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Safety And Efficacy Of 12 Weeks Of Varenicline For Smoking Cessation In Smokers With Depression

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT01078298
Collaborator
(none)
525
Enrollment
41
Locations
2
Arms
27
Duration (Months)
12.8
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients with depression tend to have a higher prevalence of smoking as well as increased severity of nicotine dependence. Phase 2 and Phase 3 varenicline clinical trials that demonstrated its efficacy and tolerability have not included subjects with depression. This smoking cessation study focuses on the depressed population and will assess the efficacy and safety of varenicline.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
525 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 4 12-week, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating The Safety And Efficacy Of Varenicline Tartrate (CP-526,555) 1mg BID For Smoking Cessation In Subjects With Depression
Study Start Date :
Mar 1, 2010
Actual Primary Completion Date :
Jun 1, 2012
Actual Study Completion Date :
Jun 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: varenicline

Drug: varenicline
varenicline tablets titrated to 1 mg BID during 1st week and then 1 mg BID for 11 weeks
Other Names:
  • Champix/Chantix

    		•
    Placebo Comparator: placebo

    placebo

    Drug: placebo
    placebo tablets matched in appearance and dosage to varenicline tablets

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With a Four-Week Continuous Quit Rate (CQR) [Week 9 through Week 12]

      Percentage of participants who reported no use of nicotine-containing products by answering "No" to the nicotine use inventory (NUI) questions: 'Has the participant smoked cigarettes' and 'Has the participant used other nicotine-containing products' in the last 7 days (Week 9) or since last study visit (Week 9 through 12) confirmed by a measurement of an end-expiratory exhaled carbon monoxide (CO) measurement less than or equal to 10 parts per million (ppm).

    Secondary Outcome Measures

    1. Percentage of Participants With Continuous Abstinence Rate (CAR) [Week 9 through Week 24, Week 9 through Week 52]

      Percentage of participants who remained abstinent from the period defined as start of the primary endpoint (Week 9) through Week 24 and the end of follow-up (Week 52) by reporting no use of nicotine-containing products confirmed by a measurement of an end-expiratory exhaled CO measurement less than or equal to 10 ppm.

    2. Number of Participants With 7-day Point Prevalence (PP) of Abstinence [Weeks 12, 24, 52]

      Number of participants reporting no use of nicotine-containing products in the last 7 days confirmed by a measurement of an end-expiratory exhaled CO measurement less than or equal to 10 ppm.

    3. Number of Participants With 4-Week Point Prevalence (PP) of Abstinence [Week 52]

      Number of participants at Week 52 visit reporting no smoking and no use of other tobacco products in the last 4 weeks confirmed by a measurement of an end-expiratory exhaled CO measurement less than or equal to 10 ppm.

    Other Outcome Measures

    1. Number of Participants With Adverse Events (Including Solicited Neuropsychiatric Adverse Events) [Baseline up to Week 16]

      Adverse Event (AE):any untoward medical occurrence attributed to study drug in participant who received study drug.SAE:AE causing:death;initial/prolonged inpatient hospitalization;life-threatening experience(immediate risk of dying);persistent/significant disability/incapacity;congenital anomaly.Solicited AEs collected by semi-structured neuropsychiatric AEs interview inquiring about AEs:delusions,hallucinations,paranoia,psychosis,mania,panic,agitation,hostility,aggression,homicidal ideation. If participant had positive response,investigator determined if it met AE criteria.

    2. Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) [Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16, 24, 32, 40, 52]

      CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement from baseline is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected

    3. Number of Participants With Clinical Global Impression - Severity (CGI-S) Score [Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16, 24, 32, 40, 52]

      CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected

    4. Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score [Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16]

      Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Change: mean score at observation minus mean score at baseline.

    5. Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score [Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16]

      HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected. Change: mean score at observation minus mean score at baseline.

    6. Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score [Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16]

      The BIS-11 is a self-administered 30 items questionnaire to assess measure of impulsivity. Items are scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). Total score range from 30 to 120. Barratt suggested that a total score of greater than or equal to 75 could indicate an impulse-control disorder, whereas a total score in the range of 70 to 75 could indicate pathological impulsivity.

    7. Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) [Baseline, Week 1 up to 30 days after Week 12 (treatment-emergent [TE]), thereafter up to Week 52 (follow-up [FU])]

      C-SSRS assessed if participant experienced following: completed suicide (1), suicide attempt (2)(response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3)("Yes" on "preparatory acts or behavior"), suicidal ideation (4)("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Male or female cigarette smokers, 18-75 years, motivated to stop smoking and considered suitable for a smoking cessation attempt

    • Smoked an average of at least 10 cigarettes per day during past year and over past month, and exhaled carbon monoxide (CO) > 10 ppm at screening

    • Current or past diagnosis of MDD without psychotic features, either single or recurrent, using DSM IV TR based on clinical assessment and confirmed by SCID and at least one of the following:

    • On stable antidepressant treatment for MDD (stable dose for at least 2 months)

    • Major depressive episode, using DSM IV TR, in the past 2 years successfully treated

    Exclusion Criteria:

    • Current or past diagnosis of dementia, schizophrenia, schizoaffective disorder, or other psychotic disorder, bipolar I disorder, bipolar II disorder.

    • Subjects with antisocial, schizotypal, or any other personality disorder severe enough to compromise the subject's ability to comply with the study requirements..

    • Current use of either bupropion or nortryptiline.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Collaborative Neuroscience Network, Inc. Garden Grove California United States 92845
    2 California Neuroscience Research Medical Group, Inc Sherman Oaks California United States 91403
    3 Behavioral Health and Wellness Program, University of Colorado Denver Aurora Colorado United States 80045
    4 Comprehensive Psychiatric Care Norwich Connecticut United States 06360
    5 Emerald Coast Mood & Memory, PA Fort Walton Beach Florida United States 32547
    6 Clinical Neuroscience Solutions Incorporated Jacksonville Florida United States 32216
    7 Clinical Neuroscience Solutions Incorporated Orlando Florida United States 32806
    8 Vince and Associates Clinical Research Overland Park Kansas United States 66212
    9 Vince and Associates Clinical Research Overland Kansas United States 66211
    10 Heartland Research Associates, LLC Wichita Kansas United States 67207
    11 NorthCoast Clinical Trials Inc. Beachwood Ohio United States 44122
    12 University of Cincinnati Cincinnati Ohio United States 45219
    13 University of Cincinnati Cincinnati Ohio United States 45237
    14 CRI Worldwide LLC Philadelphia Pennsylvania United States 19139
    15 Clinical Trials of Memphis Bartlett Tennessee United States 38134
    16 FutureSearch Trials Austin Texas United States 78731
    17 Claghorn-Lesem Research Clinic, Ltd. Houston Texas United States 77008
    18 Psychiatric Clinic, Clinical Center Banja Luka Banja Luka Bosnia and Herzegovina 78000
    19 Clinic of Psychiatry, Clinical Center University of Sarajevo Sarajevo Bosnia and Herzegovina 71000
    20 "Poliklinika Neuron" - Croatian Institute for Brain Research Zagreb Croatia 10000
    21 Psychiatric Hospital Vrapce Zagreb Croatia 10000
    22 Universitaetsklinikum Freiburg Freiburg Germany 79104
    23 Ludwig Maximilians-Universitaet Muenchen Muenchen Germany 80336
    24 Universitaetsklinik Tuebingen, Klinik fuer Psychiatrie und Psychotherapie Tuebingen Germany 72076
    25 Fovarosi Onkormanyzat Nyiro Gyula Korhaz, II. Pszichiatriai Osztaly Budapest Hungary 1135
    26 Processus Kft., Varoskapu Rendelo Budapest Hungary 1137
    27 Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza, Pszichiatriai Osztaly Gyula Hungary 5700
    28 Varosi Egeszsegugyi Kozpont Kunszentmarton Hungary 5440
    29 Fejer Megyei Szent Gyorgy Korhaz, Pszichiatriai Osztaly Szekesfehervar Hungary 8000
    30 Donatella 99 Bt. Szentes Hungary 6600
    31 Spitalul Psihiatrie "Prof. Dr. Al. Obregia" Bucuresti Sector 4 Romania
    32 Spitalul Clinic de Psihiatrie Prof. Dr. Al. Obregia, sectia 2 Bucuresti Romania 041902
    33 Spitalul Clinic de Psihiatrie Socola, sectia VII Iasi Romania 700282
    34 Federal State Institution Moscow Scientific Research Institute of Psychiatry of Roszdrav Moscow Russian Federation 107076
    35 Institution of Russian Academy of Medical Sciences Mental Health Research Center Moscow Russian Federation 115522
    36 Moscow State Healthcare Institution Clinical Mental Hospital No 12 Moscow Russian Federation 125367
    37 St-Petersburg State Healthcare Institution St. Nicholas Mental Hospital St-Petersburg Russian Federation 190121
    38 Centro de Salud Mental Ii "La Corredoria" Oviedo Asturias Spain 33011
    39 Hospital de La Santa Creu I Sant Pau Barcelona Spain 08025
    40 Hospital General de La Vall D'Hebron Barcelona Spain 08035
    41 Centro de Salud Torrero La Paz Zaragoza Spain 50007

    Sponsors and Collaborators

    • Pfizer

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT01078298
    Other Study ID Numbers:
    • A3051122
    First Posted:
    Mar 2, 2010
    Last Update Posted:
    Apr 16, 2013
    Last Verified:
    Mar 1, 2013
    Keywords provided by Pfizer
    smoking
    smoking cessation
    smoking cessation in depressed subjects
    Additional relevant MeSH terms:
    Depression
    Depressive Disorder
    Varenicline

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
    Period Title: Overall Study
    STARTED 256 269
    COMPLETED 175 179
    NOT COMPLETED 81 90

    Baseline Characteristics

    Arm/Group Title Varenicline Placebo Total
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Total of all reporting groups
    Overall Participants 256 269 525
    Age, Customized (participants) [Number]
    18 to 44 years
    106
    41.4%
    98
    36.4%
    204
    38.9%
    45 to 64 years
    146
    57%
    160
    59.5%
    306
    58.3%
    Greater than or equal to 65 years
    4
    1.6%
    11
    4.1%
    15
    2.9%
    Sex: Female, Male (Count of Participants)
    Female
    159
    62.1%
    170
    63.2%
    329
    62.7%
    Male
    97
    37.9%
    99
    36.8%
    196
    37.3%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With a Four-Week Continuous Quit Rate (CQR)
    Description Percentage of participants who reported no use of nicotine-containing products by answering "No" to the nicotine use inventory (NUI) questions: 'Has the participant smoked cigarettes' and 'Has the participant used other nicotine-containing products' in the last 7 days (Week 9) or since last study visit (Week 9 through 12) confirmed by a measurement of an end-expiratory exhaled carbon monoxide (CO) measurement less than or equal to 10 parts per million (ppm).
    Time Frame Week 9 through Week 12

    Outcome Measure Data

    Analysis Population Description
    All participants analysis set included all the participants who were randomized and took at least one dose of randomized study medication.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
    Measure Participants 256 269
    Number [Percentage of participants]
    35.9
    14%
    15.6
    5.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Odds Ratios and p-values were obtained from a logistic regression model including the main effects of treatment, pooled center and cohort.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.35
    Confidence Interval (2-Sided) 95%
    2.16 to 5.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Participants With Continuous Abstinence Rate (CAR)
    Description Percentage of participants who remained abstinent from the period defined as start of the primary endpoint (Week 9) through Week 24 and the end of follow-up (Week 52) by reporting no use of nicotine-containing products confirmed by a measurement of an end-expiratory exhaled CO measurement less than or equal to 10 ppm.
    Time Frame Week 9 through Week 24, Week 9 through Week 52

    Outcome Measure Data

    Analysis Population Description
    All participants analysis set included all the participants who were randomized and took at least one dose of randomized study medication.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
    Measure Participants 256 269
    Week 9 through Week 24
    25.0
    9.8%
    12.3
    4.6%
    Week 9 through Week 52
    20.3
    7.9%
    10.4
    3.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments For Week 9 through 24, odds ratio and p-value were calculated from logistic regression model including the main effects of treatment, pooled center and cohort.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.53
    Confidence Interval (2-Sided) 95%
    1.56 to 4.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments For Week 9 through 52, odds ratio and p-value were calculated from logistic regression model including the main effects of treatment, pooled center and cohort.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0011
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.36
    Confidence Interval (2-Sided) 95%
    1.40 to 3.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Number of Participants With 7-day Point Prevalence (PP) of Abstinence
    Description Number of participants reporting no use of nicotine-containing products in the last 7 days confirmed by a measurement of an end-expiratory exhaled CO measurement less than or equal to 10 ppm.
    Time Frame Weeks 12, 24, 52

    Outcome Measure Data

    Analysis Population Description
    All participants analysis set included all the participants who were randomized and took at least one dose of randomized study medication.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
    Measure Participants 256 269
    Week 12
    118
    46.1%
    54
    20.1%
    Week 24
    80
    31.3%
    49
    18.2%
    Week 52
    73
    28.5%
    47
    17.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments For Week 12, odds ratio and p-values were obtained from a logistic regression model including the main effects of treatment, pooled center and cohort.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.82
    Confidence Interval (2-Sided) 95%
    2.53 to 5.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments For Week 24, odds ratio and p-values were obtained from a logistic regression model including the main effects of treatment, pooled center and cohort.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0004
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.16
    Confidence Interval (2-Sided) 95%
    1.40 to 3.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments For Week 52, odds ratio and p-values were obtained from a logistic regression model including the main effects of treatment, pooled center and cohort.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0020
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.98
    Confidence Interval (2-Sided) 95%
    1.28 to 3.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Number of Participants With 4-Week Point Prevalence (PP) of Abstinence
    Description Number of participants at Week 52 visit reporting no smoking and no use of other tobacco products in the last 4 weeks confirmed by a measurement of an end-expiratory exhaled CO measurement less than or equal to 10 ppm.
    Time Frame Week 52

    Outcome Measure Data

    Analysis Population Description
    All participants analysis set included all the participants who were randomized and took at least one dose of randomized study medication.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
    Measure Participants 256 269
    Number [participants]
    70
    27.3%
    45
    16.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Varenicline, Placebo
    Comments Odds Ratios and p-values were obtained from a logistic regression model including the main effects of treatment, pooled center and cohort.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0027
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.97
    Confidence Interval (2-Sided) 95%
    1.26 to 3.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Other Pre-specified Outcome
    Title Number of Participants With Adverse Events (Including Solicited Neuropsychiatric Adverse Events)
    Description Adverse Event (AE):any untoward medical occurrence attributed to study drug in participant who received study drug.SAE:AE causing:death;initial/prolonged inpatient hospitalization;life-threatening experience(immediate risk of dying);persistent/significant disability/incapacity;congenital anomaly.Solicited AEs collected by semi-structured neuropsychiatric AEs interview inquiring about AEs:delusions,hallucinations,paranoia,psychosis,mania,panic,agitation,hostility,aggression,homicidal ideation. If participant had positive response,investigator determined if it met AE criteria.
    Time Frame Baseline up to Week 16

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all participants who took at least 1 dose of randomized study medication, including partial doses, and had a safety measurement.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
    Measure Participants 256 269
    Number [participants]
    185
    72.3%
    180
    66.9%
    6. Other Pre-specified Outcome
    Title Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I)
    Description CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement from baseline is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected
    Time Frame Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16, 24, 32, 40, 52

