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Interim Results of Abbott's PROGRESS Study Show Rapid Viral Decline in Dual-Therapy Regimen of Kaletra® (lopinavir/ritonavir) and Raltegravir - Abbott press release
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Lopinavir/Ritonavir (LPV/r) Combined With Raltegravir (RAL ... Presented at BHIVA April 1 2009
Lopinavir/Ritonavir (LPV/r) Combined With Raltegravir (RAL) Provides More Rapid Viral Decline Than LPV/r Combined With Tenofovir Disoproxil ...
www.natap.org/2009/HIV/042009_06.htm
Liverpool, United Kingdom, April 28, 2009 - Interim results of Abbott's PROGRESS study showed that Kaletra® combined with raltegravir suggested a more rapid initial viral load decline when compared to a traditional triple-drug combination therapy of Kaletra and Truvada®. PROGRESS is an open-label, 96-week evaluation of the safety and efficacy of Abbott's HIV protease inhibitor Kaletra (lopinavir/ritonavir) in combination with raltegravir, the integrase inhibitor manufactured by Merck, compared to Kaletra and the nucleoside reverse transcriptase inhibitor (NRTI) Truvada (tenofovir and emtricitabine) in antiretroviral-naive, HIV-1-infected patients. Abbott conducted an eight-week analysis to compare rates of viral decay between the two regimens. The study results were presented at the 15th Annual Conference of the British HIV Association (BHIVA).
"These interim results from the PROGRESS study are the first data to suggest that more rapid viral suppression may be possible with a dual regimen that includes Kaletra and raltegravir versus a standard triple-therapy regimen," said Scott C. Brun, M.D., divisional vice president, infectious diseases and immunology development, Global Pharmaceutical Research and Development, Abbott. "Lowering a patient's viral load to an undetectable level and maintaining viral load suppression are key success markers for patients beginning antiretroviral treatment."
Other key findings of the study include:
· A greater proportion of patients had HIV-1 RNA levels <40 copies/mL at weeks two, four and eight when treated with Kaletra and raltegravir compared with Kaletra and Truvada. Intent-to-treat results were similar to the observed data.
· Both treatment groups had statistically significant mean increases from baseline in CD4+ T-cell count at weeks four and eight (p<0.001).
· Overall, the incidences of treatment-emergent adverse events were similar between treatment groups. The most commonly-reported events in both treatment groups, regardless of severity or relationship to study drug, were gastrointestinal in nature, including diarrhea, nausea and flatulence. Headache was also commonly reported and did not differ between groups.
· Cholesterol elevations (≥7.77 mmol/L [≥300 mg/dL]) were observed in 7 percent (seven out of 101 patients) of Kaletra and raltegravir patients and 3 percent (three out of 102 patients) of Kaletra and Truvada patients.
· Triglyceride increases (≥8.475 mmol/L [≥750 mg/dL]) were detected in 6 percent (six out of 101) of Kaletra and raltegravir patients, but were not observed in Kaletra and Truvada patients (p=.014).
Kaletra is a protease inhibitor and is always used in combination with other anti-HIV-1 medicines for the treatment of HIV-1 infection. Kaletra is indicated for adults and for children age two years and older. Raltegravir is an integrase inhibitor indicated for use in combination therapy in treatment-experienced adult patients who have HIV-1 that is resistant to multiple antiretroviral medications. The safety and efficacy of raltegravir have not been established in treatment-naïve adult patients or pediatric patients.
The rapid viral suppression observed for Kaletra and raltegravir is consistent with the Merck 004 Study, in which raltegravir in combination with two NRTIs was shown to be as effective in suppressing viral load in treatment-naïve HIV-infected patients as efavirenz administered with two NRTIs in a triple-therapy regimen. In the study, viral decay rates were significantly higher for the raltegravir arm compared to the efavirenz arm.
"The initial PROGRESS results suggest that a nucleoside-free dual regimen may perform as well as the standard triple-therapy regimen," said Jose Arribas, M.D., senior attending physician, HIV Unit, Hospital Universitario La Paz, Madrid, Spain.
About the PROGRESS Study
· PROGRESS is an open-label 96-week evaluation of the safety and efficacy of Kaletra in combination with raltegravir, compared to Kaletra and Truvada in antiretroviral-naïve subjects.
· The PROGRESS study combines Kaletra with raltegravir, an integrase inhibitor.
· PROGRESS is a global, multicenter study of approximately 200 patients. The study is fully enrolled and 48-week data are planned for the first half of 2010.
· Merck supplied raltegravir for the PROGRESS study.
· The primary endpoints of the 96-week PROGRESS study evaluate the antiviral activity, safety and tolerability of the two regimens. Secondary endpoints include metabolic effects, fat distribution, time to loss of virologic response, incidence of resistance to each drug in the study and patient-reported outcomes.
More Information on Kaletra
· Kaletra was studied for seven years in Abbott Study 720, one of the longest clinical trials for any antiretroviral agent, which was completed in April 2005.
· The Kaletra tablet is the first and only co-formulated protease inhibitor tablet that does not require refrigeration and can be taken with or without food, two important factors in delivering HIV medicine, especially in developing countries.
More Information on Raltegravir
· Raltegravir is the first medicine to be approved in a new class of antiretroviral drugs called integrase inhibitors.
· Raltegravir is approved for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.
· The safety and efficacy of raltegravir have not been established in treatment-naïve adult patients or pediatric patients.
· Raltegravir works by inhibiting the insertion of HIV-1 DNA into human DNA by the integrase enzyme. Inhibiting integrase from performing this essential function limits the ability of the virus to replicate and infect new cells. There are drugs in use that inhibit two other enzymes critical to the HIV-1 replication process - protease and reverse transcriptase - but raltegravir is the only drug approved that inhibits the integrase enzyme.
Indication and Important Safety Information for Kaletra
Indication
Kaletra is indicated for the treatment of HIV-1 infected adults and children above the age of two years and older, used in combination with other antiretroviral agents.
Kaletra does not cure HIV infection or AIDS and does not reduce the risk of passing HIV to others.
Kaletra Important Safety Information
Kaletra should not be taken by patients who have had an allergic reaction to any of its ingredients, including lopinavir or ritonavir, or any of the excipients, or by patients with severe liver problems.
Do not take Kaletra with any of the following medicines: astemizole, terfenadine, oral midazolam, triazolam, pimozide, cisapride, ergotamine, dihydroergotamine, ergonovine, and methylergonovine, amiodarone, vardenafil and products containing St. John's Wort (Hypericum perforatum).
Kaletra may interact with certain other medications with possible clinical effects. The use of the following medicines together with Kaletra should only take place on the basis of medical advice: medicines used to lower blood cholesterol (e.g. lovastatin, simvastatin, rosuvastatin or atorvastatin), some medicines affecting the immune system (e.g. cyclosporin, sirolimus (rapamycin), tacrolimus), various steroids (e.g. dexamethasone, fluticasone propionate), other protease inhibitors, certain heart medicines such as: digoxin, calcium channel blockers (e.g. felodipine, nifedipine, nicardipine) and medicines used to correct heart rhythm (e.g. bepridil, systemic lidocaine, quinidine), antifungals (e.g. ketoconazole, itraconazole), morphine-like medicines (e.g. methadone), anticonvulsants (e.g. carbamazepine, phenytoin, phenobarbital), warfarin, certain antibiotics (e.g. rifampicin, rifabutin, clarithromycin), certain antidepressants (e.g. trazodone), voriconazole, sedative agents (e.g. midazolam administered by injection), anticancer agents (e.g. vincristine, vinblastine), erectile dysfunction agents (e.g. sildenafil and tadalafil) and oral contraceptive or patch contraceptive containing ethinyl oestradiol.
Kaletra oral solution contains alcohol. Patients should discuss with their doctor if taking or planning to take metronidazole or disulfiram. Severe nausea and vomiting may occur.
Taking certain medicines with Kaletra may result in increased levels in the body of these other medicines and could increase or prolong their effect and/or adverse reactions. Patients must tell their doctor about all the medicines, including those medicines they can buy without a prescription; they are taking or are planning to take before taking Kaletra. This is because taking Kaletra with some medicines can result in serious or life threatening problems.
Pregnant or nursing mothers should not take Kaletra unless specifically directed by their doctor.
Cases of pancreatitis have been reported in patients taking Kaletra. Patients should contact their doctor if they have nausea, vomiting, or abdominal pain, which may be signs of pancreatitis.
Liver problems, which can be fatal, have also been reported. Patients should tell their doctor if they have had liver disease such as chronic hepatitis B or C as they are at increased risk for severe and potentially fatal liver adverse events. These patients may require blood tests for control of liver function.
Redistribution, accumulation or loss of body fat may occur in patients receiving combination antiretroviral therapy. The long-term consequences of these events are currently unknown.
In patients taking protease inhibitors, increased bleeding (in patients with hemophilia type A and B) has been reported.
New onset diabetes mellitus, hyperglycaemia or exacerbation of existing diabetes mellitus has been reported in patients receiving protease inhibitors.
Treatment with Kaletra has resulted in increases, sometimes marked, in the concentration of total triglycerides and cholesterol.
In some patients with advanced HIV infection and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. Symptoms of infection should be reported to a doctor immediately.
Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis. Signs are joint stiffness, aches and pains (especially in the hip, knee and shoulder) and difficulty in movement. These symptoms require that patients contact their doctor.
Kaletra has been shown to cause modest asymptomatic prolongation of the PR interval in some healthy adult subjects. Rare reports of 2nd or 3rd degree atroventricular block in patients with underlying structural heart disease and pre-existing conduction system abnormalities or in patients receiving drugs known to prolong the PR interval (such as verapamil or atazanavir) have been reported in patients receiving Kaletra. Kaletra should be used with caution in such patients.
In Kaletra adult clinical trials, the very common and commonly reported side effects of moderate to severe intensity were diarrhea, insomnia, headache, burning or prickling sensation around the mouth and extremities, nausea, vomiting, abdominal pain, abnormal stools, dyspepsia, flatulence, gastrointestinal disorder, rash, lipodystrophy, acne, and weakness. This is not a complete list of reported side effects.
For more information about Kaletra, please consult your local prescribing information.
Storage Conditions:
Kaletra tablets do not require any special storage conditions.
Kaletra oral solution: Store in a refrigerator (2o-8o C). If kept outside of the refrigerator, do not store above 25o C and discard any unused contents after 42 days (6 weeks). 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
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 72,000 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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