A Study of the Potential Effects of Trimethoprim on the Pharmacokinetics of ER OROS Paliperidone

This study has been completed.
Sponsor:
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00892541
First received: November 20, 2008
Last updated: June 6, 2011
Last verified: March 2010
  Purpose

The purpose of this study is to evaluate the effects of an organic cation transporter inhibitor, trimethoprim, on the pharmacokinetics of orally administered ER OROS paliperidone and to assess the safety and tolerability of the treatments in healthy male volunteers.


Condition Intervention Phase
Schizophrenia
Drug: ER OROS paliperidone
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: Investigation of the Potential Effects of Trimethoprim on the Pharmacokinetics of ER OROS Paliperidone in Healthy Male Subjects

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 an organic cation transporter inhibitor, trimethoprim, on the pharmacokinetics of orally administered ER OROS paliperidone

Secondary Outcome Measures:
  • To evaluate the safety and tolerability of the treatments in healthy male volunteers

Enrollment: 30
Study Start Date: October 2004
Study Completion Date: November 2004
Detailed Description:

This study was designed as a single center, open-label, randomized, 2 treatment period crossover study in healthy male volunteers. The study consists of a screening period (within 21 days before the first study drug administration) before randomization; an open-label treatment phase consisting of 2 periods during which subjects will receive a single oral dose of ER OROS paliperidone alone (Treatment A) or in combination with 200 mg trimethoprim twice daily (Treatment B); and end-of-study evaluations upon completion of all the study procedures in Period 2 or early withdrawal. The pharmacokinetic blood and urine samples will be collected over a 96 hour period after ER OROS paliperidone administration. Successive ER OROS paliperidone administrations will be separated by at least 14 days. Given that the main elimination route of paliperidone is renal clearance and about half of this is through active secretion in the renal tubule, competition for this route of elimination can occur when other actively secreted drugs are coadministered. Therefore, the possible influence on the renal excretion of paliperidone will be investigated when a competitor for active renal secretion, trimethoprim, is coadministered. Safety and tolerability will be monitored throughout the study. Treatment A: a single oral dose of 6 mg ER OROS paliperidone on Day 1; Treatment B: a 200 mg trimethoprim tablet twice daily from Day 1 to Day 8 and a single oral dose of 6 mg ER OROS paliperidone on Day 5.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male, aged 18 to 55 years, inclusive
  • Volunteers must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study
  • Body Mass Index (BMI, 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
  • Healthy on the basis of a prestudy physical examination, medical history, 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 subject can be included only if the investigator judges that the deviations are not clinically significant
  • Creatinine clearance value greater than or equal to 80 mL/min
  • Signed an informed consent for genetic testing, indicating whether the volunteer does or does not wish to participate in the genetic part of the study.

Exclusion Criteria:

  • Drug allergy to risperidone, paliperidone, trimethoprim, any of its excipients or history of hypersensitivity to heparin, in case a heparin lock will be used
  • Past or current history of folic acid deficiency or megaloblastic anemia
  • Recent history of alcohol or substance abuse or dependence or a positive test result for the urine drug screen at screening
  • Relevant history or presence of any cardiovascular (including myocardial infarct or cardiac arrhythmia), respiratory, neurological (including seizures, cerebrovascular disorders), psychiatric, renal, hepatic, gastrointestinal (including surgeries, severe gastrointestinal narrowing, and malabsorption problems), endocrinal, hematological or immunological disease. History of any cancer, with the exception of basal cell carcinomas
  • At screening, has a 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 <45 bpm) as determined by screening ECG
  • A positive result for any of the tests for hepatitis B, C, and human immunodeficiency virus (HIV).
  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: NCT00892541

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00892541     History of Changes
Other Study ID Numbers: CR004150
Study First Received: November 20, 2008
Last Updated: June 6, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Schizophrenia
Mood disorders
Antipsychotic drugs
Renal secretion
ER OROS paliperidone

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
9-hydroxy-risperidone
Trimethoprim
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 16, 2014