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

Stein EA, Roth EM, Rhyne JM, Burgess T, Kallend D, Robinson JG - Eur. Heart J. (2010)

Bottom Line: 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.Dalcetrapib 900 mg administered for up to 48 weeks showed no clinically relevant changes in lymph nodes, BP, or other safety parameters.

View Article: PubMed Central - PubMed

Affiliation: Metabolic and Atherosclerosis Research Center, Cincinnati, OH 45212, USA. esteinmrl@aol.com

ABSTRACT

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.

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Related in: MedlinePlus

High-density lipoprotein cholesterol per cent change (Ā±95% confidence interval) from baseline (BL) by time over 48 weeks.
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EHP601F2: High-density lipoprotein cholesterol per cent change (Ā±95% confidence interval) from baseline (BL) by time over 48 weeks.

Mentions: There was a significantly greater increase in HDL-C from baseline with dalcetrapib at Weeks 24 and 48 (each P < 0.0001 vs. placebo; TableĀ 2). The absolute change in HDL-C (least squares mean) with dalcetrapib was 12.8 mg/dL at Week 24 and 13.8 mg/dL at Week 48 from baseline levels of 41.4 and 42.4 mg/dL, respectively. The absolute change for placebo was 0.5 mg/dL at Week 24 and 1.4 mg/dL at Week 48 from baseline 41.0 and 41.8 mg/dL, respectively. Percent change in HDL-C was 33.4% for dalcetrapib vs. 3.5% for placebo at Week 24, and 33.8 vs. 3.7% at Week 48 (each P < 0.0001 vs. placebo; TableĀ 2). High-density lipoprotein cholesterol levels reached a plateau at Week 2 with dalcetrapib and were sustained throughout both treatment phases (FigureĀ 2). In the dalcetrapib group, CETP activity decreased (āˆ’53.5% at Week 24; āˆ’56.5% at Week 48) and CETP mass increased (80.8% at Week 24; 86.5% at Week 48) from baseline (each P < 0.0001 vs. placebo; TableĀ 2).


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

Stein EA, Roth EM, Rhyne JM, Burgess T, Kallend D, Robinson JG - Eur. Heart J. (2010)

High-density lipoprotein cholesterol per cent change (Ā±95% confidence interval) from baseline (BL) by time over 48 weeks.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2821630&req=5

EHP601F2: High-density lipoprotein cholesterol per cent change (Ā±95% confidence interval) from baseline (BL) by time over 48 weeks.
Mentions: There was a significantly greater increase in HDL-C from baseline with dalcetrapib at Weeks 24 and 48 (each P < 0.0001 vs. placebo; TableĀ 2). The absolute change in HDL-C (least squares mean) with dalcetrapib was 12.8 mg/dL at Week 24 and 13.8 mg/dL at Week 48 from baseline levels of 41.4 and 42.4 mg/dL, respectively. The absolute change for placebo was 0.5 mg/dL at Week 24 and 1.4 mg/dL at Week 48 from baseline 41.0 and 41.8 mg/dL, respectively. Percent change in HDL-C was 33.4% for dalcetrapib vs. 3.5% for placebo at Week 24, and 33.8 vs. 3.7% at Week 48 (each P < 0.0001 vs. placebo; TableĀ 2). High-density lipoprotein cholesterol levels reached a plateau at Week 2 with dalcetrapib and were sustained throughout both treatment phases (FigureĀ 2). In the dalcetrapib group, CETP activity decreased (āˆ’53.5% at Week 24; āˆ’56.5% at Week 48) and CETP mass increased (80.8% at Week 24; 86.5% at Week 48) from baseline (each P < 0.0001 vs. placebo; TableĀ 2).

Bottom Line: 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.Dalcetrapib 900 mg administered for up to 48 weeks showed no clinically relevant changes in lymph nodes, BP, or other safety parameters.

View Article: PubMed Central - PubMed

Affiliation: Metabolic and Atherosclerosis Research Center, Cincinnati, OH 45212, USA. esteinmrl@aol.com

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus