| Title | Exposure-Response Analysis in Patients With Schizophrenia to Assess the Effect of Asenapine on QTc Prolongation. | | Author(s) | Chapel S, Hutmacher MM, Haig G, Bockbrader H, de Greef R, Preskorn SH, Lalonde RL | | Institution | Ann Arbor Pharmacometrics Group (A2PG), 110 E Miller Ave, Garden Suite, Ann Arbor, MI 48104; e-mail: sunny.chapel@a2pg.com. | | Source | J Clin Pharmacol 2009 Nov; 49(11):1297-308. | | Abstract | An exposure-response (E-R) analysis using linear mixed effects modeling was conducted on data from a thorough QTc trial for asenapine in 148 patients with schizophrenia. In a parallel design, patients received asenapine 5 mg twice daily (BID) for 10 days (10d) followed by 10 mg BID (6d), asenapine 15 mg BID (10d) followed by 20 mg BID (6d), quetiapine 375 mg BID (for assay sensitivity; 16d) or placebo (16d). Triplicate 12-lead electrocardiograms and concentration measurements were obtained on day -1 (baseline), 1, 10, and 16 at 8 scheduled times on each day. At mean C(max) for all asenapine doses, the E-R model predicted that the mean QTcF increase was less than 5 milliseconds, the International Conference on Harmonisation-established threshold for clinical concern. The model predicted a mean increase of 7 to 8 milliseconds for quetiapine. The corresponding upper bounds of the 95% confidence intervals were 7.5 milliseconds and 11.2 milliseconds for asenapine and quetiapine, respectively. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19843656 |
|
