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

Hepatic Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04887064
• Other study ID #: 20200362
• Status: Completed
• Phase: Phase 1
• Start date: April 22, 2021
• Est. completion date: March 9, 2022

Study information

• Verified date: January 2023
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 9, 2022
• Est. primary completion date: March 9, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Sotorasib
Sotorasib will be administered as an oral tablet.

Locations

Country	Name	City	State
United States	Clinical Pharmacology Of Miami LLC	Miami	Florida
United States	Orlando Clinical Research Center	Orlando	Florida
United States	American Research Corporation	San Antonio	Texas
United States	Pinnacle Clinical Research - San Antonio	San Antonio	Texas
United States	Orange County Research Center	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of Sotorasib		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
Primary	Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib		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
Primary	Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Sotorasib		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	Number of Participants Who Experienced One or More Treatment Emergent Adverse Events (TEAEs)	TEAEs were defined as any adverse events (AEs) that started during or after dosing, or started prior to dosing and increased in severity after dosing.; Any clinically significant changes in clinical laboratory evaluations, 12-lead electrocardiograms (ECGs) and vital signs were also reported as TEAEs.	Day 1 to Day 8
Secondary	Unbound Cmax (Cmax,u) of Sotorasib		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	Unbound AUClast (AUClast,u) of Sotorasib		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	Unbound AUCinf (AUCinf,u) of Sotorasib		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	Unbound Apparent Total Plasma Clearance (CLu/F) of Sotorasib		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	Unbound Apparent Volume of Distribution During the Terminal Phase (Vz,u/F) of Sotorasib		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

External Links

•   AmgenTrials clinical trials website