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' is signifying those participants who were evaluated for this measure at the time point for each group respectively.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
    Measure Participants 250 263
    Week 1: very much improved(n=250,263)
    1
    0.4%
    2
    0.7%
    Week 1: much improved(n=250,263)
    12
    4.7%
    6
    2.2%
    Week 1: minimally improved(n=250,263)
    31
    12.1%
    21
    7.8%
    Week 1: no change(n=250,263)
    189
    73.8%
    222
    82.5%
    Week 1: minimally worse(n=250,263)
    16
    6.3%
    11
    4.1%
    Week 1: much worse(n=250,263)
    1
    0.4%
    1
    0.4%
    Week 2: very much improved(n=244,255)
    2
    0.8%
    1
    0.4%
    Week 2: much improved(n=244,255)
    18
    7%
    12
    4.5%
    Week 2: minimally improved(n=244,255)
    33
    12.9%
    38
    14.1%
    Week 2: no change(n=244,255)
    159
    62.1%
    181
    67.3%
    Week 2: minimally worse(n=244,255)
    27
    10.5%
    21
    7.8%
    Week 2: much worse(n=244,255)
    5
    2%
    2
    0.7%
    Week 3: very much improved(n=241,248)
    10
    3.9%
    4
    1.5%
    Week 3: much improved(n=241,248)
    17
    6.6%
    14
    5.2%
    Week 3: minimally improved(n=241,248)
    42
    16.4%
    45
    16.7%
    Week 3: no change(n=241,248)
    146
    57%
    165
    61.3%
    Week 3: minimally worse(n=241,248)
    26
    10.2%
    17
    6.3%
    Week 3: much worse(n=241,248)
    0
    0%
    3
    1.1%
    Week 4: very much improved(n=230,245)
    8
    3.1%
    6
    2.2%
    Week 4: much improved(n=230,245)
    18
    7%
    12
    4.5%
    Week 4: minimally improved(n=230,245)
    35
    13.7%
    51
    19%
    Week 4: no change(n=230,245)
    152
    59.4%
    154
    57.2%
    Week 4: minimally worse(n=230,245)
    15
    5.9%
    19
    7.1%
    Week 4: much worse(n=230,245)
    2
    0.8%
    3
    1.1%
    Week 5: very much improved(n=227,233)
    13
    5.1%
    9
    3.3%
    Week 5: much improved(n=227,233)
    14
    5.5%
    11
    4.1%
    Week 5: minimally improved(n=227,233)
    34
    13.3%
    46
    17.1%
    Week 5: no change(n=227,233)
    146
    57%
    151
    56.1%
    Week 5: minimally worse(n=227,233)
    19
    7.4%
    14
    5.2%
    Week 5: much worse(n=227,233)
    1
    0.4%
    2
    0.7%
    Week 6: very much improved(n=224,226)
    11
    4.3%
    6
    2.2%
    Week 6: much improved(n=224,226)
    20
    7.8%
    14
    5.2%
    Week 6: minimally improved(n=224,226)
    39
    15.2%
    41
    15.2%
    Week 6: no change(n=224,226)
    139
    54.3%
    148
    55%
    Week 6: minimally worse(n=224,226)
    13
    5.1%
    17
    6.3%
    Week 6: much worse(n=224,226)
    2
    0.8%
    0
    0%
    Week 7: very much improved(n=226,226)
    19
    7.4%
    9
    3.3%
    Week 7: much improved(n=226,226)
    23
    9%
    18
    6.7%
    Week 7: minimally improved(n=226,226)
    32
    12.5%
    34
    12.6%
    Week 7: no change(n=226,226)
    136
    53.1%
    150
    55.8%
    Week 7: minimally worse(n=226,226)
    14
    5.5%
    13
    4.8%
    Week 7: much worse(n=226,226)
    2
    0.8%
    2
    0.7%
    Week 8: very much improved(n=221,217)
    19
    7.4%
    12
    4.5%
    Week 8: much improved(n=221,217)
    18
    7%
    15
    5.6%
    Week 8: minimally improved(n=221,217)
    37
    14.5%
    40
    14.9%
    Week 8: no change(n=221,217)
    131
    51.2%
    139
    51.7%
    Week 8: minimally worse(n=221,217)
    15
    5.9%
    10
    3.7%
    Week 8: much worse(n=221,217)
    0
    0%
    1
    0.4%
    Week 8: very much worse(n=221,217)
    1
    0.4%
    0
    0%
    Week 9: very much improved(n=218,214)
    19
    7.4%
    13
    4.8%
    Week 9: much improved(n=218,214)
    19
    7.4%
    16
    5.9%
    Week 9: minimally improved(n=218,214)
    36
    14.1%
    31
    11.5%
    Week 9: no change(n=218,214)
    129
    50.4%
    141
    52.4%
    Week 9: minimally worse(n=218,214)
    15
    5.9%
    13
    4.8%
    Week 10: very much improved(n=212,211)
    20
    7.8%
    13
    4.8%
    Week 10: much improved(n=212,211)
    21
    8.2%
    18
    6.7%
    Week 10: minimally improved(n=212,211)
    30
    11.7%
    35
    13%
    Week 10: no change(n=212,211)
    124
    48.4%
    133
    49.4%
    Week 10: minimally worse(n=212,211)
    16
    6.3%
    11
    4.1%
    Week 10: much worse(n=212,211)
    1
    0.4%
    1
    0.4%
    Week 11: very much improved(n=211,205)
    23
    9%
    15
    5.6%
    Week 11: much improved(n=211,205)
    17
    6.6%
    14
    5.2%
    Week 11: minimally improved(n=211,205)
    38
    14.8%
    35
    13%
    Week 11: no change(n=211,205)
    120
    46.9%
    129
    48%
    Week 11: minimally worse(n=211,205)
    13
    5.1%
    10
    3.7%
    Week 11: much worse(n=211,205)
    0
    0%
    2
    0.7%
    Week 12: very much improved(n=210,204)
    19
    7.4%
    17
    6.3%
    Week 12: much improved(n=210,204)
    19
    7.4%
    13
    4.8%
    Week 12: minimally improved(n=210,204)
    34
    13.3%
    39
    14.5%
    Week 12: no change(n=210,204)
    127
    49.6%
    124
    46.1%
    Week 12: minimally worse(n=210,204)
    11
    4.3%
    11
    4.1%
    Week 13: very much improved(n=211,200)
    18
    7%
    16
    5.9%
    Week 13: much improved(n=211,200)
    19
    7.4%
    13
    4.8%
    Week 13: minimally improved(n=211,200)
    34
    13.3%
    40
    14.9%
    Week 13: no change(n=211,200)
    127
    49.6%
    121
    45%
    Week 13: minimally worse(n=211,200)
    12
    4.7%
    10
    3.7%
    Week 13: much worse(n=211,200)
    1
    0.4%
    0
    0%
    Week 16: very much improved(n=203,199)
    17
    6.6%
    15
    5.6%
    Week 16: much improved(n=203,199)
    27
    10.5%
    16
    5.9%
    Week 16: minimally improved(n=203,199)
    26
    10.2%
    33
    12.3%
    Week 16: no change(n=203,199)
    119
    46.5%
    119
    44.2%
    Week 16: minimally worse(n=203,199)
    14
    5.5%
    12
    4.5%
    Week 16: much worse(n=203,199)
    0
    0%
    4
    1.5%
    Week 24: very much improved(n=196,193)
    17
    6.6%
    13
    4.8%
    Week 24: much improved(n=196,193)
    17
    6.6%
    18
    6.7%
    Week 24: minimally improved(n=196,193)
    24
    9.4%
    31
    11.5%
    Week 24: no change(n=196,193)
    127
    49.6%
    125
    46.5%
    Week 24: minimally worse(n=196,193)
    10
    3.9%
    6
    2.2%
    Week 24: much worse(n=196,193)
    1
    0.4%
    0
    0%
    Week 32: very much improved(n=188,188)
    15
    5.9%
    19
    7.1%
    Week 32: much improved(n=188,188)
    19
    7.4%
    21
    7.8%
    Week 32: minimally improved(n=188,188)
    27
    10.5%
    31
    11.5%
    Week 32: no change(n=188,188)
    118
    46.1%
    113
    42%
    Week 32: minimally worse(n=188,188)
    9
    3.5%
    3
    1.1%
    Week 32: much worse(n=188,188)
    0
    0%
    1
    0.4%
    Week 40: very much improved(n=180,182)
    10
    3.9%
    17
    6.3%
    Week 40: much improved(n=180,182)
    23
    9%
    15
    5.6%
    Week 40: minimally improved(n=180,182)
    23
    9%
    32
    11.9%
    Week 40: no change(n=180,182)
    117
    45.7%
    109
    40.5%
    Week 40: minimally worse(n=180,182)
    6
    2.3%
    7
    2.6%
    Week 40: much worse(n=180,182)
    0
    0%
    2
    0.7%
    Week 40: very much worse(n=180,182)
    1
    0.4%
    0
    0%
    Week 52: very much improved(n=178,180)
    20
    7.8%
    22
    8.2%
    Week 52: much improved(n=178,180)
    20
    7.8%
    13
    4.8%
    Week 52: minimally improved(n=178,180)
    25
    9.8%
    26
    9.7%
    Week 52: no change(n=178,180)
    110
    43%
    112
    41.6%
    Week 52: minimally worse(n=178,180)
    3
    1.2%
    7
    2.6%
    7. Other Pre-specified Outcome
    Title Number of Participants With Clinical Global Impression - Severity (CGI-S) Score
    Description CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected
    Time Frame Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16, 24, 32, 40, 52

