Exposure-Response (E-R) of Lurasidone in Pediatric Patients With Bipolar Depression: Simulation and Comparison to Adults

December 21, 2017

This poster was presented at the 30th annual  Psych Congress, held Sept. 16-19, 2017, in New Orleans, Louisiana.

Objective: To evaluate the consistency of the E-R relationship of lurasidone between children/adolescent and adult patients with bipolar depression.

Methods: An external posterior predictive check (PPC) was conducted to evaluate the utility of an adult E-R model [Clin Ther. 2016;38:4-15] in predicting efficacy for children and adolescent patients with bipolar depression (N=343) who were randomized in a double-blind, placebo-controlled, 6-week study of flexibly dosed lurasidone (20-80 mg/d). If the external PPC demonstrated differences in the efficacy between pediatric and adult patients, further model development was planned to help explain the discrepancy. The updated model was then to be used to determine pediatric doses that produce similar efficacy to the adults. In the pediatric study, the Children's Depression Rating Scale, Revised (CDRS-R) was administered weekly and converted to the adult efficacy measure, the Montgomery-Ѓsberg Depression Rating Scale (MADRS) total score [JAACAP. 2007;46:1204-12] to compare with the adult model.

Results: A model based on combined adult and pediatric data that included a separate baseline MADRS for pediatric and adult patients, and that did not include the effect of age on maximum placebo effect, adequately described the dose-response relationship for a fixed dose study design in pediatric populations. Using this model, the simulated dose-response relationship in pediatric patients was shown to be similar to that in adult patients.

Conclusions: This modeling and simulation indicated that, as in adults, higher doses of lurasidone are likely to result in greater drug-related improvements in depressive symptoms for children and adolescent patients with bipolar depression.

Authors: 
Sunny Chapel, PhD; Yu-Yuan Chiu, PhD; Jongtae Lee, PhD; Felix Agbo, PhD; Antony Loebel, MD
Sponsoring Organization: 
Sunovion Pharmaceuticals Inc.
Year: 
2017
Tracks: 
Child & Adolescent Psychiatry
Mood Disorders