pharmacokinetics of sotorasib in healthy participants and participants with moderate or severe hepatic impairment

Conditions: Hepatic Impairment

Summary: 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.


Eligibility 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

Keywords: hepatic impairment sotorasib