A Pharmacokinetics and Pharmacodynamics Study Under Fasting and Fed Conditions With Paliperidone Extended-release and Immediate-release Formulations
Information source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Schizophrenia
Intervention: ER Paliperidone (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Official(s) and/or principal investigator(s): Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Study Director, Affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Summary
The purpose of this study is to compare the bioavailability of 2 extended release
paliperidone pellet formulations under fasting and fed conditions with a 2 mg paliperidone
oral solution under fasting conditions. Additional objectives are to compare the
pharmacodynamic effects (postural changes in blood pressure and heart rate), to evaluate the
safety and tolerability of each treatment, and to explore the relationship between CYP2D6
genotype and paliperidone exposure.
Clinical Details
Official title: A Comparative Evaluation of the Pharmacokinetics and Pharmacodynamics Under Fasting and Fed Conditions of 2 Paliperidone Extended-release Pellet Formulations With Paliperidone Oral Solution in Healthy Adults
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To evaluate the pharmacokinetics of 2 ER pellet formulations of 2 mg-eq paliperidone in comparison to 2 mg IR paliperidone oral solution and to evaluate the effect of food on the pharmacokinetics of the ER pellet formulations
Secondary outcome: To compare the pharmacodynamic effects of all treatments, to evaluate safety and tolerability as well as the relationship between genotypes (CYP2D6 and CYP3A4/5) and paliperidone exposure
Detailed description:
This is a single-center, open-label, randomized, 5-way crossover Phase 1 study in
non-smoking healthy men and women, aged between 18 and 55 years. The study consists of a
screening period; a 5-way crossover, open-label treatment phase with 14 days washout between
treatments; and end-of-study evaluations upon completion or at early withdrawal. Eligible
volunteers will be randomly assigned to 1 of 5 treatment sequences. Each volunteer will
receive the following treatments in random order: (A) paliperidone ER pellet formulation-1,
as 1 capsule of 2. 5 mg, under fasting conditions; (B) paliperidone ER pellet formulation-1,
as capsule of 2. 5 mg with food (high-fat breakfast); (C) paliperidone ER pellet
formulation-2 as 1 capsule of 2. 5 mg, under fasting conditions; (D) paliperidone ER pellet
formulation-2 as 1 capsule of 2. 5 mg with food (high-fat breakfast); (E) immediate release
(IR) paliperidone oral solution, 2 mg (2 mL) of a 1-mg/mL solution, under fasting
conditions. Alternative paliperidone ER formulations are being developed with the aim to
increase bioavailability and reduce variability, without compromising the favorable effect
on orthostatic hypotension as seen with ER OROS paliperidone. Therefore, in this study, the
pharmacokinetics and pharmacodynamic properties, as well as the effect of food, of 2
alternative paliperidone ER pellet formulations will be investigated. Safety and
tolerability will be monitored throughout the study.. Single doses of paliperidone ER pellet
formulation-1, as 1 capsule of 2. 5 mg, fasted; paliperidone ER pellet formulation-1, as 1
capsule of 2. 5 mg with food (high-fat breakfast); paliperidone ER pellet formulation-2 as 1
capsule of 2. 5 mg, fasted; paliperidone ER pellet formulation-2 as 1 capsule of 2. 5 mg with
food (high-fat breakfast); IR paliperidone oral solution, 2 mg (2 mL) of a 1-mg/mL solution,
fasted.
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Body mass index (weight [kg]/height (m)²) range of 18. 0 to 28. 0 kg/m², inclusive
- Normotensive with supine (5 minutes) blood pressure between 100 and 140 mmHg
systolic, inclusive, and diastolic between 60 and 90 mmHg, inclusive
- Healthy on the basis of a prestudy physical examination, medical history,
electrocardiogram, and the laboratory results of blood biochemistry, hematology and
urinalysis performed within 21 days before the first dose. If the results of the
biochemistry, 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 liver function tests (alanine
transaminase, aspartate transaminase, and bilirubin), the values must be contained
within 2 times the upper limits of the normal laboratory reference ranges and for
renal function tests, the values must be within the normal laboratory reference
ranges
- Women must be postmenopausal for at least 1 year, surgically sterile, or practicing
an effective method of birth control (e. g., prescription oral contraceptives,
contraceptive injections, intrauterine device, double-barrier method, contraceptive
patch, male partner sterilization and at the discretion of the investigator, total
abstinence) before entry and throughout the study, as well as have a negative serum
pregnancy test at screening. To ensure continued eligibility, women must have a
negative urine test before each dose of study drug (Day - 1 for each period).
Exclusion Criteria:
- Known allergy or history of significant hypersensitivity to heparin
- Recent history of alcohol or substance abuse. Test positive for the urine drug screen
at screening or the urine drug screen or alcohol breath test at Day - 1 for Period 1
- Relevant history of any cardiovascular, respiratory, neuropsychiatric, renal,
hepatic, gastrointestinal (including surgeries, and malabsorption problems),
endocrine, or immunologic diseases
- A decrease of greater than or equal to 20 mmHg systolic blood pressure 3 minutes
after standing, or with symptoms of lightheadedness, dizziness or fainting upon
standing at screening
- Positive result for any of the serology tests (hepatitis B, C and HIV)
- Have less than 1 bowel movement on average each day
- History of any cancer, with the exception of basal cell carcinoma
- 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. (Volunteers must
agree to refrain from use throughout the study.)
Locations and Contacts
Additional Information
A pharmacokinetics and pharmacodynamics study under fasting and fed conditions with paliperidone extended-release and immediate-release formulations
Starting date: September 2003
Last updated: June 6, 2011
|