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

June 6, 2011 updated by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigation of the Potential Effects of Trimethoprim on the Pharmacokinetics of ER OROS Paliperidone in Healthy Male Subjects

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To evaluate the effects of an organic cation transporter inhibitor, trimethoprim, on the pharmacokinetics of orally administered ER OROS paliperidone

Secondary Outcome Measures

Outcome Measure
To evaluate the safety and tolerability of the treatments in healthy male volunteers

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2004

Study Completion (Actual)

November 1, 2004

Study Registration Dates

First Submitted

November 20, 2008

First Submitted That Met QC Criteria

April 30, 2009

First Posted (Estimate)

May 4, 2009

Study Record Updates

Last Update Posted (Estimate)

June 8, 2011

Last Update Submitted That Met QC Criteria

June 6, 2011

Last Verified

March 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR004150

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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