A Study of Paliperidone Enantiomer Disposition With Different Formulations and the Bioavailability of Immediate- and Extended-release Paliperidone

• Status: Completed
• Trial end date: 2004-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to characterize the pharmacokinetics of paliperidone in plasma and urine after intravenous (i.v.) administration of the racemate, administration of the immediate-release (IR) racemate oral solution, administration of the ER OROS tablet, and administration of the oral solutions of the individual enantiomers R078543 (+) and R078544 (-); to determine the absolute oral bioavailability of IR and ER OROS paliperidone; to document the (+) and (-) paliperidone enantiomer ratio after i.v. and oral administration (IR and ER OROS paliperidone); to document the possible interconversion between the (+) and (-) enantiomers of paliperidone after oral treatment with the separate enantiomers; to document the possible relationship between the subject's CYP2D6 phenotype and the (+) and (-) enantiomer disposition of paliperidone (CYP2D6 genotyping was used to corroborate the phenotype). In addition, the safety and tolerability of all treatments will be evaluated.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

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

Criteria

Inclusion Criteria:

• Known dextromethorphan (i.e., previously determined) metabolic ratio of <0.02 or >0.35, as determined according to the standard procedures of the study center

• Acceptable weight as defined by body mass index (weight [kg]/height [m²]) range of 18 to 28 kg/m², inclusive

• Normotensive with supine (5 minutes) blood pressure between the range of 100 to 140 mmHg systolic, inclusive, and 60 to 90 mmHg diastolic, inclusive

• Nonsmoking or habitually smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes of tobacco per day for at least 6 months prior to study enrollment

• Healthy on the basis of prestudy screening physical examination, medical history, ECG, and the laboratory results of blood biochemistry, hematology, and urinalysis performed within 21 days before the first study drug dose. If the results of the biochemistry, hematology, or urinalysis testing are not within the reference laboratory ranges, the volunteer can be included only if the investigator judges that the deviations are not clinically significant. For renal function tests, the values must be within the normal laboratory reference ranges

• Women must be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double barrier method, contraceptive transdermal patch, male partner sterilization, and at the discretion of the investigator, total abstinence), postmenopausal for at least 1 year, or surgically sterile before entry and throughout the study

• Women volunteers must also have a negative serum pregnancy test at screening.

Exclusion Criteria:

• Known allergy or history of significant hypersensitivity to heparin, in case a heparin lock will be used

• Drug allergy to risperidone, paliperidone, or any of its excipients

• Recent history of alcohol or substance abuse and/or testing positive for a urine drug screen at study screening

• Relevant history of any cardiovascular, respiratory, neuropsychiatric, renal, hepatic, gastrointestinal (including surgeries, malabsorption problems, or a history of any severe preexisting gastrointestinal narrowing [pathologic or iatrogenic]), endocrine, immunologic diseases, or significant findings on the physical examination

• History of any cancer, with the exception of basal cell carcinoma

• At screening, sustained drops in systolic (>20 mmHg) or diastolic (>10 mmHg) blood pressure after standing for at least 2 minutes which are not associated with an increase in pulse rate of >15 beats per minute

• Positive result for any of the serology tests (hepatitis BsAg, CAb, and HIV-1)

• Consuming more than 450 mg of caffeine per day. This equals 5 cups of tea, 3 cups of coffee, or 8 cans of cola