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
PPT Slide
PPT Slide
PPT Slide
PPT Slide
PPT Slide
PPT Slide
Recrudescence with Artesunate
Cumulative Number of Recrudescences at Day 28
Cumulative Recrudescence Rates Across Time in Study 6
PPT Slide
PPT Slide
Recrudescence with Artesunate
Summary
Summary (cont’d)
|