Kowa Pharmaceuticals America, Inc. announces INTREPID trial results in The Lancet HIV showing superior LDL cholesterol reduction with Livalo (pitavastatin) compared with pravastatin in adults with HIV and dyslipidemia.
Kowa Pharmaceuticals America, Inc. today announced publication of results of the INTREPID trial (HIV-infected patients and treatment with pitavastatin vs. pravastatin for dyslipidemia) in The Lancet HIV.
Results of the Phase 4 trial showed that Livalo (pitavastatin) 4 mg was superior to pravastatin 40 mg in reducing LDL cholesterol (LDL-C) in adults with HIV and dyslipidemia and had a comparable safety profile.
“Dyslipidemia affects more than three-fourths of people with HIV, putting them at significantly increased risk for cardiovascular disease. However, treatment of elevated LDL cholesterol in this patient population is challenging because of drug interactions between statins and commonly used antiretroviral agents,” said Douglas Ward, M.D., co-author of the INTREPID study publication, Clinical Associate Professor of Medicine at George Washington University Medical School and physician at the Dupont Circle Physicians Group.
“The finding that Livalo was more effective than pravastatin in lowering LDL cholesterol and was well tolerated in HIV patients with dyslipidemia suggests it could be a viable treatment option for managing dyslipidemia and contributing factors in adults with HIV,” Ward added.
“The INTREPID trial is the first to evaluate the efficacy and safety of Livalo in this difficult-to-treat patient population. The results not only demonstrate that Livalo is superior to pravastatin in lowering LDL cholesterol, but also in maintaining moderate-intensity LDL cholesterol reduction similar to the non-HIV infected adult population,” said Craig Sponseller, M.D., Chief Medical Officer, Medical Affairs, of Kowa Pharmaceuticals America, Inc.
“Furthermore, Livalo can be used in patients receiving complex antiretroviral therapy at the highest dose of Livalo because it is not mainly metabolized via the cytochrome P450 enzyme system,” Sponseller continued. “This study, along with the landmark REPRIEVE trial to evaluate the effect of Livalo on primary prevention of cardiovascular disease in adults with HIV, underscores our commitment to providing a safe and effective treatment option for clinically complex patient populations, such as the elderly, patients with diabetes or patients who take multiple medications for co-morbid conditions.”
INTREPID Study Design and Results
The prospective, randomized, double-blind, active-controlled, Phase 4 superiority trial enrolled adults with HIV (CD4 cell counts >200 cel ls/mm3 and HIV-1 RNA <200 copies/mL) and dyslipidemia (LDL-C between 130-220 mg/dL, triglycerides ≤ 400 mg/dL) at 45 sites in the United States and Puerto Rico. A total of 252 study participants were randomized to Livalo 4 mg (126 patients) or pravastatin 40 mg (126 patients) with matching placebos once-daily for 12 weeks, followed by a 40-week safety extension.
The primary endpoint was percent change in fasting serum LDL-C from baseline to week 12 in the modified intention-to-treat population. The safety analysis included all participants who took at least one dose of study medication.
Results showed that Livalo demonstrated a statistically significant and superior reduction in LDL-C compared with pravastatin at 12 weeks (31.1 percent vs. 20.9 percent; p<0.0001); significant differences between the two treatment groups were sustained through week 52.Reductions in non-HDL-cholesterol and apo B from baseline were significantly greater with Livalo than with pravastatin after 12 weeks of therapy (-26.9 percent and -18.7 percent in non-HDL-cholesterol, p<0.0001; and -23.3 percent and -16.5 percent in apo B, p<0.0001) and after 52 weeks of therapy (-26.1 percent and -19.0 percent in non-HDL-cholesterol, p=0.012; and -25.4 percent and -19.6 percent in apo B, p=0.018).
There were no significant changes in parameters of glucose metabolism and insulin resistance for either treatment at week 12 or week 52. Compared to baseline, no significant effects on fasting glucose or HbA1c were observed for either Livalo or pravastatin at 52 weeks of treatment, and no participant had a post-baseline abnormal fasting glucose or HbA1c level that was reported as a treatment-emergent adverse event (TEAE). The change in fasting plasma insulin also was not significantly different from baseline for either treatment.
In a pre-specified safety assessment, there were no significant between-treatment differences from baseline to week 52 in HIV-1 RNA (0.03 log copies for Livalo and 0.07 log copies for pravastatin; p=0.82) or CD4 cell counts (-8.3 cells/mm3 for Livalo and 36.5 cells/mm3 for pravastatin; p=0.19). The percentage of patients with virologic failure was similar in the two groups (3 percent in the Livalo group and 5 percent in the pravastatin group).
TEAEs were reported in 85 (67.5 percent) Livalo-treated participants and 88 (69.8 percent) pravastatin-treated participants. The majority of these events were of mild (59.9 percent overall) or moderate (28.6 percent overall) severity. The most common TEAEs were diarrhea in the Livalo group (9.5 percent) and upper respiratory tract infection in the pravastatin group (11.1 percent). Myalgia occurred in two (1.6 percent) Livalo participants and three (2.4 percent) pravastatin participants, and caused study discontinuation in one (0.8 percent) participant in each treatment group.
Treatment-related TEAEs were reported for 16 (12.7 percent) Livalo-treated participants and 12 (9.5 percent) pravastatin-treated participants. Treatment-emergent serious adverse events (SAEs) occurred in seven participants (5.6 percent) in the Livalo group and three participants (2.4 percent) in the pravastatin group. No SAE was assessed to be treatment-related. One SAE (cerebrovascular accident in the pravastatin group) resulted in study discontinuation.
(Source: Business Wire)
Filed Under: Drug Discovery