Study Evaluating and Comparing Single Dose and Multiple Dose Pharmacokinetics of ER OROS Paliperidone in Healthy Japanese and Caucasian Adults.

This study has been completed.
Sponsor:
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00758030
First received: September 19, 2008
Last updated: June 6, 2011
Last verified: March 2010
  Purpose

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


Condition Intervention Phase
Schizophrenia
Drug: Paliperidone ER OROS
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Dose Study to Evaluate and Compare the Pharmacokinetics of ER OROS Paliperidone in Healthy Japanese and Caucasian Subjects.

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Safety and tolerability of extended-release (ER) OROS paliperidone in healthy Japanese and Caucasian adults. Paliperidone plasma concentrations, time profiles and PK parameters after single and multiple dosing for Japanese and Caucasian patients.

Secondary Outcome Measures:
  • Pharmacogenomics: Relationships between composite genetic description or predicted observable traits and the pharmacokinetic parameters of paliperidone and its enantiomers were explored graphically.

Enrollment: 60
Study Start Date: March 2004
Study Completion Date: July 2004
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.

  Eligibility

Ages Eligible for Study:   20 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy Japanese and Caucasian patients. Japanese patients had to be born in Japan of Japanese parents and not to have lived outside of Japan for more than 5 years
  • Normotensive (5 minute lying down systolic blood pressure of 100-139 mmHg and diastolic blood pressure of 60-89 mmHg)
  • Body Mass Index of 18 to 25 kg/m2
  • Considered healthy based on medical history, prestudy physical examination findings, electrocardiogram, and clinical laboratory evaluation of chemistry, hematology, and urinalysis values.

Exclusion Criteria:

  • History of any significant cardiovascular, respiratory, neurologic, renal, hepatic, endocrine, psychiatric, or immunologic disorders
  • Use of concomitant medication, except for paracetamol and hormonal contraceptives
  • Has received an experimental drug and/or used an experimental medical device in the 60 days before the first dose.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00758030

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00758030     History of Changes
Other Study ID Numbers: CR004933
Study First Received: September 19, 2008
Last Updated: June 6, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Schizophrenia
Paliperidone

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
9-hydroxy-risperidone
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on August 19, 2014