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Clinical Study Demonstrates Similar Effectiveness Of Once-Daily vs. Twice-Daily Dosing of Abbott's Kaletra(lopinavir/ritonavir) Tablet in HIV-Infected Patients New to Antiretroviral Therapy. Abbott press release
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Flexible Dosing Option Supports Convenience Benefits in HIV Treatment
BOSTON, Feb. 8, 2008 - Abbott presented 48-week results of a clinical study, demonstrating that once-daily and twice-daily dosing of its protease inhibitor (PI)
Kaletra (lopinavir/ritonavir) tablet, given in a regimen containing tenofovir/emtricitabine, is similarly effective at controlling the virus (reducing the amount of HIV-1) and improving the immune system (increasing CD4 cells) in HIV-1 positive patients new to antiretroviral treatment. The results were presented at the 15th Conference on Retroviruses and Opportunistic Infections (CROI) this week.
Key findings include:
· Once-daily dosing of the tablet achieved similar virologic suppression regardless of a patient's baseline viral load or baseline CD4 cell count before starting antiretroviral therapy. Seventy-seven percent of once-daily treated patients and 76 percent of twice-daily treated patients achieved a viral load of less than 50 copies/mL at 48 weeks. In line with previous Abbott studies, Kaletra demonstrated similar response in patients with a wide range of baseline viral loads and CD4 counts.
· The well-established resistance profile of Kaletra was similar in both once-daily and twice-daily treatment regimens. Through 48 weeks of therapy, no protease inhibitor or tenofovir-associated resistance mutations were observed in HIV patients from either treatment group.
· Once-daily and twice-daily dosing of the Kaletra tablet were similarly well tolerated. Fifteen percent of patients in the twice-daily group experienced moderate or severe diarrhea, compared to 17 percent in the once-daily group. Less than 5 percent of patients, overall, discontinued the study due to side effects.
· Surveys from the multi-country study showed that patients preferred the tablet formulation of Kaletra to the soft-gel capsules (SGC). In the once-daily and twice-daily groups, 75 percent and 80 percent of patients, respectively, who switched from soft-gel capsules to tablet preferred the tablet, while only 3 percent and 5 percent, respectively, preferred the SGC.
"Kaletra tablets offer fundamental advantages that are important to patients - like being able to take the tablet with or without a meal or not having to worry about refrigeration," said Joseph Gathe, Jr., M.D., clinical instructor, Department of Internal Medicine, Baylor College of Medicine and lead investigator of the study. "These benefits are especially important for patients who are concerned about convenience and privacy."
"In the last decade, we have seen a shift from simply treating and helping extend life for those infected with HIV to creating therapies that also offer improved convenience for patients," said Scott C. Brun, M.D., divisional vice president, infectious diseases and renal development, Global Pharmaceutical Research and Development, Abbott. "The tablet formulation of Kaletra dosed as once-daily combination therapy is a real advantage for therapy-naive patients and physicians, offering a convenient and effective HIV treatment option, as indicated by the results of this study."
About the 730 Study - 48-week Data
Design and Primary Endpoints:
· M05-730 study is a 96-week Phase 3 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 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 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. The primary safety endpoint was the proportion of patients reporting a treatment-emergent adverse event of diarrhea during the first eight weeks of dosing.
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 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 (7 percent versus 5 percent), vomiting (3 percent versus 4 percent), and increased triglycerides (2 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.
Important Safety Information
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 dihydro_ergotamine, ergonovine, ergotamine, or methylergonovines such as Cafergot, Migranal, D.H.E. 45, ergotrate maleate, and methergine, as well as Halcion (triazolam), Orap (pimozide), Propulsid (cisapride), or Versed (midazolam). KALETRA must not be taken with rifampin, also known as Rimactane, Rifadin, Rifater, or Rifamate; St. John's wort (Hypericum perforatum); Mevacor (lovastatin), or Zocor (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 (atorvastatin), Crestor (rosuvastatin), Viagra (sildenafil), Cialis (tadalafil), Levitra (vardenafil), oral contraceptives ("the pill") or the contraceptive patch, Mycobutin (rifabutin), inhaled Flonase (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 (efavirenz), Viramune (nevirapine), Agenerase (amprenavir), fosamprenavir, Viracept (nelfinavir), phenobarbital, phenytoin (Dilantin) or carbamazepine (Tegretol).
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 2 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 77iF (25iC), KALETRA oral solution should be used within 2 months.
Avoid exposure to excessive heat. For full prescribing information visit www.kaletra.com.
About Abbott
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.
Expanding on its scientific contributions, Abbott and the Abbott Fund have invested more than $100 million in developing countries to improve the lives of people affected by HIV/AIDS through programs targeting critical areas of need, including strengthening health care systems, supporting children affected by HIV/AIDS, and advancing HIV testing and treatment. For more information on Abbott's HIV/AIDS programs, please visit www.abbott.com/HIVAIDS and www.abbottglobalcare.org.
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 65,000 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 www.abbott.com.
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