Skip to main content
OpenTrials
Completed

NCT Number: NCT02063204

To Assess the Pharmacokinetics, Safety and Tolerability of Selumetinib in Renal Impaired Subjects 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

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Solid Tumours Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Male Urogenital Diseases Renal Insufficiency Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Research Site

Orlando, Florida, United States

About this study

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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Selumetinib

Drug

selumetinib 50 mg (2x25mg) administered by mouth as capsules

Primary outcomes

  1. Description of the pharmacokinetic(PK) profile in terms of maximum observed plasma concentration (Cmax)

    Time frame: 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

  2. Description of PK profile in terms of area under plasma concentration-time curve from zero extrapolated to infinity (AUC)

    Time frame: 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

  3. 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

    Time frame: 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 outcomes

  1. Description of the safety profile in terms of adverse events, physical examinations, ophthalmologic assessments, vital signs, clinical laboratory assessments and 12-lead electrocardiograms.

    Time frame: From screening until follow up. Approximately 6 weeks for healthy volunteers and 8 weeks for renal patients

  2. Description of the PK profile in terms of time to reach maximum observed concentration administration (tmax)

    Time frame: 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

  3. Description of PK profile in terms of area under the plasma concentration time curve from zero to 12 hours postdose (AUC[0-12])

    Time frame: 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

  4. Description of PK profile in terms of terminal rate constant (λz), terminal elimination half-life (t1/2), apparent oral clearance (CL/F)

    Time frame: 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

  5. 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)

    Time frame: 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

  6. 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)

    Time frame: 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

  7. 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)

    Time frame: 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

  8. Description of the PK profile in terms of the metabolite to parent AUC and Cmax ratios (MRAUC and MRCmax)

    Time frame: 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

  9. Description of the PK profile in terms of Ae, fe, and CLR for N-desmethyl selumetinib (and the amide metabolite, if deemed appropriate)

    Time frame: 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

  10. 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])

    Time frame: 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

  11. Description of the PK profile in terms of cumulative amount extracted during dialysis (Ad[1-5]), and dialysis clearance (CLD)

    Time frame: 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

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

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

Important dates

Study start
2014
Primary completion
2014
Study completion
2014
First posted
Feb 14, 2014
Registry last updated
Jun 30, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.