A Study of Plasma Concentrations, Metabolism and Excretion of 14C-paliperidone After a Single Oral Dose
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
14C-paliperidone
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, Mood disorders, Antipsychotic drugs: 14C-paliperidone
Eligibility Criteria
Inclusion Criteria:
- Dextromethorphan metabolic ratio of >0.345 (poor metabolizer) or <0.0255 (extensive metabolizer)
- Body Mass Index: (weight [kg]/height [m]2) between 20 and 28 kg/m2, 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
- Healthy based on a prestudy physical examination, medical history, ECG, the results of hematology and serum chemistry tests, and a urinalysis carried out within the 3 weeks prior to administration of study drug. If the results of the hematology tests, serum chemistry tests (except for liver enzymes and serum creatinine), or the urinalysis are not within the laboratory's reference ranges, the volunteer can be included only on the condition that the investigator judges that the deviations are not clinically significant.
Exclusion Criteria:
- Relevant history of cardiac arrhythmias, bronchospastic or cardiovascular disease (e.g., history of ischemic heart disease or cerebrovascular accident)
- respiratory, neuropsychiatric, renal, hepatic, gastrointestinal (including surgeries, and malabsorption problems), endocrine (including diabetes mellitus and thyrotoxicosis), or immunologic diseases
- parkinsonism
- or drug allergy
- History of any cancer, with the exception of basal cell carcinoma
- Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment
- History of smoking or use of nicotine-containing substances within the last 2 months, as determined by medical history and/or volunteer's verbal report
- History of alcohol or substance abuse. Positive test results for urine drug screen or alcohol breath test upon admission to the study center on Day 1
- Positive results for any of the serology tests (hepatitis B surface antigen, human immunodeficiency virus [HIV] antibody, and hepatitis C viral antibody)
- Liver function tests or serum creatinine exceeding normal limits at screening
Sites / Locations
Outcomes
Primary Outcome Measures
To investigate the metabolic pathways of paliperidone and excretion of paliperidone and its metabolites in healthy adult male volunteers,both poor and extensive metabolizers for CYP2D6,after administration of a single 1 mg oral dose of 14C paliperidone
Secondary Outcome Measures
To evaluate the safety and tolerability of paliperidone, as well as the relationship between genotypes (CYP2D6, CYP3A4, CYP3A5, UGT1A1, and UGT1A6) and exposure to paliperidone and its metabolites
Full Information
NCT ID
NCT00796029
First Posted
November 20, 2008
Last Updated
June 6, 2011
Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
1. Study Identification
Unique Protocol Identification Number
NCT00796029
Brief Title
A Study of Plasma Concentrations, Metabolism and Excretion of 14C-paliperidone After a Single Oral Dose
Official Title
Plasma Concentrations, Metabolism and Excretion of 14C-paliperidone After a Single Oral Dose in Healthy Male Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
March 2010
Overall Recruitment Status
Completed
Study Start Date
July 2003 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2003 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
4. Oversight
5. Study Description
Brief Summary
The purposes of this study are to investigate the metabolic pathways of paliperidone and excretion of paliperidone and its metabolites in healthy adult male volunteers, both CYP2D6 poor and extensive metabolizers, after administration of a single 1-mg oral dose of 14C-paliperidone, to evaluate the safety and tolerability of paliperidone, and to determine the relationship between genotypes (CYP2D6, CYP3A4, CYP3A5, UGT1A1, and UGT1A6) and exposure to paliperidone and its metabolites.
