Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib

Roche

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment

Treatments: Drug: Alectinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02621047

2015-002976-25 (EudraCT Number)

NP29783

Details and patient eligibility

About

This is a multicenter, non-randomized, single-dose, open-label study conducted in male and surgically sterile or post-menopausal female participants with stable chronic hepatic impairment and in healthy participants matched by age, gender, and body weight to assess the effect of hepatic impairment on the pharmacokinetics of alectinib.

Enrollment: 28 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

All Participants

• Body mass index between 18 to 35 kilograms per square meter (kg/m^2) inclusive and weight greater than (>) 50 kilograms (kg)
• Female participants must be surgically sterile or post-menopausal
• Male participants and their partners of child-bearing potential must be willing to use 2 effective methods of contraception, one of which must be a barrier method

Participants with Hepatic Impairment

• Documented chronic stable liver disease (Child-Pugh Class A, B or C)

Exclusion criteria

All Participants

• Pregnant or lactating women, males with female partners who are pregnant or lactating, or women of child bearing potential
• Positive test for drugs of abuse or alcohol
• Participation in an investigational drug or device study within 45 days or 5 half-lives (whichever time period is longer) or 6 months for biologic therapies prior to study drug administration
• History of hypersensitivity to any of the additives in the alectinib formulation
• Participants under judicial supervision, guardianship, or curatorship
• History of severe drug-related allergic reactions or drug-induced hepatotoxicity

Healthy Participants

• Use of any medications (prescription or over-the-counter), within 2 weeks or 5 half-lives (whichever longer) prior to study drug administration
• Use of any herbal supplements or any metabolic inducers within 4 weeks, or 5 half-lives (whichever is longer) prior to study drug administration

Participants with Hepatic Impairment

• Positive screening test for human immunodeficiency virus (HIV)
• History of liver transplantation
• Hepatocellular carcinoma or acute liver disease
• Severe ascites at screening or admission to the clinic
• Recent history (past 2 years) or current severe hepatic encephalopathy (Grade 3 or higher)
• Any evidence of progressive liver disease within the last 4 weeks
• Presence of surgically created or transjugular intrahepatic portal systemic shunts

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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28 participants in 3 patient groups

Alectinib: Moderate Hepatic Impairment

Experimental group

Description:

Participants with moderate hepatic impairment (based on Child-Pugh score) will receive alectinib at a single oral dose of 300 milligrams (mg) on Day 1.

Treatment:

Drug: Alectinib

Alectinib: Severe Hepatic Impairment

Experimental group

Description:

Participants with severe hepatic impairment (based on Child-Pugh score) will receive alectinib at a single oral dose of 300 mg on Day 1.

Treatment:

Drug: Alectinib

Alectinib: Normal Hepatic Function

Experimental group

Description:

Participants with normal hepatic function will receive alectinib at a single oral dose of 300 mg on Day 1.

Treatment:

Drug: Alectinib