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A Pharmacokinetics and Pharmacodynamics Study Under Fasting and Fed Conditions With Paliperidone Extended-release and Immediate-release Formulations

A Comparative Evaluation of the Pharmacokinetics and Pharmacodynamics Under Fasting and Fed Conditions of 2 Paliperidone Extended-release Formulations With Paliperidone Oral Solution in Healthy Adults

The purpose of this study is to evaluate the pharmacokinetics of 2 extended-release (ER) formulations of 2 mg-eq paliperidone in comparison to the 2 mg immediate-release (IR) paliperidone oral solution and to evaluate the effect of food on the pharmacokinetics of these ER formulations. Additional objectives are to compare the pharmacodynamic effects (postural changes in blood pressure and heart rate), safety, and tolerability are to be evaluated in addition to exploring the relationship between CYP2D6 and CYP3A4/5genotype and paliperidone exposure.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

This study is designed as a single-center, open-label, randomized, 5 treatment-period, crossover study in healthy adults. The study consists of a screening phase and a treatment phase during which each volunteer will receive 5 treatments of study drug in a random order and separated by a washout period of at least 7 to 14 days. Treatments consist of a single oral dose of: A) paliperidone ER pellet formulation, (2 mg-eq) as 1 capsule of 2.5 mg, fasted; B) the same formulation as A but with food; C) paliperidone-coated ER OROS formulation (2 mg eq) as 2 tablets of 2 mg, fasted; D) the same formulation as C but with food; E) IR paliperidone oral solution, 2 mg (2 mL) of a 1 mg/mL solution, fasted. Alternative paliperidone ER formulations are being developed with the aim to increase the bioavailability without compromising the favorable effect on the orthostatic hypotension as seen with ER OROS paliperidone. Therefore, in this study, the pharmacokinetic and pharmacodynamic properties, as well as the effect of food, of 2 alternative paliperidone ER formulations using different mechanisms to achieve extended release of the drug will be investigated: a multiparticulate ER capsule formulation, containing coated pellets comprised of 3 coating layers, with both immediate and extended drug-release properties (pellet formulation; drug ratio extended- versus immediate-release layer: 9:1), and an OROS trilayer longitudinally compressed tablet formulation (Push-Pull delivery system) (overcoated-OROS formulation). Safety and tolerability will be monitored throughout the study. Single doses of paliperidone ER pellet formulation, (2 mg-eq) as 1 capsule of 2.5 mg, fasted; paliperidone ER pellet formulation, (2 mg-eq) as 1 capsule of 2.5 mg with food (high-fat breakfast); paliperidone-coated OROS ER formulation (2 mg-eq) as 2 tablets of 2 mg, fasted; paliperidone-coated OROS ER formulation (2 mg-eq) as 2 tablets of 2 mg with food (high-fat breakfast); IR paliperidone oral solution, 2 mg (2 mL) of a 1 mg/mL solution, fasted.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

35

Fase

  • Fase 1

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 55 jaar (Volwassen)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Acceptable weight as defined by 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 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, 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)
  • 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.)
  • Drug allergy to risperidone, paliperidone, or any of its excipients

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Crossover-opdracht
  • Masker: Geen (open label)

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
To evaluate the pharmacokinetics of 2 ER formulations of 2 mg-eq paliperidone in comparison with 2 mg IR paliperidone oral solution and to evaluate the effect of food on the pharmacokinetics of these ER formulations

Secundaire uitkomstmaten

Uitkomstmaat
To compare the pharmacodynamic effects (postural changes in blood pressure and heart rate) of all treatments

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 juni 2003

Primaire voltooiing

6 december 2022

Studie voltooiing (Werkelijk)

1 augustus 2003

Studieregistratiedata

Eerst ingediend

20 november 2008

Eerst ingediend dat voldeed aan de QC-criteria

20 november 2008

Eerst geplaatst (Schatting)

24 november 2008

Updates van studierecords

Laatste update geplaatst (Schatting)

8 juni 2011

Laatste update ingediend die voldeed aan QC-criteria

6 juni 2011

Laatst geverifieerd

1 maart 2010

Meer informatie

Termen gerelateerd aan deze studie

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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