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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

Blood pressure over time in the 24-week core and 24-week extension study.
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EHP601F3: Blood pressure over time in the 24-week core and 24-week extension study.

Mentions: Blood pressure remained stable throughout the 48-week study (FigureĀ 3). Mean (SD) BP values for dalcetrapib were (systolic BP/diastolic BP) 127 (14.1)/76 (8.9) mmHg at baseline and 127 (12.6)/77 (11.1) mmHg at study end. Shifts in systolic BP and diastolic BP were of a similar magnitude and direction in both treatment groups. Pulse rates generally remained stable (data not shown). In the dalcetrapib group, increased heart rate and irregular heart rate were each experienced by one participant. Two participants administered dalcetrapib had abnormal electrocardiograms, one of which was considered remotely related to treatment.


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)

Blood pressure over time in the 24-week core and 24-week extension study.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

EHP601F3: Blood pressure over time in the 24-week core and 24-week extension study.
Mentions: Blood pressure remained stable throughout the 48-week study (FigureĀ 3). Mean (SD) BP values for dalcetrapib were (systolic BP/diastolic BP) 127 (14.1)/76 (8.9) mmHg at baseline and 127 (12.6)/77 (11.1) mmHg at study end. Shifts in systolic BP and diastolic BP were of a similar magnitude and direction in both treatment groups. Pulse rates generally remained stable (data not shown). In the dalcetrapib group, increased heart rate and irregular heart rate were each experienced by one participant. Two participants administered dalcetrapib had abnormal electrocardiograms, one of which was considered remotely related to treatment.

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