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

Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT04887064
Collaborator
(none)
20
Enrollment
5
Locations
3
Arms
9.9
Actual Duration (Months)
4
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
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
Actual Study Start Date :
May 12, 2021
Actual Primary Completion Date :
Mar 9, 2022
Actual Study Completion Date :
Mar 9, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Normal Hepatic Function

Drug: Sotorasib
Sotorasib will be administered as an oral tablet.
Other Names:
  • AMG 510
  • Experimental: Moderate Hepatic Impairment

    Drug: Sotorasib
    Sotorasib will be administered as an oral tablet.
    Other Names:
  • AMG 510
  • Experimental: Severe Hepatic Impairment

    Drug: Sotorasib
    Sotorasib will be administered as an oral tablet.
    Other Names:
  • AMG 510
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Observed Plasma Concentration (Cmax) of Sotorasib [Day 1 to Day 8]

    2. Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of Sotorasib [Day 1 to Day 8]

    3. Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Sotorasib [Day 1 to Day 8]

    Secondary Outcome Measures

    1. Number of Participants with a Treatment-emergent Adverse Event (TEAE) [Day 1 to Day 8]

    2. Number of Participants with a Clinically Significant Change from Baseline in Clinical Laboratory Evaluations [Baseline to Day 8]

    3. Number of Participants with a Clinically Significant Change from Baseline in 12-lead Electrocardiograms (ECGs) [Baseline to Day 8]

    4. Number of Participants with a Clinically Significant Change from Baseline in Vital Signs [Baseline to Day 8]

    5. Unbound Maximum Observed Plasma Concentration (Cmax,u) of Sotorasib [Day 1 to Day 8]

    6. 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]

    7. Unbound Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf,u) of Sotorasib [Day 1 to Day 8]

    8. Unbound Apparent Total Plasma Clearance (CLu/F) of Sotorasib [Day 1 to Day 8]

    9. Unbound Apparent Volume of Distribution During the Terminal Phase (Vz,u/F) of Sotorasib [Day 1 to Day 8]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes

    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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Orange County Research CenterTustinCaliforniaUnited States92780
    2Clinical Pharmacology Of Miami LLCMiamiFloridaUnited States33014
    3Orlando Clinical Research CenterOrlandoFloridaUnited States32809
    4American Research CorporationSan AntonioTexasUnited States78215
    5Pinnacle Clinical Research - San AntonioSan AntonioTexasUnited States78229

    Sponsors and Collaborators

    • Amgen

    Investigators

    • Study Director: MD, Amgen

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT04887064
    Other Study ID Numbers:
    • 20200362
    First Posted:
    May 14, 2021
    Last Update Posted:
    Apr 4, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Amgen
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 4, 2022