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

Solid Tumours Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02063204
• Other study ID #: D1532C00081
• Status: Completed
• Phase: Phase 1
• First received: February 13, 2014
• Last updated: June 29, 2015
• Start date: March 2014
• Est. completion date: July 2014

Study information

• Verified date: June 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

A study to assess the pharmacokinetics, safety and tolerability of Selumetinib (AZD6244, ARRY-142886) in subjects with renal impairment and healthy subjects

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 information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria all participants:

1. Male and female (non childbearing potential) subjects aged 18 years or more with suitable veins for cannulation or repeated venipuncture.

2. 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:

3. 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:

4. Stable renal function

Exclusion Criteria all participants:

1. Subjects of Japanese or non Japanese Asian ethnicity.

2. 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.

3. Subjects who smoke more than 10 cigarettes or the equivalent in tobacco per day

4. 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:

5. 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).

6. Acute coronary syndrome within 6 months prior to administration of the investigational product.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Solid Tumours

Intervention

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

Locations

Country	Name	City	State
United States	Research Site	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Description of the pharmacokinetic(PK) profile in terms of maximum observed plasma concentration (Cmax)	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	No
Primary	Description of PK profile in terms of area under plasma concentration-time curve from zero extrapolated to infinity (AUC)	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	No
Primary	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	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	No
Secondary	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	Yes
Secondary	Description of the PK profile in terms of time to reach maximum observed concentration administration (tmax)	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	No
Secondary	Description of PK profile in terms of area under the plasma concentration time curve from zero to 12 hours postdose (AUC[0-12])	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, and12h	No
Secondary	Description of PK profile in terms of terminal rate constant (?z), terminal elimination half-life (t1/2), apparent oral clearance (CL/F)	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	No
Secondary	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)	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	No
Secondary	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)	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	No
Secondary	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, ?z, AUC(0-12) and AUC(0-t)	These collection will be taken on visit 2 for the healthy volunteers and on visit 2 and 3 if the patients can produce urine	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	No
Secondary	Description of the PK profile in terms of the metabolite to parent AUC and Cmax ratios (MRAUC and MRCmax)	These samples will be taken on visit 2 for the healthy volunteers and on both visit 2 and visit 3	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	No
Secondary	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	No
Secondary	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])	This will only be taken at the visit when dose is given 1h before dialyse start	Sample taken predose, at 1h just before dialyse and at 5h after the end of the dialyse	No
Secondary	Description of the PK profile in terms of cumulative amount extracted during dialysis (Ad[1-5]), and dialysis clearance (CLD)	This will only be collected during visit 2 and only on end stage renal disease patients	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	No

External Links

•   CSR_Synopsis_D1532C00081.pdf