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all participants who took at least 1 dose of randomized study medication, including partial doses, and had a safety measurement. Here, the 'n' is signifying those participants who were evaluable for this measure at the specific categories for each arm group.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
    Measure Participants 256 269
    Baseline:Normal; Week 1:Normal (n=250,263)
    105
    41%
    100
    37.2%
    Baseline:Borderline; Week 1:Normal (n=250,263)
    7
    2.7%
    8
    3%
    Baseline:Mildly; Week 1:Normal (n=250,263)
    4
    1.6%
    1
    0.4%
    Baseline:Moderately; Week 1:Normal (n=250,263)
    1
    0.4%
    0
    0%
    Baseline:Normal; Week 1:Borderline (n=250,263)
    3
    1.2%
    3
    1.1%
    Baseline:Borderline; Week 1:Borderline (n=250,263)
    31
    12.1%
    42
    15.6%
    Baseline:Mildly; Week 1:Borderline (n=250,263)
    9
    3.5%
    3
    1.1%
    Baseline:Moderately; Week 1:Borderline (n=250,263)
    2
    0.8%
    3
    1.1%
    Baseline:Normal; Week 1:Mildly (n=250,263)
    0
    0%
    2
    0.7%
    Baseline:Borderline; Week 1:Mildly (n=250,263)
    4
    1.6%
    1
    0.4%
    Baseline:Mildly; Week 1:Mildly (n=250,263)
    46
    18%
    56
    20.8%
    Baseline:Moderately; Week 1:Mildly (n=250,263)
    6
    2.3%
    9
    3.3%
    Baseline:Borderline; Week 1:Moderately (n=250,263)
    1
    0.4%
    2
    0.7%
    Baseline:Mildly; Week 1:Moderately (n=250,263)
    1
    0.4%
    0
    0%
    Baseline:Moderately; Week 1:Moderately (n=250,263)
    28
    10.9%
    30
    11.2%
    Baseline:Markedly; Week 1:Moderately (n=250,263)
    1
    0.4%
    0
    0%
    Baseline:Markedly; Week 1:Markedly (n=250,263)
    1
    0.4%
    3
    1.1%
    Baseline:Normal; Week 2:Normal (n=244,254)
    102
    39.8%
    96
    35.7%
    Baseline:Borderline; Week 2:Normal (n=244,254)
    13
    5.1%
    12
    4.5%
    Baseline:Mildly; Week 2:Normal (n=244,254)
    5
    2%
    0
    0%
    Baseline: Moderately; Week 2:Normal (n=244,254)
    0
    0%
    1
    0.4%
    Baseline:Normal; Week 2:Borderline (n=244,254)
    1
    0.4%
    5
    1.9%
    Baseline:Borderline; Week 2:Borderline (n=244,254)
    22
    8.6%
    37
    13.8%
    Baseline:Mildly; Week 2:Borderline (n=244,254)
    10
    3.9%
    7
    2.6%
    Baseline:Moderately; Week 2:Borderline (n=244,254)
    4
    1.6%
    4
    1.5%
    Baseline:Normal; Week 2:Mildly (n=244,254)
    3
    1.2%
    2
    0.7%
    Baseline:Borderline; Week 2:Mildly (n=244,254)
    4
    1.6%
    0
    0%
    Baseline:Mildly; Week 2:Mildly (n=244,254)
    40
    15.6%
    48
    17.8%
    Baseline:Moderately; Week 2:Mildly (n=244,254)
    10
    3.9%
    12
    4.5%
    Baseline:Markedly; Week 2:Mildly (n=244,254)
    1
    0.4%
    0
    0%
    Baseline:Normal; Week 2:Moderately (n=244,254)
    2
    0.8%
    0
    0%
    Baseline:Borderline; Week 2:Moderately (n=244,254)
    1
    0.4%
    1
    0.4%
    Baseline:Mildly; Week 2:Moderately (n=244,254)
    2
    0.8%
    2
    0.7%
    Baseline:Moderately; Week 2:Moderately (n=244,254)
    20
    7.8%
    24
    8.9%
    Baseline:Markedly; Week 2:Moderately (n=244,254)
    0
    0%
    1
    0.4%
    Baseline: Moderately; Week 2:Markedly (n=244,254)
    3
    1.2%
    0
    0%
    Baseline:Markedly; Week 2:Markedly (n=244,254)
    1
    0.4%
    2
    0.7%
    Baseline:Normal; Week 3:Normal (n=241,247)
    101
    39.5%
    95
    35.3%
    Baseline:Borderline; Week 3:Normal (n=241,247)
    18
    7%
    16
    5.9%
    Baseline:Mildly; Week 3:Normal (n=241,247)
    6
    2.3%
    4
    1.5%
    Baseline:Moderately; Week 3:Normal (n=241,247)
    2
    0.8%
    0
    0%
    Baseline:Normal; Week 3:Borderline (n=241,247)
    3
    1.2%
    2
    0.7%
    Baseline:Borderline; Week 3:Borderline (n=241,247)
    16
    6.3%
    34
    12.6%
    Baseline:Mildly; Week 3:Borderline (n=241,247)
    8
    3.1%
    7
    2.6%
    Baseline:Moderately; Week 3:Borderline (n=241,247)
    4
    1.6%
    2
    0.7%
    Baseline:Normal; Week 3:Mildly (n=241,247)
    2
    0.8%
    0
    0%
    Baseline:Borderline; Week 3:Mildly (n=241,247)
    6
    2.3%
    2
    0.7%
    Baseline:Mildly; Week 3:Mildly (n=241,247)
    42
    16.4%
    42
    15.6%
    Baseline:Moderately; Week 3:Mildly (n=241,247)
    10
    3.9%
    17
    6.3%
    Baseline:Markedly; Week 3:Mildly (n=241,247)
    1
    0.4%
    0
    0%
    Baseline:Normal; Week 3:Moderately (n=241,247)
    0
    0%
    2
    0.7%
    Baseline:Mildly; Week 3:Moderately (n=241,247)
    2
    0.8%
    1
    0.4%
    Baseline:Moderately; Week 3:Moderately (n=241,247)
    19
    7.4%
    20
    7.4%
    Baseline:Markedly; Week 3:Moderately (n=241,247)
    0
    0%
    1
    0.4%
    Baseline:Moderately; Week 3:Markedly (n=241,247)
    0
    0%
    1
    0.4%
    Baseline:Markedly; Week 3:Markedly (n=241,247)
    1
    0.4%
    1
    0.4%
    Baseline:Normal; Week 4:Normal (n=230,244)
    101
    39.5%
    92
    34.2%
    Baseline:Borderline; Week 4:Normal (n=230,244)
    17
    6.6%
    17
    6.3%
    Baseline:Mildly; Week 4:Normal (n=230,244)
    7
    2.7%
    5
    1.9%
    Baseline:Moderately; Week 4:Normal (n=230,244)
    4
    1.6%
    1
    0.4%
    Baseline:Normal; Week 4:Borderline (n=230,244)
    2
    0.8%
    5
    1.9%
    Baseline:Borderline; Week 4:Borderline (n=230,244)
    17
    6.6%
    27
    10%
    Baseline:Mildly; Week 4:Borderline (n=230,244)
    8
    3.1%
    7
    2.6%
    Baseline:Moderately; Week 4:Borderline (n=230,244)
    1
    0.4%
    3
    1.1%
    Baseline:Normal; Week 4:Mildly (n=230,244)
    0
    0%
    2
    0.7%
    Baseline:Borderline; Week 4:Mildly (n=230,244)
    3
    1.2%
    2
    0.7%
    Baseline:Mildly; Week 4:Mildly (n=230,244)
    39
    15.2%
    43
    16%
    Baseline:Moderately; Week 4:Mildly (n=230,244)
    11
    4.3%
    15
    5.6%
    Baseline:Markedly; Week 4:Mildly (n=230,244)
    1
    0.4%
    1
    0.4%
    Baseline:Borderline; Week 4:Moderately (n=230,244)
    2
    0.8%
    0
    0%
    Baseline:Mildly; Week 4:Moderately (n=230,244)
    2
    0.8%
    2
    0.7%
    Baseline:Moderately; Week 4:Moderately (n=230,244)
    12
    4.7%
    2
    0.7%
    Baseline:Markedly; Week 4:Moderately (n=230,244)
    1
    0.4%
    18
    6.7%
    Baseline:Borderline; Week 4:Markedly (n=230,244)
    1
    0.4%
    0
    0%
    Baseline:Moderately; Week 4:Markedly (n=230,244)
    1
    0.4%
    0
    0%
    Baseline:Markedly; Week 4:Markedly (n=230,244)
    0
    0%
    2
    0.7%
    Baseline:Normal; Week 5:Normal (n=227,232)
    98
    38.3%
    88
    32.7%
    Baseline:Borderline; Week 5:Normal (n=227,232)
    19
    7.4%
    16
    5.9%
    Baseline:Mildly; Week 5:Normal (n=227,232)
    8
    3.1%
    6
    2.2%
    Baseline:Moderately; Week 5:Normal (n=227,232)
    4
    1.6%
    4
    1.5%
    Baseline:Normal; Week 5:Borderline (n=227,232)
    2
    0.8%
    1
    0.4%
    Baseline:Borderline; Week 5:Borderline (n=227,232)
    13
    5.1%
    30
    11.2%
    Baseline:Mildly; Week 5:Borderline (n=227,232)
    8
    3.1%
    4
    1.5%
    Baseline:Moderately; Week 5:Borderline (n=227,232)
    2
    0.8%
    3
    1.1%
    Baseline:Normal; Week 5:Mildly (n=227,232)
    2
    0.8%
    1
    0.4%
    Baseline:Borderline; Week 5:Mildly (n=227,232)
    6
    2.3%
    2
    0.7%
    Baseline:Mildly; Week 5:Mildly (n=227,232)
    36
    14.1%
    39
    14.5%
    Baseline:Moderately; Week 5:Mildly (n=227,232)
    11
    4.3%
    15
    5.6%
    Baseline:Markedly; Week 5:Mildly (n=227,232)
    2
    0.8%
    1
    0.4%
    Baseline:Normal; Week 5:Moderately (n=227,232)
    0
    0%
    1
    0.4%
    Baseline:Borderline; Week 5:Moderately (n=227,232)
    1
    0.4%
    0
    0%
    Baseline:Mildly; Week 5:Moderately (n=227,232)
    2
    0.8%
    4
    1.5%
    Baseline:Moderately; Week 5:Moderately (n=227,232)
    12
    4.7%
    15
    5.6%
    Baseline:Markedly; Week 5:Moderately (n=227,232)
    0
    0%
    1
    0.4%
    Baseline:Moderately; Week 5:Markedly (n=227,232)
    1
    0.4%
    1
    0.4%
    Baseline:Normal; Week 6:Normal (n=224,225)
    96
    37.5%
    84
    31.2%
    Baseline:Borderline; Week 6:Normal (n=224,225)
    22
    8.6%
    18
    6.7%
    Baseline:Mildly; Week 6:Normal (n=224,225)
    10
    3.9%
    4
    1.5%
    Baseline:Moderately; Week 6:Normal (n=224,225)
    3
    1.2%
    1
    0.4%
    Baseline:Normal; Week 6:Borderline (n=224,225)
    3
    1.2%
    3
    1.1%
    Baseline:Borderline; Week 6:Borderline (n=224,225)
    11
    4.3%
    24
    8.9%
    Baseline:Mildly; Week 6:Borderline (n=224,225)
    6
    2.3%
    7
    2.6%
    Baseline:Moderately; Week 6:Borderline (n=224,225)
    5
    2%
    4
    1.5%
    Baseline:Normal; Week 6:Mildly (n=224,225)
    2
    0.8%
    2
    0.7%
    Baseline:Borderline; Week 6:Mildly (n=224,225)
    5
    2%
    2
    0.7%
    Baseline:Mildly; Week 6:Mildly (n=224,225)
    38
    14.8%
    37
    13.8%
    Baseline:Moderately; Week 6:Mildly (n=224,225)
    8
    3.1%
    15
    5.6%
    Baseline:Markedly; Week 6:Mildly (n=224,225)
    2
    0.8%
    1
    0.4%
    Baseline:Normal; Week 6:Moderately (n=224,225)
    0
    0%
    3
    1.1%
    Baseline:Borderline; Week 6:Moderately (n=224,225)
    1
    0.4%
    1
    0.4%
    Baseline:Mildly; Week 6:Moderately (n=224,225)
    1
    0.4%
    3
    1.1%
    Baseline:Moderately; Week 6:Moderately (n=224,225)
    10
    3.9%
    14
    5.2%
    Baseline:Moderately; Week 6:Markedly (n=224,225)
    1
    0.4%
    1
    0.4%
    Baseline:Markedly; Week 6:Markedly (n=224,225)
    0
    0%
    1
    0.4%
    Baseline:Normal; Week 7:Normal (n=226,225)
    93
    36.3%
    88
    32.7%
    Baseline:Borderline; Week 7:Normal (n=226,225)
    23
    9%
    20
    7.4%
    Baseline:Mildly; Week 7:Normal (n=226,225)
    14
    5.5%
    5
    1.9%
    Baseline:Moderately; Week 7:Normal (n=226,225)
    3
    1.2%
    1
    0.4%
    Baseline:Normal; Week 7:Borderline (n=226,225)
    5
    2%
    2
    0.7%
    Baseline:Borderline; Week 7:Borderline (n=226,225)
    13
    5.1%
    23
    8.6%
    Baseline:Mildly; Week 7:Borderline (n=226,225)
    4
    1.6%
    6
    2.2%
    Baseline:Moderately; Week 7:Borderline (n=226,225)
    5
    2%
    8
    3%
    Baseline:Markedly; Week 7:Borderline (n=226,225)
    1
    0.4%
    0
    0%
    Baseline:Normal; Week 7:Mildly (n=226,225)
    2
    0.8%
    0
    0%
    Baseline:Borderline; Week 7:Mildly (n=226,225)
    2
    0.8%
    2
    0.7%
    Baseline:Mildly; Week 7:Mildly (n=226,225)
    36
    14.1%
    37
    13.8%
    Baseline:Moderately; Week 7:Mildly (n=226,225)
    10
