Clinical trial NCT04887064: Pharmacokinetics of Sotorasib in Healthy Participants and Participants With Moderate or Severe Hepatic Impairment
Official title: An Open-label Single-dose Study to Evaluate the Pharmacokinetics of Sotorasib in Healthy Subjects and Subjects With Moderate or Severe Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Hepatic Impairment
Sotorasib
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2021-05-14
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Sotorasib
timeFrame: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose following administration of sotorasib on Day 1
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib
timeFrame: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose following administration of sotorasib on Day 1
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Sotorasib
timeFrame: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose following administration of sotorasib on Day 1
Secondary outcomes:
measure: Number of Participants Who Experienced One or More Treatment Emergent Adverse Events (TEAEs)
timeFrame: Day 1 to Day 8
measure: Unbound Cmax (Cmax,u) of Sotorasib
timeFrame: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose following administration of sotorasib on Day 1
measure: Unbound AUClast (AUClast,u) of Sotorasib
timeFrame: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose following administration of sotorasib on Day 1
measure: Unbound AUCinf (AUCinf,u) of Sotorasib
timeFrame: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose following administration of sotorasib on Day 1
measure: Unbound Apparent Total Plasma Clearance (CLu/F) of Sotorasib
timeFrame: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose following administration of sotorasib on Day 1
measure: Unbound Apparent Volume of Distribution During the Terminal Phase (Vz,u/F) of Sotorasib
timeFrame: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose following administration of sotorasib on Day 1
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Miami
country: United States
facility: Clinical Pharmacology Of Miami LLC
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: San Antonio
country: United States
facility: American Research Corporation
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research - San Antonio
state: Texas
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: