The efficacy of Artesunate rectal suppositories

7/19/02


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Table of Contents

The efficacy of Artesunate rectal suppositories

FDA Review Team for NDA 21-242

Background

Rationale for product development

Goal of applicant

Indication

Rectal artesunate- a suitable candidate?

Clinical pharmacology Adult healthy subjects, 400-mg single dose

Clinical pharmacology

Bioequivalence between formulation in clinical trials and formulation to be marketed

Bioequivalence between formulation in clinical trials and formulation to be marketed (cont.)

Challenge to develop appropriate clinical studies

Challenge to develop appropriate clinical studies

Other problems in modeling the projected use

Other problems in modeling the projected use (cont’d)

Selection of endpoints

Studies of efficacy

Overview of clinical studies

Overview of clinical studies (cont’d)

Drug regimens in pivotal studies

Comment on study drugs

Comment on study drugs (cont’d)

Inclusion and exclusion criteria

Baseline characteristics

Criteria for providing rescue therapy

FDA-defined study endpoints

Study-related events with an impact on clinical results

24-hour clinical success

24-hour parasitological success

28-day recrudescences/new infections

What can we conclude from pivotal studies?

What can we not conclude from the pivotal studies?

Equivalence study with clinical endpoints (014)

Treatment regimen (Study 014)

Study population

Median parasite counts/µl following treatment with 3 formulations of rectal artesunate

Recrudescences/new infections?

Conclusion (study 014)

Studies 003 and 004

Studies 003 and 004

“Consolidation therapy”

Study populations in 003 and 004

24-hour clinical success rate

ᢒ% clearance of baseline parasitemia at 12 and 24 hours

Recurrent parasitemia during 2-3 weeks after therapy

What did we learn from 003 and 004?

Summary

Considerations

Statistical issues

NDA 21-242 Rectal Artesunate

NDA 21-242 – Rectal Artesunate

Parasite Count Endpoint

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Recrudescence with Artesunate

Cumulative Number of Recrudescences at Day 28

Cumulative Recrudescence Rates Across Time in Study 6

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Recrudescence with Artesunate

Summary

Summary (cont’d)

Author: Ruthanna C. Davi