    3.9%
    10
    3.7%
    Baseline:Markedly; Week 7:Mildly (n=226,225)
    1
    0.4%
    1
    0.4%
    Baseline:Normal; Week 7:Moderately (n=226,225)
    0
    0%
    1
    0.4%
    Baseline:Borderline; Week 7:Moderately (n=226,225)
    1
    0.4%
    1
    0.4%
    Baseline:Mildly; Week 7:Moderately (n=226,225)
    2
    0.8%
    4
    1.5%
    Baseline:Moderately; Week 7:Moderately (n=226,225)
    10
    3.9%
    14
    5.2%
    Baseline:Markedly; Week 7:Moderately (n=226,225)
    0
    0%
    1
    0.4%
    Baseline:Moderately; Week 7:Markedly (n=226,225)
    1
    0.4%
    1
    0.4%
    Baseline:Normal; Week 8:Normal (n=221,216)
    92
    35.9%
    87
    32.3%
    Baseline:Borderline; Week 8:Normal (n=221,216)
    21
    8.2%
    19
    7.1%
    Baseline:Mildly; Week 8:Normal (n=221,216)
    12
    4.7%
    6
    2.2%
    Baseline:Moderately; Week 8:Normal (n=221,216)
    3
    1.2%
    3
    1.1%
    Baseline:Normal; Week 8:Borderline (n=221,216)
    4
    1.6%
    2
    0.7%
    Baseline:Borderline; Week 8:Borderline (n=221,216)
    14
    5.5%
    19
    7.1%
    Baseline:Mildly; Week 8:Borderline (n=221,216)
    6
    2.3%
    7
    2.6%
    Baseline:Moderately; Week 8:Borderline (n=221,216)
    7
    2.7%
    5
    1.9%
    Baseline:Markedly; Week 8:Borderline (n=221,216)
    2
    0.8%
    0
    0%
    Baseline:Normal; Week 8:Mildly (n=221,216)
    2
    0.8%
    0
    0%
    Baseline:Borderline; Week 8:Mildly (n=221,216)
    3
    1.2%
    2
    0.7%
    Baseline:Mildly; Week 8:Mildly (n=221,216)
    32
    12.5%
    35
    13%
    Baseline:Moderately; Week 8:Mildly (n=221,216)
    9
    3.5%
    13
    4.8%
    Baseline:Markedly; Week 8:Mildly (n=221,216)
    0
    0%
    1
    0.4%
    Baseline:Normal; Week 8:Moderately (n=221,216)
    1
    0.4%
    0
    0%
    Baseline:Mildly; Week 8:Moderately (n=221,216)
    3
    1.2%
    3
    1.1%
    Baseline:Moderately; Week 8:Moderately (n=221,216)
    9
    3.5%
    12
    4.5%
    Baseline:Markedly; Week 8:Moderately (n=221,216)
    0
    0%
    1
    0.4%
    Baseline:Mildly; Week 8:Markedly (n=221,216)
    0
    0%
    1
    0.4%
    Baseline:Moderately; Week 8:Markedly (n=221,216)
    1
    0.4%
    0
    0%
    Baseline:Normal; Week 9:Normal (n=218,213)
    91
    35.5%
    87
    32.3%
    Baseline:Borderline; Week 9:Normal (n=218,213)
    22
    8.6%
    18
    6.7%
    Baseline:Mildly; Week 9:Normal (n=218,213)
    11
    4.3%
    5
    1.9%
    Baseline:Moderately; Week 9:Normal (n=218,213)
    4
    1.6%
    4
    1.5%
    Baseline:Normal; Week 9:Borderline (n=218,213)
    3
    1.2%
    2
    0.7%
    Baseline:Borderline; Week 9:Borderline (n=218,213)
    13
    5.1%
    19
    7.1%
    Baseline:Mildly; Week 9:Borderline (n=218,213)
    6
    2.3%
    3
    1.1%
    Baseline:Moderately; Week 9:Borderline (n=218,213)
    6
    2.3%
    8
    3%
    Baseline:Markedly; Week 9:Borderline (n=218,213)
    2
    0.8%
    1
    0.4%
    Baseline:Normal; Week 9:Mildly (n=218,213)
    3
    1.2%
    0
    0%
    Baseline:Borderline; Week 9:Mildly (n=218,213)
    2
    0.8%
    4
    1.5%
    Baseline:Mildly; Week 9:Mildly (n=218,213)
    34
    13.3%
    38
    14.1%
    Baseline:Moderately; Week 9:Mildly (n=218,213)
    10
    3.9%
    9
    3.3%
    Baseline:Mildly; Week 9:Moderately (n=218,213)
    1
    0.4%
    0
    0%
    Baseline:Moderately; Week 9:Moderately (n=218,213)
    8
    3.1%
    12
    4.5%
    Baseline:Markedly; Week 9:Moderately (n=218,213)
    0
    0%
    1
    0.4%
    Baseline:Mildly; Week 9:Markedly (n=218,213)
    1
    0.4%
    1
    0.4%
    Baseline:Moderately; Week 9:Markedly (n=218,213)
    1
    0.4%
    1
    0.4%
    Baseline:Normal; Week 10:Normal (n=212,210)
    88
    34.4%
    85
    31.6%
    Baseline:Borderline; Week 10:Normal (n=212,210)
    20
    7.8%
    21
    7.8%
    Baseline:Mildly; Week 10:Normal (n=212,210)
    13
    5.1%
    5
    1.9%
    Baseline:Moderately; Week 10:Normal (n=212,210)
    7
    2.7%
    5
    1.9%
    Baseline:Normal; Week 10:Borderline (n=212,210)
    5
    2%
    1
    0.4%
    Baseline:Borderline; Week 10:Borderline (n=212,210
    14
    5.5%
    18
    6.7%
    Baseline:Mildly; Week 10:Borderline (n=212,210)
    6
    2.3%
    6
    2.2%
    Baseline:Moderately; Week 10:Borderline(n=212,210)
    4
    1.6%
    7
    2.6%
    Baseline:Markedly; Week 10:Borderline(n=212,210)
    2
    0.8%
    1
    0.4%
    Baseline:Normal; Week 10:Mildly (n=212,210)
    1
    0.4%
    1
    0.4%
    Baseline:Borderline; Week 10:Mildly (n=212,210)
    1
    0.4%
    2
    0.7%
    Baseline:Mildly; Week 10:Mildly (n=212,210)
    29
    11.3%
    35
    13%
    Baseline:Moderately; Week 10:Mildly (n=212,210)
    8
    3.1%
    11
    4.1%
    Baseline:Normal; Week 10:Moderately (n=212,210)
    1
    0.4%
    0
    0%
    Baseline:Mildly; Week 10:Moderately (n=212,210)
    3
    1.2%
    1
    0.4%
    Baseline:Moderately; Week 10:Moderately(n=212,210)
    9
    3.5%
    9
    3.3%
    Baseline:Markedly; Week 10:Moderately (n=212,210)
    0
    0%
    1
    0.4%
    Baseline:Moderately; Week 10:Markedly (n=212,210)
    1
    0.4%
    1
    0.4%
    Baseline:Normal; Week 11:Normal (n=211,205)
    90
    35.2%
    81
    30.1%
    Baseline:Borderline; Week 11:Normal (n=211,205)
    23
    9%
    22
    8.2%
    Baseline:Mildly; Week 11:Normal (n=211,205)
    13
    5.1%
    6
    2.2%
    Baseline:Moderately; Week 11:Normal (n=211,205)
    7
    2.7%
    5
    1.9%
    Baseline:Markedly; Week 11:Normal (n=211,205)
    1
    0.4%
    0
    0%
    Baseline:Normal; Week 11:Borderline (n=211,205)
    3
    1.2%
    2
    0.7%
    Baseline:Borderline; Week 11:Borderline(n=211,205)
    10
    3.9%
    15
    5.6%
    Baseline:Mildly; Week 11:Borderline (n=211,205)
    6
    2.3%
    3
    1.1%
    Baseline:Moderately; Week 11:Borderline(n=211,205)
    3
    1.2%
    6
    2.2%
    Baseline:Markedly; Week 11:Borderline (n=211,205)
    1
    0.4%
    1
    0.4%
    Baseline:Normal; Week 11:Mildly (n=211,205)
    1
    0.4%
    0
    0%
    Baseline:Borderline; Week 11:Mildly (n=211,205)
    2
    0.8%
    3
    1.1%
    Baseline:Mildly; Week 11:Mildly (n=211,205)
    30
    11.7%
    34
    12.6%
    Baseline:Moderately; Week 11:Mildly (n=211,205)
    9
    3.5%
    13
    4.8%
    Baseline:Normal; Week 11:Moderately (n=211,205)
    0
    0%
    1
    0.4%
    Baseline:Mildly; Week 11:Moderately (n=211,205)
    3
    1.2%
    1
    0.4%
    Baseline:Moderately; Week 11:Moderately(n=211,205)
    8
    3.1%
    10
    3.7%
    Baseline:Markedly; Week 11:Moderately (n=211,205)
    0
    0%
    1
    0.4%
    Baseline:Mildly; Week 11:Markedly (n=211,205)
    0
    0%
    1
    0.4%
    Baseline:Normal; Week 12:Normal (n=210,203)
    89
    34.8%
    79
    29.4%
    Baseline:Borderline; Week 12:Normal (n=210,203)
    23
    9%
    22
    8.2%
    Baseline:Mildly; Week 12:Normal (n=210,203)
    13
    5.1%
    6
    2.2%
    Baseline:Moderately; Week 12:Normal (n=210,203)
    6
    2.3%
    8
    3%
    Baseline:Markedly; Week 12:Normal (n=210,203)
    1
    0.4%
    0
    0%
    Baseline:Normal; Week 12:Borderline (n=210,203)
    4
    1.6%
    2
    0.7%
    Baseline:Borderline; Week 12:Borderline(n=210,203)
    12
    4.7%
    16
    5.9%
    Baseline:Mildly; Week 12:Borderline (n=210,203)
    6
    2.3%
    4
    1.5%
    Baseline:Moderately; Week 12:Borderline(n=210,203)
    4
    1.6%
    3
    1.1%
    Baseline:Markedly; Week 12:Borderline (n=210,203)
    1
    0.4%
    1
    0.4%
    Baseline:Normal; Week 12:Mildly (n=210,203)
    0
    0%
    2
    0.7%
    Baseline:Borderline; Week 12:Mildly (n=210,203)
    0
    0%
    1
    0.4%
    Baseline:Mildly; Week 12:Mildly (n=210,203)
    30
    11.7%
    34
    12.6%
    Baseline:Moderately; Week 12:Mildly (n=210,203)
    9
    3.5%
    14
    5.2%
    Baseline:Borderline; Week 12:Moderately(n=210,203)
    0
    0%
    1
    0.4%
    Baseline:Mildly; Week 12:Moderately (n=210,203)
    3
    1.2%
    3
    1.1%
    Baseline:Moderately; Week 12:Moderately(n=210,203)
    8
    3.1%
    6
    2.2%
    Baseline:Markedly; Week 12:Moderately(n=210,203)
    0
    0%
    1
    0.4%
    Baseline:Moderately; Week 12:Markedly(n=210,203)
    1
    0.4%
    0
    0%
    Baseline:Normal; Week 13:Normal (n=211,199)
    92
    35.9%
    78
    29%
    Baseline:Borderline; Week 13:Normal (n=211,199)
    22
    8.6%
    21
    7.8%
    Baseline:Mildly; Week 13:Normal (n=211,199)
    13
    5.1%
    5
    1.9%
    Baseline:Moderately; Week 13:Normal (n=211,199)
    6
    2.3%
    9
    3.3%
    Baseline:Markedly; Week 13:Normal (n=211,199)
    2
    0.8%
    0
    0%
    Baseline:Normal; Week 13:Borderline (n=211,199)
    3
    1.2%
    3
    1.1%
    Baseline:Borderline; Week 13:Borderline(n=211,199)
    11
    4.3%
    17
    6.3%
    Baseline:Mildly; Week 13:Borderline (n=211,199)
    7
    2.7%
    6
    2.2%
    Baseline:Moderately; Week 13:Borderline(n=211,199)
    5
    2%
    4
    1.5%
    Baseline:Markedly; Week 13:Borderline(n=211,199)
    0
    0%
    1
    0.4%
    Baseline:Borderline; Week 13:Mildly (n=211,199)
    0
    0%
    3
    1.1%
    Baseline:Mildly; Week 13:Mildly (n=211,199)
    30
    11.7%
    32
    11.9%
    Baseline:Moderately; Week 13:Mildly (n=211,199)
    9
    3.5%
    11
    4.1%
    Baseline:Mildly; Week 13:Moderately (n=211,199)
    3
    1.2%
    1
    0.4%
    Baseline:Moderately; Week 13:Moderately(n=211,199)
    7
    2.7%
    7
    2.6%
    Baseline:Markedly; Week 13:Moderately(n=211,199)
    0
    0%
    1
    0.4%
    Baseline:Moderately; Week 13:Markedly (n=211,199)
    1
    0.4%
    0
    0%
    Baseline:Normal; Week 16:Normal (n=203,198)
    91
    35.5%
    78
    29%
    Baseline:Borderline; Week 16:Normal (n=203,198)
    19
    7.4%
    20
    7.4%
    Baseline:Mildly; Week 16:Normal (n=203,198)
    14
    5.5%
    6
    2.2%
    Baseline:Moderately; Week 16:Normal (n=203,198)
    7
    2.7%
    11
    4.1%
    Baseline:Markedly; Week 16:Normal (n=203,198)
    2
    0.8%
    0
    0%
    Baseline:Normal; Week 16:Borderline (n=203,198)
    2
    0.8%
    2
    0.7%
    Baseline:Borderline; Week 16:Borderline(n=203,198)
    11
    4.3%
    16
    5.9%
    Baseline:Mildly; Week 16:Borderline (n=203,198)
    4
    1.6%
    5
    1.9%
    Baseline:Moderately; Week 16:Borderline(n=203,198)
    2
    0.8%
    2
    0.7%
    Baseline:Markedly; Week 16:Borderline (n=203,198)
    0
    0%
    1
    0.4%
    Baseline:Normal; Week 16:Mildly (n=203,198)
    1
    0.4%
    2
    0.7%
    Baseline:Borderline; Week 16:Mildly (n=203,198)
    0
    0%
    3
    1.1%
    Baseline:Mildly; Week 16:Mildly (n=203,198)
    30
    11.7%
    30
    11.2%
    Baseline:Moderately; Week 16:Mildly (n=203,198)
    11
    4.3%
    8
    3%
    Baseline:Borderline; Week 16:Moderately(n=203,198)
    0
    0%
    2
    0.7%
    Baseline:Mildly; Week 16:Moderately (n=203,198)
    3
    1.2%
    2
    0.7%
    Baseline:Moderately; Week 16:Moderately(n=203,198)
    4
    1.6%
    8
    3%
    Baseline:Markedly; Week 16:Moderately (n=203,198)
    0
    0%
    1
    0.4%
    Baseline:Moderately; Week 16:Markedly (n=203,198)
    2
    0.8%
    1
    0.4%
    Baseline:Normal; Week 24:Normal (n=196,192)
    88
    34.4%
    78
    29%
    Baseline:Borderline; Week 24:Normal (n=196,192)
    18
    7%
    19
    7.1%
    Baseline:Mildly; Week 24:Normal (n=196,192)
    15
    5.9%
    6
    2.2%
    Baseline:Moderately; Week 24:Normal (n=196,192)
    5
    2%
    8
    3%
    Baseline:Markedly; Week 24:Normal (n=196,192)
    2
    0.8%
    0
    0%
    Baseline:Normal; Week 24:Borderline (n=196,192)
    0
    0%
    3
    1.1%
    Baseline:Borderline; Week 24:Borderline(n=196,192)
    13
    5.1%
    14
    5.2%
    Baseline:Mildly; Week 24:Borderline (n=196,192)
    4
    1.6%
    6
    2.2%
    Baseline:Moderately; Week 24:Borderline(n=196,192)
    2
    0.8%
    2
    0.7%
    Baseline:Markedly; Week 24:Borderline (n=196,192)
    0
    0%
    1
    0.4%
    Baseline:Normal; Week 24:Mildly (n=196,192)
    2
    0.8%
    1
    0.4%
    Baseline:Borderline; Week 24:Mildly (n=196,192)
    0
    0%
    3
    1.1%
    Baseline:Mildly; Week 24:Mildly (n=196,192)
    27
    10.5%
    31
    11.5%
    Baseline:Moderately; Week 24:Mildly (n=196,192)
    8
    3.1%
    12
    4.5%
    Baseline:Mildly; Week 24:Moderately (n=196,192)
    4
    1.6%
    0
    0%
    Baseline:Moderately; Week 24:Moderately(n=196,192)
    7
    2.7%
    7
    2.6%
    Baseline:Markedly; Week 24:Moderately (n=196,192)
    0
    0%
    1
    0.4%
    Baseline:Moderately; Week 24:Markedly (n=196,192)
    1
    0.4%
    0
    0%
    Baseline:Normal; Week 32:Normal (n=188,187)
    82
    32%
    77
    28.6%
    Baseline:Borderline; Week 32:Normal (n=188,187)
    16
    6.3%
    20
    7.4%
    Baseline:Mildly; Week 32:Normal (n=188,187)
    10
    3.9%
    8
    3%
    Baseline:Moderately; Week 32:Normal (n=188,187)
    4
    1.6%
    9
    3.3%
    Baseline:Markedly; Week 32:Normal (n=188,187)
    2
    0.8%
    0
    0%
    Baseline:Normal; Week 32:Borderline (n=188,187)
    0
    0%
    1
    0.4%
    Baseline:Borderline; Week 32:Borderline(n=188,187)
    12
    4.7%
    15
    5.6%
    Baseline:Mildly; Week 32:Borderline (n=188,187)
    9
    3.5%
    7
    2.6%
    Baseline:Moderately; Week 32:Borderline(n=188,187)
    4
    1.6%
    1
    0.4%
    Baseline:Markedly; Week 32:Borderline (n=188,187)
    0
    0%
    1
    0.4%
    Baseline:Normal; Week 32:Mildly (n=188,187)
    2
    0.8%
    0
    0%
    Baseline:Borderline; Week 32:Mildly (n=188,187)
    0
    0%
    1
    0.4%
    Baseline:Mildly; Week 32:Mildly (n=188,187)
    28
    10.9%
    29
    10.8%
    Baseline:Moderately; Week 32:Mildly (n=188,187)
    8
    3.1%
    11
    4.1%
    Baseline:Markedly; Week 32:Mildly (n=188,187)
    0
    0%
    1
    0.4%
    Baseline:Mildly; Week 32:Moderately (n=188,187)
    3
    1.2%
    0
    0%
    Baseline:Moderately; Week 32:Moderately(n=188,187)
    7
    2.7%
    5
    1.9%
    Baseline:Borderline; Week 32:Markedly (n=188,187)
    0
    0%
    1
    0.4%
    Baseline:Moderately; Week 32:Markedly (n=188,187)
    1
    0.4%
    0
    0%
    Baseline:Normal; Week 40:Normal (n=180,181)
    81
    31.6%
    71
    26.4%
    Baseline:Borderline; Week 40:Normal (n=180,181)
    17
    6.6%
    20
    7.4%
    Baseline:Mildly; Week 40:Normal (n=180,181)
    11
    4.3%
    7
    2.6%
    Baseline:Moderately; Week 40:Normal (n=180,181)
    2
    0.8%
    7
    2.6%
    Baseline:Markedly; Week 40:Normal (n=180,181)
    2
    0.8%
    0
    0%
    Baseline:Normal; Week 40:Borderline (n=180,181)
    0
    0%
    2
    0.7%
    Baseline:Borderline; Week 40:Borderline(n=180,181)
    9
    3.5%
    15
    5.6%
    Baseline:Mildly; Week 40:Borderline (n=180,181)
    8
    3.1%
    6
    2.2%
    Baseline:Moderately; Week 40:Borderline(n=180,181)
    4
    1.6%
    2
    0.7%
    Baseline:Markedly; Week 40:Borderline (n=180,181)
    0
    0%
    1
    0.4%
    Baseline:Normal; Week 40:Mildly (n=180,181)
    1
    0.4%
    0
    0%
    Baseline:Borderline; Week 40:Mildly (n=180,181)
    2
    0.8%
    2
    0.7%
    Baseline:Mildly; Week 40:Mildly (n=180,181)
    25
    9.8%
    28
    10.4%
    Baseline:Moderately; Week 40:Mildly (n=180,181)
    11
    4.3%
    12
    4.5%
    Baseline:Markedly; Week 40:Mildly (n=180,181)
    0
    0%
    1
    0.4%
    Baseline:Normal; Week 40:Moderately (n=180,181)
    0
    0%
    1
    0.4%
    Baseline:Mildly; Week 40:Moderately (n=180,181)
    2
    0.8%
    1
    0.4%
    Baseline:Moderately; Week 40:Moderately(n=180,181)
    4
    1.6%
    3
    1.1%
    Baseline:Moderately; Week 40:Markedly (n=180,181)
    1
    0.4%
    2
    0.7%
    Baseline:Normal; Week 52:Normal (n=178,179)
    81
    31.6%
    69
    25.7%
    Baseline:Borderline; Week 52:Normal (n=178,179)
    19
    7.4%
    20
    7.4%
    Baseline:Mildly; Week 52:Normal (n=178,179)
    12
    4.7%
    7
    2.6%
    Baseline:Moderately; Week 52:Normal (n=178,179)
    4
    1.6%
    7
    2.6%
    Baseline:Markedly; Week 52:Normal (n=178,179)
    2
    0.8%
    0
    0%
    Baseline:Normal; Week 52:Borderline (n=178,179)
    1
    0.4%
    4
    1.5%
    Baseline:Borderline; Week 52:Borderline(n=178,179)
    8
    3.1%
    14
    5.2%
    Baseline:Mildly; Week 52:Borderline (n=178,179)
    8
    3.1%
    8
    3%
    Baseline:Moderately; Week 52:Borderline(n=178,179)
    4
    1.6%
    4
    1.5%
    Baseline:Markedly; Week 52:Borderline (n=178,179)
    0
    0%
    1
    0.4%
    Baseline:Normal; Week 52:Mildly (n=178,179)
    1
    0.4%
    0
    0%
    Baseline:Borderline; Week 52:Mildly (n=178,179)
    0
    0%
    2
    0.7%
    Baseline:Mildly; Week 52:Mildly (n=178,179)
    24
    9.4%
    26
    9.7%
    Baseline:Moderately; Week 52:Mildly (n=178,179)
    8
    3.1%
    11
    4.1%
    Baseline:Mildly; Week 52:Moderately (n=178,179)
    1
    0.4%
    1
    0.4%
    Baseline:Moderately; Week 52:Moderately(n=178,179)
    4
    1.6%
    4
    1.5%
    Baseline:Markedly; Week 52:Moderately (n=178,179)
    0
    0%
    1
    0.4%
    Baseline:Moderately; Week 52:Markedly (n=178,179)
    1
    0.4%
    0
    0%
    8. Other Pre-specified Outcome
    Title Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score
    Description Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Change: mean score at observation minus mean score at baseline.
    Time Frame Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all participants who took at least 1 dose of randomized study medication, including partial doses, and had a safety measurement. 'n' is signifying those participants who were evaluated for this measure at the satisfaction level for each group respectively.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
    Measure Participants 256 269
    Baseline(n=256,269)
    7.6
    (7.38)
    7.9
    (7.51)
    Change at Week 1(n=250,265)
    -1.2
    (3.95)
    -0.6
    (4.17)
    Change at Week 2(n= 245, 255)
    -1.0
    (6.06)
    -1.1
    (5.33)
    Change at Week 3(n= 241, 249)
    -1.9
    (5.19)
    -1.8
    (4.96)
    Change at Week 4(n= 230, 246)
    -2.2
    (5.62)
    -1.5
    (5.96)
    Change at Week 5(n=228, 235)
    -2.1
    (6.01)
    -2.3
    (6.09)
    Change at Week 6(n=224, 227)
    -2.2
    (6.15)
    -2.3
    (5.84)
    Change at Week 7(n=226, 227)
    -2.3
    (6.57)
    -2.4
    (5.94)
    Change at Week 8(n=221, 218)
    -2.7
    (6.51)
    -2.6
    (6.02)
    Change at Week 9(n=218, 216)
    -2.9
    (6.11)
    -2.5
    (6.55)
    Change at Week 10(n=214, 212)
    -2.9
    (6.21)
    -2.8
    (6.15)
    Change at Week 11(n= 211, 206)
    -3.2
    (6.30)
    -2.9
    (6.13)
    Change at Week 12(n= 210, 205)
    -3.4
    (6.20)
    -3.2
    (6.34)
    Change at Week 13(n= 211, 201)
    -3.0
    (6.39)
    -3.6
    (5.88)
    Change at Week 16(n= 202, 197)
    -3.1
    (6.36)
    -3.2
    (6.61)
    9. Other Pre-specified Outcome
    Title Change From Baseline in Hamilton Anxiety Scale (HAM-A) - Total Score
    Description HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); possible range 0 to 56. Lower score indicates less affected. Change: mean score at observation minus mean score at baseline.
    Time Frame Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all participants who took at least 1 dose of randomized study medication, including partial doses, and had a safety measurement. 'n' is signifying those participants who were evaluated for this measure at the satisfaction level for each group respectively.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
    Measure Participants 256 269
    Baseline(n=256,269)
    6.1
    (5.23)
    6.4
    (5.17)
    Change at Week 1(n=250,265)
    -0.5
    (2.54)
    -0.7
    (3.15)
    Change at Week 2(n= 245, 255)
    -0.7
    (3.98)
    -0.5
    (3.79)
    Change at Week 3(n= 241, 249)
    -1.3
    (3.41)
    -1.2
    (3.68)
    Change at Week 4(n= 230, 246)
    -1.6
    (3.72)
    -1.2
    (3.87)
    Change at Week 5(n=228, 235)
    -1.6
    (4.05)
    -1.6
    (4.00)
    Change at Week 6(n=224, 227)
    -1.7
    (4.03)
    -1.6
    (4.00)
    Change at Week 7(n=226, 227)
    -2.0
    (4.40)
    -1.8
    (4.32)
    Change at Week 8(n=221, 218)
    -1.9
    (4.65)
    -1.9
    (4.10)
    Change at Week 9(n=218, 216)
    -2.0
    (4.40)
    -1.9
    (3.94)
    Change at Week 10(n=214, 212)
    -2.2
    (4.24)
    -2.0
    (4.12)
    Change at Week 11(n= 211, 206)
    -2.3
    (4.48)
    -2.1
    (4.31)
    Change at Week 12(n= 210, 205)
    -2.3
    (4.27)
    -2.4
    (4.47)
    Change at Week 13(n= 211, 201)
    -2.4
    (4.49)
    -2.7
    (4.34)
    Change at Week 16(n= 202, 197)
    -2.7
    (4.67)
    -2.5
    (4.28)
    10. Other Pre-specified Outcome
    Title Change From Baseline in Barratt Impulsiveness Scale (BIS-11) - Total Score
    Description The BIS-11 is a self-administered 30 items questionnaire to assess measure of impulsivity. Items are scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). Total score range from 30 to 120. Barratt suggested that a total score of greater than or equal to 75 could indicate an impulse-control disorder, whereas a total score in the range of 70 to 75 could indicate pathological impulsivity.
    Time Frame Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 16

