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

This study has been completed.
Sponsor:
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00791713
First received: November 13, 2008
Last updated: May 18, 2011
Last verified: January 2009
  Purpose

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


Condition Intervention Phase
Schizophrenia
Drug: Paliperidone ER
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Single-center, Crossover Study of the Potential Effects of Paroxetine on the Pharmacokinetics of a Single Dose of Paliperidone Extended-release in Healthy Men

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To evaluate the effects of a CYP2D6 inhibitor, paroxetine, on the pharmacokinetics of a single dose of orally administered paliperidone ER

Secondary Outcome Measures:
  • To evaluate the safety and tolerability of the 3 mg tablet of paliperidone ER administered with and without paroxetine to healthy men

Enrollment: 60
Study Start Date: March 2006
Study Completion Date: July 2006
Detailed Description:

This is a randomized, open-label, single-center, single-dose, 2 treatment, 2 way crossover study. It consists of 3 phases: a screening phase beginning within 21 days before the first study drug administration; an open label treatment phase consisting of 2 treatment periods (Period 1 and Period 2), during which patients will receive 2 single doses of 3 mg paliperidone ER; and end of study evaluations upon completion of all the study procedures in Period 2 or at early withdrawal. All volunteers will receive each of the following 2 treatments in random order: Treatment A: 1 tablet of 3 mg paliperidone ER in the fasted state; Treatment B: one 20 mg paroxetine tablet once a day from Day 1 to Day 13 and 1 tablet of 3 mg paliperidone ER on Day 10 in the fasted state. Successive paliperidone ER administrations will be separated by a washout period of at least 14 days and no more than 28 days. Paroxetine is a potent and selective CYP2D6 inhibitor. Inhibitors of CYP2D6 such as paroxetine have been reported to increase the plasma concentrations of antipsychotics such as perphenazine, clozapine, and risperidone. Because paliperidone ER and paroxetine could potentially be used in combination in schizophrenic patients, the potential for a drug-drug interaction between paroxetine and paliperidone ER needs to be explored.The safety and tolerability of the 3 mg tablet of paliperidone ER administered with and without paroxetine to healthy men will be monitored.

Two single oral doses of paliperidone ER 3-mg; 20-mg paroxetine orally once a day for 13 days

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00791713

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

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00791713     History of Changes
Other Study ID Numbers: CR007561
Study First Received: November 13, 2008
Last Updated: May 18, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Paliperidone ER
Antipsychotic drugs
Selective serotonin reuptake inhibitors
Mood disorders
Schizophrenia

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 September 18, 2014