Smoking Cessation
Conditions
Brief summary
Study will determine whether patients with schizophrenia or schizoaffective disorder can be helped to quit smoking safely while using varenicline and receiving smoking cessation counseling.
Detailed description
This is a safety study.
Interventions
DRUGplacebo
Randomization 2:1 treatment to placebo
One week of titration up to 1mg bid and 11 weeks of dosing at 1mg bid
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis (using the SCID-I/P at screening visit) of schizophrenia or schizoaffective disorder and judged to be stable (without hospitalization or acute exacerbation and functioning in society) on psychiatric treatment for at least the past 6 month. * Current cigarette smokers (at least 15/day during the past year with no period of abstinence greater than 3 months in the past year) male or female, between the ages of 18 and 75 inclusive, who are motivated to stop smoking. * Score 7 or higher on the Contemplation Ladder at the Screening, Week -1, and Baseline Visits.
Exclusion criteria
* PANSS score \>70 at Screen or Baseline Visit. * Subjects hospitalized within the past six months due to suicidal ideation or suicidal behavior or subjects considered to have serious suicidal ideation or suicidal behavior within the past six moth. * Subjects having active suicidal ideation or behavior identified at Screen, Week -1, or Baseline Visit. * Subjects taking Bupropion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | Baseline, Week 24 | CGI-I: 7-point clinician rated scale ranging from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, to 7=very much worse. Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Scores above 4 reflect worsening of illness state as compared to baseline. |
| Number of Participants With Shift From Baseline to Week 12 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Baseline (Bsl) to Week 12 | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1=normal, not ill at all, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill patients. Higher scores reflect higher severity of current illness states. |
| Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Baseline to Week 24 | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1=normal, not ill at all, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill patients. Higher scores reflect higher severity of current illness states. |
| Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | Baseline, Week 1 | CGI-I: 7-point clinician rated scale ranging from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, to 7=very much worse. Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Scores above 4 reflect worsening of illness state as compared to baseline. |
| Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | Baseline, Week 12 | CGI-I: 7-point clinician rated scale ranging from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, to 7=very much worse. Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Scores above 4 reflect worsening of illness state as compared to baseline. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to 30 days after last dose of study treatment or up to Week 16 | AEs are any untoward medical occurrence in a clinical investigation participant administered a product or medical device. The event does not need to be causally related to the study treatment or usage. SAEs include any untoward medical occurrence that results in death, are life threatening, requires hospitalization or prolongation of hospitalization, results in disability or incapacity or are a congenital anomaly or birth defect in the offspring of a study participant. Lack of efficacy was to be reported as an AE when it was associated with an SAE. |
| Number of Participants With Psychiatric Adverse Events | Baseline up to Week 24 | Psychiatric Adverse Event symptoms included, but were not restricted to, depression, anxiety, hostility, perceptual / thinking disturbance, suicidal ideation, or suicidal behavior based on clinical judgment and use of the Positive and Negative Syndrome Scale and Columbia Classification Algorithm of Suicide assessments. |
| Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Total Score | Baseline to Week 12 | PANSS includes 30 items rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme) organized as 7 positive symptom subscale items, 7 negative symptom subscale items and 16 general psychopathology items. Total scores range from 30 to 210 with higher scores indicating more extreme symptoms. |
| Change From Baseline to Week 24 in Positive and Negative Syndrome Scale (PANSS): Total Score | Baseline to Week 24 | PANSS includes 30 items rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme) organized as 7 positive symptom subscale items, 7 negative symptom subscale items and 16 general psychopathology items. Total scores range from 30 to 210 with higher scores indicating more extreme symptoms. |
| Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Positive Symptoms Score | Baseline to Week 12 | PANSS includes 30 items rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme) organized as 7 positive symptom subscale items, 7 negative symptom subscale items and 16 general psychopathology items. Positive symptoms (productive symptoms) associated with schizophrenia (delusions, conceptual disorganization, and hallucinatory behavior) are rated on a scale from 1 (absent) to 7 (extreme); total positive subscale scores range from 7 to 49 with higher scores indicating more extreme symptoms. |
| Change From Baseline to Week 24 in Positive and Negative Syndrome Scale (PANSS): Positive Symptoms Score | Baseline to Week 24 | PANSS includes 30 items rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme) organized as 7 positive symptom subscale items, 7 negative symptom subscale items and 16 general psychopathology items. Positive symptoms (productive symptoms) associated with schizophrenia (delusions, conceptual disorganization, and hallucinatory behavior) are rated on a scale from 1 (absent) to 7 (extreme); total positive subscale scores range from 7 to 49 with higher scores indicating more extreme symptoms. |
| Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Negative Symptoms Score | Baseline to Week 12 | PANSS includes 30 items rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme) organized as 7 positive symptom subscale items, 7 negative symptom subscale items and 16 general psychopathology items. Negative symptoms (deficit features) associated with schizophrenia (blunted affect, emotional withdrawal, poor rapport, and passive / apathetic social withdrawal) are rated on a scale from 1 (absent) to 7 (extreme); total negative subscale scores range from 7 to 49 with higher scores indicating more extreme symptoms. |
| Change From Baseline to Week 24 in Positive and Negative Syndrome Scale (PANSS): Negative Symptoms Score | Baseline to Week 24 | PANSS includes 30 items rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme) organized as 7 positive symptom subscale items, 7 negative symptom subscale items and 16 general psychopathology items. Negative symptoms (deficit features) associated with schizophrenia (blunted affect, emotional withdrawal, poor rapport, and passive / apathetic social withdrawal) are rated on a scale from 1 (absent) to 7 (extreme); total negative subscale scores range from 7 to 49 with higher scores indicating more extreme symptoms. |
| Change From Baseline to Week 12 in Simpson Angus Rating Scale (SARS) | Baseline to Week 12 | 10-item rating scale to assess the severity of extrapyramidal symptoms rated on a 5-point scale 0 (normal) to 4 (highest severity). Items measured are gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella tap, tremor, and salivation. Global score calculated by summing individual item scores and dividing by the total number of items; range is 0 to 40 with higher scores indicating greater severity. |
| Change From Baseline to Week 24 in Simpson Angus Rating Scale (SARS) | Baseline to Week 24 | 10-item rating scale to assess the severity of extrapyramidal symptoms rated on a 5-point scale 0 (normal) to 4 (highest severity). Items measured are gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella tap, tremor, and salivation. Global score calculated by summing individual item scores and dividing by the total number of items; range is 0 to 40 with higher scores indicating greater severity. |
| Number of Participants With Suicidal Behavior and / or Ideation (Yes Response) on the Columbia Suicide Severity Rating Scale (C-SSRS) During the Treatment Phase | Week 1 to Week 12 (Treatment phase) | C-SSRS is a clinician rated assessment of suicidal behavior and / or intent categorized as: Suicidal behavior=a yes response to any of 5 suicidal behavior questions (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide); Suicidal ideation=a yes response to any one of 5 suicidal ideation questions which includes wish to be dead, and 4 different categories of active suicidal ideation (thought, thought with method, thought with intent, thought with plan and intent). |
| Number of Participants With Suicidal Behavior or Suicical Ideation (Yes Response ) on the Columbia Suicide-Severity Rating Scale (C-SSRS) During the Post Treatment Phase | Week 13 to Week 24 (Post treatment phase) | C-SSRS is a clinician rated assessment of suicidal behavior and / or intent categorized as: Suicidal behavior=a yes response to any of 5 suicidal behavior questions (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide); Suicidal ideation=a yes response to any one of 5 suicidal ideation questions which includes wish to be dead, and 4 different categories of active suicidal ideation (thought, thought with method, thought with intent, thought with plan and intent). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 7-day Point Prevalence of Non-smoking at Week 24 | Week 24 | 7-day point prevalence of non-smoking measured as the number of participants who maintained complete abstinence from cigarette smoking or other nicotine use in the previous 7 days before the Week 24 visit and had an end-expiratory carbon monoxide (CO) measurement of ≤10 parts per million (ppm). |
| Number of Participants With at Least a 50 Percent (%) Reduction From Baseline to Week 12 and Week 24 in the Number of Cigarettes Smoked Per Day | Baseline, Week 12, Week 24 | Measured as at least a 50% reduction from baseline in cigarettes smoked per day averaged over the past 7 days at Week 12 and Week 24. |
| Change From Baseline to Week 12 and Week 24 in the Number of Cigarettes Smoked Per Day | Baseline, Week 12, Week 24 | Measured as mean number of cigarettes smoked per day averaged over the past 7 days at Week 12 and Week 24. |
| Number of Participants With 7-day Point Prevalence of Non-smoking at Week 12 | Week 12 | 7-day point prevalence of non-smoking measured as the number of participants who maintained complete abstinence from cigarette smoking or other nicotine use in the previous 7 days before the Week 12 visit and had an end-expiratory carbon monoxide (CO) measurement of ≤10 parts per million (ppm). |
Countries
Canada, United States
Participant flow
Pre-assignment details
Double-blind treatment phase Week 1 to Week 12. Treatment discontinued at Week 12 and participants continued in Post treatment phase (non-treatment follow up) up to Week 24. Participants could discontinue treatment at any time during treatment phase and remain on study through the non-treatment follow up period.
