Clinical trial NCT02063230: To Assess the Pharmacokinetics, Safety and Tolerability of Selumetinib in Patients With Hepatic Impairment and Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Phase I, healthy, pharmacokinetic, hepatic impairment
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-02-14
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

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.

Eligibility criteria: 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. -

Primary outcomes:
measure: AUC (0 to Infinity) of Total Selumetinib
timeFrame: 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
measure: Cmax of Total Selumetinib
timeFrame: 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
measure: Dose Normalized AUC, Total Selumetinib
timeFrame: 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
measure: Dose Normalized Cmax, Total Selumetinib
timeFrame: 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
measure: Dose Normalized AUC, Unbound Selumetinib
timeFrame: 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
measure: Dose Normalized Cmax, Unbound Selumetinib
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Research Site
state: Florida
Study officials:
affiliation: Orlando Clinical Research Center, 5055 S Orange Avenue, Orlando, Florida, United States.
name: Thomas C Marbury, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Astrazeneca, UK
name: Ian Smith, MD
role: STUDY_DIRECTOR
References: