Pharmacokinetics of Sotorasib in Healthy Participants and Participants With Moderate or Severe Hepatic Impairment
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 Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Normal Hepatic Function
|
Drug: Sotorasib
Sotorasib will be administered as an oral tablet.
Other Names:
|
| Experimental: Moderate Hepatic Impairment
|
Drug: Sotorasib
Sotorasib will be administered as an oral tablet.
Other Names:
|
| Experimental: Severe Hepatic Impairment
|
Drug: Sotorasib
Sotorasib will be administered as an oral tablet.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum Observed Plasma Concentration (Cmax) of Sotorasib [Day 1 to Day 8]
- Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of Sotorasib [Day 1 to Day 8]
- Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Sotorasib [Day 1 to Day 8]
Secondary Outcome Measures
- Number of Participants with a Treatment-emergent Adverse Event (TEAE) [Day 1 to Day 8]
- Number of Participants with a Clinically Significant Change from Baseline in Clinical Laboratory Evaluations [Baseline to Day 8]
- Number of Participants with a Clinically Significant Change from Baseline in 12-lead Electrocardiograms (ECGs) [Baseline to Day 8]
- Number of Participants with a Clinically Significant Change from Baseline in Vital Signs [Baseline to Day 8]
- Unbound Maximum Observed Plasma Concentration (Cmax,u) of Sotorasib [Day 1 to Day 8]
- 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]
- Unbound Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf,u) of Sotorasib [Day 1 to Day 8]
- Unbound Apparent Total Plasma Clearance (CLu/F) of Sotorasib [Day 1 to Day 8]
- Unbound Apparent Volume of Distribution During the Terminal Phase (Vz,u/F) of Sotorasib [Day 1 to Day 8]
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Orange County Research Center | Tustin | California | United States | 92780 |
| 2 | Clinical Pharmacology Of Miami LLC | Miami | Florida | United States | 33014 |
| 3 | Orlando Clinical Research Center | Orlando | Florida | United States | 32809 |
| 4 | American Research Corporation | San Antonio | Texas | United States | 78215 |
| 5 | Pinnacle Clinical Research - San Antonio | San Antonio | Texas | United States | 78229 |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 20200362