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Boehringer Ingelheim Initiates SPRING Study of Aptivus(R) (tipranavir) in Diverse Group of Highly Treatment-Experienced HIV-Positive Patients

Ingelheim, Germany (ots/PRNewswire)

Boehringer Ingelheim GmbH announced today that it has begun to
enroll patients in the SPRING study. The SPRING study will be one of
the largest racially and gender diverse international studies of
highly treatment-experienced HIV-1 infected patients. The trial will
examine the safety, efficacy and pharmacokinetics of Aptivus(R)
(tipranavir) in a racially diverse group of 200 female and 200 male
treatment-experienced patients across eight countries in three
continents. SPRING is also the largest randomized controlled trial to
use Therapeutic Drug Monitoring (TDM) in a study of highly
treatment-experienced HIV patients.
"Clinical trials have shown that the efficacy of antiretroviral
treatments may vary across races and genders. The 48-week data from
the RESIST studies have already demonstrated the efficacy of APTIVUS
in treatment-experienced patients, and SPRING is designed to further
examine its utility in diverse patients within this population," said
SPRING investigator Sharon Walmsley, M.D., professor of medicine,
University of Toronto, senior scientist, Toronto Hospital Research
Institute, and director, Clinical Research, Immunodeficiency Clinic,
Toronto Hospital.
The SPRING (Safety, efficacy and Pharmacokinetics of tipRanavir
boosted with low dose ritonavir (500 mg/200 mg) twice daily IN 400
racially and Gender diverse HIV-positive treatment-experienced
population) study is a Phase IIIb, open-label, multicenter,
multinational trial with a primary endpoint of treatment response at
48 weeks, defined as having an undetectable viral load of less than
50 copies/mL. Patients will also be included in a randomized
evaluation to assess the impact of TDM on the efficacy and safety of
APTIVUS boosted with ritonavir. TDM is the measurement of specific
drug levels in a patient's blood at certain intervals of time that is
used to tailor medication dosages to fit the specific needs of the
individual patient. (i)
Worldwide, there are more HIV-positive women than ever before,
with nearly 18 million now living with the disease. Women of African
and Latin American decent are disproportionately affected and account
for a large number of infections in developed countries, including
those in Europe. (ii)
"Boehringer Ingelheim is committed to studying the benefits of
APTIVUS in different treatment-experienced patient populations and
hopes that SPRING will play a critical role in advancing knowledge
about HIV care," said Dr. Andreas Barner, Vice-Chairman, Board of
Managing Directors and Head of Corporate Board Division Pharma
Research, Development and Medicine, Boehringer Ingelheim.
About SPRING
The SPRING study will enroll 400 patients in 72 sites in the
United States, Canada, Mexico, Germany, Italy, Spain, Argentina and
Brazil. Patients 18 years and older will have received prior
treatment from at least three classes of antiretroviral agents and
have documented resistance to at least one protease inhibitor. At
screening, patients will have a CD4 cell count of greater than or
equal to 50 cells/mm3 and a HIV-1 viral load greater than or equal to
1,000 copies/mL.
Fifty percent of patients will receive standard of care (SOC) 500
mg of APTIVUS boosted with 200 mg of ritonavir twice daily in
conjunction with an optimized background regimen for 48 weeks. The
remaining 200 patients will additionally be included in the
randomized pilot evaluation to assess the impact of TDM on the
efficacy of APTIVUS. Both the SOC and TDM groups will have an equal
number of patients in the race-gender strata.
For additional information on inclusion and exclusion criteria and
SPRING study sites, visit www.clinicaltrials.gov.
About APTIVUS
APTIVUS 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 is active
against most strains of HIV-1 that are resistant to commercially
available protease inhibitors.
Currently, phase II and III studies in paediatric and other
populations are fully enrolled and ongoing.
The most commonly reported side effects of at least moderate
intensity in patients enrolled in the RESIST studies taking APTIVUS
are gastrointestinal, including diarrhoea, nausea, vomiting and
abdominal pain. Fever, fatigue, headache, bronchitis, depression and
rash also occurred. Gastrointestinal symptom disorders and elevated
transaminase, cholesterol and triglycerides were more frequent in the
APTIVUS arm than in the comparator-ritonavir group but necessitated
discontinuation of treatment in a minority of cases.
APTIVUS boosted with low-dose ritonavir has been associated with
reports of hepatic adverse events, which have included some
fatalities. These have generally occurred in patients with advanced
HIV disease taking multiple concomitant medications. 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-containing HAART regimens have been associated with
reports of both fatal and non-fatal intracranial hemorrhage (ICH) in
some highly treatment-experienced patients. Caution should be used
when prescribing APTIVUS/r in patients who may be at risk of
increased bleeding or who are receiving medications known to increase
the risk of bleeding.
APTIVUS 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 has received U.S. marketing
authorization by the FDA and was launched there in June 2005.
Additional marketing authorizations from different countries have
been received or are expected.
About Boehringer Ingelheim
Boehringer Ingelheim is committed to the research and development
of novel antiretroviral agents. Apart from Aptivus(R) (tipranavir),
Viramune(R) (nevirapine) is a product of original research done at
Boehringer Ingelheim. VIRAMUNE 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.
Boehringer Ingelheim is actively conducting clinical trial
programs to further evaluate APTIVUS and VIRAMUNE for the treatment
of HIV-1 infection. The APTIVUS clinical trial program is comprised
of ongoing and planned studies in more than 1,400
treatment-experienced patients. In addition to the SPRING study for
APTIVUS, Boehringer Ingelheim just announced the initiation of the
ArTEN trial, which will compare the efficacy and safety of VIRAMUNE
dosed once-or twice-daily versus atazanavir boosted with ritonavir in
HIV-positive antiretroviral-naive patients.
For more information on Boehringer Ingelheim HIV Franchise, please
see www.boehringer-ingelheim.com/hiv.
Please be advised
This release is from the Corporate Headquarters of Boehringer
Ingelheim and is intended for all international markets. This being
the case, please be aware that there may be some differences between
countries regarding specific medical information including licensed
uses. Please take account of this when referring to the material.
References:
(i) Lab Tests Online. American Association for Clinical Chemistry.
Therapeutic Drug Monitoring. Available at: http://www.labtestsonline.
org/understanding/analytes/thdm/glance.html. Accessed on March 27,
2007.
(ii) UNAIDS/WHO: 2006 Report on the global AIDS epidemic
Web site: http://www.boehringer-ingelheim.com/hiv
              http://www.clinicaltrials.gov

Contact:

Judith von Gordon for Boehringer Ingelheim GmbH, +49-61-32-77-3582,
or fax, +49-61-32-77-6601

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