Smoking Cessation Study for Patients With Schizophrenia or Schizoaffective Disorder

• ClinicalTrials.gov Identifier: NCT00644969
• Recruitment Status: Completed
• First Posted: March 27, 2008
• Results First Posted: April 15, 2011
• Last Update Posted: April 15, 2011
• Sponsor: Pfizer
• Information provided by: Pfizer

Tracking Information

• First Submitted Date: March 21, 2008
• First Posted Date: March 27, 2008
• Results First Submitted Date: March 23, 2011
• Results First Posted Date: April 15, 2011
• Last Update Posted Date: April 15, 2011
• Study Start Date: May 2008
• Actual Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 23, 2011)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).
• Number of Participants With Shift From Baseline to Week 12 in Clinical Global Impressions Scale-Severity (CGI-S) Score [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Clinical Global Impression of Improvement Scale (CGI-I) Score at Week 24 [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: March 21, 2008): Safety assessments: adverse events, PANSS, SARS, C-SSRS, CGI-S, and CGI-I [ Time Frame: 12 weeks ]

Current Secondary Outcome Measures (submitted: March 23, 2011)

• Number of Participants With 7-day Point Prevalence of Non-smoking at Week 12 [ Time Frame: 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).
• Number of Participants With 7-day Point Prevalence of Non-smoking at Week 24 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: March 21, 2008)

• 7-day point prevalence of non-smoking at Week 12 [ Time Frame: 7 days ]
• 7- day point prevalence of non-smoking at Week 24 [ Time Frame: 7 days ]
• Proportion of subjects with 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: 7 days ]
• Change from baseline in mean number of cigarettes smoked per day over the past 7 days at Week 12 and Week 24 [ Time Frame: 7 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Smoking Cessation Study for Patients With Schizophrenia or Schizoaffective Disorder
• Official Title: 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.
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator)
• Condition: Smoking Cessation

Intervention

• Drug: placebo
  Randomization 2:1 treatment to placebo
• Drug: varenicline (CP-526,555)
  One week of titration up to 1mg bid and 11 weeks of dosing at 1mg bid
  Other Name: Chantix, Champix

Study Arms

• Placebo Comparator: Placebo Arm
  Randomization 2:1 treatment to placebo
  Intervention: Drug: placebo
• Active Comparator: Treatment Arm
  Intervention: Drug: varenicline (CP-526,555)

• Publications *: Williams JM, Anthenelli RM, Morris CD, Treadow J, Thompson JR, Yunis C, George TP. A randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of varenicline for smoking cessation in patients with schizophrenia or schizoaffective disorder. J Clin Psychiatry. 2012 May;73(5):654-60. doi: 10.4088/JCP.11m07522. Erratum in: J Clin Psychiatry. 2012 Jul;73(7):1035.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 27, 2010): 128
• Original Estimated Enrollment (submitted: March 21, 2008): 120
• Actual Study Completion Date: April 2010
• Actual Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00644969
• Other Study ID Numbers: A3051072
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

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

• PRS Account: Pfizer
• Verification Date: March 2011