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

Primary Purpose

Hepatic Impairment

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Sotorasib

About this trial

This is an interventional basic science trial for Hepatic Impairment focused on measuring Hepatic Impairment, Sotorasib

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)Accepts Healthy Volunteers

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

Sites / Locations

Orange County Research Center
Clinical Pharmacology Of Miami LLC
Orlando Clinical Research Center
American Research Corporation
Pinnacle Clinical Research - San Antonio

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Normal Hepatic Function

Moderate Hepatic Impairment

Severe Hepatic Impairment

Arm Description

Outcomes

Primary Outcome Measures

Maximum Observed Plasma Concentration (Cmax) of Sotorasib

Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of Sotorasib

Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Sotorasib

Secondary Outcome Measures

Number of Participants with a Treatment-emergent Adverse Event (TEAE)

Number of Participants with a Clinically Significant Change from Baseline in Clinical Laboratory Evaluations

Number of Participants with a Clinically Significant Change from Baseline in 12-lead Electrocardiograms (ECGs)

Number of Participants with a Clinically Significant Change from Baseline in Vital Signs

Unbound Maximum Observed Plasma Concentration (Cmax,u) of Sotorasib

Unbound Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast,u) of Sotorasib

Unbound Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf,u) of Sotorasib

Unbound Apparent Total Plasma Clearance (CLu/F) of Sotorasib

Unbound Apparent Volume of Distribution During the Terminal Phase (Vz,u/F) of Sotorasib

Full Information

NCT ID

NCT04887064

First Posted

May 11, 2021

Last Updated

November 9, 2022

Sponsor

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT04887064

Brief Title

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

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Completed

Study Start Date

May 12, 2021 (Actual)

Primary Completion Date

March 9, 2022 (Actual)

Study Completion Date

March 9, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatic Impairment

Keywords

Hepatic Impairment, Sotorasib

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Normal Hepatic Function

Arm Type

Experimental

Arm Title

Moderate Hepatic Impairment

Arm Type

Experimental

Arm Title

Severe Hepatic Impairment

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Sotorasib

Other Intervention Name(s)

AMG 510

Intervention Description

Sotorasib will be administered as an oral tablet.

Primary Outcome Measure Information:

Title

Maximum Observed Plasma Concentration (Cmax) of Sotorasib

Time Frame

Day 1 to Day 8

Title

Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of Sotorasib

Time Frame

Day 1 to Day 8

Title

Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Sotorasib

Time Frame

Day 1 to Day 8

Secondary Outcome Measure Information:

Title

Number of Participants with a Treatment-emergent Adverse Event (TEAE)

Time Frame

Day 1 to Day 8

Title

Number of Participants with a Clinically Significant Change from Baseline in Clinical Laboratory Evaluations

Time Frame

Baseline to Day 8

Title

Number of Participants with a Clinically Significant Change from Baseline in 12-lead Electrocardiograms (ECGs)

Time Frame

Baseline to Day 8

Title

Number of Participants with a Clinically Significant Change from Baseline in Vital Signs

Time Frame

Baseline to Day 8

Title

Unbound Maximum Observed Plasma Concentration (Cmax,u) of Sotorasib

Time Frame

Day 1 to Day 8

Title

Unbound Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast,u) of Sotorasib

Time Frame

Day 1 to Day 8

Title

Unbound Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf,u) of Sotorasib

Time Frame

Day 1 to Day 8

Title

Unbound Apparent Total Plasma Clearance (CLu/F) of Sotorasib

Time Frame

Day 1 to Day 8

Title

Unbound Apparent Volume of Distribution During the Terminal Phase (Vz,u/F) of Sotorasib

Time Frame

Day 1 to Day 8

10. Eligibility

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Organizational Affiliation

Amgen

Official's Role

Study Director

Facility Information:

Facility Name

Orange County Research Center

City

Tustin

State/Province

California

ZIP/Postal Code

92780

Country

United States

Facility Name

Clinical Pharmacology Of Miami LLC

City

Miami

State/Province

Florida

ZIP/Postal Code

33014

Country

United States

Facility Name

Orlando Clinical Research Center

City

Orlando

State/Province

Florida

ZIP/Postal Code

32809

Country

United States

Facility Name

American Research Corporation

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78215

Country

United States

Facility Name

Pinnacle Clinical Research - San Antonio

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

IPD Sharing Time Frame

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

IPD Sharing Access Criteria

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

IPD Sharing URL

http://www.amgen.com/datasharing

Links:

URL

http://www.amgentrials.com

Description

AmgenTrials clinical trials website

Learn more about this trial

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

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