BMS/Merck compound effective in phase III diabetes trial

In the trial, the investigational compound decreased hemoglobin A1C levels (a measure of average blood glucose over a two- to three-month time period) at 24 weeks versus placebo. Additional effects were seen on triglycerides and HDL-C.

In the study there were two cohorts: a double-blind, placebo-controlled cohort with an entry A1C level between 7% and 10%, and an open-label cohort with entry A1C levels between 10% and 12%. In the double-blind study group, mean baseline A1C for all patient groups was 7.89% to 8.02%.

At 24 weeks, mean changes in A1C versus baseline were -0.32%, -1.05%, and -1.23% in the placebo, muraglitazar 2.5mg, and muraglitazar 5mg groups, respectively. In the open-label cohort (mean baseline A1C 10.68%), mean change in A1C versus baseline was -2.62% after 24 weeks of treatment with muraglitazar 5mg once daily.

The American Association of Clinical Endocrinologists (AACE) recommended A1C target level of less than or equal to 6.5% was achieved by 18%, 36%, and 58% of patients taking placebo, muraglitazar 2.5mg, and muraglitazar 5mg, respectively in the double-blind cohort.

In terms of secondary endpoints, mean HDL-C levels increased 2%, 10%, and 16% from baseline in the placebo, 2.5mg, and 5mg groups of the double-blind study and increased 12% from baseline in the 5mg open-label group, respectively.

Other secondary endpoints showed that muraglitazar was associated with significant reductions from baseline in mean fasting plasma glucose (FPG), fasting plasma insulin, free fatty acid, apoB, and non-HDL cholesterol levels. Muraglitazar treatment was also associated with increased insulin sensitivity as measured by a decrease in homeostasis model assessment of insulin resistance (HOMA-IR).

The new drug application (NDA) for muraglitazar is currently under review by the FDA. If approved, muraglitazar would become the first agent in a new class of investigational compounds called glitazars available in the US.