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Abbott's Kaletra(R) Tablet Dosed Once-Daily or Twice-Daily Demonstrated Similar Clinical Results Across Race and Gender Lines
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Abbott press announcement
August 5, 2008 2:20 PM EDT
MEXICO CITY, Aug. 5 -- Initial treatment regimens containing once-daily or twice-daily dosing of Abbott's (NYSE: ABT) protease inhibitor Kaletra(R) (lopinavir/ritonavir) tablet provided similar results for controlling the virus (reducing the amount of HIV-1) and improving the immune system (increasing CD4 cells) in women compared to men and in non-whites compared to whites, according to 48-week data presented by Abbott today at the XVII International AIDS Conference (AIDS 2008).
A retrospective sub-analysis of study M05-730 at week 48 of 96 weeks offered data on the impact of gender and race on a Kaletra-based regimen. Women and non-whites have traditionally been underrepresented in HIV studies, although these patient groups increasingly account for the vast majority of HIV infections. According to the World Health Organization, by the end of 2007, 22.5 million of the total 33.2 million people infected with HIV lived in sub-Saharan Africa. Additionally, 15.4 million of the total number of HIV-infected patients worldwide are women.
"The results showed that regardless of gender or race, Kaletra dosed once-daily or twice-daily as part of a treatment regimen achieved consistent virologic suppression in patients new to antiretroviral therapy," said Scott Brun, M.D., divisional vice president, Infectious Diseases and Immunology Development, Global Pharmaceutical Research and Development, Abbott. "Additionally, the Kaletra tablet formulation is a convenient HIV treatment option that can be taken with or without food and does not require refrigeration, which is particularly important to patients in the developing world who are disproportionately affected by HIV."
M05-730 Analysis Results
Through 48 weeks, the proportions of males and females who achieved an undetectable HIV viral load were similar. In addition, the proportions of whites and non-whites who achieved an undetectable HIV viral load were similar. Specifically, 72 percent of women and 78 percent of men, and 75 percent of non-whites and 77 percent of whites had undetectable HIV viral loads (less than 50 copies/mL) at 48 weeks.
CD4+ cell count mean increases over 48 weeks were similar for females and males, independent of baseline CD4+ cell count, except among women with baseline CD4+ cell counts of fewer than 50 cells/mm3, who experienced statistically significant greater mean increases in CD4+ cell counts than males. In addition, CD4+ cell count mean increases over 48 weeks were similar for whites and non-whites. At 48 weeks, the overall rate of moderate to severe and related adverse events of diarrhea was 15.8 percent. A similar rate of diarrhea was observed in whites (17.8 percent), while non-whites experienced a rate of 9.7 percent.
"This sub-analysis of M05-730 provides additional clinical information on race and gender response with Kaletra," said Joseph Gathe, Jr., M.D., clinical instructor, Department of Internal Medicine, Baylor College of Medicine. "The information can help physicians in making treatment decisions for the patient populations most affected by HIV."
About the M05-730 Study -- 48-week Data
Design and Primary Endpoints:
-- M05-730 study is a 96-week Phase III open-label, randomized, multi-center, multi-country study that enrolled 664 ARV-naive patients with HIV-1 RNA >1000 copies/mL and any CD4+ T-cell count. Patients were randomized equally to lopinavir/ritonavir 800/200 mg once-daily soft gel capsule (SGC), 400/100 mg twice-daily (BID) SGC, 800 mg/200 mg once-daily tablet or 400/100 mg twice-daily tablet for eight weeks. All patients also received emtricitabine (FTC) 200 mg once-daily and tenofovir disoproxil fumarate 300 mg once-daily. At week eight, all patients receiving SGC were switched to the tablet formulation of Kaletra, matching their previous dosing schedule of once- or twice-daily.
-- The primary efficacy endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at week 48, using an intent to treat noncompleter equals failure approach comparing once-daily and twice-daily groups. A secondary efficacy endpoint was mean change from baseline in CD4+ T-cell count.
