Dalcetrapib: Difference between revisions
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Dalcetrapib or JTT-705 is a [[CETP inhibitor]] which was being developed by Hoffmann–La Roche until May 2012. The drug was aimed at raising the blood levels of "good cholesterol" (cholesterol carried in HDL particles, ''aka'' HDL-C). Prevailing observations indicate that high HDL levels correlate with better overall cardiovascular health, though it remains unclear whether raising HDL levels consequently leads to an increase in cardiovascular health. | Dalcetrapib or JTT-705 is a [[CETP inhibitor]] which was being developed by Hoffmann–La Roche until May 2012. The drug was aimed at raising the blood levels of "good cholesterol" (cholesterol carried in HDL particles, ''aka'' HDL-C). Prevailing observations indicate that high HDL levels correlate with better overall cardiovascular health, though it remains unclear whether raising HDL levels consequently leads to an increase in cardiovascular health. | ||
==Development and Research== | |||
A 24 week [[clinical trial]] showed that dalcetrapib did increase HDL-C levels, supporting the agent's desired effect. Further, the dal-PLAQUE phase IIb trial found evidence of [[Atheroma|plaque]] reduction. Plaque reduction is an anticipated observation following an increase in HDL. | A 24 week [[clinical trial]] showed that dalcetrapib did increase HDL-C levels, supporting the agent's desired effect. Further, the dal-PLAQUE phase IIb trial found evidence of [[Atheroma|plaque]] reduction. Plaque reduction is an anticipated observation following an increase in HDL. | ||
As of 2010 five phase II trials had started and there was no evidence of the raised blood pressure seen with [[torcetrapib]]. | As of 2010 five phase II trials had started and there was no evidence of the raised blood pressure seen with [[torcetrapib]]. | ||
dal-VESSEL phase IIb trial found no evidence of flow-mediated dilatation improvement. A 17% increase of [[Lipoprotein-associated phospholipase A2|Lp-PLA<sub>2</sub>]] mass level was noted. Lp-PLA<sub>2</sub> is associated with [[coronary heart disease]] and [[stroke]].<ref name="pmid23126252">{{cite journal |author=Schwartz GG, Olsson AG, Abt M, ''et al.'' |title=Effects of dalcetrapib in patients with a recent acute coronary syndrome |journal=[[The New England Journal of Medicine]] |volume=367 |issue=22 |pages=2089–99 |year=2012 |month=November |pmid=23126252 |doi=10.1056/NEJMoa1206797 |url=}}</ref> | dal-VESSEL phase IIb trial found no evidence of flow-mediated dilatation improvement. A 17% increase of [[Lipoprotein-associated phospholipase A2|Lp-PLA<sub>2</sub>]] mass level was noted. Lp-PLA<sub>2</sub> is associated with [[coronary heart disease]] and [[stroke]].<ref name="pmid23126252">{{cite journal |author=Schwartz GG, Olsson AG, Abt M, ''et al.'' |title=Effects of dalcetrapib in patients with a recent acute coronary syndrome |journal=[[The New England Journal of Medicine]] |volume=367 |issue=22 |pages=2089–99 |year=2012 |month=November |pmid=23126252 |doi=10.1056/NEJMoa1206797 |url=}}</ref><ref name="pmid23400900">{{cite journal |author=Phelan M, Anzures-Cabrera J, Carlile DJ, ''et al.'' |title=Effect of hepatic and renal impairment on the pharmacokinetics of dalcetrapib : altered distribution of the active thiol? |journal=[[Clinical Pharmacokinetics]] |volume=52 |issue=4 |pages=255–65 |year=2013 |month=April |pmid=23400900 |doi=10.1007/s40262-013-0035-z |url=}}</ref> | ||
dal-OUTCOMES phase III trial passed its first interim review in July, 2011, however, development was halted on May 7, 2012 “due to a lack of clinically meaningful efficacy”. The results of dal-OUTCOMES III were published in November, 2012.<ref name="pmid23317399">{{cite journal |author=Bochem AE, Kuivenhoven JA, Stroes ES |title=The Promise of Cholesteryl Ester Transfer Protein (CETP) Inhibition in the Treatment of Cardiovascular Disease |journal=[[Current Pharmaceutical Design]] |volume=19 |issue=17 |pages=3143–9 |year=2013 |pmid=23317399 |doi= |url=}}</ref> | dal-OUTCOMES phase III trial passed its first interim review in July, 2011, however, development was halted on May 7, 2012 “due to a lack of clinically meaningful efficacy”. The results of dal-OUTCOMES III were published in November, 2012.<ref name="pmid23317399">{{cite journal |author=Bochem AE, Kuivenhoven JA, Stroes ES |title=The Promise of Cholesteryl Ester Transfer Protein (CETP) Inhibition in the Treatment of Cardiovascular Disease |journal=[[Current Pharmaceutical Design]] |volume=19 |issue=17 |pages=3143–9 |year=2013 |pmid=23317399 |doi= |url=}}</ref> | ||
Latest revision as of 13:10, 26 April 2013
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]
Overview
Dalcetrapib or JTT-705 is a CETP inhibitor which was being developed by Hoffmann–La Roche until May 2012. The drug was aimed at raising the blood levels of "good cholesterol" (cholesterol carried in HDL particles, aka HDL-C). Prevailing observations indicate that high HDL levels correlate with better overall cardiovascular health, though it remains unclear whether raising HDL levels consequently leads to an increase in cardiovascular health.
Development and Research
A 24 week clinical trial showed that dalcetrapib did increase HDL-C levels, supporting the agent's desired effect. Further, the dal-PLAQUE phase IIb trial found evidence of plaque reduction. Plaque reduction is an anticipated observation following an increase in HDL.
As of 2010 five phase II trials had started and there was no evidence of the raised blood pressure seen with torcetrapib.
dal-VESSEL phase IIb trial found no evidence of flow-mediated dilatation improvement. A 17% increase of Lp-PLA2 mass level was noted. Lp-PLA2 is associated with coronary heart disease and stroke.[1][2]
dal-OUTCOMES phase III trial passed its first interim review in July, 2011, however, development was halted on May 7, 2012 “due to a lack of clinically meaningful efficacy”. The results of dal-OUTCOMES III were published in November, 2012.[3]
References
- ↑ Schwartz GG, Olsson AG, Abt M; et al. (2012). "Effects of dalcetrapib in patients with a recent acute coronary syndrome". The New England Journal of Medicine. 367 (22): 2089–99. doi:10.1056/NEJMoa1206797. PMID 23126252. Unknown parameter
|month=ignored (help) - ↑ Phelan M, Anzures-Cabrera J, Carlile DJ; et al. (2013). "Effect of hepatic and renal impairment on the pharmacokinetics of dalcetrapib : altered distribution of the active thiol?". Clinical Pharmacokinetics. 52 (4): 255–65. doi:10.1007/s40262-013-0035-z. PMID 23400900. Unknown parameter
|month=ignored (help) - ↑ Bochem AE, Kuivenhoven JA, Stroes ES (2013). "The Promise of Cholesteryl Ester Transfer Protein (CETP) Inhibition in the Treatment of Cardiovascular Disease". Current Pharmaceutical Design. 19 (17): 3143–9. PMID 23317399.