Healthy Participants
Conditions
Keywords
AMG 510, Sotorasib, Rosuvastatin, Healthy participants
Brief summary
A study to determine the effect of sotorasib on the pharmacokinetics (PK) of rosuvastatin, and to assess the PK of rosuvastatin when administered alone, in healthy participants.
Interventions
DRUGRosuvastatin
Oral dose
DRUGSotorasib
Oral dose
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects or female subjects, between 18 and 60 years of age (inclusive), at the time of Screening. * Body mass index, between 18 and 30 kg/m2 (inclusive), at the time of Screening. * Females of nonchildbearing potential
Exclusion criteria
* Inability to swallow oral medication or history of malabsorption syndrome. * History of hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee) and in consultation with the Sponsor. * Poor peripheral venous access. * History or evidence, at Screening or Check in, of clinically significant disorder, condition, or disease, including history of myolysis, not otherwise excluded that, in the opinion of the Investigator (or designee), would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Rosuvastatin | Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6 | The pharmacokinetic (PK) parameters were determined using standard non-compartmental methods. |
| Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Rosuvastatin | Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6 | The PK parameters were determined using standard non-compartmental methods. |
| AUC From Time Zero to Infinity (AUCinf) of Rosuvastatin | Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6 | The PK parameters were determined using standard non-compartmental methods. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Any Treatment-Emergent Adverse Events (TEAEs) | Day 1 to Day 41 | Any clinically significant changes in clinical laboratory tests, 12-lead electrocardiograms (ECGs), and vital signs results were recorded as AEs. |
| AUCinf of Sotorasib | Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Day 6 | The PK parameters were determined using standard non-compartmental methods. |
| Cmax of Sotorasib | Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Day 6 | The PK parameters were determined using standard non-compartmental methods. |
| AUClast of Sotorasib | Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Day 6 | The PK parameters were determined using standard non-compartmental methods. |
Countries
United States
Participant flow
Recruitment details
13 participants were enrolled at a single center in the United States between 20 August 2021 and 10 October 2021.
Pre-assignment details
The participants received 10 mg rosuvastatin on Day 1 and 960 mg sotorasib coadministered with 10 mg rosuvastatin on Day 6.
Participants by arm
| Arm | Count |
|---|---|
| All Participants On Day 1, rosuvastatin was administered as a single 10 mg dose. On Day 6, sotorasib was administered as a single 960 mg dose and was followed immediately by a single dose of 10 mg rosuvastatin. All participants fasted overnight (at least 10 hours) until 4 hours postdose and refrained from consuming water for 1 hour prior to dosing and 2 hours postdose. | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 41.5 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 0 / 13 | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Rosuvastatin
The PK parameters were determined using standard non-compartmental methods.
Time frame: Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6
Population: The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Rosuvastatin | 33.20 h*ng/mL | Geometric Coefficient of Variation 57 |
| Sotorasib + Rosuvastatin | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Rosuvastatin | 44.50 h*ng/mL | Geometric Coefficient of Variation 73.6 |
Comparison: The ratios of GLSMs and CIs were obtained by taking the exponential of the corresponding differences and CIs on the ln scale.90% CI: [1.0334, 1.7347]
Primary
AUC From Time Zero to Infinity (AUCinf) of Rosuvastatin
The PK parameters were determined using standard non-compartmental methods.
Time frame: Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6
Population: The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | AUC From Time Zero to Infinity (AUCinf) of Rosuvastatin | 36.20 h*ng/mL | Geometric Coefficient of Variation 60.1 |
| Sotorasib + Rosuvastatin | AUC From Time Zero to Infinity (AUCinf) of Rosuvastatin | 48.40 h*ng/mL | Geometric Coefficient of Variation 78.9 |
Comparison: The ratios of GLSMs and CIs were obtained by taking the exponential of the corresponding differences and CIs on the ln scale.90% CI: [0.9856, 1.8169]
Primary
Maximum Observed Plasma Concentration (Cmax) of Rosuvastatin
The pharmacokinetic (PK) parameters were determined using standard non-compartmental methods.
Time frame: Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 hours postdose following administration of rosuvastatin on Days 1 and 6
Population: The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Maximum Observed Plasma Concentration (Cmax) of Rosuvastatin | 3.80 ng/mL | Geometric Coefficient of Variation 57.8 |
| Sotorasib + Rosuvastatin | Maximum Observed Plasma Concentration (Cmax) of Rosuvastatin | 6.47 ng/mL | Geometric Coefficient of Variation 136 |
Comparison: The ratios of geometric least squares means (GLSMs) and confidence intervals (CIs) were obtained by taking the exponential of the corresponding differences and CIs on the natural-log (ln) scale.90% CI: [1.186, 2.4363]
Secondary
AUCinf of Sotorasib
The PK parameters were determined using standard non-compartmental methods.
Time frame: Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Day 6
Population: The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | AUCinf of Sotorasib | 22900 h*ng/mL | Geometric Coefficient of Variation 71.7 |
Secondary
AUClast of Sotorasib
The PK parameters were determined using standard non-compartmental methods.
Time frame: Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Day 6
Population: The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | AUClast of Sotorasib | 22500 h*ng/mL | Geometric Coefficient of Variation 74.3 |
Secondary
Cmax of Sotorasib
The PK parameters were determined using standard non-compartmental methods.
Time frame: Predose (Hour 0), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Day 6
Population: The PK population included all participants who received at least 1 dose of rosuvastatin or sotorasib and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Cmax of Sotorasib | 4650 ng/mL | Geometric Coefficient of Variation 86.2 |
Secondary
Number of Participants Reporting Any Treatment-Emergent Adverse Events (TEAEs)
Any clinically significant changes in clinical laboratory tests, 12-lead electrocardiograms (ECGs), and vital signs results were recorded as AEs.
Time frame: Day 1 to Day 41
Population: The safety population included all participants who received at least 1 dose of sotorasib or rosuvastatin and had at least 1 postdose safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rosuvastatin | Number of Participants Reporting Any Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
| Sotorasib + Rosuvastatin | Number of Participants Reporting Any Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |