Boehringer chooses dose for phase III studies of tipranavir/ritonavir PI combination
Boehringer Ingelheim (BI) is developing tipranavir, the first non-peptidic protease inhibitor (NPPI). The company recently submitted preliminary results from ongoing Phase II clinical trials to the US Food and Drug Administration (FDA). This data is the basis for initiating the pivotal Phase III trials for tipranavir.
After reviewing the data from the Phase IIb dose optimisation study and other clinical studies performed to date, the FDA has concurred with BI’s recommendation of 500 mg of tipranavir (TPV) taken with 200 mg of ritonavir (r) twice daily. This dose combination will be used in the upcoming RESIST Phase III clinical trials and other clinical studies.
Background on Choosing the Dose
The following three doses of tipranavir were studied in the Phase IIb dose optimisation study (BI 1182.52):
- 500mg /100mg TPV/r
- 500mg /200mg TPV/r
- 750mg /200mg TPV/r
These doses were chosen because data from earlier studies showed that each dose achieved:
- the preliminary target plasma concentration
- acceptable virologic suppression
- tolerable adverse event profile
Each regimen was given twice daily in combination with a genotypically-defined optimised background regimen. All eligible patients must have received drugs from both the NRTI and NNRTI classes, at least two protease inhibitor (PI) regimens and must have had virus containing at least one primary PI mutation prior to enrolment. BI examined viral load reductions through 14 days and safety endpoints through 28 days. The study was conducted at 85 sites in nine countries – the United States, Canada, Australia, the Netherlands, Italy, Spain, France, Germany and the United Kingdom.
The tipranavir, 500mg / ritonavir, 200mg dose was chosen as the optimal dose to pursue because data from the Phase IIb study showed that it provided the most favourable benefit/risk profile (ie viral load suppression and safety) in this highly treatment experienced patient population. These data will be presented publicly in February 2003 at the 10th Annual Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.
The dose is now being inserted into the RESIST 1 and RESIST 2 study protocols, and these are being sent to investigators and Internal Review Boards/Ethical Review Committees.
Source: Boehringer Ingelheim