Kaletra(R) (lopinavir/ritonavir) Based Regimens Demonstrate Favorable Resistance in Clinical Trials
14 Juillet 2004 - 3:30PM
PR Newswire (US)
Kaletra(R) (lopinavir/ritonavir) Based Regimens Demonstrate
Favorable Resistance in Clinical Trials BANGKOK, Thailand, July 14
/PRNewswire-FirstCall/ -- In two clinical studies, no primary
protease inhibitor (PI) resistance was reported in
antiretroviral-naive patients taking a Kaletra(R)
(lopinavir/ritonavir) based regimen once daily (QD) or twice daily
(BID) in combination with other antiretroviral agents. These data
were presented at the 15th International AIDS Conference (IAC) in
Bangkok, Thailand. The majority of patients in both studies
maintained an undetectable viral load of less than 50 copies per
milliliter (as measured by HIV RNA). In study 720, no primary PI
resistance has been reported through five years (252 weeks) of
follow up in patients new to therapy (ARV-naive). Consistent with
these findings, a separate trial of 190 ARV-naive patients, study
418, which evaluated Kaletra dosed once daily versus Kaletra dosed
twice daily in combination with other agents, demonstrated no
confirmed lopinavir resistance through one year (48 weeks) of
therapy. The adult recommended dosage of Kaletra is 400/100 mg
(three capsules or five milliliters of oral solution) twice daily
with food. "These resistance data, though based on a relatively
small number of patients, are important because of the long
duration of follow-up. They demonstrate that it is possible to
achieve long term viral suppression while minimizing resistance.
This may be especially important for ARV-naive patients, whose
first regimen may be the best opportunity for success long- term,"
said Charles Hicks, M.D., lead study investigator, Duke University
Medical Center, Durham, NC. Study 418: Once-Daily vs. Twice-Daily
Kaletra Data from this randomized, open-label, study of patients
new to therapy showed an HIV treatment regimen based on a
once-daily dose of Kaletra had comparable viral suppression when
compared to a twice-daily dose through one year (48 weeks).
Patients received either Kaletra (800 mg lopinavir/200 mg
ritonavir) once daily or Kaletra (400 mg lopinavir/100 mg
ritonavir) twice daily. Patients in both arms also received
once-daily emtricitabine and tenofovir. In an intent-to-treat
analysis (ITT), which categorizes any patient who does not complete
the study as a treatment failure, the data showed 70 percent of
patients in the once daily group and 64 percent of patients in the
twice daily group achieved HIV RNA less than 50 copies per
milliliter at week 48. These data demonstrated comparable
effectiveness between the once-daily regimen and the twice-daily
regimen of Kaletra with emtricitabine and tenofovir. Mean increases
in CD4 cell count from baseline to the one-year visit were 185 and
188 cells per cubic millimeter in the once-daily and twice- daily
arms, respectively. Data also show that of 15 patients who had
genotypic resistance testing results available (HIV RNA greater
than 500 copies per milliliter), no patient (0/8 in the once-daily
arm and 0/7 in the twice daily arm) was confirmed to have developed
lopinavir resistance or tenofovir resistance. The incidence of
emtricitabine resistance was low (2/8 in the once daily arm and 1/7
in the twice daily arm). Twenty-two patients (11 in the once-daily
arm and 11 in the twice daily arm) had samples available for
resistance testing (HIV RNA > 500 copies/mL) at any time between
week 12 and week 48. Resistance testing results were available for
27 samples from 15 of the 22 patients. "Kaletra dosed once daily
was comparable in virologic efficacy to Kaletra dosed twice daily
for patients new to therapy. This patient population could benefit
from the development of more treatment options that provide once
daily dosing schedules without sacrificing efficacy," said
Jean-Michel Molina, M.D., lead study investigator, Department of
Infectious Diseases, Saint-Louis Hospital, University of Paris,
Paris, France. "As part of our commitment to the HIV community,
Abbott continues to explore additional treatment options with an
aim to offer dosing flexibility to patients. In this study, a
majority of patients had undetectable viral load, and no protease
inhibitor resistance was detected after one year," said Scott Brun,
M.D., global project head, Antiviral Global Project Team, Abbott
Laboratories. Kaletra was generally well tolerated in both arms of
the study. The most common drug-related adverse events of moderate
or greater intensity reported were diarrhea and nausea. Diarrhea
was reported more frequently in patients on once-daily therapy (16
percent) versus patients on twice-daily therapy (5 percent).
Findings from study 418 demonstrated that the mean fasting lipid
value changes from baseline to 48 weeks were lower in both the
once-daily and twice- daily arms than in a previous Phase III study
(M98-863) of Kaletra at 48 weeks in combination with stavudine and
lamivudine with lipid values obtained under non-fasting conditions.
