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

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

Disposition of Paliperidone Enantiomers After Treatment With Different Formulations of the Racemate and the Separate Enantiomers and the Determination of the Absolute Bioavailability of IR and ER OROS Paliperidone

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a single-center, single-dose, open-label, randomized, crossover study in healthy adults, following a 5-sequence, 5-treatment, 5-period Latin square design. The study consists of a screening phase (within 21 days before the first administration of study drug), and a treatment phase consisting of 5 periods during which volunteers will receive a single dose of study drug under fasting conditions [orally with 240 mL of water or intravenously (i.v.)] in a random order. Pharmacokinetic blood and urine samples will be collected over a 96-hour period following study drug administration during each treatment period. Volunteers will be confined to the testing facility from at least 10 hours before dosing until 72 hours after dosing in each treatment period and will return for additional assessments. Each administration of study drug will be separated by a washout period of at least 7 to a maximum of 14 days. The duration of volunteer participation is maximally 12 weeks, including the 3 week screening period. CYP2D6 metabolizer status will be assessed by phenotyping and will be corroborated by genotyping of a DNA sample to be collected from volunteers who consent to this part of the study. Pharmacokinetic data are available after oral administration of immediate release and extended release formulations of paliperidone. No data are available after i.v. administration of paliperidone. The data obtained in this study for the i.v. route are important to further characterize the pharmacokinetics of paliperidone, and for future population pharmacokinetics modeling of paliperidone. For chiral substances, it is requested by regulatory authority guidelines to document the disposition of the enantiomers. Therefore, the disposition of the (+) and (-) enantiomers of paliperidone for different administration routes (i.v. and oral) and formulations (immediate release and extended release [ER OROS]) will be documented. Separate enantiomers will be administered in this study, as it is important for the full understanding of the pharmacokinetics of paliperidone to document the possible chiral interconversion. Safety and tolerability will be monitored throughout the study. 5 single doses, one each of: Treatment A, 1 mg IR paliperidone oral solution; Treatment B, 3 mg ER OROS paliperidone oral; Treatment C, 1 mg paliperidone as a 30-min i.v. infusion; Treatment D, 1 mg (+)-paliperidone (R078543) oral solution; and Treatment E, 1 mg (-)-paliperidone (R078544) oral solution.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
To characterize and document the pharmacokinetics of paliperidone in plasma and urine;the (+) and (-) paliperidone ratio;the possible interconversion between the (+)- and (-)- enantiomers of paliperidone;the absolute oral bioavailability of paliperidone

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
To document the possible relationship between the volunteer's CYP2D6 phenotype and the disposition of the (+) and (-) enantiomers of paliperidone and to evaluate the safety and tolerability of the treatments in healthy volunteers

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2004

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2004

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 20, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 20, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 24, 2008

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 8, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 6, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR004216

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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