Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

 

Antiviral Drugs Advisory Committee

 

May 19, 2005

 

FINAL QUESTIONS TO THE COMMITTEE

 

Question 1:

        Do the data demonstrate that tipranavir/ritonavir (TPV/r) is safe and effective for the multi-drug resistant HIV-1 infected population?

 

         If no, what additional data are needed to provide evidence of safety and efficacy?

 

         If yes, please address the appropriate population for TPV/r use considering the following:

        limited inclusion criteria of the RESIST trials

        drug-drug interactions

        resistance information and patterns associated with optimal use

        safety considerations

 

Question 2:

        Given the data on transaminase elevations, please provide your recommendations for:

         TPV/r use in patients with underlying liver disease

         Monitoring and management of hepatotoxicity during clinical use

         Future studies

 

Question 3:

        The limited amount of data in females with HIV infection in the TPV program shows an increased incidence of rash in females. Please provide your recommendations for:

        Investigation of this safety signal in future studies with TPV

 

Question 4:

        Current information indicates the net effect of TPV/r on substrates of CYP1A2, CYP2C9, CYP2C19 and CYP2D6 is not known, and there are competing effects of TPV/r on CYP3A (inhibition) and P-glycoprotein (induction). Please comment on additional post-marketing drug interaction studies.

 

Question 5:

        Given the high inter-patient variability in TPV exposures following fixed doses and exposure (blood levels)-virologic response relationships, could a biomarker such as Cmin/IC50 be used for the individualization of TPV/r therapy? Please discuss the studies that would supplement the data presented today.

 

Question 6

        Please provide your recommendations regarding the display of TPV/r resistance data/analyses in the TPV package insert that would be useful to clinicians.

 

Background referring to Question 6 on next page

 

 

 

 

(Question 6 Continued: Background)

 

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Question 7:

        Please discuss and recommend future study designs /data acquisition for the heavily pretreated population.