A Pharmacokinetics and Pharmacodynamics Study Under Fasting and Fed Conditions With Paliperidone Extended-release and Immediate-release Formulations
The purpose of this study is to compare the bioavailability of 2 extended release paliperidone pellet formulations under fasting and fed conditions with a 2 mg paliperidone oral solution under fasting conditions. Additional objectives are to compare the pharmacodynamic effects (postural changes in blood pressure and heart rate), to evaluate the safety and tolerability of each treatment, and to explore the relationship between CYP2D6 genotype and paliperidone exposure.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Comparative Evaluation of the Pharmacokinetics and Pharmacodynamics Under Fasting and Fed Conditions of 2 Paliperidone Extended-release Pellet Formulations With Paliperidone Oral Solution in Healthy Adults|
- To evaluate the pharmacokinetics of 2 ER pellet formulations of 2 mg-eq paliperidone in comparison to 2 mg IR paliperidone oral solution and to evaluate the effect of food on the pharmacokinetics of the ER pellet formulations
- To compare the pharmacodynamic effects of all treatments, to evaluate safety and tolerability as well as the relationship between genotypes (CYP2D6 and CYP3A4/5) and paliperidone exposure
|Study Start Date:||September 2003|
|Study Completion Date:||November 2003|
This is a single-center, open-label, randomized, 5-way crossover Phase 1 study in non-smoking healthy men and women, aged between 18 and 55 years. The study consists of a screening period; a 5-way crossover, open-label treatment phase with 14 days washout between treatments; and end-of-study evaluations upon completion or at early withdrawal. Eligible volunteers will be randomly assigned to 1 of 5 treatment sequences. Each volunteer will receive the following treatments in random order: (A) paliperidone ER pellet formulation-1, as 1 capsule of 2.5 mg, under fasting conditions; (B) paliperidone ER pellet formulation-1, as capsule of 2.5 mg with food (high-fat breakfast); (C) paliperidone ER pellet formulation-2 as 1 capsule of 2.5 mg, under fasting conditions; (D) paliperidone ER pellet formulation-2 as 1 capsule of 2.5 mg with food (high-fat breakfast); (E) immediate release (IR) paliperidone oral solution, 2 mg (2 mL) of a 1-mg/mL solution, under fasting conditions. Alternative paliperidone ER formulations are being developed with the aim to increase bioavailability and reduce variability, without compromising the favorable effect on orthostatic hypotension as seen with ER OROS paliperidone. Therefore, in this study, the pharmacokinetics and pharmacodynamic properties, as well as the effect of food, of 2 alternative paliperidone ER pellet formulations will be investigated. Safety and tolerability will be monitored throughout the study.. Single doses of paliperidone ER pellet formulation-1, as 1 capsule of 2.5 mg, fasted; paliperidone ER pellet formulation-1, as 1 capsule of 2.5 mg with food (high-fat breakfast); paliperidone ER pellet formulation-2 as 1 capsule of 2.5 mg, fasted; paliperidone ER pellet formulation-2 as 1 capsule of 2.5 mg with food (high-fat breakfast); IR paliperidone oral solution, 2 mg (2 mL) of a 1-mg/mL solution, fasted.
|Study Director:||Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial||Johnson & Johnson Pharmaceutical Research & Development, L.L.C.|