Denne siden ble automatisk oversatt og nøyaktigheten av oversettelsen er ikke garantert. Vennligst referer til engelsk versjon for en kildetekst.

A Study to Assess the Pharmacokinetics of a Modified-release Tacrolimus Based Immunosuppression Regimen in Stable Liver Transplant Patients

1. august 2013 oppdatert av: Astellas Pharma Inc

A Phase 2, Open-Label, Multi-Center Study to Assess the Pharmacokinetics, Long-term Safety and Tolerability of Tacrolimus in Stable Liver Transplant Patients Converted From a Prograf® Based Immunosuppression Regimen to a Modified Release (MR) Tacrolimus Based Immunosuppression Regimen

A study to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable liver transplant patients converted from a tacrolimus (Prograf®) based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

A one arm study to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable liver transplant patients converted from a tacrolimus (Prograf®) based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen.

Studietype

Intervensjonell

Registrering (Faktiske)

70

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • California
      • Palo Alto, California, Forente stater
    • Colorado
      • Denver, Colorado, Forente stater, 80262
    • Maryland
      • Baltimore, Maryland, Forente stater, 21287
    • Michigan
      • Ann Arbor, Michigan, Forente stater, 48109
    • Minnesota
      • Minneapolis, Minnesota, Forente stater, 55455
      • Rochester, Minnesota, Forente stater, 55905
    • New York
      • New York, New York, Forente stater, 10029
    • Ohio
      • Cincinnati, Ohio, Forente stater, 45267
    • Texas
      • Dallas, Texas, Forente stater, 75246
    • Wisconsin
      • Madison, Wisconsin, Forente stater, 53792

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 65 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • Patient is currently receiving Prograf ® based immunosuppressive therapy for liver transplantation.
  • Patient has stable whole blood trough level concentrations of Prograf® and is clinically stable

Exclusion Criteria:

  • Patient has previously received an organ transplant other than a liver
  • Patient is currently receiving sirolimus immunosuppression therapy.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Forebygging
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Tacrolimus MR

After enrollment in the pharmacokinetic period, patients were maintained on their usual dose of tacrolimus twice daily on Day 1 through Day 14 and on Day 15 were converted to tacrolimus modified release (MR) once-daily in the morning for 14 days, converted back to tacrolimus twice daily for 14 days and then converted back to tacrolimus MR formulation once-daily in the morning for 14 days, all based on a 1:1 mg for mg total daily dose conversion. The extended treatment period began on day 57 and consisted of a single dose of tacrolimus extended-release formulation once every morning through the end of the study.

Dose adjustments were allowed in order to maintain the target tacrolimus trough level within the range of 5 to 20 ng/mL and for clinical reasons.
Legemiddel: takrolimus
Muntlig
Andre navn:
  • FK506
  • Prograf,
Legemiddel: takrolimus modifisert frigjøring (MR)
Muntlig
Andre navn:
  • Astagraf XL
  • Advagraf,
  • FK506E,
  • MR4,
  • FKMR,

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus
Tidsramme: Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
The area under the concentration-time curve was calculated from whole blood tacrolimus concentrations for both the tacrolimus and tacrolimus MR treatment periods at steady state using the linear trapezoidal rule. The AUC0-24 for tacrolimus was calculated as the sum of the AUC0-12 for the morning (0-12 hour) and afternoon (12-24 hour) doses.
Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
Minimum Observed Concentration of Tacrolimus (Cmin)
Tidsramme: Days 14 and 42 at 12 hours post-dose (tacrolimus) and Days 28 and 56 at 24 hours post-dose (for tacrolimus MR).
The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 12 hour post-dose concentration based on the evening dose (i.e., the 8 am concentration) for tacrolimus and the 24-hour time point post-dose for tacrolimus MR, prior to receiving the next dose.
Days 14 and 42 at 12 hours post-dose (tacrolimus) and Days 28 and 56 at 24 hours post-dose (for tacrolimus MR).
Patient Survival
Tidsramme: From enrollment until the end of study (up to 60 months).
Patient survival was defined as any participant known to be alive at the time of analysis.
From enrollment until the end of study (up to 60 months).
Graft Survival
Tidsramme: From enrollment until the end of study (up to 60 months).
Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was defined as graft failure (re-transplant) or participant death.
From enrollment until the end of study (up to 60 months).