Participants by arm
| Arm | Count |
|---|---|
| Varenicline Varenicline 0.5 milligrams (mg) once a day (QD) for 3 days followed by titration to 0.5 mg twice a day (BID) for 4 days, then 1 mg BID up to Week 12. | 85 |
| Placebo Placebo (matching study treatment) 0.5 mg QD for 3 days followed by titration to 0.5 mg BID for 4 days, then 1 mg BID up to Week 12. | 43 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Post Treatment Phase | Death | 1 | 0 |
| Post Treatment Phase | Lost to Follow-up | 4 | 1 |
| Post Treatment Phase | Other | 1 | 0 |
| Post Treatment Phase | Withdrawal by Subject | 4 | 2 |
| Treatment Phase | Adverse Event | 3 | 0 |
| Treatment Phase | Lost to Follow-up | 2 | 2 |
| Treatment Phase | Other | 4 | 1 |
| Treatment Phase | Randomized, not treated | 1 | 0 |
| Treatment Phase | Withdrawal by Subject | 4 | 0 |
Baseline characteristics
| Characteristic | Varenicline | Placebo | Total |
|---|---|---|---|
| Age, Customized 18 to 34 years | 33 participants | 11 participants | 44 participants |
| Age, Customized 35 to 44 years | 10 participants | 9 participants | 19 participants |
| Age, Customized 45 to 64 years | 42 participants | 23 participants | 65 participants |
| Number of participants with suicidal behavior and / or ideation on Columbia Suicide Severity Rating | 0 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 20 Participants | 10 Participants | 30 Participants |
| Sex: Female, Male Male | 65 Participants | 33 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 48 / 84 | 25 / 43 |
| serious Total, serious adverse events | 5 / 84 | 4 / 43 |
Outcome results
Primary
Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Negative Symptoms Score
PANSS includes 30 items rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme) organized as 7 positive symptom subscale items, 7 negative symptom subscale items and 16 general psychopathology items. Negative symptoms (deficit features) associated with schizophrenia (blunted affect, emotional withdrawal, poor rapport, and passive / apathetic social withdrawal) are rated on a scale from 1 (absent) to 7 (extreme); total negative subscale scores range from 7 to 49 with higher scores indicating more extreme symptoms.
Time frame: Baseline to Week 12
Population: Safety analysis set; (n)=number of participants with analyzable data at observation for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Negative Symptoms Score | Baseline mean | 14.75 scores on a scale | Standard Deviation 4.12 |
| Varenicline | Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Negative Symptoms Score | Mean change at Week 12 (n=68, 39) | -1 scores on a scale | Standard Deviation 3.37 |
| Placebo | Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Negative Symptoms Score | Baseline mean | 14.79 scores on a scale | Standard Deviation 4.95 |
| Placebo | Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Negative Symptoms Score | Mean change at Week 12 (n=68, 39) | -1.33 scores on a scale | Standard Deviation 2.97 |
Primary
Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Positive Symptoms Score
PANSS includes 30 items rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme) organized as 7 positive symptom subscale items, 7 negative symptom subscale items and 16 general psychopathology items. Positive symptoms (productive symptoms) associated with schizophrenia (delusions, conceptual disorganization, and hallucinatory behavior) are rated on a scale from 1 (absent) to 7 (extreme); total positive subscale scores range from 7 to 49 with higher scores indicating more extreme symptoms.
