# Presentation: 531186

## 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)**

- 	**Clozaril****	****Zyprexa**
**	****N = 421****	****N = 473**
**Type 1****	****80****	****135**
**Type 2****	****95****	****154**

## Suicide History at Baseline

**	****	****	****Patients, n (%)**
**	****	****Clozaril****®****	****	****Zyprexa****®****	****	****N = 490****	****	****N = 490**

**Suicide history**
**	****Lifetime attempts, n                        ****490****	****                  489**
**	****0****	****77****	****(15.7)****	****86****	****(17.6)**
**	****1****	****124****	****(25.3)****	****99****	****(20.2)****	****2 - 3****	****154****	****(31.4)****	****157****	****(32.0)**
**	****4 - 5****	****60****	****(12.2)****	****75****	****(15.3)**
**	****> 5****	****75****	****(15.3)****	****72****	****(14.7)**
**	****Missing****	****0****	****(0.0)****	****1****	****(0.2)**
**	****Mean****	****3.6****	****(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**

## Number and Percent of Type 1 or Type 2 Events by Diagnosis Subgroup

|  | Clozaril® |  |  |  | Zyprexa® |  |  |  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Events | n/N | % | K-M§ (%) |  | n/N |  | % | K-M§ (%) |
| Schizophrenia |  |  |  |  |  |  |  |  |
| Type 1 | 51/300 | 17.0 |  | 19.5 |  | 82/309 | 26.5 | 29.3 |
| Type 2 | 67/300 | 22.3 |  | 25.9 |  | 98/309 | 31.7 | 35.1 |
| Schizoaffective |  |  |  |  |  |  |  |  |
| Type 1 | 51/190 | 26.8 |  | 31.0 |  | 59/181 | 32.6 | 37.2 |
| Type 2 | 53/190 | 27.8 |  | 32.1 |  | 63/181 | 34.8 | 39.5 |

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**§Kaplan-Meier estimates of cumulative probability of event at Week 104.**

## Retrieved Dropout Patients With Type 1 Events

|  | Events, (%) |  |
| --- | --- | --- |
|  | Clozaril®
N = 61 | Zyprexa®
N = 60 |
| No Type 1 event | 41 (67.2) | 35 (58.3) |
| Type 1 event | 20 (32.8) | 25 (41.7) |

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**12 Clozaril and 3 Zyprexa patients had Type 1 events after discontinuation.**

## WLW and Cox’s Analyses of Type 1 and Type 2 Events Excluding Followup Data After Discontinuations

## 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) | 13
 | 8
 |
| Change in a BP occurred after         Type 2 event | 7
 | 5
 |
| Change in BP before Type 2 event | 6 | 3 |

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## 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

## Cox’s Analyses of Patients With Type 1 Events as Determined by SMB and BP

- 19

|  | Hazard ratio | 95% CI | P value |
| --- | --- | --- | --- |
| SMB | 0.74 | 0.57, 0.96 | .021 |
| BP | 0.86 | 0.67, 1.11 | .236 |
| Both SMB and BP agreed | 0.84 | 0.64, 1.10 | .195 |

## 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**

|  | Clozaril | Zyprexa |
| --- | --- | --- |
| Schizoaffective | N = 190 | N = 181 |
| Baseline mean | 81.9 | 80.5 |
| Mean change from baseline | -20.4 | -19.9 |
| P value | < .001 | < .001 |
| Schizophrenia | N = 300 | N = 309 |
| Baseline mean | 86.7 | 83.8 |
| Mean change from baseline | -21.3 | -18.1 |
| P value | < .001 | < .001 |