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SS- 1 Use of Clozaril ® and Zyprexa ® as Concomitant Medication (Simultaneous Use)  69 Clozaril patients used Olanzapine as concomitant medication  17.

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Presentation on theme: "SS- 1 Use of Clozaril ® and Zyprexa ® as Concomitant Medication (Simultaneous Use)  69 Clozaril patients used Olanzapine as concomitant medication  17."— Presentation transcript:

1 SS- 1 Use of Clozaril ® and Zyprexa ® as Concomitant Medication (Simultaneous Use)  69 Clozaril patients used Olanzapine as concomitant medication  17 Zyprexa patients used Clozapine as concomitant medication  WLW analysis results after excluding above patients (P =.021) ClozarilZyprexa N = 421N = 473 Type 180135 Type 295154

2 SS- 2 Suicide History at Baseline Patients, n (%) Clozaril ® Zyprexa ® N = 490N = 490 Suicide history Lifetime attempts, n 490 489 077(15.7)86(17.6) 1124(25.3)99(20.2) 2 - 3154(31.4)157(32.0) 4 - 560(12.2)75(15.3) > 575(15.3)72(14.7) Missing0(0.0)1(0.2) Mean3.6(7.5)3.2(4.5) Median 2 2 Range 0 - 120 0 - 50 Suicide history Lifetime attempts, n 490 489 077(15.7)86(17.6) 1124(25.3)99(20.2) 2 - 3154(31.4)157(32.0) 4 - 560(12.2)75(15.3) > 575(15.3)72(14.7) Missing0(0.0)1(0.2) Mean3.6(7.5)3.2(4.5) Median 2 2 Range 0 - 120 0 - 50 CSR ABA 451-Clozaril §Treatment resistance determined by clinical assessment. 8

3 SS- 3 Number and Percent of Type 1 or Type 2 Events by Diagnosis Subgroup Clozaril ® Zyprexa ® Eventsn/N%K-M § (%)n/N%K-M § (%) Schizophrenia Type 151/30017.019.582/30926.529.3 Type 267/30022.325.998/30931.735.1 Schizoaffective Type 151/19026.831.059/18132.637.2 Type 253/19027.832.163/18134.839.5 19 §Kaplan-Meier estimates of cumulative probability of event at Week 104.

4 SS- 4 Retrieved Dropout Patients With Type 1 Events Events, (%) Clozaril ® N = 61 Zyprexa ® N = 60 No Type 1 event41 (67.2)35 (58.3) Type 1 event20 (32.8)25 (41.7) 22 12 Clozaril and 3 Zyprexa patients had Type 1 events after discontinuation.

5 SS- 5 WLW and Cox’s Analyses of Type 1 and Type 2 Events Excluding Followup Data After Discontinuations Hazard ratio95% CIP value WLW.006 Cox’s proportional hazard analysis Type 10.660.51, 0.87.003 Type 20.700.55, 0.90.005

6 SS- 6 Influence of Change in Blinded Psychiatrist Number (%) of Patients With Worsening in CGI-SS-BP of Type 2 Event Clozaril ® Zyprexa ® Worsening CGI-SS-BP, score 6 or 7 (with a change in BP) 138 Change in a BP occurred after Type 2 event 75 Change in BP before Type 2 event63 19

7 SS- 7 Agreement Between SMB and Blinded Psychiatrist With Regard to Occurrence of Type 1 Events  Concordance 90.5% (84% all)  2 possible explanations for discrepancies – BP evaluation of Type 1 event was not subject to challenge. All SMB determinations required consensus of all 3 SMB members – SMB reviewed all PEP (n = 577) whereas BP assessed on average 8 - 9 PEPs (range (0 - 42); less variability in reviewing PEP by SMB could be expected  Primary endpoint, patient’s first SMB-determined Type 1 event, prospectively defined and agreed upon with FDA  High degree of agreement between SMB and BPs regarding this endpoint confirms validity of endpoint for demonstrating efficacy in patients at risk for suicidal behavior 19

8 SS- 8 Cox’s Analyses of Patients With Type 1 Events as Determined by SMB and BP 19 Hazard ratio95% CIP value SMB0.740.57, 0.96.021 BP0.860.67, 1.11.236 Both SMB and BP agreed 0.840.64, 1.10.195

9 SS- 9 Number of Patients with Score of 6 or 7 on CGI-SS-BP (Type 2 Event) Clozaril ® 38 Zyprexa ® 42 CGI-SS-BP not assessed after discontinuation

10 SS- 10 ClozarilZyprexa SchizoaffectiveN = 190N = 181 Baseline mean81.980.5 Mean change from baseline -20.4-19.9 P value<.001 SchizophreniaN = 300N = 309 Baseline mean86.783.8 Mean change from baseline -21.3-18.1 P value<.001


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