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

Study Overview
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Brief Summary
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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.

Official Title
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An Open-label Single-dose Study to Evaluate the Pharmacokinetics of Sotorasib in Healthy Subjects and Subjects With Moderate or Severe Hepatic Impairment

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: Sotorasib


Participation Criteria
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Eligibility Criteria
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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

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: Normal Hepatic Function<br> | Drug: Sotorasib<br>* Sotorasib will be administered as an oral tablet.<br>* Other names: AMG 510;|
| Experimental: Moderate Hepatic Impairment<br> | Drug: Sotorasib<br>* Sotorasib will be administered as an oral tablet.<br>* Other names: AMG 510;|
| Experimental: Severe Hepatic Impairment<br> | Drug: Sotorasib<br>* Sotorasib will be administered as an oral tablet.<br>* Other names: AMG 510;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Sotorasib |  | Day 1 to Day 8 | 
| Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of Sotorasib |  | Day 1 to Day 8 | 
| Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Sotorasib |  | Day 1 to Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with a Treatment-emergent Adverse Event (TEAE) |  | Day 1 to Day 8 | 
| Number of Participants with a Clinically Significant Change from Baseline in Clinical Laboratory Evaluations |  | Baseline to Day 8 | 
| Number of Participants with a Clinically Significant Change from Baseline in 12-lead Electrocardiograms (ECGs) |  | Baseline to Day 8 | 
| Number of Participants with a Clinically Significant Change from Baseline in Vital Signs |  | Baseline to Day 8 | 
| Unbound Maximum Observed Plasma Concentration (Cmax,u) of Sotorasib |  | Day 1 to Day 8 | 
| Unbound Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast,u) of Sotorasib |  | Day 1 to Day 8 | 
| Unbound Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf,u) of Sotorasib |  | Day 1 to Day 8 | 
| Unbound Apparent Total Plasma Clearance (CLu/F) of Sotorasib |  | Day 1 to Day 8 | 
| Unbound Apparent Volume of Distribution During the Terminal Phase (Vz,u/F) of Sotorasib |  | Day 1 to Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic Impairment, Sotorasib