NCT04887064

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

Completed Phase 1 Results posted Last updated 19 April 2024

What this trial tests

Phase 1 trial testing Sotorasib in Hepatic Impairment in 20 participants. Completed in 9 March 2022.

Timeline

22 April 2021

Primary endpoint
9 March 2022

9 March 2022

Quick facts

Lead sponsor	Amgen
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	basic science
Enrollment	20
Start date	22 April 2021
Primary completion	9 March 2022
Estimated completion	9 March 2022
Sites	5 locations across United States

Drugs / interventions tested

• Sotorasib (SOTORASIB) — full drug profile →

Conditions studied

• Hepatic Impairment — all drugs for Hepatic Impairment →

Sponsor

Amgen — full company profile →

Who can join

Adults 18 to 70, any sex, with Hepatic Impairment. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Observed Plasma Concentration (Cmax) of Sotorasib Primary · 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

Group	Value	95% CI
Normal Hepatic Function	5080	± 108.5
Moderate Hepatic Impairment	4850	± 60.6
Severe Hepatic Impairment	7250	± 15.7

Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib Primary · 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

Group	Value	95% CI
Normal Hepatic Function	28700	± 87.8
Moderate Hepatic Impairment	21500	± 58.2
Severe Hepatic Impairment	29900	± 12.6

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

Group	Value	95% CI
Normal Hepatic Function	29000	± 86.4
Moderate Hepatic Impairment	21700	± 58.2
Severe Hepatic Impairment	30100	± 12.2

Number of Participants Who Experienced One or More Treatment Emergent Adverse Events (TEAEs) Secondary · Day 1 to Day 8

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.

Group	Value	95% CI
Normal Hepatic Function	1
Moderate Hepatic Impairment	2
Severe Hepatic Impairment	1

Unbound Cmax (Cmax,u) of Sotorasib Secondary · 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

Group	Value	95% CI
Normal Hepatic Function	183	± 240.8
Moderate Hepatic Impairment	400	± 110.9
Severe Hepatic Impairment	1220	± 9.8

Unbound AUClast (AUClast,u) of Sotorasib Secondary · 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

Group	Value	95% CI
Normal Hepatic Function	694	± 146.3
Moderate Hepatic Impairment	1320	± 71.0
Severe Hepatic Impairment	4680	± 29.4

Unbound AUCinf (AUCinf,u) of Sotorasib Secondary · 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

Group	Value	95% CI
Normal Hepatic Function	742	± 156.7
Moderate Hepatic Impairment	1340	± 69.6
Severe Hepatic Impairment	4680	± 29.4

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

Group	Value	95% CI
Normal Hepatic Function	1290	± 156.7
Moderate Hepatic Impairment	715	± 69.6
Severe Hepatic Impairment	205	± 29.4

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

Group	Value	95% CI
Normal Hepatic Function	7080	± 275.6
Moderate Hepatic Impairment	3820	± 115.2
Severe Hepatic Impairment	928	± 39.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 to Day 8. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Normal Hepatic Function

Serious: 0/7 (0%)

Deaths: 0/7

Moderate Hepatic Impairment

Serious: 0/8 (0%)

Deaths: 0/8

Severe Hepatic Impairment

Serious: 0/5 (0%)

Deaths: 0/5

Other adverse events (9 terms — click to expand)

Reaction	System	Normal Hepatic Function	Moderate Hepatic Impairment	Severe Hepatic Impairment
Abdominal distension	Gastrointestinal disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—
Electrocardiogram qt prolonged	Investigations	—	—	—
Sensory disturbance	Nervous system disorders	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—

Data from ClinicalTrials.gov NCT04887064 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Sotorasib: First Approval.
   Blair HA. · · 2021 · cited 161× · PMID 34357500 · DOI 10.1007/s40265-021-01574-2