Last Thursday (6th February) Boehringer Ingelheim announced the launch of the Phase III clinical trial programme designed to further study the efficacy and safety of tipranavir for use in combination therapy for HIV infection. Phase III of clinical development is the final stage of testing before a drug is submitted to worldwide regulatory authorities for review and consideration for marketing approval.
Tipranavir is the first non-peptidic protease inhibitor (NPPI) in development for the treatment of HIV-1 infection. This means tipranavir can bind more flexibly to the active site of the HIV protease. This flexibility appears to explain why the resistance profile of tipranavir is different from available peptidic PIs.
The Phase III trials will evaluate triple class-experienced patients (that is experience of nucleoside analogues, NNRTIs and protease inhibitors) in more than 280 clinical trial sites worldwide.
Based on available clinical and in vitro data, tipranavir shows activity against multi-drug resistant HIV virus, offering hope for patients with multi-drug resistant virus.
"This is an important milestone in the development of tipranavir," said Dr Andreas Barner, Member of the Board of Managing Directors of Boehringer Ingelheim. "We have designed a clinically relevant Phase III trial program that includes resistance testing for all patients, allows the use of other expanded access HIV/AIDS therapies, and provides access to a significant number of triple class-experienced patients worldwide. It is the largest trial programme ever conducted in this patient population, recruiting over 1,500 patients in total."
The Phase III RESIST (Randomized Evaluation of Strategic Intervention in multi-drug ReSistant patients with Tipranavir) clinical trial programme has been designed to study the safety and efficacy of tipranavir (boosted with low-dose ritonavir) versus a low-dose ritonavir-boosted comparator protease inhibitor (PI) that is chosen by the patient`s physician on the basis of treatment history and baseline resistance testing. Study participants will all be highly treatment-experienced HIV-positive adults. The RESIST Program consists of two Phase III pivotal trials (RESIST 1 and RESIST 2) and two companion trials (study 1182.51 and RESIST 3) available at some sites for even more advanced patients.
RESIST 1 will enroll more than 500 patients in the USA, Canada and Australia. RESIST 2 will enroll more than 800 patients in Europe and in South America. The clinical endpoint for the RESIST 1 study is at 24 weeks and for the RESIST 2 study the endpoints are at 16- and 24 weeks. All participants will receive resistance testing at baseline to determine the optimal drugs to combine with tipranavir, as each patient will receive an individualised background treatment regimen.
Boehringer Ingelheim will also study tipranavir in treatment-naïve adult patients and conduct trials in children. The dose for tipranavir that will be studied in the Phase III clinical program is 500 mg of tipranavir taken with 200 mg of ritonavir (to boost tipranavir drug levels in the body) twice daily.