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Antall deltakere med flere avvisningsepisoder
Tidsramme: Fra påmelding til studieslutt (inntil 60 måneder).
Denne analysen inkluderer avstøtningsepisoder som enten ble bekreftet av biopsi av patologen på det kliniske stedet eller som ble klinisk behandlet.
Fra påmelding til studieslutt (inntil 60 måneder).
Antall deltakere med klinisk behandlede akutte avvisningsepisoder
Tidsramme: Fra påmelding til studieslutt (inntil 60 måneder).
En klinisk behandlet akutt avstøtningsepisode var enhver biopsibekreftet eller mistenkt avstødningsepisode som ble behandlet med immunsuppressiv terapi.
Fra påmelding til studieslutt (inntil 60 måneder).
Antall deltakere med kronisk avslag
Tidsramme: Fra påmelding til studieslutt (inntil 60 måneder).
På grunn av det lave antallet deltakere med biopsibekreftede akutte avstøtningsepisoder, ble ikke kronisk avslag analysert.
Fra påmelding til studieslutt (inntil 60 måneder).
Antall deltakere med behandlingssvikt
Tidsramme: Fra påmelding til studieslutt (inntil 60 måneder).
Behandlingssvikt ble definert som seponering av studiemedikamentet uansett årsak. På grunn av sponsorens seponering av studien, ble ikke behandlingssvikt analysert.
Fra påmelding til studieslutt (inntil 60 måneder).
Maximum Observed Concentration of Tacrolimus (Cmax)
Tidsramme: Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
The maximum concentration was calculated from whole blood tacrolimus concentrations for both the tacrolimus and tacrolimus MR treatment periods at steady state, without interpolation.
Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
Time to Maximum Observed Concentration of Tacrolimus (Tmax)
Tidsramme: Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
Time to the first occurrence to reach the maximum concentration of tacrolimus was calculated from whole blood tacrolimus concentrations for both the tacrolimus and tacrolimus MR treatment periods at steady state, without interpolation.
Days 14 and 42 (tacrolimus) and Days 28 and 56 (tacrolimus MR), pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (pre-dose for tacrolimus only), 12.5, 13, 14, 15, 16, 18, 20, and 24 hours post-dose.
Percentage of Participants With Biopsy-confirmed Acute Rejection
Tidsramme: From enrollment until the end of study (up to 60 months).
Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute liver allograft rejection that was confirmed by biopsy results and was Banff grade ≥ I. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria for grading of acute liver allograft rejection: Indeterminate: Portal inflammatory infiltrate that fails to meet the criteria for diagnosis of acute rejection; Grade I (Mild): Rejection infiltrate in a minority of the triads that is generally mild and confined within the portal spaces; Grade II (Moderate): Rejection infiltrate, expanding to most or all of the triads; Grade III (Severe): Rejection infiltrate, expanding to most or all of the triads, with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis.
From enrollment until the end of study (up to 60 months).
Time to Event for Patient Non-survival
Tidsramme: From enrollment until the end of study (up to 60 months).
For participants who died on study, the median number of days from first dose of study drug to death due to any cause.
From enrollment until the end of study (up to 60 months).
Time to Event for Graft Non-survival
Tidsramme: From enrollment until the end of study (up to 60 months).
For participants with graft loss, the median number of days from the first dose of study drug to graft loss. Graft loss was defined as graft failure (re-transplant) or participant death.
From enrollment until the end of study (up to 60 months).
Time to First Biopsy-confirmed Acute Rejection
Tidsramme: From enrollment until the end of study (up to 60 months).
For participants with a biopsy-confirmed acute rejection (BCAR), the median number of days from the first dose of study drug to the date of biopsy confirmation. BCAR is defined as an episode of acute liver allograft rejection that was confirmed by biopsy results and was Banff grade ≥ I. Biopsies were graded by the clinical site pathologist according to the 1997 Banff criteria for grading acute liver allograft rejection: Indeterminate: Portal inflammatory infiltrate that fails to meet the criteria for diagnosis of acute rejection; Grade I: Rejection infiltrate in a minority of the triads that is generally mild and confined within the portal spaces; Grade II: Rejection infiltrate, expanding to most or all of the triads; Grade III: Rejection infiltrate, expanding to most or all of the triads, with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis.
From enrollment until the end of study (up to 60 months).
Grade of Biopsy-confirmed Acute Rejection Episodes
Tidsramme: From enrollment until the end of study (up to 60 months).
Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute liver allograft rejection that was confirmed by biopsy results and was Banff grade ≥ I. Biopsies were graded by the clinical site pathologist according to the 1997 Banff criteria for grading of acute liver allograft rejection: Indeterminate: Portal inflammatory infiltrate that fails to meet the criteria for diagnosis of acute rejection; Grade I (Mild): Rejection infiltrate in a minority of the triads that is generally mild and confined within the portal spaces; Grade II (Moderate): Rejection infiltrate, expanding to most or all of the triads; Grade III (Severe): Rejection infiltrate, expanding to most or all of the triads, with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis. For participants with more than one biopsy-confirmed acute rejection episode, the worst case grade is reported.
From enrollment until the end of study (up to 60 months).
Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection
Tidsramme: From enrollment until the end of study (up to 60 months).
Steroid-resistant rejection episodes were treated with anti-lymphocyte antibodies. If a participant had a histologically proven Banff Grade II or III rejection, they could be initiated on anti-lymphocyte antibody treatment per institutional practice.
From enrollment until the end of study (up to 60 months).
Primary Reason for Graft Loss
Tidsramme: From enrollment until the end of study (up to 60 months).
The primary reason for graft loss was recorded by the Investigator. Graft loss was defined as graft failure (re-transplant) or participant death.
From enrollment until the end of study (up to 60 months).
Change From Baseline in Alanine Aminotransferase (ALT)
Tidsramme: Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).
Hepatic function was assessed by measuring alanine aminotransferase levels over the course of the study.
Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).
Change From Baseline in Aspartate Aminotransferase (AST)
Tidsramme: Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).
Hepatic function was assessed by measuring aspartate aminotransferase levels over the course of the study.
Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).
Change From Baseline in Total Bilirubin
Tidsramme: Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).
Hepatic function was assessed by measuring total bilirubin over the course of the study.
Baseline (the last day of tacrolimus on Day 14 prior to the first conversion to tacrolimus MR), Day 56 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).
Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs
Tidsramme: From the first dose of tacrolimus MR formulation through the last dose day plus 10 days (approximately 60 months).

An adverse event is defined as any reaction, side effect or other untoward medical occurrence, regardless of the relationship to study drug which occurred during the conduct of a clinical study. Clinically significant adverse changes in clinical status, routine laboratory studies or physical examinations were considered adverse events.

A serious adverse event was any adverse event occurring at any dose that resulted in any of the following outcomes:

  • Death
  • Life-threatening adverse event
  • Inpatient hospitalization or prolongation of existing hospitalization
  • Persistent or significant disability or incapacity
  • Congenital abnormality or birth defect
  • Important medical event.
From the first dose of tacrolimus MR formulation through the last dose day plus 10 days (approximately 60 months).

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Astellas Pharma Inc

Etterforskere

  • Studieleder: Central Contact, Astellas Pharma US, Inc.

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.

Generelle publikasjoner

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. februar 2003

Primær fullføring (Faktiske)

1. oktober 2008

Studiet fullført (Faktiske)

1. oktober 2008

Datoer for studieregistrering

Først innsendt

24. januar 2006

Først innsendt som oppfylte QC-kriteriene

24. januar 2006

Først lagt ut (Anslag)

26. januar 2006

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

30. september 2013

Siste oppdatering sendt inn som oppfylte QC-kriteriene

1. august 2013

Sist bekreftet

1. august 2013

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 02-0-152

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Kliniske studier på Levertransplantasjon

Kliniske studier på takrolimus

Søk i lignende forsøk

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

CROs by country

CROs in Qatar

Forhold

Sjeldne sykdommer

Legemiddelintervensjoner

Kosttilskudd

Sponsor / samarbeidspartnere

Steder

3
Abonnere