Tipranavir study halted in treatment-naive

Keith Alcorn
Published: 21 June 2006

Boehringer-Ingelheim has halted a three-year study of its new protease inhibitor tipranavir (Aptivus) in treatment-naïve patients because tipranavir-treated patients receiving a dose of 500mg with 100mg of ritonavir were found to be experiencing inferior viral load outcomes when compared to patients receiving lopinavir/ritonavir (Kaletra).

The company had already closed one arm of the study, code named BI 1182.33, in which patients received the dose of tipranavir/ritonavir that is already licensed for treatment-experienced patients (500/200mg). This arm was closed in February 2006 due to a higher rate of asymptomatic liver enzyme elevations when the data were examined at 48 weeks by the trial’s independent Data Safety Monitoring Board.

The decision to close the study altogether came after an analysis of data when all patients had reached week 60 of treatment. This analysis found that the proportion of patients who had achieved a viral load below 50 copies at week 48 was just over 15% lower in the tipranavir 500/100mg arm than in the Kaletra arm. The statistical definition of non-inferiority in this study required that the difference between tipranavir and Kaletra should not exceed 15%, so Boehringer-Ingelheim decided that the study must end.

However the company stresses that a post-hoc 60 week analysis of the 500mg/200mg tipranavir arm did not demonstrate the inferiority of this tipranavir/ritonavir dose at week 48, and that the closure of the study does not change the positive benefit/risk profile of tipranavir/ritonavir for the highly treatment-experienced patient population for which it is currently indicated.

The BI 1182.33 study recruited patients in Argentina, Australia, Bahamas, Brazil, Canada, Colombia, France, Germany, Mexico, Poland, Romania, Russia, Spain, Thailand and the United Kingdom. Boehringer Ingleheim says that it will continue to support treatment for those without access to antiretroviral treatment for the planned duration of the study.