Anacetrapib

Anacetrapib (USAN, pINN; codenamed MK-0859, Merck) is a CETP inhibitor being developed to treat hypercholesterolemia (elevated cholesterol levels) and prevent cardiovascular disease.

Clinical trials
At the 16th International Symposium on Drugs Affecting Lipid Metabolism (New York, Oct 4-7, 2007), Merck reported on a Phase IIb study. The eight week study reported dosage correlated reduction in LDL-C and increases in HDL-C levels with no corresponding increases in blood pressure in any cohort. The increase in HDL was particularly significant, averaging 44 percent, 86 percent, 139 percent and 133 percent at doses of 10 mg, 40 mg, 150 mg and 300 mg.

Merck performed a dose-ranging study of anacetrapib, with the results presented in 2009

Phase III trial (DEFINE)
Merck started a Phase III trial to assess the drug's effects on LDL, HDL, clinically measurable cardiovascular events, and safety; It was code-named DEFINE (Determining the Efficacy and Tolerability of CETP Inhibition with Anacetrapib), and was described as a medium sized safety and efficacy trial.

Early results from the DEFINE trial were presented on November 17 at AHA2010, a meeting of the American Heart Association. At 100 mg dosage, LDL decreased by 36% while HDL increased by 138%. Systolic blood pressure showed no increase, and there was no association with increased CVD death or events.

Cardiologist Steve Nissen described DEFINE as a medium-sized safety trial intended to find out "whether anacetrapib would show the same increase in adverse cardiovascular events that was seen with torcetrapib." Fortunately, anacetrapib did not. In his opinion the DEFINE study was too small to show a clear benefit, but the trends in the major adverse cardiovascular events were going in the right direction.

Two year follow up due to complete by December 2012.