Smoking Cessation Study for Patients With Schizophrenia or Schizoaffective Disorder

Study Overview
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Brief Summary
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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
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This is a safety study.

Official Title
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A Phase 3B 12-Week, Double -Blind, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of Varenicline Tartrate (CP-526,555) 1 mg BID for Smoking Cessation in Subjects With Schizophrenia and Schizoaffective Disorder.

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: placebo
* Drug: varenicline (CP-526,555)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Arm<br>Randomization 2:1 treatment to placebo | Drug: placebo<br>* Randomization 2:1 treatment to placebo<br>|
| Active Comparator: Treatment Arm<br> | Drug: varenicline (CP-526,555)<br>* One week of titration up to 1mg bid and 11 weeks of dosing at 1mg bid<br>* Other names: Chantix, Champix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline up to 30 days after last dose of study treatment or up to Week 16 | 
| 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. | Baseline up to Week 24 | 
| 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. | Baseline to Week 12 | 
| 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. | Baseline to Week 24 | 
| 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. | Baseline to Week 12 | 
| 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. | Baseline to Week 24 | 
| 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. | Baseline to Week 12 | 
| 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. | Baseline to Week 24 | 
| 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. | Baseline to Week 12 | 
| 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. | Baseline to Week 24 | 
| 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). | Week 1 to Week 12 (Treatment phase) | 
| 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). | Week 13 to Week 24 (Post treatment phase) | 
| 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. | Baseline (Bsl) to Week 12 | 
| 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. | Baseline to Week 24 | 
| 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. | Baseline, Week 1 | 
| 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. | Baseline, Week 12 | 
| 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. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Week 12 | 
| 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). | Week 24 | 
| 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. | Baseline, Week 12, Week 24 | 
| 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. | Baseline, Week 12, Week 24 |