Boehringer stops tipranavir trial in treatment-naive patients

On 13 June 2006, Boehringer Ingelheim announced that it was closing a clinical trial of HIV drug tipranavir (Aptivus) in treatment-naive patients due to insufficient effectiveness at 60 weeks.

Tipranavir was approved in Europe in October 2005 and is currently only indicated in combination with ritonavir in treatment-experienced patients who are resistant to other PIs.

The study that has now been closed, BI 1182.33, recruited 558 treatment-naive patients in 15 countries including France, Germany and the UK, and was a non-inferiority trial against lopinavir/r (Kaletra), whose primary endpoint was the proportion of patients with an undetectable viral load (< 50 copies/mL).

Patients in both tipranavir arms received 500 mg tipranavir twice daily. Only the ritonavir dose varied, at 200 mg or 100 mg twice daily.

For both doses of ritonavir, tipranavirs non-inferiority was proved at 48 weeks.

However, following this, the 200 mg ritonavir arm was closed due to an asymptomatic elevation of liver enzyme levels. This phenomenon had already been observed in the RESIST treatment-experienced trials.

A subsequent 60-week analysis, showed that the effect of tipranavir/ritonavir (500 mg/100 mg twice daily) had declined and that this therapy was now inferior to Kaletra in terms of virologic success.

The press release does not specify the proportion of patients with undetectable viral loads, but says that there was a 15.03% difference between the lopinavir/r and tipranavir arms, 0.3% above the limit fixed in the trial protocol.

Boehringer Ingelheim decided at this point to halt the whole trial, specifying that this does not change the positive benefit-risk profile of tipranavir/ritonavir (500 mg/200 mg) for the highly treatment-experienced patient population for which it is currently indicated.