To Assess the Pharmacokinetics, Safety and Tolerability of Selumetinib in Renal Impaired Subjects and Healthy Subjects
29 juni 2015 bijgewerkt door: AstraZeneca
An Open Label Comparative Study of the Pharmacokinetics, Safety and Tolerability of Selumetinib (AZD6244, ARRY 142886) (Hyd Sulfate) Following a Single Oral Dose in Subjects With Renal Impairment and Healthy Subjects
A study to assess the pharmacokinetics, safety and tolerability of Selumetinib (AZD6244, ARRY-142886) in subjects with renal impairment and healthy subjects
Studie Overzicht
Gedetailleerde beschrijving
An open label study to assess the pharmacokinetics, safety and tolerability of 50 mg single oral dose of Selumetinib (AZD6244, ARRY-142886) in subjects with renal impairment and healthy subjects
Studietype
Ingrijpend
Inschrijving (Werkelijk)
24
Fase
- Fase 1
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Florida
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Orlando, Florida, Verenigde Staten
- Research Site
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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 en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
Inclusion Criteria all participants:
- Male and female (non childbearing potential) subjects aged 18 years or more with suitable veins for cannulation or repeated venipuncture.
Have a weight of at least 50 kg (110 lbs) and body mass index (BMI) between 18 and 40 kg/m2, inclusive.
Inclusion healthy volunteers only:
Must be in good health as determined by a medical history, physical examination, 12 lead ECG, clinical laboratory evaluations, and an ophthalmic examination performed before the administration of the investigational product.
Inclusion renal impaired patients only:
- Stable renal function
Exclusion Criteria all participants:
- Subjects of Japanese or non Japanese Asian ethnicity.
- Any one parent or grandparent (maternal or paternal) is Japanese or non-Japanese Asian (e.g. China, Taiwan, Korea, Philippines, Thailand, Vietnam and Malaysia). Asian Indians are acceptable.
- Subjects who smoke more than 10 cigarettes or the equivalent in tobacco per day
In the opinion of the investigator, any evidence of additional severe or uncontrolled systemic disease (eg, currently unstable or uncompensated hepatic, cardiovascular, or respiratory disease) or laboratory finding, physical examination, hematology, clinical chemistry, urinalysis, vital signs, or 12-lead ECG that makes it undesirable for the subject to participate in the study.
Exclusion renal impaired patients only:
- Subjects with an active renal transplant (subjects who have previously received a renal transplant and are currently undergoing dialysis due to transplant failure may be enrolled).
- Acute coronary syndrome within 6 months prior to administration of the investigational product.
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: Fundamentele wetenschap
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: HV selumetinib Stage 1
Healthy volunteer (HV)group to receive selumetinib 50mg (2x25mg) orally
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selumetinib 50 mg (2x25mg) administered by mouth as capsules
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Experimenteel: ESRD selumetinib Stage 1
End stage renal disease (ESRD)patients to recieve selumetinib 50mg (2x25mg) orally
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selumetinib 50 mg (2x25mg) administered by mouth as capsules
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Experimenteel: Selumetinib stage 2
If deemed necessary patients with mild and/or moderate and/or severe renal impairment will recieve selumetinib 50mg(2x25mg) orally
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selumetinib 50 mg (2x25mg) administered by mouth as capsules
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Description of the pharmacokinetic(PK) profile in terms of maximum observed plasma concentration (Cmax)
Tijdsspanne: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of area under plasma concentration-time curve from zero extrapolated to infinity (AUC)
Tijdsspanne: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of area under plasma concentration-time curve to time of last measurable concentration (AUC[0-t]) for selumetinib if AUC is not reportable in more than 80% of subjects
Tijdsspanne: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Description of the safety profile in terms of adverse events, physical examinations, ophthalmologic assessments, vital signs, clinical laboratory assessments and 12-lead electrocardiograms.
