As Study of the Pharmacokinetics of Paliperidone Extended-release and Risperidone Immediate-release Formulations

• Status: Completed
• Trial end date: 2004-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Treatments: Paliperidone Palmitate; Risperidone

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