-- The primary safety endpoint was the proportion of patients reporting a treatment-emergent adverse event of diarrhea during the first eight weeks of dosing. Additional safety analyses included the proportion of subjects reporting treatment-emergent adverse events, grade 3+ lab abnormalities, and mean changes from baseline for lab determinations through 48 weeks.
Primary Efficacy Results:
-- At week 48, the primary efficacy analysis showed that 77 percent of the once-daily-treated patients and 76 percent of the twice-daily treated patients achieved a viral load <50 copies/mL. The once-daily regimen was determined to be non-inferior to the twice-daily regimen.
-- Through week 48, 14.7 percent and 16.6 percent of the patients discontinued treatment on the once-daily and twice-daily regimens, respectively. A similar percentage of patients on the once-daily regimen discontinued due to adverse events, as on the twice-daily regimen (4.8 percent and 3 percent, respectively).
-- With respect to the comparison of the SGC to the tablet formulation through week eight, there were no statistically significant differences in the following areas: the number of patients discontinuing due to gastrointestinal adverse events or other adverse events; the incidence of treatment-emergent adverse events of diarrhea of any severity and of moderate or greater severity and related to the study drug; the proportion of patients with Grade 3+ lab abnormalities; or the mean change from baseline for total cholesterol or triglycerides at any time point during the first eight weeks of treatment.
-- The most common moderate/severe related adverse events in the once-daily and twice-daily groups respectively were: diarrhea (17 percent versus 15 percent), nausea (seven percent versus five percent), vomiting (three percent versus four percent), and increased triglycerides (two percent in both groups). There was no statistical difference between the groups.
-- At week 48, the overall impact of Kaletra, dosed once-daily or twice-daily, on grade 3-4 lab abnormalities, including cholesterol and triglycerides, the liver enzymes, SGOT/AST, and creatinine clearance was similar.
-- At week 48, there was a statistically significant difference in the increase of total cholesterol between the once-daily and twice-daily group.
About Abbott's Commitment to Fighting HIV/AIDS
HIV/AIDS is a global problem that demands shared commitment and shared responsibility. Abbott is committed to working with governments, multilateral organizations, nongovernmental organizations and patient groups to expand access to HIV treatments around the world. Abbott has also made significant investments in expanding manufacturing capacity to meet the growing demand for HIV treatment in developing countries.
Abbott's lopinavir/ritonavir formulations are among the lowest-priced protease inhibitors in the developing world. Abbott has been providing its HIV medicines at a price of US$500 per adult patient per year in all African and least developed countries since 2002, making these medicines more affordable than any generic copies.
Abbott and the company's philanthropic foundation, Abbott Fund, have invested more than US$100 million in the fight against HIV/AIDS in Africa and the developing world. Abbott Fund-supported programs have served more than 700,000 children and families. In addition, more than 250,000 patients have been tested through Abbott Fund-supported voluntary counseling and testing programs, with thousands being referred to treatment programs. Abbott also has donated more than eight million rapid HIV tests to help prevent mother-to-child HIV transmission.
Abbott and Abbott Fund have announced several efforts to expand access to treatment and care for children living with HIV/AIDS, including an additional investment of US$12 million in grants and product donations this year.
For more information about Abbott's commitment to fighting HIV/AIDS, please visit http://www.abbott.com/hiv.
About Kaletra
Indication
KALETRA (lopinavir/ritonavir) is a human immunodeficiency virus-1 (HIV-1) protease inhibitor. KALETRA is always used in combination with other anti-HIV-1 medicines for the treatment of HIV-1 infection. KALETRA is a combination of two medicines, lopinavir and ritonavir. KALETRA is for adults and for children age six months and older.
Important Safety Information
KALETRA does not cure HIV-1 infection or AIDS and does not reduce the risk of passing HIV-1 to others.
