In a Phase II dose-finding study of highly treatment-experienced HIV-positive adults, three tipranavir doses showed significant reductions in viral load. Researchers evaluated more than 200 patients, and determined the maximum tolerated dose and the resistance profile of tipranavir in this advanced treatment group. Tipranavir is the first non-peptidic protease inhibitor (NPPI), and is in Phase III clinical development for the treatment of HIV-1 infection. Study results were presented today at the 10th Conference on Retroviruses and Opportunistic Infections in Boston.
"To find the best dose for use in our Phase III RESIST trials, we began with three doses in Phase II and found one that we considered safe while still reducing the viral load in these advanced patients," said Scott McCallister, Senior Associate Director, Clinical Virology at Boehringer Ingelheim. "These data show that all three doses reduce viral load, yet the 500mg/200mg dose had the most favorable safety and pharmacokinetic profile. We determined that 500mg/200mg is the best dose to continue studying in the highly treatment-experienced participating in our pivotal trials."
Tipranavir recently entered Phase III of clinical development -- the final stage of testing prior to the submission of data to worldwide regulatory authorities for review and consideration for marketing approval. The two large-scale, international pivotal trials (RESIST 1 and RESIST 2) are designed to compare the effect of tipranavir to a ritonavir-boosted comparator PI in HIV+ adults that have taken at least two PI-based treatment regimens and have at least one primary PI mutation. The studies are being conducted at more than 280 centers in North America, South America, Europe and Australia.
The Phase II trial (BI 1182.52) was an international, multi-center, randomized, blinded study where three doses of tipranavir, boosted with low-dose of ritonavir (TPV/r) were evaluated in 216 highly treatment-experienced patients. The TPV/r doses studied were 500mg/100mg, 500mg/200mg and 750mg/200mg. After two weeks of functional monotherapy* with TPV/r, the levels of virus in study participants decreased by 0.9 log, 1.0 log and 1.2 log in the 500mg/100mg, 500mg/200mg and 750mg/200mg treatment arms, respectively.
"This study shows tipranavir is active against HIV that has reduced sensitivity to commercially available protease inhibitors," explained one of the study investigators, Joseph Gathe, Jr., of Therapeutic Concepts in Houston, Texas. "These preliminary results suggest that tipranavir may be a promising option for patients who have few or no treatment options because of drug resistance. We look forward to data from the RESIST Phase III trials, that are designed to confirm initial studies."
In this study, the most common adverse events seen in association with tipranavir use were diarrhea, nausea, fatigue, headache, vomiting and elevations of liver transaminases. These findings are consistent with previous tipranavir studies.