 |
Press Release
|
Clinical Trial Statement
Boehringer Ingelheim Provides Update on Study Arms of Aptivus® (tipranavir) Clinical Trial in Treatment-Naïve HIV-Infected Patients
February 23, 2006 - Boehringer Ingelheim is actively conducting a clinical trial program to further evaluate Aptivus® (tipranavir) capsules for the treatment of HIV-1 infection. The program is comprised of ongoing and planned studies in over 1,000 pediatric, antiretroviral-naïve, racially and gender diverse, or hepatitis co-infected patients.
Recently, Boehringer Ingelheim and the external independent Data Safety Monitoring Board (DSMB) met to review data from study 1182.33, which is designed to evaluate the efficacy and safety of APTIVUS/ritonavir in treatment-naïve HIV-infected patients. Following a thorough review of the 48-week data from the treatment-naïve patients in this study, and with the recommendation of the DSMB, Boehringer Ingelheim has decided to close the APTIVUS/ritonavir 500 mg/200 mg study arm. Specifically, the rate of asymptomatic liver enzyme elevations reported in the APTIVUS/ritonavir 500 mg/200 mg study arm was higher than in the other study arms and presented a less favorable benefit-risk profile for these treatment-naïve patients.
The DSMB did not raise any concerns regarding the efficacy in this trial.
Importantly, after completion of this thorough review of efficacy and safety data, Boehringer Ingelheim and the DSMB support the continuation of the APTIVUS/ritonavir 500 mg/100 mg study arm and lopinavir/ritonavir comparator arm in this trial of treatment-naïve patients.
The benefit-risk profile has not changed for the highly treatment-experienced patient population for which APTIVUS/ritonavir (500 mg/200 mg) is currently indicated. The rate of asymptomatic liver enzyme elevations in highly treatment-experienced patients in the RESIST clinical trial program was lower than that observed in the 500 mg/200 mg arm of study 1182.33 in treatment-naïve patients.
As part of the ongoing evaluation of 1182.33 and other studies, Boehringer Ingelheim provides data to an external independent DSMB that advises the company about the safety of individuals participating in the trial, as well as the continuing validity and scientific merit of the trial.
Boehringer Ingelheim is informing regulatory authorities and 1182.33 study investigators about the protocol change for this study and will continue to share any new information as it becomes available.
Boehringer Ingelheim study 1182.33 is a multinational study in 558 treatment-naïve patients conducted outside of the United States. It has clinical trial sites in Argentina, Australia, Bahamas, Brazil, Canada, Colombia, France, Germany, Mexico, Poland, Romania, Russia, Spain, Thailand and the UK. The study is designed to evaluate the efficacy and safety of two doses of APTIVUS combined with ritonavir (500 mg/200 mg BID, 500 mg/100 mg BID) versus lopinavir combined with ritonavir (400 mg/100 mg BID) in treatment-naïve HIV-infected patients, as part of combination antiretroviral treatment.
APTIVUS/ritonavir is approved for combination antiretroviral treatment of HIV-1 infected adult patients with evidence of viral replication, who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors. In this patient population, the approved dose of APTIVUS is 500 mg taken with 200 mg of ritonavir, twice daily. The accelerated approval of APTIVUS for treatment-experienced patients is based on 24-week data from the ongoing RESIST studies using surrogate endpoints, including changes in viral load and CD4 cell count. It was demonstrated that a significantly greater percentage of HIV-positive patients taking an APTIVUS/ritonavir-based regimen achieved a treatment response versus those taking a regimen containing one of several ritonavir-boosted comparator protease inhibitors.
Accelerated approval is a regulatory process that expedites the approval of therapies for serious or life-threatening illnesses that provide meaningful benefit to patients over existing treatments. The long-term effects of APTIVUS/r therapy are not confirmed at this time; however, Boehringer Ingelheim is evaluating longer term APTIVUS data from the RESIST studies to confirm the 24-week findings in highly treatment-experienced patients and complete the traditional approval package for submission to FDA.
The RESIST trials are randomized, controlled, open-label Phase 3 trials designed to study APTIVUS combined with ritonavir (APTIVUS/r) versus a group of ritonavir-boosted comparator protease inhibitors (CPI/r) in patients previously treated with all three classes of antiretroviral agents. Patients enrolled in the RESIST studies had received at least two previous PI-based regimens and were failing a PI-based regimen at the time of study entry. APTIVUS/r and the ritonavir-boosted comparator PIs were taken in conjunction with other anti-HIV agents as part of combination antiretroviral therapy. CPIs included lopinavir, saquinavir, amprenavir and indinavir. All patients had baseline genotypic resistance testing prior to randomization to aid investigators in the selection of the CPI/r. Of these highly treatment-experienced patients in the RESIST trials, the majority (86%) were at least possibly resistant to the CPI/r chosen.
Boehringer Ingelheim is committed to further studying APTIVUS capsules for the treatment of HIV-1 and improving therapy by discovering and developing innovative antiretroviral and anti-hepatitis C drugs.
For more information about APTIVUS please visit www.APTIVUS.com. APTIVUS clinical trial information is available on www.clinicaltrials.gov.