Time frame: Baseline to Week 12
Population: Safety analysis set; (n)=number of participants with analyzable data at observation for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Positive Symptoms Score | Baseline mean | 13.43 scores on a scale | Standard Deviation 3.23 |
| Varenicline | Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Positive Symptoms Score | Mean change at Week 12 (n=68, 39) | -1.87 scores on a scale | Standard Deviation 3.34 |
| Placebo | Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Positive Symptoms Score | Baseline mean | 13.53 scores on a scale | Standard Deviation 4.15 |
| Placebo | Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Positive Symptoms Score | Mean change at Week 12 (n=68, 39) | -1.33 scores on a scale | Standard Deviation 2.83 |
Primary
Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Total Score
PANSS includes 30 items rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme) organized as 7 positive symptom subscale items, 7 negative symptom subscale items and 16 general psychopathology items. Total scores range from 30 to 210 with higher scores indicating more extreme symptoms.
Time frame: Baseline to Week 12
Population: Safety analysis set; (n)=number of participants with analyzable data at observation for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Total Score | Baseline mean | 55.88 scores on a scale | Standard Deviation 9.5 |
| Varenicline | Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Total Score | Mean change at Week 12 (n=68, 39) | -5.19 scores on a scale | Standard Deviation 8.99 |
| Placebo | Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Total Score | Baseline mean | 54.47 scores on a scale | Standard Deviation 10.67 |
| Placebo | Change From Baseline to Week 12 in Positive and Negative Syndrome Scale (PANSS): Total Score | Mean change at Week 12 (n=68, 39) | -3.46 scores on a scale | Standard Deviation 7.52 |
Primary
Change From Baseline to Week 12 in Simpson Angus Rating Scale (SARS)
10-item rating scale to assess the severity of extrapyramidal symptoms rated on a 5-point scale 0 (normal) to 4 (highest severity). Items measured are gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella tap, tremor, and salivation. Global score calculated by summing individual item scores and dividing by the total number of items; range is 0 to 40 with higher scores indicating greater severity.
Time frame: Baseline to Week 12
Population: Safety analysis set; (n)=number of participants with analyzable data at observation for varenicline and placebo, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | Change From Baseline to Week 12 in Simpson Angus Rating Scale (SARS) | Mean change at Week 12 (n=68, 39) | -0.42 scores on a scale | Standard Deviation 1.341 |
| Varenicline | Change From Baseline to Week 12 in Simpson Angus Rating Scale (SARS) | Baseline mean | 1.452 scores on a scale | Standard Deviation 2.061 |
| Placebo | Change From Baseline to Week 12 in Simpson Angus Rating Scale (SARS) | Mean change at Week 12 (n=68, 39) | 0.102 scores on a scale | Standard Deviation 1.984 |
| Placebo | Change From Baseline to Week 12 in Simpson Angus Rating Scale (SARS) | Baseline mean | 1.139 scores on a scale | Standard Deviation 1.846 |
Primary
Change From Baseline to Week 24 in Positive and Negative Syndrome Scale (PANSS): Negative Symptoms Score
PANSS includes 30 items rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme) organized as 7 positive symptom subscale items, 7 negative symptom subscale items and 16 general psychopathology items. Negative symptoms (deficit features) associated with schizophrenia (blunted affect, emotional withdrawal, poor rapport, and passive / apathetic social withdrawal) are rated on a scale from 1 (absent) to 7 (extreme); total negative subscale scores range from 7 to 49 with higher scores indicating more extreme symptoms.
Time frame: Baseline to Week 24
Population: Safety analysis set; N=number of participants with analyzable data at observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Change From Baseline to Week 24 in Positive and Negative Syndrome Scale (PANSS): Negative Symptoms Score | -1.43 scores on a scale | Standard Deviation 3.68 |
| Placebo | Change From Baseline to Week 24 in Positive and Negative Syndrome Scale (PANSS): Negative Symptoms Score | -0.68 scores on a scale | Standard Deviation 3.76 |
Primary
Change From Baseline to Week 24 in Positive and Negative Syndrome Scale (PANSS): Positive Symptoms Score
PANSS includes 30 items rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme) organized as 7 positive symptom subscale items, 7 negative symptom subscale items and 16 general psychopathology items. Positive symptoms (productive symptoms) associated with schizophrenia (delusions, conceptual disorganization, and hallucinatory behavior) are rated on a scale from 1 (absent) to 7 (extreme); total positive subscale scores range from 7 to 49 with higher scores indicating more extreme symptoms.
