Healthy Volunteers
Conditions
Keywords
Healthy volunteers, Sotorasib, AMG 510, Omeprazole
Brief summary
The primary objective of the study is to evaluate the effects of omeprazole (a proton-pump inhibitor) and an acidic beverage (Coca-Cola) on sotorasib pharmacokinetics (PK) when administered orally in healthy volunteers.
Interventions
DRUGOmeprazole
Omeprazole will be administered as an oral capsule.
DRUGSotorasib
Sotorasib will be administered as an oral tablet.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion: * Healthy male participants or female participants, between 18 and 60 years of age (inclusive), at the time of Screening. * Body mass index, between 18 and 30 kg/m\^2 (inclusive), at the time of Screening. * Females of nonchildbearing potential. Exclusion: * 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 participant safety or interfere with the study evaluation, procedures, or completion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Sotorasib | Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Days 1 and 9 |
| Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of Sotorasib | Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Days 1 and 9 |
| Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) of Sotorasib | Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Days 1 and 9 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | Day 1 to Day 11 | An adverse event is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE was defined as an adverse event that starts during or after the first dose, or starts prior to the first dose and increases in severity after the first dose. Any clinically significant changes in clinical laboratory tests, 12-lead electrocardiograms and vital signs were recorded as an adverse event. |
Countries
United States
Participant flow
Recruitment details
16 participants were enrolled at 1 center in the United States.
Pre-assignment details
Participants were screened to assess their eligibility to enter the study within 28 days prior to the first dose administration.
Participants by arm
| Arm | Count |
|---|---|
| Sotorasib and Omeprazole: All Participants On Day 1, participants received 960 mg sotorasib (8 x 120 mg tablets) administered orally with 240 mL of water after an overnight fast of at least 10 hours. On Days 4 to 8, participants received 40 mg omeprazole (delayed release capsule) administered orally with 240 mL of water QD after an overnight fast of at least 10 hours. On Day 9, participants received 40 mg omeprazole (delayed release capsule) followed by 960 mg sotorasib (8 x 120 mg tablets) administered orally within 5 minutes with 240 mL of an acidic beverage after an overnight fast of at least 10 hours. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 2: Omeprazole Alone | Withdrawal by Subject | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Sotorasib and Omeprazole: All Participants |
|---|---|
| Age, Continuous | 36.7 years STANDARD_DEVIATION 10.18 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 1 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 | 3 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 14 |
| other Total, other adverse events | 0 / 16 | 2 / 16 | 0 / 14 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 14 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of Sotorasib
Time frame: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Days 1 and 9
Population: Measured in the Pharmacokinetic Population for the primary endpoint analyses, which included all participants who received both sotorasib, and sotorasib in combination with omeprazole and an acidic beverage, and had evaluable pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sotorasib Alone | Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of Sotorasib | 30200 h*ng/mL | Geometric Coefficient of Variation 33.3 |
| Omeprazole Co-administered With Sotorasib | Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of Sotorasib | 23500 h*ng/mL | Geometric Coefficient of Variation 60.4 |
Comparison: Ratios of geometric least squares means, and corresponding confidence intervals were obtained by taking the exponential of the least square means (LSMs), differences in LSMs, and corresponding confidence intervals on the natural log (ln) scale.90% CI: [0.628, 0.948]
Primary
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) of Sotorasib
Time frame: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Days 1 and 9
Population: Measured in the Pharmacokinetic Population for the primary endpoint analyses, which included all participants who received both sotorasib, and sotorasib in combination with omeprazole and an acidic beverage, and had evaluable pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sotorasib Alone | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) of Sotorasib | 30000 h*ng/mL | Geometric Coefficient of Variation 33.3 |
| Omeprazole Co-administered With Sotorasib | Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-tlast) of Sotorasib | 23200 h*ng/mL | Geometric Coefficient of Variation 62.2 |
Comparison: Ratios of geometric least squares means, and corresponding confidence intervals were obtained by taking the exponential of the least square means (LSMs), differences in LSMs, and corresponding confidence intervals on the natural log (ln) scale.90% CI: [0.619, 0.948]
Primary
Maximum Observed Plasma Concentration (Cmax) of Sotorasib
Time frame: Predose (Hour 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on Days 1 and 9
Population: Measured in the Pharmacokinetic Population for the primary endpoint analyses, which included all participants who received both sotorasib, and sotorasib in combination with omeprazole and an acidic beverage, and had evaluable pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sotorasib Alone | Maximum Observed Plasma Concentration (Cmax) of Sotorasib | 7160 ng/mL | Geometric Coefficient of Variation 22.9 |
| Omeprazole Co-administered With Sotorasib | Maximum Observed Plasma Concentration (Cmax) of Sotorasib | 4850 ng/mL | Geometric Coefficient of Variation 65.6 |
Comparison: Ratios of geometric least squares means, and corresponding confidence intervals were obtained by taking the exponential of the least square means (LSMs), differences in LSMs, and corresponding confidence intervals on the natural log (ln) scale.90% CI: [0.547, 0.839]
Secondary
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
An adverse event is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE was defined as an adverse event that starts during or after the first dose, or starts prior to the first dose and increases in severity after the first dose. Any clinically significant changes in clinical laboratory tests, 12-lead electrocardiograms and vital signs were recorded as an adverse event.
Time frame: Day 1 to Day 11
Population: Measured in the Safety Population, which included all participants who received at least 1 dose of study treatment and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotorasib Alone | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 0 Participants |
| Omeprazole Co-administered With Sotorasib | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 2 Participants |
| Omeprazole Co-administered With Sotorasib | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 0 Participants |