Clinical Review of Protopic Safety, Potential Risk, and Efficacy

4/23/01


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Table of Contents

Clinical Review of Protopic Safety, Potential Risk, and Efficacy

Protopic Safety

Protopic Safety Data Base

Adverse Events--Adults: 3 weeks treatment

Adverse Events--Adults: 3 weeks treatment

Adverse Events--Adults: 12 weeks treatment

Adverse Events--Adults: 12 weeks treatment

Adverse Events--Adults: 6-12 months treatment

Adverse Events--Adults: 6-12 months treatment

Adverse Events--Pediatrics: 3 weeks treatment

Adverse Events--Pediatrics: 3 weeks treatment

Adverse Events--Pediatrics: 12 weeks treatment

Adverse Events--Pediatrics: 12 weeks treatment

Adverse Events--Pediatrics: 1 year treatment

Adverse Events--Pediatrics: 1 year treatment

Lymphadenopathy in Clinical Studies

Lymphadenopathy Etiology

Common Adverse Events: 3 Twelve Week Studies

Common Adverse Events: 2 One Year Studies with 0.1% ointment

Safety Conclusions

Safety Conclusions (cont’d)

Efficacy Database

Study Subjects

Study Protocol

Complete or ? 90% Clearing

Efficacy Outcomes

Power Analysis

-035 and -036 Population Subsets: 0.03% vs. 0.1%

-037 Population Subsets: 0.03% vs. 0.1%

037 Population Subsets: 0.03% vs. 0.1%

Secondary Endpoint Outcomes: 0.03% vs. 0.1%

Efficacy Conclusions:

Efficacy Conclusions (2):

Potential Risk

Systemic Immunosuppression in Organ Transplant Recipients

Lymphoproliferative Disorder in Adults

Lymphoproliferative Disorder in Children

Time from Initiation of Immunosuppression to Development of Lymphoproliferative Disease

Target Trough Whole Blood Levels of Tacrolimus for Immunosuppression in Transplant Patients

Tacrolimus Blood Levels in Pivotal Controlled Studies

Maximum Tacrolimus Blood Concentrations: -037

Maximum Tacrolimus Blood Concentrations: -035,-036

What accounts for the isolated elevated tacrolimus blood levels?

Clinical Outcome and Blood Levels

Percentage of Patients with Moderate Improvement or Better by Week 1

Blood Levels in a Long-term Study

Persistent Blood Tacrolimus Levels in the One Year Study

Persistent Blood Tacrolimus Levels in the One Year Study

Potential Risk: Topical Vs. Systemic Exposure

Potential Risk: Unresolved Issues

Tacrolimus 0.03% vs. 0.1% ointment: 0.03%

Tacrolimus 0.03% vs. 0.1% ointment: 0.1%

Advisory Committee Question #1

Advisory Committee Question #2

Advisory Committee Question #3

Advisory Committee Question #4

Advisory Committee Question #4

Advisory Committee Question #4

Advisory Committee Question #5

Author: CDER User