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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02063230

Enrollment

Registered

2014-02-14

Start date

2014-03-31

Completion date

2014-11-30

Last updated

2016-07-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Solid Tumors

Keywords

Phase I, healthy, pharmacokinetic, hepatic impairment

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.

Interventions

DRUGSelumetinib 50mg

HV and hepatic impaired patients with mild and moderat severity will recived selumetinib 50mg orally on day 1

DRUGSelumetinib 25mg

Severe (Child Pugh C) hepatic impaired patients will receive selumetinib 25mg orally on Day 1

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 130 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

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

Countries

United States

Participant flow

Participants by arm

Arm	Count
Mild Mild (Child Pugh A) hepatic impaired subjects (all subjects received Selumetinib 50 mg)	8
Moderate Moderate (Child Pugh B) hepatic impaired subjects). 6 subjects received Selumetinib 50 mg, 2 received Selumetinib 25mg	8
Severe Severe (Child Pugh C) hepatic impaired subjects. All subjects received Selumetinib 20mg.	8
Normal Healthy volunteers. All volunteers received Selumetinib 50mg.	8
Total	32

Baseline characteristics

Characteristic	Mild	Moderate	Severe	Normal	Total
Age, Continuous	55 Years STANDARD_DEVIATION 4	57 Years STANDARD_DEVIATION 5	55 Years STANDARD_DEVIATION 9	57 Years STANDARD_DEVIATION 7	56 Years STANDARD_DEVIATION 6
Sex: Female, Male Female	1 Participants	3 Participants	2 Participants	3 Participants	9 Participants
Sex: Female, Male Male	7 Participants	5 Participants	6 Participants	5 Participants	23 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	2 / 8	2 / 8	0 / 8	1 / 8
serious Total, serious adverse events	0 / 8	0 / 8	0 / 8	0 / 8