As Study of the Pharmacokinetics of Paliperidone Extended-release and Risperidone Immediate-release Formulations
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to compare the steady-state pharmacokinetics of paliperidone
      after oral administration of 15 mg extended-release (ER) OROS paliperidone once daily with
      the steady-state pharmacokinetics of paliperidone after oral administration of 8 mg
      immediate-release (IR) risperidone twice daily; and to explore the dose-proportionality of 9
      mg and 15 mg ER OROS paliperidone. Other objectives are to 1) document the disposition of the
      enantiomers of paliperidone; 2) explore the relationship between genotype (CYP2D6, CYP3A4,
      CYP3A5, UGT1A1, and UGT1A6) and pharmacokinetic parameters; and 3) assess safety and
      tolerability.
    

Detailed description: 
      This is an open-label, multiple-dose, parallel-group study in patients with schizophrenia or
      schizoaffective disorder. The study consists of a screening period (2 weeks maximum); a
      1-week run-in or washout (Days 1 to 7) during which patients taking risperidone prestudy and
      randomly assigned to paliperidone treatment will receive replacement antipsychotic therapy,
      and other patients continue to take their prestudy antipsychotic medication; a 14-day
      open-label treatment period (Days 8 to 21); and a 5-day follow-up period. On Day 1 of the
      washout period, eligible patients will be randomized to receive ER OROS paliperidone (PAL) or
      risperidone (RIS). All patients will receive their first dose of study medication on Day 8
      after randomization as follows: Patients randomized to PAL will receive 9 mg of ER OROS
      paliperidone daily from Day 8 to Day 14, followed by 15 mg of ER OROS paliperidone q.d. from
      Day 15 to Day 21. Patients randomized to RIS will receive dose-escalation up to 7 mg
      risperidone twice daily (b.i.d.) from Day 8 to Day 14, followed by 8 mg risperidone b.i.d.
      from Day 15 to Day 21. The study medication on Days 14 and 21 in the PAL group and on Day 21
      in the RIS group will be administered after completion of a standardized high fat, high
      caloric breakfast. Patients will be confined to the testing facility from the morning of Day
      8 (or earlier at the discretion of the investigator) until completion of the study procedures
      on Day 23. On all other assessment days, patients will return to the testing facility and
      remain there for the duration of the assessments.The highest dose of paliperidone currently
      being studied is 12 mg given as 6 tablets of 2 mg ER OROS paliperidone. In the currently
      proposed study, data on the safety and tolerability of the 15-mg dose will be monitored and
      collected. Paliperidone ER oral administration of 9 mg q.d. on Day 8 to 14, and 15 mg daily
      on Day 15 to 21; oral administration of escalating doses up to 7 mg risperidone twice daily
      (b.i.d.) between Days 8 and 14, inclusive, and 8 mg risperidone b.i.d. on Day 15 to 21
    

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