Abstract 1272: Efficacy and Safety Following Cessation of Treatment With Cholesteryl Ester Transfer Protein Inhibitor Anacetrapib (MK-0859) in Patients With Primary Hypercholesterolemia or Mixed Hyperlipidemia
The effects on lipids and safety of cessation of treatment with the cholesteryl ester transfer protein inhibitor anacetrapib (ANA; MK-0859) as monotherapy or coadministered with atorvastatin (ATV) 20 mg in patients (pts) with primary hypercholesterolemia or mixed hyperlipidemia were assessed. In Phase A of this study (base study), 589 pts with primary hypercholesterolemia or mixed hyperlipidemia (≥30% with low HDL-C: ≤44 mg/dL in men and ≥54 mg/dL in women) were randomized equally to placebo (Pbo), ATV 20 mg, ANA 10 mg, 40 mg, 150 mg, or 300 mg doses as monotherapy and coadministered with ATV 20 mg daily for 8 wks. A total of 526 pts entered Phase B (reversal phase) in which ANA treatment was stopped for 8 wks. At completion of Phase B (Wk 16), LDL-C values returned to pre-dose Phase A values for the ANA 10 mg and 40 mg monotherapy groups versus Pbo, and there was no remaining additional LDL-C-lowering for the ANA 10 and 40 mg coadministration groups versus ATV 20 mg. In contrast, for the ANA 150 mg and 300 mg monotherapy treatments, persistent Pbo-adjusted mean percent reductions from baseline of −9.3% and −15.3%, respectively, were still evident at Wk 16 (~22–37% of Pbo-adjusted LDL-C reductions observed at Wk 8), and mean percent reductions from baseline of ~−11% (~40–50% of reductions at Wk 8) versus ATV 20 mg were observed for the ANA 150 mg and 300 mg coadministraton groups. For HDL-C, at Wk 16, there was no evidence of a persistent treatment effect observed for the ANA 10 mg monotherapy group, while there were still notable mean percent increases from baseline versus P for the ANA 40 mg (18.6%), 150 mg (40.5%) and 300 mg (43.4%) monotherapy treatments (~23–34% of increases at Wk 8). Similarly, for the ANA coadministration groups, there were still notable persistent mean percent increases (13.1– 41.8%) versus ATV 20 mg for the same ANA treatments (≥40 mg) at Wk 16 (~16–34% of increases at Wk 8). No patterns of clinically important BP elevations or adverse experiences were observed between the treatment groups. In conclusion, 8 weeks after stopping active therapy with ANA, persistent, favorable lipid effects remained in the higher dose arms for both the monotherapy and coadministration treatment groups. Cessation of ANA treatment was well tolerated.