Lack of effect of dalcetrapib on QT interval in healthy subjects following multiple dosing.
Evaluate dalcetrapib's potential to prolong QT intervals in healthy subjects. This was a single-center, randomized, active and placebo-controlled, six-sequence, three-period cross-over study. Participants [18-65 years; body mass index (BMI) 18-30 kg/m2] were randomized to daily doses of dalcetrapib...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 66; no. 8; pp. 775 - 784 |
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| Autores principales: | , , , |
| Formato: | clinical trial research Journal Article |
| Publicado: |
Springer Nature
Aug2010
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105057532&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105057532 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Aug2010 vid: 66 iid: 8 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 105057532 2010717660 10.1007/s00228-010-0841-2 NLM20521033 105057532 ppf: 775 ppct: 9 formats: fmt: @attributes: type: P tig: atl: Lack of effect of dalcetrapib on QT interval in healthy subjects following multiple dosing. aug: au: Derks M Abt M Mwangi A Meneses-Lorente G affil: F. Hoffmann-La Roche Ltd, Building 663, Office 2139 Basel 4070 Switzerland sug: subj: Drugs, Investigational Electrocardiography Methods Hyperlipidemia Therapy Clinical Trials Funding Source Human Risk Management Methods ab: Evaluate dalcetrapib's potential to prolong QT intervals in healthy subjects. This was a single-center, randomized, active and placebo-controlled, six-sequence, three-period cross-over study. Participants [18-65 years; body mass index (BMI) 18-30 kg/m2] were randomized to daily doses of dalcetrapib 600 mg (therapeutic) or 3,900 mg (supratherapeutic) or to dalcetrapib-matched placebo for 7 days. On Day 8, subjects received single-dose moxifloxacin 400 mg (active control) or placebo, following the placebo or dalcetrapib, respectively. Electrocardiographic parameters were recorded on Days -1, 1, 7, and 8. The primary endpoint was the difference to placebo of time-matched change from baseline in the study-specific corrected QT interval (QTcS) at seven time-points within 24 h after dalcetrapib 3,900 mg on Day 7. An upper 95% confidence interval (CI) <10 ms confirmed the absence of a significant effect. Pharmacokinetic and lipid-related parameters were measured. Subjects ( n = 49) were predominantly male (71%), and all were white, with a mean age of 45 years and mean BMI of 25 kg/m2. For the primary analysis, the upper 95% CI for dalcetrapib 3,900 mg was <10 ms at all time-points. Similar findings were obtained for dalcetrapib 600 mg. Following the administration of moxifloxacin, the QTcS increased by >5 ms. At Day 7, exposure for dalcetrapib 3,900 mg was approximately eightfold higher than that for dalcetrapib 600 mg [mean area under the plasma concentration-time curve between time 0 and 24 h 68,500 vs. 8,280 ng*h/mL; mean peak concentration 6,810 vs. 861 ng/mL]. Cholesteryl ester transfer protein activity was inhibited by 30%, and high-density lipoprotein cholesterol increased by 26% for dalcetrapib 600 mg. Dalcetrapib was well tolerated. Dalcetrapib is not associated with QT interval prolongation, even at doses markedly greater than intended therapeutically. pubtype: Academic Journal doctype: clinical trial research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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