Pharmacokinetics of Sotorasib in Healthy Participants and Participants With Moderate or Severe Hepatic Impairment

Amgen

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment

Treatments: Drug: Sotorasib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04887064

20200362

Details and patient eligibility

About

The main purpose of the study is to evaluate the pharmacokinetics (PK) of a single oral dose of sotorasib administered in participants with moderate or severe hepatic impairment compared to participants with normal hepatic function.

Enrollment: 20 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria

All Participants

• Participant has provided informed consent before initiation of any study-specific activities/procedures
• Participants between 18 and 70 years of age
• Body mass index between 18 and 38 kg/m^2
• Females of nonchildbearing potential defined as permanently sterile or postmenopausal

Participants with Normal Hepatic Function

• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations

Participants with Hepatic Impairment

• Child-Pugh B or C classification with clinical laboratory values and clinical examination findings
• Documented medical history of chronic liver disease

Key Exclusion Criteria

All Participants

• Female participants with a positive pregnancy test at Screening or Check-in
• Male participants with a pregnant partner or partner planning to become pregnant who are unwilling to practice abstinence or use a condom for 7 days after dosing
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
• Participant has received a dose of an investigational drug (new chemical entity) within the past 30 days or 5 half-lives, whichever is longer, prior to Check-in
• Use of any over-the-counter or prescription medications within 30 days or 5 half-lives (whichever is longer)
• All herbal medicines vitamins, and supplements consumed by the subject within the 30 days prior to enrollment
• Alcohol consumption from 48 hours prior to Check-in
• Positive test for illicit drugs, cotinine (tobacco or nicotine use), and/or alcohol use at Check-in
• Positive human immunodeficiency virus test at Screening

Participants with Normal Hepatic Function

• Positive hepatitis B or hepatitis C panel at Screening. Subjects whose results are compatible with prior immunity (vaccination or prior infection) may be included
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > upper limit of normal (ULN) at Screening or Check-in
• Total bilirubin levels > ULN at Screening or Check-in
• A QT interval corrected for heart rate based on the Fridericia correction (QTcF) interval > 450 msec in male subjects or > 470 msec in female subjects or history/evidence of long QT syndrome at Screening or Check-in, confirmed by calculating the mean of the original value and 2 repeats

Participants with Hepatic Impairment

• Values outside the normal range for liver function tests that are not consistent with their hepatic condition, as determined by the Investigator (or designee)
• A QTcF interval > 470 msec in male subjects or > 480 msec in female subjects at Screening or Check-in, confirmed by calculating the mean of the original value and 2 repeats
• Use of a new medication, or a change in dose, for the treatment, or worsening of, hepatic encephalopathy within 30 days prior to Check-in
• Presence of a portosystemic shunt
• Evidence of severe ascites

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 3 patient groups

Normal Hepatic Function

Experimental group

Treatment:

Drug: Sotorasib

Moderate Hepatic Impairment

Experimental group

Treatment:

Drug: Sotorasib

Severe Hepatic Impairment

Experimental group

Treatment:

Drug: Sotorasib