Time frame: Baseline to Week 24
Population: Safety analysis set; N=number of participants with analyzable data at observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Change From Baseline to Week 24 in Positive and Negative Syndrome Scale (PANSS): Positive Symptoms Score | -1.49 scores on a scale | Standard Deviation 3.8 |
| Placebo | Change From Baseline to Week 24 in Positive and Negative Syndrome Scale (PANSS): Positive Symptoms Score | -1.68 scores on a scale | Standard Deviation 2.82 |
Primary
Change From Baseline to Week 24 in Positive and Negative Syndrome Scale (PANSS): Total Score
PANSS includes 30 items rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme) organized as 7 positive symptom subscale items, 7 negative symptom subscale items and 16 general psychopathology items. Total scores range from 30 to 210 with higher scores indicating more extreme symptoms.
Time frame: Baseline to Week 24
Population: Safety analysis set; N=number of participants with analyzable data at observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Change From Baseline to Week 24 in Positive and Negative Syndrome Scale (PANSS): Total Score | -4.77 scores on a scale | Standard Deviation 10.63 |
| Placebo | Change From Baseline to Week 24 in Positive and Negative Syndrome Scale (PANSS): Total Score | -3.27 scores on a scale | Standard Deviation 7.98 |
Primary
Change From Baseline to Week 24 in Simpson Angus Rating Scale (SARS)
10-item rating scale to assess the severity of extrapyramidal symptoms rated on a 5-point scale 0 (normal) to 4 (highest severity). Items measured are gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella tap, tremor, and salivation. Global score calculated by summing individual item scores and dividing by the total number of items; range is 0 to 40 with higher scores indicating greater severity.
Time frame: Baseline to Week 24
Population: Safety analysis set; N=number of participants with analyzable data at observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Change From Baseline to Week 24 in Simpson Angus Rating Scale (SARS) | -0.37 scores on a scale | Standard Deviation 1.253 |
| Placebo | Change From Baseline to Week 24 in Simpson Angus Rating Scale (SARS) | -0.29 scores on a scale | Standard Deviation 1.221 |
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs are any untoward medical occurrence in a clinical investigation participant administered a product or medical device. The event does not need to be causally related to the study treatment or usage. SAEs include any untoward medical occurrence that results in death, are life threatening, requires hospitalization or prolongation of hospitalization, results in disability or incapacity or are a congenital anomaly or birth defect in the offspring of a study participant. Lack of efficacy was to be reported as an AE when it was associated with an SAE.
Time frame: Baseline up to 30 days after last dose of study treatment or up to Week 16
Population: Safety analysis set: all participants who took at least 1 dose of randomized study medication, including partial doses and had a safety measurement. Safety assessed Baseline through Week 12 (treatment phase) plus a 30 day lag period after last dose of study treatment).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 70 participants |
| Varenicline | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 5 participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 4 participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 35 participants |
Primary
Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1
CGI-I: 7-point clinician rated scale ranging from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, to 7=very much worse. Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Scores above 4 reflect worsening of illness state as compared to baseline.
Time frame: Baseline, Week 1
Population: Safety analysis set; N=number of participants with analyzable data at observation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | Much worse | 0 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | Much improved | 3 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | Minimally improved | 4 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | No change | 67 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | Minimally worse | 5 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | Very much worse | 0 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | Very much improved | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | Minimally improved | 3 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | Very much improved | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | Much worse | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | Much improved | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | Minimally worse | 3 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | Very much worse | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 1 | No change | 37 participants |
Primary
Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12
CGI-I: 7-point clinician rated scale ranging from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, to 7=very much worse. Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Scores above 4 reflect worsening of illness state as compared to baseline.
