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A Study of the Effect of Multiple Doses of Rifampin on the Single Dose Pharmacokinetics of RO5424802

1. november 2016 oppdatert av: Hoffmann-La Roche

An Open-Label, Three-Period, Fixed Sequence Study to Investigate the Effect of Multiple Oral Doses of Rifampin, a Potent Cytochrome P450 3A Inducer, on the Single Dose Pharmacokinetics of RO5424802 in Healthy Subjects

This single center, open-label, 3-period, fixed-sequence study will evaluate the effect of multiple oral doses of rifampin on the pharmacokinetics of a single oral dose of RO5424802 in healthy volunteers. Subjects will receive a single dose of RO5424802 on Days 1 and 17 and rifampin daily from Days 8 to Day 20.

Studieoversikt

Status

Fullført

Forhold

Studietype

Intervensjonell

Registrering (Faktiske)

24

Fase

  • Fase 1

Kontakter og plasseringer

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

Studiesteder

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

Ja

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • Healthy male and female volunteers, 18 to 55 years of age inclusive. Healthy status will be defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, and a complete physical examination
  • Body mass index (BMI) between 18 to 32 kg/m2 inclusive
  • Nonsmoking subjects and former smoking subjects (who have not smoked for the past six months before first dosing)
  • Female subjects must be surgically sterile or postmenopausal for the past year
  • Male subjects and their partners of childbearing potential must be willing to use two effective methods of contraception, one of which must be a barrier method (e.g., condom) during the study and for 90 days after the last drug administration

Exclusion Criteria:

  • Women of childbearing potential, pregnant or lactating women, or males with female partners who are pregnant or lactating
  • Positive urine test for drugs of abuse, alcohol, or cotinine test at screening or prior to admission to the study unit
  • Suspicion of regular consumption of drug(s) of abuse including marijuana
  • Current smokers or subjects who have discontinued smoking less than six months prior to first dosing
  • History (within three months of Screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol). Alcohol consumption will be prohibited 72 hours prior to entry in the clinical site center and throughout the entire study (including the washout period) until discharge
  • Positive for hepatitis B, hepatitis C, or HIV infection
  • Participation in an investigational drug or device study within 45 days or 5 half-lives (whichever time period is longer) or 6 months for biologic therapies prior to first dosing
  • Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, absorption, distribution, metabolism or excretion of study medication, or that would, in the opinion of the PI, pose an unacceptable risk to the subject in this study
  • History of hypersensitivity to any of the additives in the RO5424802 formulation (lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, hydroxypropyl cellulose, sodium lauryl sulphate, magnesium stearate)
  • Any history of hypersensitivity to or contraindication to the use of rifampin or other rifamycins or history of severe drug-related allergic reactions or hepatoxicity

Studieplan

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

Hvordan er studiet utformet?

Designdetaljer

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

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Sunne fag
Single dose without (Day 1) and with (Day 17) co-administration of rifampin
Multiple doses Days 8-16 and Days 17-20

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Alectinib
Tidsramme: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
AUC(0-inf) is the area under the alectinib plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of a drug over time. AUC(0-inf) is presented in nanogram times (*) hour per milliliter (ng*hour/mL).
Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Maximum Observed Plasma Concentration (Cmax) of Alectinib
Tidsramme: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Cmax is the maximum observed alectinib plasma concentration, presented in nanogram per milliliter (ng/mL).
Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
AUC(0-inf) of RO5468924
Tidsramme: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
AUC(0-inf) is the area under the RO5468924 (the major pharmacologically active metabolite of alectinib) plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of the drug over time. AUC(0-inf) is presented in ng*hour/mL.
Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Cmax of RO5468924
Tidsramme: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Cmax is the maximum observed RO5468924 (the major pharmacologically active metabolite of alectinib) plasma concentration, presented in ng/mL.
Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for AUC(0-inf)
Tidsramme: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
AUC(0-inf) is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib) over time. The molecular weight adjusted M/P ratio (RO5468924/alectinib) for AUC(0-inf) is presented.
Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Molecular Weight Adjusted Metabolite to Parent (M/P) Ratio for Cmax
Tidsramme: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Cmax is the maximum observed plasma concentration of the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib). The molecular weight adjusted M/P ratio (RO5468924/alectinib) for Cmax is presented.
Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of Alectinib and RO5468924
Tidsramme: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
AUC(0-last) is the area under the alectinib and RO5468924 (major pharmacologically active metabolite of alectinib) plasma concentration time-curve from time zero to the last measured concentration. AUC is a measure of the plasma concentration of a drug over time. AUC(0-last) is presented in ng*hour/mL.
Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alectinib and RO5468924
Tidsramme: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
The Tmax is the time from alectinib administration to reach Cmax for alectinib and RO5468924 (the major pharmacologically active metabolite of alectinib).
Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Plasma Terminal Half-Life (t1/2) of Alectinib and RO5468924
Tidsramme: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Plasma terminal half-life is the time measured during drug elimination phase for the plasma drug concentration to decrease by one half. RO5468924 is the major pharmacologically active metabolite of alectinib.
Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Apparent Oral Clearance (CL/F) of Alectinib
Tidsramme: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Apparent Volume of Distribution (Vz/F) of Alectinib
Tidsramme: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction of drug absorbed.
Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Total Molar Concentration of Alectinib and RO5468924 as Derived by AUC(0-inf)
Tidsramme: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
AUC(0-inf) is the area under the alectinib + RO5468924 (major pharmacologically active metabolite of alectinib) molar plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the molar plasma concentration of the alectinib + RO5468924 over time. AUC(0-inf) is presented in nanomoles times (*) hour per liter (nmol*hour/L).
Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Total Molar Concentration of Alectinib and RO5468924 as Derived by Cmax
Tidsramme: Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period
Cmax is the maximum observed molar plasma concentration for alectinib + RO5468924 (major pharmacologically active metabolite of alectinib). Cmax is presented in nanomoles per liter (nmol/L).
Predose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours post alectinib-dose in each intervention period

Samarbeidspartnere og etterforskere

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

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. oktober 2013

Primær fullføring (Faktiske)

1. oktober 2013

Studiet fullført (Faktiske)

1. oktober 2013

Datoer for studieregistrering

Først innsendt

9. september 2013

Først innsendt som oppfylte QC-kriteriene

9. september 2013

Først lagt ut (Anslag)

12. september 2013

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

21. desember 2016

Siste oppdatering sendt inn som oppfylte QC-kriteriene

1. november 2016

Sist bekreftet

1. november 2016

Mer informasjon

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. .

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