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Pharmacokinetic Study of Raltegravir in Human Immunodeficiency Virus/Hepatitis C Virus (HIV/VHC) Coinfected Patients With Advanced (Child-Pugh C) Hepatic Cirrhosis (LIVERAL)

31. januar 2013 opdateret af: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Phase I, Open Label, Unicentric Study of Multiple-dose Pharmacokinetics of Raltegravir in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus With and Without Advanced (Child-Pugh C) Hepatic Cirrhosis.

Raltegravir is the first integrase inhibitor used in humans. It has been shown to be highly efficacious and well tolerated in phase III clinical trials in multidrug experienced human immunodeficiency virus(HIV)-infected patients, as well as initial therapy in untreated patients. Pharmacokinetic studies in healthy adult subjects indicate that the major mechanism of clearance of the drug is glucuronidation mediated by UGT1A1, with a minor contribution of renal excretion of unchanged parent compound. Unlike CYP-based metabolism, glucuronidation is generally found to be relatively unaffected by hepatic disease. A single dose pharmacokinetic study of raltegravir in patients with mild to moderate hepatic insufficiency (Steigbigel et al. 2008) found no clinically important effect on the drug pharmacokinetic profile, with no dosage adjustment being necessary. The liver safety and tolerability of boosted atazanavir (ATV/r) has been evaluated in human immunodeficiency virus and hepatitis C virus (HIV/HCV) coinfected patients with advanced liver disease (decompensated cirrhosis) (Hermida JM et al. 4th IAS: Sidney, 2007). Similar to Raltegravir, ATV is also mainly metabolized by conjugation through UGT1A1. There is an urgent need for potent and efficacious ARV drugs with a clean safety liver profile even in patients with severe liver disease. The investigators hypothesized that pharmacokinetics will not be altered in HIV/HCV patients with advanced (Child-Pugh grade C) cirrhosis or in those with no histologic liver damage.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

10

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Spanien
      • Madrid, Spanien, 28034
        • Hospital Universitario Ramón y Cajal.

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Adults, clinically stable HIV/HCV coinfected patients on HAART with controlled viremia (<50 copies/ml) for at least 6 months. HAART will be based on a boosted protease inhibitor (lopinavir, fosamprenavir or darunavir). Hepatic Stability is defined by the absence of new events of descompensation (Child-Pugh score) in the previous six weeks with no data of progressive hepatic insufficiency.
  • Liver biopsy performed during the previous year showing no liver damage (F0-F1 in the Metavir score) or by elastometry results ≤ 6 Kpa, to classify patients in group B.
  • Liver cirrhosis guided by biopsy (F4 in the Metavir score) or elastometry: results ≥ 14 Kpa, to classify patients in group A.
  • Body mass index (BMI) in the range of 19-35 kg/m2.

Exclusion Criteria:

  • HBV surface antigen positive.
  • Clinical demonstration of a new descompensation event in the previous 6 weeks.
  • Alcohol abuse as an average daily consumption > 20g.
  • Treatment with boosted atazanavir, saquinavir or indinavir.
  • Concomitant treatment with phenytoin, phenobarbital and rifampinor other UGT1A1 inhibitors.
  • Use of any investigational agents (other than ART on expanded access) within 90 days of randomization.
  • Active or previous HCV treatment with Ribavirin and /or Peg-interferon if sustained virological response achieved.
  • Women taking oral contraceptives
  • Pregnancy and lactancy.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Patients with Child-Pugh C hepatic-cirrhosis.
VIH/VHC coinfected patients with advanced (Child-Pugh C) hepatic cirrhosis.
Medicin: Raltegravir 400 mg/12hours
Aktiv komparator: VIH/VHC coinfected patients without liver damage.
Medicin: Raltegravir 400 mg/12hours

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
The area under the curve (AUC0-12) calculated from plasma concentrations, the maximum concentration (Cmax) and the the minimum concentration (Cmin) of Raltegravir 400 mg/12 hours in the steady state for both arms.
Tidsramme: On the fifth day of treatment with raltegravir
On the fifth day of treatment, patient will be hospitalized in the clinical trial unit in order to obtaine plasma concentrations previous to the administration of the corresponding dose (basal) and at the following times post-administration: 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, and 12h. With these measures, (AUC0-12), Cmax and Cmin will be calculated in order to describe the pharmacokinetic of Raltegravir 400 mgBID in the steady state in both arms
On the fifth day of treatment with raltegravir

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change from baseline in hematology and biochemistry parameters at day 5 and 15, number of adverse events (serious and non serious) notified and number of patients who discontinue the study (drop-out rate).
Tidsramme: On day 1, 5 and 15
Hematology and biochemistry parameters, adverse events notified during the study and drop-out rate will be recorded in order to evaluate the safety and tolerability of multiple doses of raltegravir in HIV/HCV coinfected patients, with no liver damage and with advanced cirrhosis.
On day 1, 5 and 15

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Samarbejdspartnere

Merck Sharp & Dohme LLC

Efterforskere

  • Ledende efterforsker: Santiago Moreno Guillen, MD, Hospital Universitario Ramón y Cajal. Madrid

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. december 2010

Primær færdiggørelse (Faktiske)

1. juni 2011

Studieafslutning (Faktiske)

1. oktober 2011

Datoer for studieregistrering

Først indsendt

1. februar 2011

Først indsendt, der opfyldte QC-kriterier

3. februar 2011

Først opslået (Skøn)

4. februar 2011

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

1. februar 2013

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

31. januar 2013

Sidst verificeret

1. januar 2013

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • LIVERAL

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Hepatitis C

Kliniske forsøg med Raltegravir 400 mg/12hours

Søg i lignende forsøg

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Narkotikainterventioner

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Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner