A Study of Plasma Concentrations, Metabolism and Excretion of 14C-paliperidone After a Single Oral Dose
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 1

Summary: 
      The purposes of this study are to investigate the metabolic pathways of paliperidone and
      excretion of paliperidone and its metabolites in healthy adult male volunteers, both CYP2D6
      poor and extensive metabolizers, after administration of a single 1-mg oral dose of
      14C-paliperidone, to evaluate the safety and tolerability of paliperidone, and to determine
      the relationship between genotypes (CYP2D6, CYP3A4, CYP3A5, UGT1A1, and UGT1A6) and exposure
      to paliperidone and its metabolites.
    

Detailed description: 
      This study is designed as a single-center, single-dose, open-label study of the absorption,
      metabolism, and excretion of paliperidone in healthy men (3 extensive and 3 poor metabolizers
      based on CYP2D6 phenotype). Eligible volunteers will be admitted to the study center the
      evening before study drug administration and will remain at the study center until 168 hours
      after dosing (or longer if required up to a maximum of 14 days). Each volunteer will receive
      a single oral dose of 14C-paliperidone with total radioactivity below 1000 µSv (16 mCi).
      Blood samples for plasma pharmacokinetic profile will be obtained immediately before study
      drug administration and 0.5, 1, 1.5, 3, 6, 12, 16, 36, 48, 72, 96, 120, 144 and 168 hours
      postdose. Blood samples will be obtained 2, 4, 8 and 24 hours postdose for determination of
      14C in whole blood. Samples for determination of serum creatinine will be obtained 2, 4, 8
      and 24 hours postdose. Urine will be collected immediately prior to drug administration and
      from 0-4, 4-8, 8-12, 12-16, 16-24, 24-36, 36-48, 48-72, 72-96, 96-120, 120-144, and 144-168
      hours after study drug administration. Fecal samples will be collected per each stool, once
      before study drug administration and in the period from 0-168 hours after study drug
      administration. Collections of urine and feces (per 24 hours) will continue beyond 168 hours,
      to a maximum of 336 hours (Day 15) for patients who excrete radioactivity slowly (2 latest
      24-hour urine collections each greater than or equal to 2% of total radioactive dose) or have
      <7 feces stool samples over the 0 to 168-hour period. 14C radioactivity will be measured in
      plasma, urine, and feces. Aliquots of the 0- through 24 hour urine collections will be
      analyzed for creatinine. Plasma concentrations of paliperidone and risperidone will be
      determined by means of a validated LC MS/MS method. The 14C-labeled moiety in plasma and
      urine will be determined by liquid scintillation counting. For all plasma samples, the lower
      limits of quantification for paliperidone and risperidone will be 0.100 ng/mL. For all plasma
      and urine samples the lower limits of quantification for 14C-paliperidone will be 72 dpm/mL
      (=2.0n g eq/mL). The rationale for the present study with a single-dose administration of 1
      mg 14C-paliperidone to healthy white men is to determine the routes of excretion for
      paliperidone and to elucidate the metabolic pathways and structures of predominant
      paliperidone metabolites. As such, this study will result in a more complete understanding of
      the pharmacokinetics of paliperidone in humans. Safety and tolerability will be monitored.
      Volunteers will receive a single oral 1 mg dose of 14C-paliperidone as a solution with a
      specific activity of 592 kBq/mg, resulting in an administered radioactivity of 592 kBq (or 16
      µCi). The total radioactive load for the subject will remain lower than 1000 µSv.
    

Intervention name(s): 14C-paliperidone
Intervention type(s): Drug
Intervention MeSH terms: Paliperidone Palmitate
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Schizophrenia; Mood disorders; Antipsychotic drugs: 14C-paliperidone