# Presentation: 769312

## Psychopharmacologic Drugs Advisory Committee
November 4, 2002

**November 4, 2002**

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## Clozaril® (clozapine)Introduction and Regulatory Overview

**Roy W. Dodsworth**
**Executive Director****Drug Regulatory Affairs**
**Novartis Pharmaceuticals Corporation**

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## Overview

**Clozaril****®**** is an antipsychotic agent belonging to the dibenzodiazepine class of drugs**
**Considered first “atypical” antipsychotic agent**
**First approved in Austria 1969**
**Original New Drug Application (NDA 19-758)**
**Approved September 26, 1989 **
**Approved in > 150 countries**
**Supplemental New Drug Application (sNDA 19-758/S-047)**
**Filed March 1, 2002**
**Submitted in Canada and Australia**
**Planned submissions worldwide (eg, EU)**

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## Current
Clozaril® is indicated for the management of severely ill schizophrenic patients who fail to respond adequately to standard drug treatment for schizophrenia.

**Clozaril****®**** is indicated for the management of severely ill schizophrenic patients who fail to respond adequately to standard drug treatment for schizophrenia.**

**Clozaril****®**** Indication(s)**

**Proposed Additional**** **
**Clozaril****®**** is indicated for reducing the risk of emergent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at risk for emergent suicidal behavior, based on history and recent clinical state. Suicidal behavior refers to actions by a patient that put him/herself at high risk for death.**

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## Study Supporting New Indication

**I****nternational ****S****uicide ****P****revention ****T****rial (****I****nter****S****e****PT****)**
**A prospective, randomized, international, parallel-group comparison of Clozaril****®****/Leponex****®**** versus Zyprexa****®**** in the reduction of suicidality in patients with schizophrenia or schizoaffective disorder who are at risk for suicide**

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## Key Interactions With the FDA (1)

**Date****	****Action**
**Mar 31, 1993****	****FDA requests assessment of ****	****	****mortality**
**May 31, 1995****	****Novartis submits “*****Mortality of ******	******People Using Clozapine” *****report**
**Aug 15, 1995****	****Novartis submits supplemental****	****application for reduction of ****	****	****suicidal behavior**
**Feb 23, 1996****	****FDA issues “not approvable” letter**

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## Key Interactions With the FDA (2)

**Date****	****Action**
**Jan 16, 1998****	****Novartis submits InterSePT protocol**
**Mar 1, 2002****	****Novartis submits NDA 19-758/S-047**
**Aug 30, 2002****	****FDA issues “approvable” letter**
**Nov 4, 2002****	****Advisory Committee Meeting**

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## Objectives of Novartis Presentations

**To demonstrate that suicidal behavior in patients with schizophrenia and schizoaffective disorder represents a new indication**
**To demonstrate that the results from the InterSePT study, together with those from other published studies, support the efficacy of Clozaril****®**** in the treatment of suicidal behavior in this patient population**

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## Agenda

**Introduction . . . . . . . . . . . . . . . . . . . . . . .Roy W. Dodsworth**
**Overview of Suicidal Behavior. . . .****	****Herbert Y. Meltzer, MD**
**InterSePT Study Results . . . . . . . . . . .****	****Rocco Zaninelli, MD**
**Suicide Monitoring Board . . . . . K. Ranga Rama Krishnan,                                                          ****	****MB, ChB**
**	****Benefit/Risk . . . . . . . . . . . . . . . . . . . . . . .****	****John M. Kane, MD**
**Question and Answer Moderator. . . .****	****Rocco Zaninelli, MD**

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