TORONTO, August 14 /PRNewswire/ --
New data on tipranavir oral solution from a Phase II dose finding study in 115 HIV-1 infected children aged 2 to 18 years were announced today at the 16th International AIDS Conference (IAC) in Toronto, Canada. Results from this 48-week analysis show that patients achieved virologic and immunologic improvements when taking tipranavir oral solution combined with ritonavir (tipranavir/r), as part of combination antiretroviral therapy. This study of tipranavir oral solution is the first to evaluate an antiretroviral drug in highly pre-treated HIV-1 infected paediatric patients.
Tipranavir oral solution is an investigational formulation of APTIVUS(R) (tipranavir). Boehringer Ingelheim plans to submit an application to the European Medicines Agency (EMEA) for tipranavir for an indication in treatment-experienced HIV-1 infected paediatric patients in 2007. APTIVUS(R) received marketing authorisation from the European Commission for combination antiretroviral treatment of HIV-1 infection in highly pre-treated adult patients with virus resistant to multiple protease inhibitors in October 2005.
"A significant need exists for paediatric formulations of antiretroviral drugs, especially for treatment-experienced children who have limited options for constructing an active and durable treatment regimen," said Pedro Cahn, M.D., director, Fundacion Huesped, Buenos Aires, Argentina. "We now have evidence that tipranavir oral solution, in combination with other antiretroviral medications, may be useful for this paediatric patient population."
This study shows that HIV-positive children receiving tipranavir/r as part of combination antiretroviral therapy achieved virologic (decrease in viral load to <400 copies/mL or <50 copies/mL) and immunologic (increase in CD4+ cell count) improvements at 48 weeks of therapy. Patients received one of two doses of tipranavir/r (290/115 mg/m(2) or 375/150 mg/m(2)) twice daily. Among patients receiving the 290/115 mg/m(2) dose of tipranavir/r, 39.7% achieved viral loads <400 copies/mL and 34.5% achieved undetectable viral loads <50 copies/mL. With regard to patients taking the 375/150 mg/m(2) dose of tipranavir/r, 45.6% achieved viral loads <400 copies/mL and 35.1% achieved undetectable viral loads <50 copies/mL. Treatment with tipranavir/r was associated with a mean CD4+ cell increase of 157 cells/mm(3) and 96 cells/mm(3) in the 290/115 mg/m(2) and 375/150 mg/m(2) dose groups, respectively.
This study is an international, multi-center, open-label, randomised trial of two doses of tipranavir/r in 115 HIV-positive children. All but three of the children randomised into the trial were treatment-experienced and infected with HIV strains showing high levels of resistance to other antiretroviral drugs. Children were stratified by age (2 to <6 years, 6 to <12 years, and 12 to 18 years). Fifty-eight children received a 290/115 mg/m(2) dose of tipranavir/r twice daily and fifty-seven children received a 375/150 mg/m(2) dose of tipranavir/r twice daily. Doses of tipranavir/r for children were based on body surface area (BSA) equivalency to the adult 500 mg/200 mg twice daily dose approved in the EU. The 375/150 mg/m(2) dose was selected based on the mean 12-year-old male BSA to allow for higher metabolism in young children.
The 2- to <6-year age group had the least prior antiretroviral experience. The 12- to 18-year age group represented a highly treatment-experienced patient population closely resembling the patient population enrolled in the RESIST Phase III clinical trials, with a median of 17 PI mutations.
Tipranavir/r was well tolerated in this study. The most commonly reported adverse events in children taking tipranavir/r were gastrointestinal-related and include vomiting, diarrhoea and nausea. The most frequent laboratory abnormalities were asymptomatic elevated liver and creatine phosphokinase enzymes (GGT/CPK).
APTIVUS(R) Clinical Trial Program
Boehringer Ingelheim is actively conducting a clinical trial program to further evaluate APTIVUS(R) for the treatment of HIV-1 infection. The APTIVUS(R) clinical trial program is comprised of ongoing and planned studies in more than 1,000 treatment-experienced patients, including paediatric, racially and gender diverse, or hepatitis co-infected patients.
APTIVUS(R)
APTIVUS(R) is a new non-peptidic protease inhibitor which works by inhibiting the viral protease, an enzyme needed to complete the HIV replication process. It is approved for combination antiretroviral treatment of HIV-1 infected adults that are highly pre-treated with virus resistant to multiple protease inhibitors.
Based on available clinical and in vitro data, APTIVUS(R) is active against most strains of HIV-1 that are resistant to commercially available protease inhibitors. The safety and efficacy of APTIVUS(R) in paediatric patients has not yet been established. Currently, phase 2 and 3 studies in paediatric and other populations are fully enrolled and ongoing.
In studies to date, APTIVUS(R) has been well tolerated by most patients and has a safety profile similar to other PIs. The most commonly reported side effects of at least moderate intensity in patients enrolled in the RESIST studies taking APTIVUS(R) are gastrointestinal, including diarrhoea, nausea, vomiting and abdominal pain. Fever, fatigue, headache, bronchitis, depression and rash also occurred.
APTIVUS(R) boosted with low-dose ritonavir has been associated with reports of hepatic adverse events, which have included some fatalities. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C co-infection, as these patients have an increased risk of liver toxicity. The most common moderate to severe laboratory abnormalities were elevated liver enzymes and elevated lipid levels. Most laboratory abnormalities were asymptomatic and most patients were successfully treated without discontinuation.
APTIVUS(R) does not cure HIV infection/AIDS or prevent the transmission of HIV to others. Patients may continue to develop opportunistic infections and other complications associated with HIV disease.
Apart from the EU, APTIVUS(R) has received US marketing authorisation by the FDA and was launched there in June 2005. Additional marketing authorisations from different countries have been received or are expected.
Boehringer Ingelheim
Boehringer Ingelheim is committed to the research and development of novel antiretroviral agents. Apart from APTIVUS(R), VIRAMUNE(R) (nevirapine) is a product of original research done at Boehringer Ingelheim. VIRAMUNE(R) was the first member of the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of anti-HIV drugs on the market. The company is involved in basic research in that area and is committed to improving HIV therapy by providing physicians and patients with innovative antiretroviral treatment options.
For more information on Boehringer Ingelheim, please see www.boehringer-ingelheim.com/hiv.
Reference:
Salazar et al. Efficacy and safety results of 48 weeks of treatment with APTIVUS oral solution co-administered with low dose ritonavir (APTIVUS/r) in children and teenagers (Phase I/IIa study); 16th International AIDS Conference; August 13 - 18, 2006, Toronto, Canada. Abstract #WEAB0301
Web site: http://www.boehringer-ingelheim.com/hiv
Judith von Gordon, CD Communications, Boehringer Ingelheim GmbH, +49-6132-773582, Fax +49-6132-776601