In both the once-daily and twice-daily arms of this study, there
was a mean total cholesterol increase from baseline of 27
milligrams per deciliter compared to 53 milligrams per deciliter in
Study 863. Similarly, both the once-daily and twice-daily arms of
this study showed mean triglyceride value changes from baseline to
48 weeks were lower than those found in study 863 at 48 weeks.
There was a mean increase from baseline of 82 milligrams per
deciliter in the once-daily arm and 76 milligrams per deciliter in
the twice-daily arm, versus 125 milligrams per deciliter in Study
863. In this study comparing once-daily and twice-daily therapy,
the proportion of patients with triglyceride levels greater than
750 milligrams per deciliter was 5 percent in the once-daily arm
and 4 percent in the twice- daily arm. Study 720: Five-Year Data
Data from the randomized, uncontrolled, prospective Phase II study
of 100 treatment-naive patients taking Kaletra in combination with
lamivudine (3TC) and stavudine (d4T) show that of 17 patients out
of 27 patients who met the criteria for resistance testing with
resistance data available through 252 weeks, none demonstrated
evidence of resistance to lopinavir (0/17) or stavudine (0/17).
Three patients (3/17) demonstrated lamivudine resistance. In
addition, 64 percent of patients (64/100) had an undetectable viral
load (HIV RNA less than 50 copies per milliliter) and 67 percent
(67/100) had HIV RNA less than 400 copies per milliliter, using an
intent-to-treat (ITT) analysis, which categorizes any patient who
does not complete the study as a treatment failure. Of the 68
patients remaining on treatment (OT) at week 252, 94 percent
(64/68) of patients had an undetectable viral load and 99 percent
(67/68) had HIV RNA less than 400 copies per milliliter. Patients
in this open-label study, in which there was no comparator group,
were given one of three doses of Kaletra in addition to the
nucleoside analogues stavudine and lamivudine. After 48 weeks of
therapy, all patients were converted to the same dose of Kaletra
(400/100 mg BID) with stavudine and lamivudine. Kaletra was
generally well tolerated through 252 weeks of therapy. The most
frequent adverse events were gastrointestinal in nature.
Non-fasting lipid elevations were reported. At week 252, no Grade 3
total cholesterol elevation was observed in study patients. Grade 3
triglyceride values were observed in four patients. A minority of
patients in this study employed appropriate lipid-lowering agents
to treat these elevations through week 252. A decrease in total
cholesterol and triglycerides were observed in these patients.
Additional Information About Kaletra Kaletra should not be taken by
patients who have had an allergic reaction to Kaletra or any of its
ingredients, including lopinavir or ritonavir. Kaletra should not
be used with certain medications. Taking certain other drugs with
Kaletra could create the potential for serious side effects that
could be life threatening. Patients should discuss all medicines,
including those without a prescription and herbal preparations,
with their physician or pharmacist. In patients taking protease
inhibitors, increased bleeding (in patients with hemophilia) and
diabetes/high blood sugar have occurred. Pancreatitis and liver
problems, which can be fatal, have been reported. Tell your doctor
if you have or have had liver disease such as hepatitis. Changes in
body fat have been seen in some patients receiving antiretroviral
therapy. Some patients receiving Kaletra have had large increases
in triglycerides and cholesterol. Varying degrees of
cross-resistance among protease inhibitors have been observed. In
Kaletra clinical trials, the most commonly reported side effects of
moderate to severe intensity were: abdominal pain, diarrhea,
feeling weak or tired, headache and nausea; children experienced
rash. This is not a complete list of reported side effects. Kaletra
oral solution contains alcohol. Kaletra does not cure HIV infection
or AIDS and does not reduce the risk of passing HIV to others.
About Abbott Laboratories Abbott Laboratories has been a leader in
HIV/AIDS research since the early years of the epidemic. In 1985,
the company developed the first licensed test to detect HIV
antibodies in the blood, and remains a leader in HIV diagnostics.
Today, Abbott retroviral and hepatitis tests are used to screen
more than half of the world's donated blood supply. To treat those
with HIV, Abbott scientists have developed two protease inhibitors.
Kaletra is the protease inhibitor market share leader in Europe,
and is the most prescribed protease inhibitor in the United States.
Abbott Laboratories is a global, broad-based health care company
devoted to the discovery, development, manufacture and marketing of
pharmaceuticals and medical products, including nutritionals,
devices and diagnostics. The company employs more than 55,000
people and markets its products in more than 130 countries.
Abbott's news releases and other information are available on the
company's Web site at http://www.abbott.com/ . Outside of the U.S.,
health care professionals can access additional information on
Kaletra at http://www.kaletra.com/ . DATASOURCE: Abbott
Laboratories CONTACT: U.S. Media, Nicole Wesley, +1-847-935-9877,
mobile, +09491 8173, or Laureen Cassidy, +1-847-938-7743, or Media
Outside the U.S., Brian Kyhos, +1-847-936-7988, mobile, +09484
7622, all for Abbott Laboratories Web site: http://www.kaletra.com/
http://www.abbott.com/ Company News On-Call:
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