SPRING Study
Will Evaluate Tipranavir (Aptivus) in Diverse and Highly Treatment-experienced
HIV Patients
Aptivus
Tablet
There
is an urgent need for safe, simple, and more effective regimens for the treatment
of highly treatment-experienced patients with HIV, especially among diverse populations,
including women, Blacks, Hispanics, Asians, and American Indians.
To
address this need, Boehringer Ingelheim has initiated enrollment in the SPRING
study (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 patients).
Following
are excerpts from a Boehringer Ingelheim press announcement concerning this planned
multinational study:
Boehringer
Ingelheim Pharmaceuticals, Inc., makers of tipranavir
capsules, announced today that it has begun to enroll patients in the SPRING
study. The goal of the SPRING study, which will be conducted at 72 sites across
eight countries, is to enroll 200 women and 200 men who are HIV-positive
and highly treatment-experienced.
A
diverse female and male population including, but not limited to, White, Black,
Hispanic, Asian, and American Indian patients will be recruited, making SPRING
one of the largest racially, ethnically and gender diverse international studies
of highly treatment-experienced HIV-1 infected patients.
SPRING
is the largest randomized controlled trial to evaluate the utility of therapeutic
drug monitoring (TDM) in highly treatment-experienced HIV patients.
The
SPRING is a Phase 3b, open-label, multicenter, multinational trial with a primary
endpoint of treatment response at 48 weeks, defined as a viral load <50 copies/mL
at two consecutive measurements at least five days apart.
Two
hundred patients will be included in a randomized evaluation to assess the impact
of TDM on the efficacy and safety of tipranavir co-administered with ritonavir
(Norvir) [tipranavir/r].
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. (Lab Tests Online. American Association for Clinical Chemistry.
Therapeutic Drug Monitoring. Available at: http://www.labtestsonline.org.
Accessed on March 27, 2007.)
"Studies have indicated that the efficacy
of antiretroviral treatments may vary across races and genders," explained
Dr. Kathleen Squires, Director, Division of Infectious Diseases and Environmental
Medicine and SPRING Coordinating Investigator, Thomas Jefferson University, Philadelphia,
PA. "Therefore, SPRING is designed to provide insight into potential treatment
differences for patient populations such as women and ethnic groups."
Worldwide, there are more HIV-positive women than ever before, with nearly
18 million now living with the disease. Racial and ethnic minorities are also
being disproportionately affected by HIV. In the United States, half of AIDS diagnoses
were among African Americans and 20 percent were among Hispanics over the three-year
period from 2001 to 2004, according to the World Health Organization (WHO). More About
the SPRING Study
The
SPRING study will enroll 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 > 50 cells/mm3 and a HIV-1 viral
load > 1,000 copies/mL.
All 400 patients entered in the trial will
begin the study by receiving the standard dose of 500 mg of tipranavir co-administered
with 200 mg of ritonavir twice daily in conjunction with an optimized background
regimen. Two hundred patients randomized to the standard tipranavir/r dosing regimen
will continue to receive this regimen for 48 weeks. The other 200 patients who
were randomized to the TDM evaluation may have their dose of tipranavir or ritonavir
modified depending in part on drug concentrations measured at various time intervals.
Adverse
Events
The
tipranavir labeling includes boxed warnings for reports of both fatal and non-fatal
intracranial hemorrhage (ICH) and reports of clinical hepatitis and hepatic decompensation
including some fatalities. Extra vigilance is warranted in patients with chronic
hepatitis B or hepatitis C coinfection, as these patients have an increased risk
of hepatotoxicity.
The most commonly reported adverse events in patients
taking tipranavir/r are diarrhea, nausea, fatigue, headache, and vomiting. The
most common laboratory abnormalities are elevated liver enzymes (AST/ALT) and
triglycerides.
Recommended
Tipranavir Indications and Usage
According
to US Food and Drug Administration (FDA) guidelines, tipranavir, co-administered
with 200 mg of ritonavir/ritonavir, is indicated 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.
This
indication is based on analyses of plasma HIV-1 RNA levels in two controlled studies
of tipranavir/ritonavir of 24 weeks duration. Both studies were conducted in clinically
advanced, 3-class antiretroviral (NRTI, NNRTI, PI) treatment-experienced adults
with evidence of HIV-1 replication despite ongoing antiretroviral therapy.
The following points should be considered when initiating therapy with tipranavir/ritonavir:
• The use of other active agents
with tipranavir/ritonavir is associated with a greater likelihood of treatment
response.
•
Genotypic or phenotypic testing and/or treatment history should guide
the use of tipranavir/ritonavir. The number of baseline primary protease inhibitor
mutations affects the virologic response to tipranavir/ritonavir.
• Use caution when prescribing
tipranavir/ritonavir in patients who may be at risk of increased bleeding or who
are receiving medications known to increase the risk of bleeding.
• Liver function tests should
be performed at initiation of therapy with tipranavir/ritonavir and monitored
frequently throughout the duration of treatment.
• Use caution when prescribing
tipranavir/ritonavir to patients with elevated transaminases, hepatitis B coinfection
or hepatitis C co-infection or other underlying hepatic impairment.
• The extensive drug-drug interaction
potential of tipranavir/ritonavir when co-administered with multiple classes of
drugs must be considered prior to and during tipranavir/ritonavir use.
• The risk-benefit of tipranavir/ritonavir
has not been established in treatment-naive adult patients or pediatric patients.
• There are no study
results demonstrating the effect of tipranavir/ritonavir on clinical progression
of HIV-1. Tipranavir/ritonavir does not cure HIV or help prevent passing HIV to
others.
For
additional information on inclusion and exclusion criteria and SPRING study sites,
visit www.clinicaltrials.gov.
06/19/07
Source Boehringer
Ingelheim. Boehringer Ingelheim Initiates SPRING Study of Aptivus (tipranavir)
capsules in Diverse Group of Highly Treatment-experienced HIV Patients. Press
Release. June 14, 2007.
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