NDA 203139 Clinical Pharmacology Review – Sildenafil ...

Table of contents 1 Executive Summary .........................................................................................................................4

1.1 Recommendations ...............................................................................................................4

2 Executive Summary .........................................................................................................................5

3 Question Based Review ...................................................................................................................8

3.1 General Attributes of the drug.............................................................................................8

3.2 General Clinical Pharmacology ..........................................................................................8

3.3 Intrinsic Factors.................................................................................................................25

3.4 Extrinsic Factors................................................................................................................26

3.5 General Biopharmaceutics ................................................................................................27

3.6 Analytical Section .............................................................................................................28

4 DRAFT Labeling Recommendations.............................................................................................29

Appendix (CLINICAL PHARMACOLOGY ? Individual Study Review) ...........................................30

List of Tables Table 1. The dosing recommendation in the proposed labeling................................................................... 7

Table 2. Pulmonary Hemodynamics (PVRI) Treatment Comparison to Placebo (n=52) ......................... 13

Table 3. Dose-response for safety of sildenafil in pediatrics during randomized portion of A1481131 .. 16

Table 4. Dose-response for mortality in pediatrics during the long-term extension Study A1481156 ..... 17

Table 5. Dose-response for mortality in pediatrics during the long-term extension Study A1481156 ..... 17

Table 6. Dose titrations by dosing group in long term extension trial ...................................................... 20

Table 7. Shift table for Randomized and Modal Dose Groups, N (deaths)............................................... 20

Table 8. Comparison of Exercise Capacity and Pulmonary Vascular Resistance Index Effect in pediatric

(medium and high doses pooled) and adult (20 mg TID) populations .............................................. 22

Table 9. Sildenafil doses (mg) given TID for the Pivotal trial in Pediatrics (Study A1481131) .............. 23

Table 10. Summary of sildenafil clearance (CL/F) in children 1-20 to ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download