To Assess the Pharmacokinetics, Safety and Tolerability of Selumetinib in Renal Impaired Subjects and Healthy Subjects
- Registration Number
- NCT02063204
- Lead Sponsor
- AstraZeneca
- Brief Summary
A study to assess the pharmacokinetics, safety and tolerability of Selumetinib (AZD6244, ARRY-142886) in subjects with renal impairment and healthy subjects
- Detailed Description
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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description HV selumetinib Stage 1 selumetinib Healthy volunteer (HV)group to receive selumetinib 50mg (2x25mg) orally Selumetinib stage 2 selumetinib If deemed necessary patients with mild and/or moderate and/or severe renal impairment will recieve selumetinib 50mg(2x25mg) orally ESRD selumetinib Stage 1 selumetinib End stage renal disease (ESRD)patients to recieve selumetinib 50mg (2x25mg) orally
- Primary Outcome Measures
Name Time Method Description of the pharmacokinetic(PK) profile in terms of maximum observed plasma concentration (Cmax) 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
Description of PK profile in terms of area under plasma concentration-time curve from zero extrapolated to infinity (AUC) 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
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 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
- Secondary Outcome Measures
Name Time Method Description of the safety profile in terms of adverse events, physical examinations, ophthalmologic assessments, vital signs, clinical laboratory assessments and 12-lead electrocardiograms. From screening until follow up. Approximately 6 weeks for healthy volunteers and 8 weeks for renal patients Description of the PK profile in terms of time to reach maximum observed concentration administration (tmax) 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
Description of PK profile in terms of terminal rate constant (λz), terminal elimination half-life (t1/2), apparent oral clearance (CL/F) 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
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) 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
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) 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
Description of PK profile in terms of area under the plasma concentration time curve from zero to 12 hours postdose (AUC[0-12]) Samples taken at predose, 30min, 1h, 1h30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h,6h,7h,8h, and12h This will be taken at visit 2 for Healthy volunteers and at visit 2 and 3 for patients with end stage renal disease
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) 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 These collection will be taken on visit 2 for the healthy volunteers and on visit 2 and 3 if the patients can produce urine
Description of the PK profile in terms of the metabolite to parent AUC and Cmax ratios (MRAUC and MRCmax) 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 These samples will be taken on visit 2 for the healthy volunteers and on both visit 2 and visit 3
Description of the PK profile in terms of Ae, fe, and CLR for N-desmethyl selumetinib (and the amide metabolite, if deemed appropriate) 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 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]) Sample taken predose, at 1h just before dialyse and at 5h after the end of the dialyse This will only be taken at the visit when dose is given 1h before dialyse start
Description of the PK profile in terms of cumulative amount extracted during dialysis (Ad[1-5]), and dialysis clearance (CLD) 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 This will only be collected during visit 2 and only on end stage renal disease patients
Trial Locations
- Locations (1)
Research Site
🇺🇸Orlando, Florida, United States