Tijdsspanne: From screening until follow up. Approximately 6 weeks for healthy volunteers and 8 weeks for renal patients
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From screening until follow up. Approximately 6 weeks for healthy volunteers and 8 weeks for renal patients
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Description of the PK profile in terms of time to reach maximum observed concentration administration (tmax)
Tijdsspanne: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of area under the plasma concentration time curve from zero to 12 hours postdose (AUC[0-12])
Tijdsspanne: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h, and12h
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This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h, and12h
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Description of PK profile in terms of terminal rate constant (λz), terminal elimination half-life (t1/2), apparent oral clearance (CL/F)
Tijdsspanne: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of apparent volume of distribution at steady state (Vss/F) and apparent volume of distribution during the terminal phase (Vz/F)
Tijdsspanne: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
|
This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
|
Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of mean residence time (MRT) and fraction unbound (fu), free Cmax (Cmax, u), free AUC (AUCu), free AUC(0-t) (AUC[0-t],u) and unbound CL/F (CL/Fu)
Tijdsspanne: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
|
This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
|
Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of PK profile in terms of the amount of drug excreted in urine (Ae) the fraction of dose excreted in urine (fe), renal clearance (CLR) for selumetinib and AUC, Cmax, tmax, t1/2, λz, AUC(0-12) and AUC(0-t)
Tijdsspanne: The urine collection intervals will be from -12 to 0 (predose), and 0 to 6, 6 to 12, 12 to 24, 24 to 36, 36 to
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These collection will be taken on visit 2 for the healthy volunteers and on visit 2 and 3 if the patients can produce urine
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The urine collection intervals will be from -12 to 0 (predose), and 0 to 6, 6 to 12, 12 to 24, 24 to 36, 36 to
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Description of the PK profile in terms of the metabolite to parent AUC and Cmax ratios (MRAUC and MRCmax)
Tijdsspanne: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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These samples will be taken on visit 2 for the healthy volunteers and on both visit 2 and visit 3
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of the PK profile in terms of Ae, fe, and CLR for N-desmethyl selumetinib (and the amide metabolite, if deemed appropriate)
Tijdsspanne: Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h,12h,18h,24h,36h,48h and 76h
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Description of the PK profile in terms of time-matched area under the plasma concentration time curve from 1 to 5 hours postdose (AUC[1-5])
Tijdsspanne: Sample taken predose, at 1h just before dialyse and at 5h after the end of the dialyse
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This will only be taken at the visit when dose is given 1h before dialyse start
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Sample taken predose, at 1h just before dialyse and at 5h after the end of the dialyse
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Description of the PK profile in terms of cumulative amount extracted during dialysis (Ad[1-5]), and dialysis clearance (CLD)
Tijdsspanne: Samples taken from dialysate collections over 1 hour intervals throughout the entire (approximately 4 hours) dialysis period ie, 0 to 1, 1 to 2, 2 to 3, 3
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This will only be collected during visit 2 and only on end stage renal disease patients
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Samples taken from dialysate collections over 1 hour intervals throughout the entire (approximately 4 hours) dialysis period ie, 0 to 1, 1 to 2, 2 to 3, 3
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Onderzoekers
- Hoofdonderzoeker: Thomas C Marbury, MD, Orlando Clinical Research Centre, US
- Studie directeur: Ian Smith, MD, Astrazeneca United kingdom
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.
Nuttige links
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 maart 2014
Primaire voltooiing (Werkelijk)
1 juli 2014
Studie voltooiing (Werkelijk)
1 juli 2014
Studieregistratiedata
Eerst ingediend
13 februari 2014
Eerst ingediend dat voldeed aan de QC-criteria
13 februari 2014
Eerst geplaatst (Schatting)
14 februari 2014
Updates van studierecords
Laatste update geplaatst (Schatting)
30 juni 2015
Laatste update ingediend die voldeed aan QC-criteria
29 juni 2015
Laatst geverifieerd
1 juni 2015
Meer informatie
Termen gerelateerd aan deze studie
Andere studie-ID-nummers
- D1532C00081
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