Safety and tolerability of dalcetrapib (RO4607381/JTT-705): results from a 48-week trial.

Aims: Co-primary objectives were to evaluate dalcetrapib (JTT-705/RO4607381), which targets cholesteryl ester transfer protein (CETP), effects on high-density lipoprotein cholesterol (HDL-C) in participants with coronary heart disease or risk equivalents and to evaluate potential changes in mesenteric lymph nodes.

Methods And Results: Double-blind trial with participants randomized (2:1) to dalcetrapib 900 mg/day (higher than 600 mg phase III dose) or placebo, both with atorvastatin, for 24 weeks (n = 135; one without post-baseline efficacy data was excluded from intent-to-treat population); a subset continued for 24-week extension (n = 77). Lipid changes and safety parameters were assessed. Mesenteric lymph nodes were evaluated by magnetic resonance imaging. Dalcetrapib increased HDL-C (33.4%, Week 24; 33.8%, Week 48), decreased CETP activity (-53.5%, Week 24; -56.5%, Week 48), and increased apolipoprotein A-I (11.4%, Week 24; 16.4%, Week 48). Dalcetrapib showed no clinically relevant differences vs. placebo in adverse events, laboratory parameters including aldosterone, electrocardiograms, and vital signs including blood pressure (BP). Dalcetrapib had no measurable, clinically relevant effect on lymph node size.

Conclusion: Dalcetrapib 900 mg administered for up to 48 weeks showed no clinically relevant changes in lymph nodes, BP, or other safety parameters. Dalcetrapib effectively increased HDL-C over 48 weeks of treatment.