Trial Outcomes & Findings for Pharmacokinetics of Sotorasib in Healthy Participants and Participants With Moderate or Severe Hepatic Impairment (NCT NCT04887064)
NCT ID: NCT04887064
Last Updated: 2024-04-19
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
20 participants
Primary outcome 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
Results posted on
2024-04-19
Participant Flow
Participants were enrolled at research centers in the United States from April 2021 to March 2022.
Participant milestones
| Measure |
Normal Hepatic Function
Participants with normal hepatic function (no impairment) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Moderate Hepatic Impairment
Participants with moderate hepatic function (Child-Pugh Class B at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Severe Hepatic Impairment
Participants with severe hepatic function (Child-Pugh Class C at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
|---|---|---|---|
|
Overall Study
STARTED
|
7
|
8
|
5
|
|
Overall Study
COMPLETED
|
7
|
8
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics of Sotorasib in Healthy Participants and Participants With Moderate or Severe Hepatic Impairment
Baseline characteristics by cohort
| Measure |
Normal Hepatic Function
n=7 Participants
Participants with normal hepatic function (no impairment) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic function (Child-Pugh Class B at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Severe Hepatic Impairment
n=5 Participants
Participants with severe hepatic function (Child-Pugh Class C at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
59.0 years
STANDARD_DEVIATION 7.35 • n=5 Participants
|
58.5 years
STANDARD_DEVIATION 5.66 • n=7 Participants
|
51.6 years
STANDARD_DEVIATION 7.37 • n=5 Participants
|
57.0 years
STANDARD_DEVIATION 7.10 • n=4 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
PRIMARY outcome
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 1Outcome measures
| Measure |
Normal Hepatic Function
n=7 Participants
Participants with normal hepatic function (no impairment) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic function (Child-Pugh Class B at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Severe Hepatic Impairment
n=5 Participants
Participants with severe hepatic function (Child-Pugh Class C at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Sotorasib
|
5080 ng/mL
Geometric Coefficient of Variation 108.5
|
4850 ng/mL
Geometric Coefficient of Variation 60.6
|
7250 ng/mL
Geometric Coefficient of Variation 15.7
|
PRIMARY outcome
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 1Outcome measures
| Measure |
Normal Hepatic Function
n=7 Participants
Participants with normal hepatic function (no impairment) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic function (Child-Pugh Class B at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Severe Hepatic Impairment
n=5 Participants
Participants with severe hepatic function (Child-Pugh Class C at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib
|
28700 h*ng/mL
Geometric Coefficient of Variation 87.8
|
21500 h*ng/mL
Geometric Coefficient of Variation 58.2
|
29900 h*ng/mL
Geometric Coefficient of Variation 12.6
|
PRIMARY outcome
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 1Outcome measures
| Measure |
Normal Hepatic Function
n=7 Participants
Participants with normal hepatic function (no impairment) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic function (Child-Pugh Class B at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Severe Hepatic Impairment
n=5 Participants
Participants with severe hepatic function (Child-Pugh Class C at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Sotorasib
|
29000 h*ng/mL
Geometric Coefficient of Variation 86.4
|
21700 h*ng/mL
Geometric Coefficient of Variation 58.2
|
30100 h*ng/mL
Geometric Coefficient of Variation 12.2
|
SECONDARY outcome
Timeframe: Day 1 to Day 8TEAEs 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.
