Healthy Participants
Conditions
Keywords
Sotorasib, AMG 510
Brief summary
The primary objective of the study is to compare the pharmacokinetics (PK) of sotorasib administered orally as 1 tablet under fasted conditions to sotorasib administered orally as 2 tablets under fasted conditions.
Interventions
DRUGSotorasib
Oral Tablet
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* 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 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 participants safety or interfere with the study evaluation, procedures, or completion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Period 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Sotorasib | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on the 1st day of each period (Days 1 and 4) |
| Period 1 and 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on the 1st day of each period (Days 1 and 4) |
| Period 1 and 2: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Sotorasib | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on on the 1st day of each period (Days 1 and 4) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Day 1 to Day 9 | A TEAE was defined as an adverse event (AE) that started during or after dosing, or started prior to dosing and increased in severity after dosing within each period. Clinically significant laboratory tests, 12-lead electrocardiogram (ECG), or vital sign results as assessed by the Investigator were also recorded as adverse events. |
| Period 3: AUCinf of Sotorasib | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on the 1st day of Period 3 (Day 7) | — |
| Period 3: Cmax of Sotorasib | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on the 1st day of Period 3 (Day 7) | — |
| Period 3: AUClast of Sotorasib | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on on the 1st day of Period 3 (Day 7) | — |
Countries
United States
Participant flow
Recruitment details
A total of 146 participants were enrolled with all participants randomized into Treatment Sequences AB and BA, including 14 participants that proceeded to receive Treatment C in the food effect substudy.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence AB Participants received a single oral dose of sotorasib under fasted conditions in the following order:
Period 1 - as 1 tablet (test 1) on Day 1 Period 2 - as 2 tablets (reference) on Day 4 | 73 |
| Treatment Sequence BA Participants received a single oral dose of sotorasib under fasted conditions in the following order:
Period 1 - as 2 tablets (reference) on Day 1 Period 2 - as 1 tablet (test 1) on Day 4 | 73 |
| Total | 146 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Periods 1 & 2 | Miscellaneous | 0 | 1 | 0 | 0 |
| Periods 1 & 2 | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Treatment Sequence AB | Treatment Sequence BA | Total |
|---|---|---|---|
| Age, Continuous | 37.6 Years STANDARD_DEVIATION 11.1 | 39.2 Years STANDARD_DEVIATION 10.74 | 38.4 Years STANDARD_DEVIATION 10.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 30 Participants | 29 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 44 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Black and African American | 27 Participants | 25 Participants | 52 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 41 Participants | 44 Participants | 85 Participants |
| Sex: Female, Male Female | 6 Participants | 14 Participants | 20 Participants |
| Sex: Female, Male Male | 67 Participants | 59 Participants | 126 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 146 | 0 / 146 | 0 / 14 |
| other Total, other adverse events | 3 / 146 | 10 / 146 | 0 / 14 |
| serious Total, serious adverse events | 0 / 146 | 0 / 146 | 0 / 14 |
Outcome results
Primary
Period 1 and 2: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Sotorasib
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on on the 1st day of each period (Days 1 and 4)
Population: All participants who received at least 1 dose of sotorasib and had evaluable PK data and evaluable observations.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Period 1 and 2: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Sotorasib | 15500 h*ng/mL | Geometric Coefficient of Variation 54.1 |
| Treatment B | Period 1 and 2: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Sotorasib | 16100 h*ng/mL | Geometric Coefficient of Variation 52.8 |
90% CI: [0.908, 1.029]
Primary
Period 1 and 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on the 1st day of each period (Days 1 and 4)
Population: All participants who received at least 1 dose of sotorasib and had evaluable PK data and evaluable observations.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Period 1 and 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib | 15300 h*ng/mL | Geometric Coefficient of Variation 56.2 |
| Treatment B | Period 1 and 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib | 15800 h*ng/mL | Geometric Coefficient of Variation 54.6 |
90% CI: [0.907, 1.033]
Primary
Period 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Sotorasib
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on the 1st day of each period (Days 1 and 4)
Population: All participants who received at least 1 dose of sotorasib and had evaluable PK data and evaluable observations.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Period 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Sotorasib | 4170 ng/mL | Geometric Coefficient of Variation 75 |
| Treatment B | Period 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Sotorasib | 4340 ng/mL | Geometric Coefficient of Variation 65.5 |
90% CI: [0.88, 1.053]
Secondary
Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
A TEAE was defined as an adverse event (AE) that started during or after dosing, or started prior to dosing and increased in severity after dosing within each period. Clinically significant laboratory tests, 12-lead electrocardiogram (ECG), or vital sign results as assessed by the Investigator were also recorded as adverse events.
Time frame: Day 1 to Day 9
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | 3 Participants |
| Treatment B | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | 10 Participants |
| Treatment C | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | 0 Participants |
Secondary
Period 3: AUCinf of Sotorasib
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on the 1st day of Period 3 (Day 7)
Population: All participants who received at least 1 dose of sotorasib and had evaluable PK data and evaluable observations.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Period 3: AUCinf of Sotorasib | 19100 h*ng/mL | Geometric Coefficient of Variation 20 |
Secondary
Period 3: AUClast of Sotorasib
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on on the 1st day of Period 3 (Day 7)
Population: All participants who received at least 1 dose of sotorasib and had evaluable PK data and evaluable observations.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Period 3: AUClast of Sotorasib | 19000 h*ng/mL | Geometric Coefficient of Variation 20.3 |
Secondary
Period 3: Cmax of Sotorasib
Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours postdose following administration of sotorasib on the 1st day of Period 3 (Day 7)
Population: All participants who received at least 1 dose of sotorasib and had evaluable PK data and evaluable observations.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Period 3: Cmax of Sotorasib | 4530 ng/mL | Geometric Coefficient of Variation 14.2 |