A Pharmacokinetic Study of the Relative Bioavailability of Paliperidone ER Formulations With Different Release Profiles and a Comparison to Paliperidone IR
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary purpose of this study is to evaluate the pharmacokinetics and relative
      bioavailability of paliperidone ER formulations with slow, target, and fast in vitro release
      rates after administration of a single 12 mg dose. The slow and fast releasing ER tablets
      have in vitro release rates outside the current commercial specifications. Therefore, in
      order to support widening of the specification limits, this study will be performed. The
      target formulation to be used is representative of the commercial formulation. Other
      objectives of this study are 1) to compare the relative bioavailability of paliperidone ER
      formulations with slow, target, and fast in vitro release rates to the paliperidone IR
      formulation; 2) to explore the in vitro in vivo correlation (IVIVC) for the paliperidone ER
      formulation; and 3) to evaluate the safety and tolerability of the different paliperidone ER
      formulations.
    

Detailed description: 
      This is a randomized, open-label, 4-way crossover, single dose study in healthy male
      volunteers to evaluate the pharmacokinetic profiles of paliperidone ER tablets with slow,
      target, and fast in vitro release rates and paliperidone IR. The study consists of a 21 day
      screening phase, an open-label treatment phase consisting of 4 single-dose treatment periods
      (IR, slow, fast, and target formulations), and an end-of-study or early withdrawal phase. A
      10- to 21 day washout period (i.e., >5 times the half-life) will separate each study drug
      administration (i.e., each open label treatment period). In the first period, all volunteers
      are given a 1-mg dose of paliperidone IR solution, administered as a single oral dose under
      fasted conditions (Treatment A). On Day 1 of Period 2, prior to study drug administration,
      all volunteers will be randomly assigned to 1 of 6 possible treatment sequences to ensure
      that they receive all of the following treatments, one in each period: 12-mg paliperidone ER
      tablet with a target in vitro release under fasted condition (Treatment B); 12-mg
      paliperidone ER tablet with a slow in vitro release under fasted condition (Treatment C);
      12-mg paliperidone ER tablet with a fast in vitro release under fasted condition (Treatment
      D). In each treatment period, volunteers will enter the study center at least 10 hours before
      the study drug administration on Day 1 and will remain there until after collection of the 96
      hour pharmacokinetic samples on Day 5 if the investigator considers that the volunteer is
      ready for discharge. It is expected that the differences in the in vitro release rate will
      not affect the relative bioavailability of paliperidone in vivo. Safety and tolerability of
      the different paliperidone ER formulations will be monitored throughout the study.

      Single oral doses of paliperidone ER 12 mg tablets with different release rates (target,
      fast, and slow); single oral dose of paliperidone IR 1 mg
    

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: Paliperidone ER; Antipsychotic drugs; Schizophrenia; Mood disorders