Outcome measures
| Measure |
Normal Hepatic Function
n=7 Participants
Participants with normal hepatic function (no impairment) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic function (Child-Pugh Class B at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Severe Hepatic Impairment
n=5 Participants
Participants with severe hepatic function (Child-Pugh Class C at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
|---|---|---|---|
|
Number of Participants Who Experienced One or More Treatment Emergent Adverse Events (TEAEs)
|
1 Participants
|
2 Participants
|
1 Participants
|
SECONDARY outcome
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 1Outcome measures
| Measure |
Normal Hepatic Function
n=7 Participants
Participants with normal hepatic function (no impairment) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic function (Child-Pugh Class B at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Severe Hepatic Impairment
n=5 Participants
Participants with severe hepatic function (Child-Pugh Class C at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
|---|---|---|---|
|
Unbound Cmax (Cmax,u) of Sotorasib
|
183 ng/mL
Geometric Coefficient of Variation 240.8
|
400 ng/mL
Geometric Coefficient of Variation 110.9
|
1220 ng/mL
Geometric Coefficient of Variation 9.8
|
SECONDARY outcome
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 1Outcome measures
| Measure |
Normal Hepatic Function
n=7 Participants
Participants with normal hepatic function (no impairment) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic function (Child-Pugh Class B at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Severe Hepatic Impairment
n=5 Participants
Participants with severe hepatic function (Child-Pugh Class C at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
|---|---|---|---|
|
Unbound AUClast (AUClast,u) of Sotorasib
|
694 h*ng/mL
Geometric Coefficient of Variation 146.3
|
1320 h*ng/mL
Geometric Coefficient of Variation 71.0
|
4680 h*ng/mL
Geometric Coefficient of Variation 29.4
|
SECONDARY outcome
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 1Outcome measures
| Measure |
Normal Hepatic Function
n=7 Participants
Participants with normal hepatic function (no impairment) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic function (Child-Pugh Class B at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Severe Hepatic Impairment
n=5 Participants
Participants with severe hepatic function (Child-Pugh Class C at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
|---|---|---|---|
|
Unbound AUCinf (AUCinf,u) of Sotorasib
|
742 h*ng/mL
Geometric Coefficient of Variation 156.7
|
1340 h*ng/mL
Geometric Coefficient of Variation 69.6
|
4680 h*ng/mL
Geometric Coefficient of Variation 29.4
|
SECONDARY outcome
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 1Outcome measures
| Measure |
Normal Hepatic Function
n=7 Participants
Participants with normal hepatic function (no impairment) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic function (Child-Pugh Class B at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Severe Hepatic Impairment
n=5 Participants
Participants with severe hepatic function (Child-Pugh Class C at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
|---|---|---|---|
|
Unbound Apparent Total Plasma Clearance (CLu/F) of Sotorasib
|
1290 L/h
Geometric Coefficient of Variation 156.7
|
715 L/h
Geometric Coefficient of Variation 69.6
|
205 L/h
Geometric Coefficient of Variation 29.4
|
SECONDARY outcome
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 1Outcome measures
| Measure |
Normal Hepatic Function
n=7 Participants
Participants with normal hepatic function (no impairment) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Moderate Hepatic Impairment
n=8 Participants
Participants with moderate hepatic function (Child-Pugh Class B at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
Severe Hepatic Impairment
n=5 Participants
Participants with severe hepatic function (Child-Pugh Class C at screening) received a single oral 960 mg dose of sotorasib under fasted conditions.
|
|---|---|---|---|
|
Unbound Apparent Volume of Distribution During the Terminal Phase (Vz,u/F) of Sotorasib
|
7080 liters
Geometric Coefficient of Variation 275.6
|
3820 liters
Geometric Coefficient of Variation 115.2
|
928 liters
Geometric Coefficient of Variation 39.1
|
Adverse Events
Normal Hepatic Function
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Moderate Hepatic Impairment
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Severe Hepatic Impairment
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Normal Hepatic Function
n=7 participants at risk
Normal Hepatic Function
|
Moderate Hepatic Impairment
n=8 participants at risk
Moderate Hepatic Impairment
|
Severe Hepatic Impairment
n=5 participants at risk
Severe Hepatic Impairment
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/7 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
12.5%
1/8 • Number of events 1 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
0.00%
0/5 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
|
Gastrointestinal disorders
Constipation
|
14.3%
1/7 • Number of events 1 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
0.00%
0/8 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
0.00%
0/5 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/7 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
12.5%
1/8 • Number of events 1 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
0.00%
0/5 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/7 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
12.5%
1/8 • Number of events 1 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
0.00%
0/5 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/7 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
12.5%
1/8 • Number of events 1 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
0.00%
0/5 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/7 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
12.5%
1/8 • Number of events 1 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
0.00%
0/5 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
|
Investigations
Electrocardiogram qt prolonged
|
0.00%
0/7 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
0.00%
0/8 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
20.0%
1/5 • Number of events 1 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
|
Nervous system disorders
Sensory disturbance
|
0.00%
0/7 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
12.5%
1/8 • Number of events 1 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
0.00%
0/5 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/7 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
0.00%
0/8 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
20.0%
1/5 • Number of events 1 • Day 1 to Day 8
All participants who received 960 mg single oral dose of sotorasib, including participants with no hepatic impairment, moderate hepatic impairment and severe hepatic impairment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER