Activx reports positive results from Phase Ib and IIa diabetes trials

In Phase IIa, KRP-104 was shown to be well tolerated and efficacious in the treatment of hyperglycemia in patients with type 2 diabetes resulting in highly significant improvements in glycemic control compared to placebo, the company said.

The open-labeled, cross-over, Phase Ib trial of KRP-104 in the US enrolled 28 patients with type 2 diabetes and showed equivalent efficacy on glucose-lowering to a competitive drug, according to Activx.

The randomized, double-blind, placebo-controlled, multi-center Phase IIa trial in the US and India enrolled 220 patients with type 2 diabetes inadequately controlled on metformin alone. The study evaluated the safety, tolerability, and efficacy of a total daily dose of 120mg of KRP-104, administered either as a once daily (QD) dose or as a split dose of 60mg (BID) added to stable metformin therapy for 12 weeks of treatment. Both dosing regimens provide greater than 95% inhibition of dipeptidyl peptidase-4 (DPP-4) during daytime hours, but the BID dosing regimen provides this high level of inhibition continuously, whereas the QD dose results in considerably less DPP-4 inhibition overnight, the company said.

At baseline, the study population had a mean hemoglobin A1c (HbA1c) of 7.9%. Both KRP-104 dose groups demonstrated comparable, highly significant reductions in HbA1c of -0.64% (p<0.0001) and -0.54% (p=0.0003) in the 60mg BID and 120mg QD groups, respectively, compared with placebo over 12 weeks. Approximately 40% of patients in both groups achieved the American Diabetes Association recommended guideline of HbA1c<7%. Similarly, KRP-104 significantly reduced the secondary efficacy endpoint of fasting plasma glucose (FPG) in the 60mg BID and 120mg QD dose group compared with placebo. No significant difference was observed between BID and QD dosages on reduction of HbA1c and FPG. The safety and tolerability of KRP-104 were not substantially different from placebo.