- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00796471
A Pharmacokinetics and Pharmacodynamics Study Under Fasting and Fed Conditions With Paliperidone Extended-release and Immediate-release Formulations
6. juni 2011 oppdatert av: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
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.
Studieoversikt
Detaljert beskrivelse
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
Intervensjonell
Registrering (Faktiske)
35
Fase
- Fase 1
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 55 år (Voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Crossover-oppdrag
- Masking: Ingen (Open Label)
Hva måler studien?
Primære resultatmål
Resultatmål |
|---|
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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
|
Sekundære resultatmål
Resultatmål |
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|
To compare the pharmacodynamic effects (postural changes in blood pressure and heart rate) of all treatments
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. juni 2003
Primær fullføring
6. desember 2022
Studiet fullført (Faktiske)
1. august 2003
Datoer for studieregistrering
Først innsendt
20. november 2008
Først innsendt som oppfylte QC-kriteriene
20. november 2008
Først lagt ut (Anslag)
24. november 2008
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
8. juni 2011
Siste oppdatering sendt inn som oppfylte QC-kriteriene
6. juni 2011
Sist bekreftet
1. mars 2010
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Psykiske lidelser
- Schizofrenispektrum og andre psykotiske lidelser
- Schizofreni
- Fysiologiske effekter av legemidler
- Nevrotransmittere agenter
- Molekylære mekanismer for farmakologisk virkning
- Sentralnervesystemdepressiva
- Antipsykotiske midler
- Beroligende midler
- Psykotropiske stoffer
- Serotoninmidler
- Dopaminmidler
- Serotonin 5-HT2-reseptorantagonister
- Serotonin-antagonister
- Dopamin D2-reseptorantagonister
- Dopaminantagonister
- Paliperidonpalmitat
Andre studie-ID-numre
- CR004282
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
produkt produsert i og eksportert fra USA
Nei
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