54, 54) 0.10  (0.04) 0.11  (0.04)
Period AD (n=54, 54) 0.09  (0.04) 0.04  (0.03)
Period AE (n=55, 54) 0.03  (0.02) 0.05  (0.03)
Period BC (n=53, 54) 0.07  (0.05) 0.08  (0.05)
Period BD (n=53, 54) 0.03  (0.02) -0.03  (0.01)
Period BE (n=53, 54) -0.04  (0.02) -0.03  (0.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.12 to 0.08
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.12 to 0.08
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.04 to 0.14
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.07 to 0.04
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.15 to 0.13
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
0.01 to 0.10
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.08 to 0.04
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
20.Secondary Outcome
Title Change From Baseline in the Minnesota Nicotine Withdrawal Scale (MNWS): Increased Appetite Subscale
Hide Description The MNWS increased appetite subscale contains 1 item (increased appetite) rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores ranged from 0 (no increased appetite) to 4 (extreme increased appetite).
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Period AB (n=54, 54) 0.14  (0.07) 0.02  (0.05)
Period AC (n=54, 54) 0.10  (0.05) 0.12  (0.06)
Period AD (n=54, 54) 0.11  (0.09) 0.15  (0.09)
Period AE (n=55, 54) -0.00  (0.05) 0.04  (0.06)
Period BC (n=53, 54) -0.03  (0.07) 0.16  (0.08)
Period BD (n=53, 54) -0.01  (0.09) 0.15  (0.10)
Period BE (n=53, 54) -0.10  (0.04) -0.03  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
-0.05 to 0.28
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.19 to 0.14
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.29 to 0.22
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.20 to 0.13
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.40 to 0.01
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BD: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.42 to 0.10
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BE: Difference varenicline versus placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference (change from baseline)
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.22 to 008
Estimation Comments Mixed Models Analysis included baseline, treatment (fixed effect), subject (random effect), week (fixed effect), and interaction of treatment-by-week.
21.Secondary Outcome
Title Number of Participants Exceeding Thresholds for the Profile of Mood States (POMS): Total Score
Hide Description POMS total mood disturbance (TMD) summary results were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance). Participants exceeding the threshold had an increase from baseline of 1 standard deviation of the TMD baseline T-score plus 1 or more.
Time Frame Baseline A (Week 0) to Week 2 (Period AB), Week 4 (Period AC), Week 12 or relapse (Period AD), and Week 12 (Period AE). Baseline B (Week 2) to Week 4 (Period BC), Week 12 or relapse (Period BD), and Week 12 (Period BE).
Hide Outcome Measure Data
Hide Analysis Population Description
FAS; (n)=number of subjects with data for analysis for varenicline and placebo, respectively.
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 (starting on Day 8, the first day of Week 2)
Placebo administered QD for the first 3 days followed by placebo administered BID for the remaining 11 weeks and 4 days (starting on Day 4)
Overall Number of Participants Analyzed 55 55
Measure Type: Number
Unit of Measure: participants
Period AB (n=55, 55) 14 11
Period AC (n=55, 55) 32 35
Period AD (n=55, 55) 37 38
Period AE (n=55, 55) 38 38
Period BC (n=53, 54) 27 33
Period BD (n=53, 54) 30 36
Period BE (n=54, 54) 32 38
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments There was no hypothesis testing or power calculation in this study. Period AB: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
0.6 to 3.3
Estimation Comments Cochran-Mantel-Haenszel
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
0.4 to 1.7
Estimation Comments Cochran-Mantel-Haenszel
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AD: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
0.4 to 2.1
Estimation Comments Cochran-Mantel-Haenszel
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period AE: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
0.4 to 2.2
Estimation Comments Cochran-Mantel-Haenszel
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
Comments Period BC: Difference varenicline versus placebo. Subjects' worst scores observed in a given period were compared with the threshold criterion for analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
0.3 to 1.4
Estimation Comments Cochran-Mantel-Haenszel
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo