Dalcetrapib
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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.[1][2] The drug was aimed at raising the blood levels of "good cholesterol" (cholesterol carried in HDL particles, aka HDL-C).[3] 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.[4]
A 24 week clinical trial showed that dalcetrapib did increase HDL-C levels, supporting the agent's desired effect.[5] Further, the dal-PLAQUE phase IIb trial found evidence of plaque reduction.[6] Plaque reduction is an anticipated observation following an increase in HDL.[citation needed]
As of 2010[update] five phase II trials had started and there was no evidence of the raised blood pressure seen with torcetrapib.[5]
dal-VESSEL phase IIb trial found no evidence of flow-mediated dilatation improvement. A 17% increase of Lp-PLA2 mass level was noted.[7] Lp-PLA2 is associated with coronary heart disease and stroke.[citation needed]
dal-OUTCOMES phase III trial passed its first interim review in July, 2011,[8] however, development was halted on May 7, 2012 “due to a lack of clinically meaningful efficacy.”.[2]
The results of dal-OUTCOMES III were published in November, 2012.[9]
See also
- CETP inhibitor, which contains links to related agents; as of November 2012: Torcetrapib, Anacetrapib, Dalcetrapib and Evacetrapib
References
- ↑ Huang Z, Inazu A, Nohara A, Higashikata T, Mabuchi H (2002). "Cholesteryl ester transfer protein inhibitor (JTT-705) and the development of atherosclerosis in rabbits with severe hypercholesterolaemia". Clin. Sci. 103 (6): 587&ndash, 594. PMID 12444911. Unknown parameter
|month=ignored (help) - ↑ 2.0 2.1 Simeon Bennett and Naomi Kresge. "Roche Drops After Halting Cholesterol Drug Development".
- ↑ Michelle Fay Cortez (November 5, 2012), "Roche's Good Cholesterol Drug Shows Negative Side Effects", Bloomberg Businessweek, retrieved November 6, 2012
- ↑ "NIH stops clinical trial on combination cholesterol treatment". National Institute of Health. NHLBI. Retrieved June 2, 2011.
- ↑ 5.0 5.1 Stein; et al. (2010). "Safety and tolerability of dalcetrapib (RO4607381/JTT-705): results from a 48-week trial". Eur. Heart J. 31 (4): 480&ndash, 4888. doi:10.1093/eurheartj/ehp601. PMC 2821630. PMID 20097702. Unknown parameter
|unused_data=ignored (help) - ↑ Zahi A Fayad; et al. (2011). "Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial". The Lancet. 378 (9802): 1547&ndash, 1559. doi:10.1016/S0140-6736(11)61383-4.
- ↑ Thomas F. Lüscher; et al. (2012). "Vascular effects and safety of dalcetrapib in patients with or at risk of coronary heart disease: the dal-VESSEL randomized clinical trial". Eur. Heart J. doi:10.1093/eurheartj/ehs019.
- ↑ Gail Parziale. "Dalcetrapib and Anacetrapib: a Tale of Two CETPs".
- ↑ PMID 23126252 (PMID 23126252)
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