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all participants who took at least 1 dose of randomized study medication, including partial doses, and had a safety measurement. 'n' is signifying those participants who were evaluated for this measure at the satisfaction level for each group respectively.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
    Measure Participants 256 269
    Baseline(n=256,269)
    65.1
    (6.42)
    64.2
    (7.30)
    Change at Week 1(n=250,265)
    -0.5
    (4.36)
    -0.8
    (4.26)
    Change at Week 2(n= 244, 255)
    -0.8
    (4.73)
    -1.1
    (4.83)
    Change at Week 3(n= 241, 249)
    -1.0
    (4.75)
    -1.3
    (4.81)
    Change at Week 4(n= 230, 246)
    -1.0
    (5.19)
    -1.2
    (4.95)
    Change at Week 5(n=228, 234)
    -1.1
    (5.27)
    -1.1
    (5.39)
    Change at Week 6(n=224, 226)
    -1.4
    (5.28)
    -1.2
    (5.43)
    Change at Week 7(n=226, 227)
    -1.6
    (5.62)
    -1.3
    (6.08)
    Change at Week 8(n=219, 216)
    -1.3
    (5.81)
    -1.2
    (6.54)
    Change at Week 9(n=218, 215)
    -1.5
    (6.25)
    -1.4
    (6.24)
    Change at Week 10(n=214, 211)
    -1.5
    (6.13)
    -1.7
    (6.94)
    Change at Week 11(n= 211, 205)
    -1.6
    (6.24)
    -1.5
    (6.78)
    Change at Week 12(n= 210, 204)
    -1.0
    (6.55)
    -1.4
    (7.31)
    Change at Week 13(n= 211, 201)
    -1.4
    (6.52)
    -1.1
    (7.00)
    Change at Week 16(n= 202, 196)
    -1.4
    (6.25)
    -1.3
    (6.85)
    11. Other Pre-specified Outcome
    Title Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS)
    Description C-SSRS assessed if participant experienced following: completed suicide (1), suicide attempt (2)(response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3)("Yes" on "preparatory acts or behavior"), suicidal ideation (4)("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").
    Time Frame Baseline, Week 1 up to 30 days after Week 12 (treatment-emergent [TE]), thereafter up to Week 52 (follow-up [FU])

