Dataset Information

Asenapine pharmacokinetics and tolerability in a pediatric population.

ABSTRACT:

Purpose

This study aimed to characterize the pharmacokinetic (PK) properties, safety, and tolerability of asenapine, and to develop a population PK model in pediatric patients with schizophrenia, bipolar disorder, or other psychiatric disorders.

Methods

Two Phase I multiple ascending-dose studies were conducted to evaluate the PK, safety, and tolerability of sublingual asenapine in pediatric patients (age 10-17 years) with schizophrenia or bipolar I disorder. Patients received asenapine 1-10 mg twice daily for up to 12 days. PK parameters (maximum concentration [C_max], area under the curve from 0 to 12 hours [AUC_0-12], time to C_max [T_max], and half-life) were summarized for asenapine with descriptive statistics, and safety parameters were collected. A population PK model, which included the two Phase I studies and two additional Phase III efficacy studies (asenapine 2.5-10 mg twice daily for up to 8 weeks, age 10-17 years), was developed using nonlinear mixed-effect modeling based on a previously developed adult PK model. The final model was used in simulations to obtain asenapine-exposure estimates across pediatric subgroups and to determine if intrinsic covariates warrant dose adjustments.

Results

The PK of asenapine showed rapid absorption (T_max ~1 hour) with an apparent terminal half-life between 16 and 32 hours. Increases in mean C_max and AUC_0-12 appeared to be dose-proportional in one study and near dose-proportional in the second study. Steady state was attained within 8 days. The most frequently occurring treatment-emergent adverse events were dysgeusia, sedation, and oral hypoesthesia. Simulation-based estimates of C_max and AUC_0-12 were similar for pediatric and adult patients; age, body-mass index, race, and sex were not associated with changes in asenapine exposure.

Conclusion

Asenapine was generally safe and well tolerated in pediatric patients aged 10-17 years. PK and safety data were similar to that observed in the adult population. Intrinsic factors had no significant impact on asenapine exposure, indicating there is no need for dose adjustments in the pediatric population.

SUBMITTER: Dogterom P

PROVIDER: S-EPMC6124477 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Asenapine pharmacokinetics and tolerability in a pediatric population.

Dogterom Peter P Riesenberg Robert R de Greef Rik R Dennie Justin J Johnson Martin M Pilla Reddy Venkatesh V Miltenburg André Mm AM Findling Robert L RL Jakate Abhijeet A Carrothers Timothy J TJ Troyer Matthew D MD

Drug design, development and therapy 20180830

<h4>Purpose</h4>This study aimed to characterize the pharmacokinetic (PK) properties, safety, and tolerability of asenapine, and to develop a population PK model in pediatric patients with schizophrenia, bipolar disorder, or other psychiatric disorders.<h4>Methods</h4>Two Phase I multiple ascending-dose studies were conducted to evaluate the PK, safety, and tolerability of sublingual asenapine in pediatric patients (age 10-17 years) with schizophrenia or bipolar I disorder. Patients received ase ...[more]

PMID: 30214156

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Dataset Information

Asenapine pharmacokinetics and tolerability in a pediatric population.

Purpose

Methods

Results

Conclusion

Publications

Asenapine pharmacokinetics and tolerability in a pediatric population.

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