Detailed Description
This study is designed as a single-center, single-dose, open-label study of the absorption, metabolism, and excretion of paliperidone in healthy men (3 extensive and 3 poor metabolizers based on CYP2D6 phenotype). Eligible volunteers will be admitted to the study center the evening before study drug administration and will remain at the study center until 168 hours after dosing (or longer if required up to a maximum of 14 days). Each volunteer will receive a single oral dose of 14C-paliperidone with total radioactivity below 1000 µSv (16 mCi). Blood samples for plasma pharmacokinetic profile will be obtained immediately before study drug administration and 0.5, 1, 1.5, 3, 6, 12, 16, 36, 48, 72, 96, 120, 144 and 168 hours postdose. Blood samples will be obtained 2, 4, 8 and 24 hours postdose for determination of 14C in whole blood. Samples for determination of serum creatinine will be obtained 2, 4, 8 and 24 hours postdose. Urine will be collected immediately prior to drug administration and from 0-4, 4-8, 8-12, 12-16, 16-24, 24-36, 36-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours after study drug administration. Fecal samples will be collected per each stool, once before study drug administration and in the period from 0-168 hours after study drug administration. Collections of urine and feces (per 24 hours) will continue beyond 168 hours, to a maximum of 336 hours (Day 15) for patients who excrete radioactivity slowly (2 latest 24-hour urine collections each greater than or equal to 2% of total radioactive dose) or have <7 feces stool samples over the 0 to 168-hour period. 14C radioactivity will be measured in plasma, urine, and feces. Aliquots of the 0- through 24 hour urine collections will be analyzed for creatinine. Plasma concentrations of paliperidone and risperidone will be determined by means of a validated LC MS/MS method. The 14C-labeled moiety in plasma and urine will be determined by liquid scintillation counting. For all plasma samples, the lower limits of quantification for paliperidone and risperidone will be 0.100 ng/mL. For all plasma and urine samples the lower limits of quantification for 14C-paliperidone will be 72 dpm/mL (=2.0n g eq/mL). The rationale for the present study with a single-dose administration of 1 mg 14C-paliperidone to healthy white men is to determine the routes of excretion for paliperidone and to elucidate the metabolic pathways and structures of predominant paliperidone metabolites. As such, this study will result in a more complete understanding of the pharmacokinetics of paliperidone in humans. Safety and tolerability will be monitored. Volunteers will receive a single oral 1 mg dose of 14C-paliperidone as a solution with a specific activity of 592 kBq/mg, resulting in an administered radioactivity of 592 kBq (or 16 µCi). The total radioactive load for the subject will remain lower than 1000 µSv.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Schizophrenia, Mood disorders, Antipsychotic drugs: 14C-paliperidone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
14C-paliperidone
Primary Outcome Measure Information:
Title
To investigate the metabolic pathways of paliperidone and excretion of paliperidone and its metabolites in healthy adult male volunteers,both poor and extensive metabolizers for CYP2D6,after administration of a single 1 mg oral dose of 14C paliperidone
Secondary Outcome Measure Information:
Title
To evaluate the safety and tolerability of paliperidone, as well as the relationship between genotypes (CYP2D6, CYP3A4, CYP3A5, UGT1A1, and UGT1A6) and exposure to paliperidone and its metabolites
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Dextromethorphan metabolic ratio of >0.345 (poor metabolizer) or <0.0255 (extensive metabolizer)
Body Mass Index: (weight [kg]/height [m]2) between 20 and 28 kg/m2, 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
Healthy based on a prestudy physical examination, medical history, ECG, the results of hematology and serum chemistry tests, and a urinalysis carried out within the 3 weeks prior to administration of study drug. If the results of the hematology tests, serum chemistry tests (except for liver enzymes and serum creatinine), or the urinalysis are not within the laboratory's reference ranges, the volunteer can be included only on the condition that the investigator judges that the deviations are not clinically significant.
Exclusion Criteria:
Relevant history of cardiac arrhythmias, bronchospastic or cardiovascular disease (e.g., history of ischemic heart disease or cerebrovascular accident)
respiratory, neuropsychiatric, renal, hepatic, gastrointestinal (including surgeries, and malabsorption problems), endocrine (including diabetes mellitus and thyrotoxicosis), or immunologic diseases
parkinsonism
or drug allergy
History of any cancer, with the exception of basal cell carcinoma
Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment
History of smoking or use of nicotine-containing substances within the last 2 months, as determined by medical history and/or volunteer's verbal report
History of alcohol or substance abuse. Positive test results for urine drug screen or alcohol breath test upon admission to the study center on Day 1
Positive results for any of the serology tests (hepatitis B surface antigen, human immunodeficiency virus [HIV] antibody, and hepatitis C viral antibody)
Liver function tests or serum creatinine exceeding normal limits at screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
Organizational Affiliation
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
18227146
Citation
Vermeir M, Naessens I, Remmerie B, Mannens G, Hendrickx J, Sterkens P, Talluri K, Boom S, Eerdekens M, van Osselaer N, Cleton A. Absorption, metabolism, and excretion of paliperidone, a new monoaminergic antagonist, in humans. Drug Metab Dispos. 2008 Apr;36(4):769-79. doi: 10.1124/dmd.107.018275. Epub 2008 Jan 28.
Results Reference
result
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=577&filename=CR004276_CSR.pdf
Description
A study of plasma concentrations, metabolism and excretion of 14C-paliperidone after a single oral dose
Learn more about this trial
A Study of Plasma Concentrations, Metabolism and Excretion of 14C-paliperidone After a Single Oral Dose
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