    Outcome Measure Data

    Analysis Population Description
    Safety analysis population included all participants who took at least 1 dose of randomized study medication, including partial doses, and had a safety measurement.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
    Measure Participants 256 269
    Baseline,Suicidal Behavior or/and Ideation
    6
    2.3%
    1
    0.4%
    Baseline,4
    6
    2.3%
    1
    0.4%
    Baseline,4: wish to be dead
    6
    2.3%
    1
    0.4%
    TE,Suicidal Behavior or/and Ideation
    15
    5.9%
    20
    7.4%
    TE,2
    0
    0%
    1
    0.4%
    TE,4
    15
    5.9%
    19
    7.1%
    TE,4: wish to be dead
    15
    5.9%
    18
    6.7%
    TE,4: non-specific active suicidal thoughts
    4
    1.6%
    7
    2.6%
    TE,4: with any methods,without intent to act
    2
    0.8%
    5
    1.9%
    TE,4: with some intent,without specific plan.
    0
    0%
    3
    1.1%
    TE,4: with specific plan and intent
    0
    0%
    1
    0.4%
    FU,Suicidal Behavior or/and Ideation
    13
    5.1%
    12
    4.5%
    FU,1
    1
    0.4%
    0
    0%
    FU,4
    12
    4.7%
    12
    4.5%
    FU,4: wish to be dead
    11
    4.3%
    12
    4.5%
    FU,4: non-specific active suicidal thoughts
    5
    2%
    3
    1.1%
    FU,4: with any methods,without intent to act
    2
    0.8%
    2
    0.7%
    FU,4: with some intent,without specific plan
    1
    0.4%
    1
    0.4%
    FU,7
    1
    0.4%
    1
    0.4%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
    Arm/Group Title Varenicline Placebo
    Arm/Group Description Varenicline 0.5 milligram (mg) tablet given orally once daily up to Day 3 followed by varenicline 0.5 mg tablet orally twice daily up to Day 7 and then varenicline 1 mg tablet given orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment. Placebo matched to varenicline 0.5 mg tablet orally once daily up to Day 3 followed by placebo matched to varenicline 0.5 mg tablet orally twice daily up to Day 7 and then placebo matched to varenicline 1 mg tablet orally twice daily up to Week 12. Participants were followed-up for additional 40 weeks post-treatment.
    All Cause Mortality
    Varenicline Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Varenicline Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/256 (2.7%) 7/269 (2.6%)
    Cardiac disorders
    Palpitations 1/256 (0.4%) 0/269 (0%)
    Gastrointestinal disorders
    Acute abdomen 1/256 (0.4%) 0/269 (0%)
    General disorders
    Chest pain 0/256 (0%) 1/269 (0.4%)
    Device dislocation 0/256 (0%) 1/269 (0.4%)
    Hepatobiliary disorders
    Autoimmune hepatitis 1/256 (0.4%) 0/269 (0%)
    Infections and infestations
    Bronchitis 0/256 (0%) 1/269 (0.4%)
    Device related infection 0/256 (0%) 1/269 (0.4%)
    Injury, poisoning and procedural complications
    Fall 0/256 (0%) 1/269 (0.4%)
    Fractured coccyx 0/256 (0%) 1/269 (0.4%)
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion 1/256 (0.4%) 0/269 (0%)
    Ligament laxity 1/256 (0.4%) 0/269 (0%)
    Psychiatric disorders
    Agitation 0/256 (0%) 1/269 (0.4%)
    Depression 0/256 (0%) 1/269 (0.4%)
    Depression suicidal 1/256 (0.4%) 1/269 (0.4%)
    Intentional sefl-injury 1/256 (0.4%) 1/269 (0.4%)
    Psychotic disorder 1/256 (0.4%) 0/269 (0%)
    Renal and urinary disorders
    Claculus ureteric 1/256 (0.4%) 0/269 (0%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/256 (0%) 1/269 (0.4%)
    Vascular disorders
    Haemodynamic instability 1/256 (0.4%) 0/269 (0%)
    Other (Not Including Serious) Adverse Events
    Varenicline Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 158/256 (61.7%) 126/269 (46.8%)
    Gastrointestinal disorders
    Constipation 15/256 (5.9%) 9/269 (3.3%)
    Diarrhoea 16/256 (6.3%) 12/269 (4.5%)
    Dry mouth 17/256 (6.6%) 14/269 (5.2%)
    Nausea 69/256 (27%) 28/269 (10.4%)
    Vomiting 13/256 (5.1%) 9/269 (3.3%)
    General disorders
    Irritability 28/256 (10.9%) 22/269 (8.2%)
    Infections and infestations
    Nasopharyngitis 14/256 (5.5%) 13/269 (4.8%)
    Upper respiratory tract infection 15/256 (5.9%) 13/269 (4.8%)
    Investigations
    Weight increased 14/256 (5.5%) 5/269 (1.9%)
    Nervous system disorders
    Headache 43/256 (16.8%) 30/269 (11.2%)
    Psychiatric disorders
    Abnormal dreams 29/256 (11.3%) 22/269 (8.2%)
    Agitation 17/256 (6.6%) 10/269 (3.7%)
    Anxiety 18/256 (7%) 25/269 (9.3%)
    Depression 17/256 (6.6%) 13/269 (4.8%)
    Insomnia 28/256 (10.9%) 13/269 (4.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT01078298
    Other Study ID Numbers:
    • A3051122
    First Posted:
    Mar 2, 2010
    Last Update Posted:
    Apr 16, 2013
    Last Verified:
    Mar 1, 2013