A Study of the Effects of Paroxetine on the Pharmacokinetics of Paliperidone ER

• Status: Completed
• Trial end date: 2006-07-01
• Target enrollment: 0
• Participant gender: Male

Summary

The purpose of this study is to evaluate the effects of a CYP2D6 inhibitor, paroxetine, on the pharmacokinetics of a single dose of orally administered paliperidone ER and to evaluate the safety and tolerability of both treatments in healthy men

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

Details

• Lead Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Treatments: Paliperidone Palmitate; Paroxetine; Serotonin Uptake Inhibitors

Criteria

Inclusion Criteria:

• Body mass index (weight [kg]/height [m2]) of 18 to 30 kg/m2, inclusive

• Extensive metabolizer of CYP2D6. Volunteers whose CYP2D6 genotype is unknown should have been phenotyped before the start of the study using dextromethorphan as a probe (i.e., have a dextromethorphan metabolic ratio <0.02, as determined according to the standard procedures of the study center)

• Have a supine (after 5 minutes rest) blood pressure between 100 and 140 mmHg systolic, inclusive, and 50 and 90 mmHg diastolic, inclusive

• Smokes no more than 10 cigarettes, or 2 cigars, or 2 pipes per day and has been following this pattern for at least 3 months before screening

• Healthy on the basis of a prestudy physical examination, medical history, 12-lead ECG, and the laboratory results of serum chemistry, hematology, and urinalysis performed within 21 days before the first dose. If the results of the serum chemistry, hematology, or urinalysis testing are not within the laboratory's reference 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

Exclusion Criteria:

• Poor or intermediate metabolizers of CYP2D6, as determined by genotyping or phenotyping using dextromethorphan

• Known drug allergy to risperidone, paliperidone, paroxetine, or any of their excipients

• Known history of drug-induced dystonia

• Recent history of alcohol or substance abuse

• Relevant history or presence of any cardiovascular (including myocardial infarct or cardiac arrhythmia), respiratory, neurologic (including seizures), psychiatric, renal, hepatic, gastrointestinal (including surgeries, severe gastrointestinal narrowing, and malabsorption problems), endocrine, hematologic, or immunologic disease

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

• At screening, has signs of autonomic dysfunction as indicated by a sustained decrease of >20 mmHg in systolic blood pressure or a decrease of >10 mmHg in diastolic blood pressure after standing for at least 2 minutes that is not associated with an increase of >15 beats per minute (bpm) in heart rate

• Bradycardia (heart rate <50 bpm) as determined by screening 12-lead ECG

• A positive test result (or history of) for any of the serology tests (hepatitis B and C, and human immunodeficiency virus) at screening