Olanzapine Plus Carbamazepine Versus Carbamazepine Alone in the Treatment of Manic or Mixed Episodes Associated With Bipolar I Disorder

简要总结

主要结局

次要结局

• Using the following assessments:
• To compare the efficacy and safety of up to 6 weeks of double-blind, concomitant use of olanzapine plus carbamazepine to the concomitant use of placebo plus carbamazepine
• rate of response and time to response over 6 weeks of the double-blind treatment phase, with response defined as a reduction of 50% or more in the YMRS total score from baseline to endpoint.
• rate of remission and time to remission of mania over 6 weeks of the double-blind treatment phase, with remission defined as a score less than or equal to 12 on the YMRS total score at endpoint
• reductions from baseline to the endpoint of the 6-week, double-blind treatment phase on the Montgomery-Asberg Depression Rating Scale (MADRS) total score
• reductions from baseline to the endpoint of the 6-week, double-blind treatment phase on the Clinical Global Impressions-Bipolar Version Severity of Illness Scale (CGI-BP)score
• rate of switch to depression and time to switch to depression, with switch to depression defined as a baseline MADRS total score less than or equal to 12 followed by
• either a post baseline MADRS total score greater than or equal to 16 over the 6 weeks of the double-blind treatment phase OR, hospitalization due to deterioration in clinical
• symptoms of depression
• longitudinal effects from baseline across visits of the double-blind treatment phase by comparing changes in YMRS total scores
• changes in vital signs and weight, laboratory analytes, and electrocardiograms (ECGs), and the incidence and severity of TEAEs and extrapyramidal symptoms (EPS)
• using the Barnes Akathisia Scale, Simpson-Angus Scale and the AIMS.
• the effect of carbamazepine on the plasma concentration of olanzapine via comparison to historic oral steady-state olanzapine concentrations
• the effect of olanzapine on the plasma concentrations of carbamazepine via a descriptive comparison of the two treatment groups
• Additional secondary objectives are to assess the maintenance of treatment effect and safety of up to 20 weeks of open-label olanzapine-plus-carbamazepine treatment
• using the following measures:
• YMRS total score change from the baseline (Visit 7) to the endpoint of the open-label treatment phase.
• rate of relapse to mania during the open-label treatment phase. Relapse to mania (patients who relapse to a bipolar I mania or mixed episode) is defined by the following:
• patient reaches remission of mania (as defined by a YMRS score less than or equal to 12) by the endpoint of the double-blind treatment phase
• patient obtains a YMRS score greater than or equal to 15 at any time during the open label treatment phase AND/OR becomes hospitalized due to deterioration in clinical symptoms of mania
• rate of switch to depression during open-label treatment phase, with switch to depression defined as a baseline MADRS total score less than or equal to 12 followed by
• either a postbaseline MADRS total score greater than or equal to 16 over the 20 weeks of the open-label treatment phase hospitalization due to deterioration in clinical symptoms of depression
• changes in vital signs and weight, laboratory analytes, and ECGs, and the incidence and severity of TEAEs and EPS using the Barnes Akathisia Scale, Simpson-Angus Scale, and the Abnormal Involuntary Movement Scale (AIMS)