NDA#21-240 Histamine Dihydrochloride

12/21/00


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Table of Contents

NDA#21-240 Histamine Dihydrochloride

CDER/DODP Review Team

Indication

Outline of FDA Review

Metastatic Melanoma

Prognostic Factors

Regulatory History

Regulatory History

MP-US-M01: Study Design

Statistical Analysis Plan

Statistical Analysis Plan

Statistical Analysis Plan

Review Issue #1

FDA Comments

Median Survival (months): ITT

Hazard Ratio and P-value: ITT

Overall Survival: ITT (Cut-off date: 3/8/00)

Overall Survival: ITT (Cut-off date: 9/8/00)

Overall Survival: ITT (FDA using most recent f/u data)

FDA Comments

FDA Comments

Median Survival (months): Subgroups

Survival in Liver Met Subgroup: N=129 (Cut-off date: 9/8/00)

Survival in No Liver Met Subgroup: N=176 (Cut-off date: 9/8/00)

Survival in Patients with Skin/Node/Lung Only Disease: N=82 (Cut-off date: 9/8/00)

FDA Comments

Secondary endpoint: Response

Difference between FDA’s TTP and the applicant’s

Time to Tumor Progression: FDA Analysis in ITT (N=243)

FDA Comments on Efficacy: ITT

Review Issue #2

FDA Comments

Patient Characteristics in the Liver Subgroup

FDA Comments

Adjusted Survival Analysis of the Liver Subgroup (Cut-off 9/8/00)

FDA Comments

Median Survival (months): Liver Subgroups

FDA Comments

Secondary endpoint: Response in the Liver Subgroup

Time to Tumor Progression: LM Subgroup (N=96)

FDA Comments on Efficacy in the Liver Subgroup

Review Issue #3

PPT Slide

IL-2 Regimen

Histamine/IL-2 Regimen

Compliance with Treatment

MP-US-M01: Safety

Death within 30 Days of Last Dose

Grade 3 Toxicity

Grade 4 Toxicity

Safety from Single Arm Study MA-0103

Safety from Single Arm Study MA-0103

Overall Summary

Overall Summary

Overall Summary

Author: CDER USER