Time frame: Baseline, Week 12
Population: Safety analysis set; N=number of participants with analyzable data at observation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | Minimally improved | 5 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | Minimally worse | 6 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | Very much worse | 0 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | Much worse | 0 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | No change | 55 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | Much improved | 1 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | Very much improved | 1 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | Very much worse | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | Very much improved | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | Much improved | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | Minimally improved | 4 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | No change | 35 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | Minimally worse | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 12 | Much worse | 0 participants |
Primary
Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24
CGI-I: 7-point clinician rated scale ranging from 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, to 7=very much worse. Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Scores above 4 reflect worsening of illness state as compared to baseline.
Time frame: Baseline, Week 24
Population: Safety analysis set; N=number of participants with analyzable data at observation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | Very much improved | 2 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | Very much worse | 0 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | Much improved | 2 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | Minimally improved | 8 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | No change | 46 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | Minimally worse | 2 participants |
| Varenicline | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | Much worse | 1 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | No change | 31 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | Minimally worse | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | Minimally improved | 5 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | Very much worse | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | Very much improved | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | Much worse | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 | Much improved | 1 participants |
Primary
Number of Participants With Psychiatric Adverse Events
Psychiatric Adverse Event symptoms included, but were not restricted to, depression, anxiety, hostility, perceptual / thinking disturbance, suicidal ideation, or suicidal behavior based on clinical judgment and use of the Positive and Negative Syndrome Scale and Columbia Classification Algorithm of Suicide assessments.
Time frame: Baseline up to Week 24
Population: Safety analysis set; Safety assessed Baseline through Week 12 (treatment phase) plus a 30 day lag period after last dose of study treatment). Neuropsychiatric events assessed through Week 24.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants With Psychiatric Adverse Events | Abnormal dreams | 6 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Anxiety | 4 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Depressed mood | 2 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Depression | 4 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Hallucination auditory | 4 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Hallucination visual | 1 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Insomnia | 8 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Nervousness | 1 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Nightmare | 1 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Panic reaction | 1 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Paranoia | 2 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Restlessness | 1 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Sleep disorder | 1 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Suicidal ideation | 5 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Suicide attempt | 1 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Tension | 1 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Aggression | 0 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Agitation | 0 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Initial insomnia | 1 participants |
| Varenicline | Number of Participants With Psychiatric Adverse Events | Psychiatric symptom | 1 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Psychiatric symptom | 0 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Abnormal dreams | 4 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Agitation | 1 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Paranoia | 0 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Restlessness | 0 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Depressed mood | 1 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Aggression | 1 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Depression | 3 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Sleep disorder | 1 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Hallucination auditory | 1 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Nightmare | 0 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Initial insomnia | 0 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Suicidal ideation | 3 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Insomnia | 2 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Anxiety | 4 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Nervousness | 0 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Suicide attempt | 0 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Hallucination visual | 0 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Panic reaction | 0 participants |
| Placebo | Number of Participants With Psychiatric Adverse Events | Tension | 0 participants |
Primary
Number of Participants With Shift From Baseline to Week 12 in Clinical Global Impressions Scale-Severity (CGI-S) Score
CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1=normal, not ill at all, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill patients. Higher scores reflect higher severity of current illness states.
Time frame: Baseline (Bsl) to Week 12
Population: Safety analysis set; N=number of participants with evaluable data at observation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants With Shift From Baseline to Week 12 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Mildly ill Bsl to Moderately ill Week 12 | 1 participants |
| Varenicline | Number of Participants With Shift From Baseline to Week 12 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Moderately ill Bsl to Mildly ill Week 12 | 4 participants |
| Varenicline | Number of Participants With Shift From Baseline to Week 12 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Moderately ill Bsl to Borderline ill Week 12 | 1 participants |
| Varenicline | Number of Participants With Shift From Baseline to Week 12 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Markedly ill Bsl to Moderately ill Week 12 | 1 participants |
| Varenicline | Number of Participants With Shift From Baseline to Week 12 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Mildly ill Bsl to Borderline ill Week 12 | 1 participants |
| Placebo | Number of Participants With Shift From Baseline to Week 12 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Markedly ill Bsl to Moderately ill Week 12 | 0 participants |
| Placebo | Number of Participants With Shift From Baseline to Week 12 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Mildly ill Bsl to Borderline ill Week 12 | 0 participants |
| Placebo | Number of Participants With Shift From Baseline to Week 12 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Mildly ill Bsl to Moderately ill Week 12 | 1 participants |
| Placebo | Number of Participants With Shift From Baseline to Week 12 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Moderately ill Bsl to Borderline ill Week 12 | 0 participants |
| Placebo | Number of Participants With Shift From Baseline to Week 12 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Moderately ill Bsl to Mildly ill Week 12 | 1 participants |
Primary
Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score
CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1=normal, not ill at all, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill patients. Higher scores reflect higher severity of current illness states.
