Study Evaluating and Comparing Single Dose and Multiple Dose Pharmacokinetics of ER OROS Paliperidone in Healthy Japanese and Caucasian Adults.
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study was to evaluate and compare the pharmacokinetics of ER OROS
      paliperidone in healthy Japanese and Caucasian patients.
    

Detailed description: 
      This was a randomized (study medication assigned by chance), double blind (neither physician
      or patient knows the name of the study medication/placebo assigned) study comparing the
      single does (SD) and multiple dose (MD) pharmacokinetics of ER OROS paliperidone in 30
      healthy Japanese and 30 healthy Caucasian adults.. The primary objectives of this study were
      to 1) evaluate the safety and tolerability of extended-release (ER) OROS paliperidone in
      healthy Japanese adults, 2) to evaluate the single dose (SD) and multiple dose (MD)
      pharmacokinetics of ER OROS paliperidone in healthy Japanese adults, and 3) to compare the SD
      and MD pharmacokinetics of ER OROS paliperidone in healthy Japanese and Caucasian adults. Of
      the 30 Japanese patients enrolled, at least 10 were to be men and 10 to be were women. An
      equal number of Caucasian patients, matched as closely as possible to the Japanese subjects
      for sex, age, and weight, were enrolled. Patients were randomly assigned to receive either ER
      OROS paliperidone or placebo (4:1 ratio). Blood samples for the determination of paliperidone
      enantiomer plasma concentrations were collected immediately prior to dosing on Days 1, 9, 10,
      11, and 19, and at 2, 4, 6, 9, 12, 16, 18, 20, 22, 24, 27, 33, 36, 48, 58, 72, and 96 hours
      after dosing on Days 1, 11, and 19. Urine samples were collected predose and over 0-12,
      12-24, 24-36, and 36-48 hour intervals after dosing on Days 1 and 19 and over 0-12 and 12-24
      hour intervals after dosing on Day 11; a separate aliquot was taken from pooled 0-24 hour
      urine for urine creatinine concentration on Days 1, 11, and 19. Plasma and urine samples were
      analyzed using a validated LC-MS/MS method with a limit of quantification of 0.200 ng/mL and
      1 ng/mL, respectively. The concentration of paliperidone in plasma and urine were calculated
      as the sum of the separate enantiomers. Based on the actual sampling times, the plasma and
      pharmacokinetic parameters were determined for paliperidone and its enantiomers.Safety
      evaluation was based on reports of adverse events, extrapyramidal symptoms (reported as
      adverse events or by Abnormal Involuntary Movement Scale [AIMS], Simpson Angus Scale [SAS],
      or Barnes Akathisia Rating Scale [BARS]), sedation (based on the Sedation Visual Analog Scale
      [VAS] and Sedation Questionnaire), and on change from baseline in clinical laboratory analyte
      values, vital sign measurements, orthostatic hypotension (based on the Orthostatic
      Hypotension Questionnaire), postural changes in blood pressure and heart rate,
      electrocardiograms, and physical examination findings. Paliperidone ER OROS tablet
      formulation (3 to 6 mg/day) to be taken orally. Patients were randomly assigned to receive
      either ER OROS paliperidone or placebo (4:1 ratio). All patients received a single dose of 3
      mg ER OROS paliperidone (or placebo) on Day 1, a once daily regimen of 3 mg ER OROS
      paliperidone (or placebo) on Days 5 to 11, and a single dose of 6 mg ER OROS paliperidone (or
      placebo) on Day 19. All doses were administered in the fasted state.
    

Intervention name(s): Paliperidone ER OROS
Intervention type(s): Drug
Intervention MeSH terms: Paliperidone Palmitate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Schizophrenia; Paliperidone