A Pharmacokinetics and Pharmacodynamics Study Under Fasting and Fed Conditions With Paliperidone Extended-release and Immediate-release Formulations
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to evaluate the pharmacokinetics of 2 extended-release (ER)
      formulations of 2 mg-eq paliperidone in comparison to the 2 mg immediate-release (IR)
      paliperidone oral solution and to evaluate the effect of food on the pharmacokinetics of
      these ER formulations. Additional objectives are to compare the pharmacodynamic effects
      (postural changes in blood pressure and heart rate), safety, and tolerability are to be
      evaluated in addition to exploring the relationship between CYP2D6 and CYP3A4/5genotype and
      paliperidone exposure.
    

Detailed description: 
      This study is designed as a single-center, open-label, randomized, 5 treatment-period,
      crossover study in healthy adults. The study consists of a screening phase and a treatment
      phase during which each volunteer will receive 5 treatments of study drug in a random order
      and separated by a washout period of at least 7 to 14 days. Treatments consist of a single
      oral dose of: A) paliperidone ER pellet formulation, (2 mg-eq) as 1 capsule of 2.5 mg,
      fasted; B) the same formulation as A but with food; C) paliperidone-coated ER OROS
      formulation (2 mg eq) as 2 tablets of 2 mg, fasted; D) the same formulation as C but with
      food; E) IR paliperidone oral solution, 2 mg (2 mL) of a 1 mg/mL solution, fasted.
      Alternative paliperidone ER formulations are being developed with the aim to increase the
      bioavailability without compromising the favorable effect on the orthostatic hypotension as
      seen with ER OROS paliperidone. Therefore, in this study, the pharmacokinetic and
      pharmacodynamic properties, as well as the effect of food, of 2 alternative paliperidone ER
      formulations using different mechanisms to achieve extended release of the drug will be
      investigated: a multiparticulate ER capsule formulation, containing coated pellets comprised
      of 3 coating layers, with both immediate and extended drug-release properties (pellet
      formulation; drug ratio extended- versus immediate-release layer: 9:1), and an OROS trilayer
      longitudinally compressed tablet formulation (Push-Pull delivery system) (overcoated-OROS
      formulation). Safety and tolerability will be monitored throughout the study. Single doses of
      paliperidone ER pellet formulation, (2 mg-eq) as 1 capsule of 2.5 mg, fasted; paliperidone ER
      pellet formulation, (2 mg-eq) as 1 capsule of 2.5 mg with food (high-fat breakfast);
      paliperidone-coated OROS ER formulation (2 mg-eq) as 2 tablets of 2 mg, fasted;
      paliperidone-coated OROS ER formulation (2 mg-eq) as 2 tablets of 2 mg with food (high-fat
      breakfast); IR paliperidone oral solution, 2 mg (2 mL) of a 1 mg/mL solution, fasted.
    

Intervention name(s): Paliperidone ER
Intervention type(s): Drug
Intervention MeSH terms: Paliperidone Palmitate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Schizophrenia; Mood Disorders; Antipsychotic drugs; Paliperidone ER