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 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

  1. 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. 2.0 2.1 Simeon Bennett and Naomi Kresge. "Roche Drops After Halting Cholesterol Drug Development".
  3. Michelle Fay Cortez (November 5, 2012), "Roche's Good Cholesterol Drug Shows Negative Side Effects", Bloomberg Businessweek, retrieved November 6, 2012
  4. "NIH stops clinical trial on combination cholesterol treatment". National Institute of Health. NHLBI. Retrieved June 2, 2011.
  5. 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)
  6. 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.
  7. 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.
  8. Gail Parziale. "Dalcetrapib and Anacetrapib: a Tale of Two CETPs".
  9. PMID 23126252 (PMID 23126252)
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