As Study of the Pharmacokinetics of Paliperidone Extended-Release and Risperidone Immediate-Release Formulations - Full Text View

Sponsored by:	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by:	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:	NCT00796185

Purpose

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.

Condition	Intervention	Phase
Schizoaffective Disorder Schizophrenia	Drug: Paliperidone ER	Phase I

MedlinePlus related topics: Schizophrenia

Drug Information available for: Risperidone Paliperidone

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Pharmacokinetics Study
Official Title:	Comparison of Steady-State Pharmacokinetics of Paliperidone After Extended-Release OROS® Paliperidone 15 mg and Immediate-Release Oral Risperidone 8 mg b.i.d. in Subjects With Schizophrenia or Schizoaffective Disorder

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

Primary Outcome Measures:

To compare the steady-state pharamacokinetics of paliperidone after administration of ER OROS paliperidone at 15 mg orally and IR risperidone at 8 mg orally, twice daily; to explore the dose-proportionality of 9 mg and 15 mg paliperidone ER

Secondary Outcome Measures:

To document the disposition of the enantiomers of paliperidone, to explore the relationship between genotypes (CYP2D6, CYP3A4, CYP3A5, UGT1A1, and UGT1A6) and pharmacokinetic parameters, and to assess safety and tolerability

Estimated Enrollment:	45
Study Start Date:	August 2003
Study Completion Date:	January 2004

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

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Currently treated with a dose of at least 6 mg of risperidone daily or the equivalent of any other antipsychotic medication or a combination thereof (an equivalence table will be provided to the sites)
Has a DSM-IV diagnosis of schizophrenia (295.10, 295.20, 295.30, 295.60, 295.90) or schizoaffective disorder
Healthy on the basis of a prestudy physical exam, medical history, ECG, and laboratory results of blood biochemistry, hematology, and urinalysis performed within 2 weeks of randomization. If the results of the biochemistry or hematology tests or the urinalysis are not within the laboratory's reference ranges the patient can be included only if the investigator judges that the deviations are not clinically significant. For liver function tests (alanine transaminase, aspartate transaminase, and bilirubin), the values must be contained within 2 times the upper limits of the normal laboratory reference ranges and for renal function tests, the values must be within the normal laboratory reference ranges
Women must be postmenopausal for at least 1 year, surgically sterile, or practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization and at the discretion of the investigator, total abstinence) before entry and throughout the study, as well as have a negative serum pregnancy test at screening. To ensure continued eligibility, women must have a negative urine test at baseline
Body weight as defined by body mass index (weight [kg]/height (m)²) within a range of 15.0 to 35.0 kg/m², inclusive
Willingness to spend 15 days as an in-patient during the treatment period
Normotensive at screening, with supine (5 minutes) blood pressure between the range of 100 to 140 mmHg systolic, inclusive, and 60 to 90 mmHg diastolic, inclusive

Exclusion Criteria:

Involuntarily committed in-patients
Has a DSM-IV diagnosis of substance dependence within 3 months before screening evaluation. Nicotine and caffeine dependence and history of recreational use of marijuana are not exclusionary
At screening, has a decrease of > = 20 mmHg systolic blood pressure or a decrease of > =10 mmHg decrease in diastolic blood pressure 2 minutes after standing, or experience symptoms of lightheadedness, dizziness, or fainting upon standing
Orthostatic hypotension
Tests positive for the urine drug screen at screening
Had an acute exacerbation of psychotic symptoms within the last 3 months before screen
Relevant history or current presence of any cardiovascular, respiratory, central nervous system, neuropsychiatric (including seizures), renal, hepatic, endocrine, or immunologic diseases
Has a DSM-IV Axis I diagnosis other than schizophrenia or schizoaffective disorder
Suicidal or homicidal ideation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00796185

Sponsors and Collaborators

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

Study Director:

Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Clinical Trial

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

More Information

As study of the pharmacokinetics of paliperidone extended-release and risperidone immediate-release formulations This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Study ID Numbers:	CR004270
Study First Received:	November 20, 2008
Last Updated:	November 20, 2008
ClinicalTrials.gov Identifier:	NCT00796185
Health Authority:	United States: Food and Drug Administration

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

Mood Disorders
Schizoaffective Disorder
Schizophrenia
Paliperidone ER
Antipsychotic druges

Study placed in the following topic categories:

Schizophrenia
Dopamine
Mental Disorders
Risperidone
Mood Disorders

9-hydroxy-risperidone
Psychotic Disorders
Serotonin
Schizophrenia and Disorders with Psychotic Features

Additional relevant MeSH terms:

Neurotransmitter Agents
Disease
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Dopamine Antagonists

Antipsychotic Agents
Pharmacologic Actions
Serotonin Antagonists
Pathologic Processes
Serotonin Agents
Therapeutic Uses
Dopamine Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 15, 2009