A 6-Week Multicenter Trial Of Varenicline Tartrate For Cognitive Impairment In Subjects With Schizophrenia

• CNS-VS-M un-normed composite score [ Time Frame: screening, wk-1,baseline,wk1,3,6 ] [ Designated as safety issue: No ]
• CNS-VS-M un-normed and normed domain scores [ Time Frame: screening, wk-1,baseline, wk1,3,6 ] [ Designated as safety issue: No ]
• University of California San Diego Performance Skills Assessment Brief (UPSA-B) total score [ Time Frame: baseline, wk 1,3,6 ] [ Designated as safety issue: No ]
• Severity Item for Cognitive Impairment-Clinician and Patient Versions (SICI-CV; SICI-PV) [ Time Frame: baseline, wk6 ] [ Designated as safety issue: No ]
• Global Improvement in Cognition Clinician and Patient Versions (GIC-CV;GIC-PV) [ Time Frame: wk 1,3,6 ] [ Designated as safety issue: No ]
• Safety assessments, including adverse events, electrocardiographic assessments, neuropsychiatric assessments (performed weekly), physical exam, and laboratory measures [ Time Frame: weekly ] [ Designated as safety issue: Yes ]

• CNS-VS-M un-normed composite score [ Time Frame: screening, wk-1,baseline,wk1,3,6 ] [ Designated as safety issue: No ]
• CNS-VS-M un-normed and normed domain scores [ Time Frame: screening, wk-1,baseline, wk1,3,6 ] [ Designated as safety issue: No ]
• Univeristy of California San Diego Performance Skills Assessment Brief (UPSA-B) total score [ Time Frame: baseline, wk 1,3,6 ] [ Designated as safety issue: No ]
• Severity Item for Cognitive Impairment-Clinician and Patient Versions (SICI-CV; SICI-PV) [ Time Frame: baseline, wk6 ] [ Designated as safety issue: No ]
• Global Improvement in Cognition Clinician and Patient Versions (GIC-CV;GIC-PV) [ Time Frame: wk 1,3,6 ] [ Designated as safety issue: No ]
• Safety assessments, including adverse events, electrocardiographic assessments, neuropsychiatric assessments (performed weekly), physical exam, and laboratory measures [ Time Frame: weekly ] [ Designated as safety issue: Yes ]

The primary objective of this protocol is to assess the efficacy of two dose strengths of varenicline (0.5 mg BID and 1mg BID) as adjunctive treatment for cognitive impairment in symptomatically stable outpatient schizophrenic subjects who are receiving treatment with atypical antipsychotic medications.

A secondary objective is to evaluate the safety and tolerability of two doses of varenicline in symptomatically stable schizophrenic subjects who are receiving treatment with atypical antipsychotic medications.

• Drug: placebo
  Subjects randomized to placebo will receive matching placebo and follow the titration schedule and dosing schedule of those randomized to varenicline.
• Drug: varenicline
  Subjects randomized to the 0.5 mg arm will be titrated to the full dose during the first week in the following manner: 0.5mg QD x 7 days, then 0.5mg BID for the remainder of the 6 week trial.
  Other Name: Chantix
• Drug: varenicline
  Subjects randomized to the 1mg arm will be titrated to the full dose during the first week in the following manner: 0.5mg QD x 3 days, 0.5mg BID x 4 days, then 1mg BID for the remainder of the 6 week trial.
  Other Name: Chantix, Champix

• Placebo Comparator: placebo
  Intervention: Drug: placebo
• Active Comparator: varenicline 0.5 mg BID
  Intervention: Drug: varenicline
• Active Comparator: varenicline 1mg BID
  Intervention: Drug: varenicline

Inclusion Criteria:

• Have a current diagnosis of schizophrenia
• Subjects must be on ongoing maintenance antipsychotic monotherapy or combination therapy with risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, or paliperidone.
• Evidence of stable symptomatology ≥3 months (eg, no hospitalizations for schizophrenia, no increase in level of psychiatric care due to worsening of symptoms of schizophrenia).

Exclusion Criteria:

• Subjects with a current DSM-IV axis I diagnosis other than schizophrenia.
• Current treatment with conventional antipsychotics (e.g. fluphenazine, haloperidol) or clozapine, or the use of adjunctive anticholinergic treatment.