Time frame: Baseline to Week 24
Population: Safety analysis set; N=number of participants with evaluable data at observation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Mildly ill Bsl to Borderline ill Week 24 | 1 participants |
| Varenicline | Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Mildly ill Bsl to Moderately ill Week 24 | 1 participants |
| Varenicline | Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Mildly ill Bsl to Markedly ill Week 24 | 1 participants |
| Varenicline | Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Moderately ill Bsl to Borderline ill Week 24 | 1 participants |
| Varenicline | Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Moderately ill Bsl to Mildly ill Week 24 | 5 participants |
| Varenicline | Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Markedly ill Bsl to Moderately ill Week 24 | 1 participants |
| Placebo | Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Moderately ill Bsl to Mildly ill Week 24 | 1 participants |
| Placebo | Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Mildly ill Bsl to Borderline ill Week 24 | 0 participants |
| Placebo | Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Moderately ill Bsl to Borderline ill Week 24 | 0 participants |
| Placebo | Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Mildly ill Bsl to Moderately ill Week 24 | 1 participants |
| Placebo | Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Markedly ill Bsl to Moderately ill Week 24 | 0 participants |
| Placebo | Number of Participants With Shift From Baseline to Week 24 in Clinical Global Impressions Scale-Severity (CGI-S) Score | Mildly ill Bsl to Markedly ill Week 24 | 0 participants |
Primary
Number of Participants With Suicidal Behavior and / or Ideation (Yes Response) on the Columbia Suicide Severity Rating Scale (C-SSRS) During the Treatment Phase
C-SSRS is a clinician rated assessment of suicidal behavior and / or intent categorized as: Suicidal behavior=a yes response to any of 5 suicidal behavior questions (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide); Suicidal ideation=a yes response to any one of 5 suicidal ideation questions which includes wish to be dead, and 4 different categories of active suicidal ideation (thought, thought with method, thought with intent, thought with plan and intent).
Time frame: Week 1 to Week 12 (Treatment phase)
Population: Safety analysis set; N=number of participants assessed for suicidal behavior and / or ideation. Yes response includes participants with continued or new suicidal behavior and / or ideation. Treatment phase includes a 7 day lag after last dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Number of Participants With Suicidal Behavior and / or Ideation (Yes Response) on the Columbia Suicide Severity Rating Scale (C-SSRS) During the Treatment Phase | 9 participants |
| Placebo | Number of Participants With Suicidal Behavior and / or Ideation (Yes Response) on the Columbia Suicide Severity Rating Scale (C-SSRS) During the Treatment Phase | 4 participants |
Primary
Number of Participants With Suicidal Behavior or Suicical Ideation (Yes Response ) on the Columbia Suicide-Severity Rating Scale (C-SSRS) During the Post Treatment Phase
C-SSRS is a clinician rated assessment of suicidal behavior and / or intent categorized as: Suicidal behavior=a yes response to any of 5 suicidal behavior questions (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide); Suicidal ideation=a yes response to any one of 5 suicidal ideation questions which includes wish to be dead, and 4 different categories of active suicidal ideation (thought, thought with method, thought with intent, thought with plan and intent).
Time frame: Week 13 to Week 24 (Post treatment phase)
Population: Safety analysis set; N=number of participants assessed for suicidal behavior and / or ideation. Yes response includes participants with new suicidal behavior and / or ideation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Number of Participants With Suicidal Behavior or Suicical Ideation (Yes Response ) on the Columbia Suicide-Severity Rating Scale (C-SSRS) During the Post Treatment Phase | 6 participants |
| Placebo | Number of Participants With Suicidal Behavior or Suicical Ideation (Yes Response ) on the Columbia Suicide-Severity Rating Scale (C-SSRS) During the Post Treatment Phase | 0 participants |
Secondary
Change From Baseline to Week 12 and Week 24 in the Number of Cigarettes Smoked Per Day
Measured as mean number of cigarettes smoked per day averaged over the past 7 days at Week 12 and Week 24.
