Kowa Pharmaceuticals America, Inc. has announced results of a pre-specified safety analysis from the INTREPID (HIV-infected patieNts and TREatment with PItavastatin vs. pravastatin for Dyslipidemia) trial evaluating the effect of LIVALO® (pitavastatin) 4 mg compared with pravastatin 40 mg in HIV-infected adults with dyslipidemia following completion of the 40-week safety extension. INTREPID was a Phase 4, multicenter, 12-week randomized superiority study demonstrating superior LDL-C reduction for LIVALO 4 mg vs. pravastatin 40 mg at Week 12 and included a 40-week safety extension (NCT01301066) with secondary objectives to compare the safety and lipid profiles at Week 52.
Results of the extension showed that, after 52 weeks of therapy, safety profiles were maintained and consistent with 12-week results with an overall incidence of treatment emergent adverse events (TEAEs) of 67.5% for pitavastatin (N=126) and 69.8% for pravastatin (N=126). The most frequently reported TEAEs overall (occurring in >5% of subjects in either group) included upper respiratory infection (19 subjects, 7.5%); diarrhea (16 subjects, 6.3%); sinusitis (14 subjects, 5.6%); nasopharyngitis (13 subjects, 5.2%); bronchitis (11 subjects, 4.4%); nausea (11 subjects, 4.4%); and headache (10 subjects, 4.0%). Eleven subjects discontinued due to TEAE (4.4%) and there were no deaths. In addition, pitavastatin 4 mg maintained significantly greater reductions in LDL-C compared with pravastatin 40 mg at 52 weeks (pitavastatin -47.8 mg/dL and pravastatin -32.6 mg/dL, 30% vs. 20% reduction in LDL-C, respectively; LS mean % change -8.4, p<0.001). The results of the 40-week extension study and the pre-specified safety and efficacy analysis are being presented this week at the National Lipid Association's Scientific Sessions in Orlando, FL.
According to the recent 2013 IDSA Update of Primary Care Guidelines for the management of persons infected with HIV, people with HIV are living longer, creating a larger need for physicians to focus on preventative care for high cholesterol and diabetes. Dyslipidemia is a common co-morbidity and HIV-infected adults are at an increased risk for cardiovascular disease due to many factors, including lipid abnormalities.
"We are pleased the results showed the adverse event profiles and overall safety was maintained and consistent with 12-week safety data," said Dr. Craig Sponseller, Vice President of Medical Affairs at Kowa Pharmaceuticals America, Inc. "Moreover, pitavastatin 4 mg continued to demonstrate significantly greater LDL-C reduction compared with pravastatin 40 mg after 52 weeks of treatment in the HIV-infected adult population with high cholesterol."
Study investigator, Dr. Judith Aberg, Director of Infectious Disease, Icahn School of Medicine at Mount Sinai, New York, NY, said, "The findings of the INTREPID study are an important advance in potential treatment options for HIV-infected adults with high cholesterol. These results will serve to further physician education on statin use for HIV-infected individuals."
Additional INTREPID data presented separately from a post-hoc analysis evaluating age as a risk factor for CVD and change in lipid profiles, revealed that over 70% of subjects had age as a risk factor and that pitavastatin 4 mg demonstrated significantly greater reductions in atherogenic lipid parameters (LDL-C, apolipoprotein B, and non-HDL-C) compared with pravastatin 40 mg in men 45 years and older and women age 55 years and older.
About the Study
In the 12-week, Phase 4, randomized (1:1), double-blind, double-dummy superiority study, 252 patients were randomized to receive once-daily doses of pitavastatin 4 mg or pravastatin 40 mg, followed by a 40-week, double-blind safety extension study. Only patients who had fasting serum LDL-C levels between 130-220 mg/dL and triglycerides levels equal to or less than 400 mg/dL after the minimum 4-week dietary stabilization period were included in these analyses. Mean changes from baseline to week 52 were compared between treatments using ANCOVA, with percent change in lipid parameter as the dependent variable, and treatment as the independent variable, adjusting for site and hepatitis B or C at randomization.
LIVALO is a HMG-CoA reductase inhibitor indicated as an adjunctive therapy to diet to reduce elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) in adult patients with primary hyperlipidemia or mixed dyslipidemia.
Limitations of Use:
- Doses of LIVALO greater than 4 mg once daily were associated with an increased risk for severe myopathy in premarketing clinical studies. Do not exceed 4 mg once daily dosing of LIVALO.
- The effect of LIVALO on cardiovascular morbidity and mortality has not been determined.
- LIVALO has not been studied in Fredrickson Type I, III, and V dyslipidemias.
LIVALO was launched in the U.S. in June 2010.
Primary Hyperlipidemia and Mixed Dyslipidemia
Primary hyperlipidemia is defined as an elevation of cholesterol, particularly "bad" cholesterol (LDL-C), triglycerides (TG), or both. Mixed dyslipidemia is usually characterized by an elevation of LDL-C, TG, and a decrease in the "good" cholesterol (HDL-C) in the blood.