KALETRA must not be taken by patients who have had an allergic reaction to KALETRA or any of its ingredients.
Taking KALETRA with certain drugs can cause serious problems or death. KALETRA must not be taken with dihydroergotamine, ergonovine, ergotamine or methylergonovines such as Cafergot(R), Migranal(R), D.H.E. 45(R), ergotrate maleate, and methergine, as well as Halcion(R) (triazolam), Orap(R) (pimozide), Propulsid(R) (cisapride), or Versed(R) (midazolam).
KALETRA must not be taken with rifampin, also known as Rimactane(R), Rifadin(R), Rifater(R), or Rifamate(R); St. John's Wort (hypericum perforatum); Mevacor(R) (lovastatin), or Zocor(R) (simvastatin).
There are drug-drug interactions with the potential for risk of serious or life-threatening side effects. Alterations in dose, increased monitoring of drug levels in the blood, or increased observations for side effects may be recommended when KALETRA is taken with: Lipitor(R) (atorvastatin), Crestor(R) (rosuvastatin), Viagra(R) (sildenafil), Cialis(R) (tadalafil), Levitra(R) (vardenafil), oral contraceptives ("the pill") or the contraceptive patch, Mycobutin(R) (rifabutin), inhaled Flonase(R) (fluticasone), metronidazole, or disulfiram. Patients should talk with their doctor about all medicines they are taking or planning to take, including those without a prescription and herbal products.
KALETRA should not be given once-daily in combination with Sustiva(R) (efavirenz), Viramune(R) (nevirapine), Agenerase(R) (amprenavir), fosamprenavir, Viracept(R) (nelfinavir), phenobarbital, Dilantin(R) (phenytoin) or Tegretol(R) carbamazepine.
Patients and/or their care providers should pay special attention to accurate administration of the KALETRA dose to reduce the risk of accidentally giving too much or too little medicine.
The most commonly reported side effects of moderate severity that are thought to be drug related are abdominal pain, abnormal bowel movements, diarrhea, feeling weak/tired, headache and nausea. Children taking KALETRA may sometimes get a skin rash. Other side effects may occur.
Pancreatitis and liver problems, which can be fatal, have been reported in patients receiving KALETRA. Patients should tell their doctor if they have nausea, vomiting, or abdominal pain, which may be signs of pancreatitis, or if they have or have had liver disease, such as hepatitis B or C.
Some patients have had large increases in triglycerides and cholesterol. Changes in body fat have been seen in some patients taking anti-HIV therapy. The long-term health effects of these conditions are not known at this time.
Diabetes and high blood sugar have occurred in patients taking protease inhibitors, such as KALETRA.
Some patients with hemophilia have increased bleeding with protease inhibitors.
The effects of KALETRA on pregnant women or their unborn babies are not known. Mothers taking KALETRA should not breast-feed.
All strengths of KALETRA tablets should be swallowed whole and not chewed, broken, or crushed.
KALETRA tablets should be stored at room temperature. Exposure of this product to high humidity outside the pharmacy container for longer than two weeks is not recommended.
Refrigerated KALETRA oral solution remains stable until the expiration date printed on the label. If stored at room temperature up to 77 degrees F (25 degrees C), KALETRA oral solution should be used within two months.
Avoid exposure to excessive heat.
Abbott and HIV/AIDS
Abbott 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. Abbott retroviral and hepatitis tests are used to screen more than half of the world's donated blood supply. Abbott has developed two protease inhibitors for the treatment of HIV.
About Abbott Fund
Abbott Fund is a philanthropic foundation established by Abbott in 1951. Abbott Fund's mission is to create healthier global communities by investing in creative ideas that promote science, expand health care and strengthen communities worldwide.
About Abbott
Abbott 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 68,000 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/hiv. For more information on Abbott's HIV/AIDS programs, please visit http://www.abbott.com/hiv. and http://www.abbottglobalcare.org.
SOURCE Abbott
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