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Exposure‐Response Analysis in Patients With Schizophrenia to Assess the Effect of Asenapine on QTc Prolongation
Author(s) -
Chapel Sunny,
Hutmacher Matt M.,
Haig George,
Bockbrader Howard,
Greef Rik,
Preskorn Sheldon H.,
Lalonde Richard L.
Publication year - 2009
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009344855
Subject(s) - asenapine , quetiapine , qt interval , placebo , medicine , confidence interval , anesthesia , schizophrenia (object oriented programming) , antipsychotic , psychiatry , alternative medicine , pathology
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.