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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: Selumetinib 50mg
* Drug: Selumetinib 25mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for all participants: 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: 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: 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: Subjects of Japanese or non-Japanese Asian ethnicity 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. Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of the investigational product Subjects who smoke more than 10 cigarettes or the equivalent in tobacco per day. Exclusion criteria for hepatic impaired patients only Undergone liver transplantation. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, healthy, pharmacokinetic, hepatic impairment