Time frame: Baseline, Week 12, Week 24
Population: FAS; (n)=number of participants with evaluable data at observation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Varenicline | Change From Baseline to Week 12 and Week 24 in the Number of Cigarettes Smoked Per Day | Week 12 (n=68, 39) | -14.23 cigarettes per day |
| Varenicline | Change From Baseline to Week 12 and Week 24 in the Number of Cigarettes Smoked Per Day | Week 24 (n=61, 37) | -9.55 cigarettes per day |
| Placebo | Change From Baseline to Week 12 and Week 24 in the Number of Cigarettes Smoked Per Day | Week 12 (n=68, 39) | -10.58 cigarettes per day |
| Placebo | Change From Baseline to Week 12 and Week 24 in the Number of Cigarettes Smoked Per Day | Week 24 (n=61, 37) | -9.32 cigarettes per day |
Comparison: Week 12 treatment differencep-value: 0.007795% CI: [-6.32, -0.99]ANCOVA
Comparison: Week 24 treatment differencep-value: 0.902295% CI: [-3.99, 3.52]ANCOVA
Secondary
Number of Participants With 7-day Point Prevalence of Non-smoking at Week 12
7-day point prevalence of non-smoking measured as the number of participants who maintained complete abstinence from cigarette smoking or other nicotine use in the previous 7 days before the Week 12 visit and had an end-expiratory carbon monoxide (CO) measurement of ≤10 parts per million (ppm).
Time frame: Week 12
Population: Full analysis set (FAS): all participants randomized into the study who received at least 1 dose of study treatment (formerly referred to as the All subjects analysis set).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Number of Participants With 7-day Point Prevalence of Non-smoking at Week 12 | 16 participants |
| Placebo | Number of Participants With 7-day Point Prevalence of Non-smoking at Week 12 | 2 participants |
p-value: 0.045795% CI: [1.03, 21.78]Regression, Logistic
Secondary
Number of Participants With 7-day Point Prevalence of Non-smoking at Week 24
7-day point prevalence of non-smoking measured as the number of participants who maintained complete abstinence from cigarette smoking or other nicotine use in the previous 7 days before the Week 24 visit and had an end-expiratory carbon monoxide (CO) measurement of ≤10 parts per million (ppm).
Time frame: Week 24
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Number of Participants With 7-day Point Prevalence of Non-smoking at Week 24 | 10 participants |
| Placebo | Number of Participants With 7-day Point Prevalence of Non-smoking at Week 24 | 1 participants |
p-value: 0.090195% CI: [0.75, 50.71]Regression, Logistic
Secondary
Number of Participants With at Least a 50 Percent (%) Reduction From Baseline to Week 12 and Week 24 in the Number of Cigarettes Smoked Per Day
Measured as at least a 50% reduction from baseline in cigarettes smoked per day averaged over the past 7 days at Week 12 and Week 24.
Time frame: Baseline, Week 12, Week 24
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Varenicline | Number of Participants With at Least a 50 Percent (%) Reduction From Baseline to Week 12 and Week 24 in the Number of Cigarettes Smoked Per Day | Week 12 | 54 participants |
| Varenicline | Number of Participants With at Least a 50 Percent (%) Reduction From Baseline to Week 12 and Week 24 in the Number of Cigarettes Smoked Per Day | Week 24 | 34 participants |
| Placebo | Number of Participants With at Least a 50 Percent (%) Reduction From Baseline to Week 12 and Week 24 in the Number of Cigarettes Smoked Per Day | Week 12 | 22 participants |
| Placebo | Number of Participants With at Least a 50 Percent (%) Reduction From Baseline to Week 12 and Week 24 in the Number of Cigarettes Smoked Per Day | Week 24 | 18 participants |
Comparison: Week 12p-value: 0.152495% CI: [0.82, 3.68]Regression, Logistic
Comparison: Week 24p-value: 0.923595% CI: [0.45, 2.05]Regression, Logistic