To Assess the Pharmacokinetics, Safety and Tolerability of Selumetinib in Patients With Hepatic Impairment and Healthy Subjects

An Open-label, Comparative Study to Assess the Pharmacokinetics, Safety and Tolerability of Selumetinib (AZD6244, ARRY-142886) (Hyd-Sulfate) Following Single Oral Dosing to Healthy Subjects and to Subjects With Mild, Moderate, and Severe Hepatic Impairment

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

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Selumetinib 50mg; Drug: Selumetinib 25mg

Detailed Description

An open label study to assess the pharmcokinetics, safety and tolerability of a single dose of Selumetinib (AZD6244, ARRY-142886) in patients with hepatic impairment and healthy subjects.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria for all participants:

1. Subjects will be males or females (non-childbearing potential) aged 18 years or more and with a weight of at least 45 kg and a BMI between 18 and 40 kg/m2 inclusive.

   Inclusion Critera only for hepatic impaired patients:

2. Subjects with stable liver cirrhosis and hepatic impairment for at least 3 months prior to the start of the study.

   Inclusion Criteria only for healthy volunteers:

3. Subjects 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.

Exclusion Criteria for 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 (eg, China, Taiwan, Korea, Philippines, Thailand, Vietnam, and Malaysia). Asian Indians are acceptable.
3. Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of the investigational product

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

   Exclusion criteria for hepatic impaired patients only

5. Undergone liver transplantation. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selumetinib HV; Healthy volunteers (HV)	Drug: Selumetinib 50mg; HV and hepatic impaired patients with mild and moderat severity will recived selumetinib 50mg orally on day 1
Experimental: Selumetinib mild impairment; Mild (Child Pugh A) hepatic impaired patients	Drug: Selumetinib 50mg; HV and hepatic impaired patients with mild and moderat severity will recived selumetinib 50mg orally on day 1
Experimental: Selumetinib moderate impairment; Moderate (Child Pugh B) hepatic impaired patients	Drug: Selumetinib 50mg; HV and hepatic impaired patients with mild and moderat severity will recived selumetinib 50mg orally on day 1
Experimental: Selumetinib severe impairment; Severe (Child Pugh C) hepatic impairment patients	Drug: Selumetinib 25mg; Severe (Child Pugh C) hepatic impaired patients will receive selumetinib 25mg orally on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC (0 to Infinity) of Total Selumetinib	0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post dose
Cmax of Total Selumetinib	0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post dose
Dose Normalized AUC, Total Selumetinib	0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post dose
Dose Normalized Cmax, Total Selumetinib	0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post dose
Dose Normalized AUC, Unbound Selumetinib	0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post dose
Dose Normalized Cmax, Unbound Selumetinib	0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post dose

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Thomas C Marbury, MD, Orlando Clinical Research Center, 5055 S Orange Avenue, Orlando, Florida, United States.; Study Director: Ian Smith, MD, Astrazeneca, UK

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: February 13, 2014
• First Submitted That Met QC Criteria: February 13, 2014
• First Posted (Estimate): February 14, 2014

Study Record Updates

• Last Update Posted (Estimate): July 21, 2016
• Last Update Submitted That Met QC Criteria: June 21, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Phase I, healthy, pharmacokinetic, hepatic impairment
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: D1532C00082