Healthy Participants
Conditions
Keywords
Sotorasib, AMG 510, Bioequivalence
Brief summary
The primary objective of this study is to compare the pharmacokinetics (PK) of sotorasib dose A administered orally as 3 tablets (test) to sotorasib dose A administered orally as 8 tablets (reference).
Interventions
DRUGSotorasib
Oral tablet
Sponsors
Amgen
Study design
Allocation
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 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 participant safety or interfere with the study evaluation, procedures, or completion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Sotorasib for Treatments A and B | Predose (Hour 0), 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 Day 1 (Period 1) and Day 4 (Period 2) | Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib. Plasma pharmacokinetic (PK) parameters of sotorasib were summarized per treatment received, regardless of treatment sequence, as pre-specified. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib for Treatments A and B | Predose (Hour 0), 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 Day 1 (Period 1) and Day 4 (Period 2) | Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib. Plasma PK parameters of sotorasib were summarized per treatment received, regardless of treatment sequence, as pre-specified. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Sotorasib for Treatments A and B | Predose (Hour 0), 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 Day 1 (Period 1) and Day 4 (Period 2) | Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib. Plasma PK parameters of sotorasib were summarized per treatment received, regardless of treatment sequence, as pre-specified. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Treatment-emergent AE (TEAE) | Day 1 to Day 9 | An AE is any untoward medical occurrence in a participant irrespective of a causal relationship with the study treatment. Any abnormal clinical laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety assessments (e.g., 12-lead electrocardiogram or vital signs measurements), including those that worsen from baseline, that are considered clinically significant in the medical and scientific judgment of the Investigator (i.e., not related to progression of underlying disease) were considered AEs. |
| Food Effect: AUCinf of Sotorasib | Predose (Hour 0), 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 Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3) | Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib. |
| Food Effect: Cmax of Sotorasib | Predose (Hour 0), 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 Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3) | Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib. |
| Food Effect: AUClast of Sotorasib | Predose (Hour 0), 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 Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3) | Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib. |
Countries
United States
Participant flow
Recruitment details
Overall, 145 participants were enrolled in the study in the United States between 16 August 2021 and 18 February 2022.
Pre-assignment details
After randomization, participants received Treatment A (test 1) and Treatment B (reference) according to the treatment sequence assigned. A group of participants from both arm proceeded to receive Treatment C (test 2) with a high-fat meal. Dose administration of sotorasib occurred on Day 1 (Period 1) and Day 4 (Period 2) under fasted conditions and on Day 7 (Period 3) under fed condition.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence AB Participants were administered 960 mg sotorasib orally in the following order:
* Period 1: Treatment A as 3 tablets (test 1).
* Period 2: Treatment B as 8 tablets (reference). | 66 |
| Treatment Sequence BA Participants were administered 960 mg sotorasib orally in the following order:
* Period 1: Treatment B as 8 tablets (reference).
* Period 2: Treatment A as 3 tablets (test 1). | 66 |
| Treatment Sequence ABC Participants were administered 960 mg sotorasib orally in the following order:
* Period 1: Treatment A as 3 tablets (test 1).
* Period 2: Treatment B as 8 tablets (reference).
* Period 3: Treatment C as 3 tablets with a high-fat meal (test 2). | 6 |
| Treatment Sequence BAC Participants were administered 960 mg sotorasib orally in the following order:
* Period 1: Treatment B as 8 tablets (reference).
* Period 2: Treatment A as 3 tablets (test 1).
* Period 3: Treatment C as 3 tablets with a high-fat meal (test 2). | 7 |
| Total | 145 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 | Adverse Event | 3 | 1 | 0 | 0 |
| Period 2 | Lost to Follow-up | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Treatment Sequence AB | Treatment Sequence BA | Treatment Sequence ABC | Treatment Sequence BAC | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 66 Participants | 66 Participants | 6 Participants | 7 Participants | 145 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants | 31 Participants | 4 Participants | 1 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 35 Participants | 2 Participants | 6 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 30 Participants | 0 Participants | 4 Participants | 60 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 39 Participants | 34 Participants | 6 Participants | 3 Participants | 82 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 1 Participants | 1 Participants | 15 Participants |
| Sex: Female, Male Male | 59 Participants | 60 Participants | 5 Participants | 6 Participants | 130 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 145 | 0 / 145 | 0 / 13 |
| other Total, other adverse events | 8 / 145 | 10 / 145 | 0 / 13 |
| serious Total, serious adverse events | 0 / 145 | 0 / 145 | 0 / 13 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Sotorasib for Treatments A and B
Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib. Plasma PK parameters of sotorasib were summarized per treatment received, regardless of treatment sequence, as pre-specified.
Time frame: Predose (Hour 0), 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 Day 1 (Period 1) and Day 4 (Period 2)
Population: The PK population included all participants who received at least 1 dose of sotorasib in Periods 1 and 2, and had evaluable PK data. A participant may have been excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 times median tmax or diarrhea within 24 hours of dosing.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Sotorasib for Treatments A and B | 28600 h*ng/mL | Geometric Coefficient of Variation 48.1 |
| Treatment B | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Sotorasib for Treatments A and B | 27700 h*ng/mL | Geometric Coefficient of Variation 41.5 |
90% CI: [0.977, 1.065]
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib for Treatments A and B
Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib. Plasma PK parameters of sotorasib were summarized per treatment received, regardless of treatment sequence, as pre-specified.
Time frame: Predose (Hour 0), 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 Day 1 (Period 1) and Day 4 (Period 2)
Population: The PK population included all participants who received at least 1 dose of sotorasib in Periods 1 and 2, and had evaluable PK data. A participant may have been excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 times median tmax or diarrhea within 24 hours of dosing.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib for Treatments A and B | 27800 h*ng/mL | Geometric Coefficient of Variation 51.1 |
| Treatment B | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Sotorasib for Treatments A and B | 27500 h*ng/mL | Geometric Coefficient of Variation 41.6 |
90% CI: [0.967, 1.055]
Primary
Maximum Observed Plasma Concentration (Cmax) of Sotorasib for Treatments A and B
Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib. Plasma pharmacokinetic (PK) parameters of sotorasib were summarized per treatment received, regardless of treatment sequence, as pre-specified.
Time frame: Predose (Hour 0), 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 Day 1 (Period 1) and Day 4 (Period 2)
Population: The PK population included all participants who received at least 1 dose of sotorasib in Periods 1 and 2, and had evaluable PK data. A participant may have been excluded from the PK summary statistics and statistical analysis if the participant had an adverse event (AE) of vomiting that occurred at or before 2 times median time of the Cmax (tmax) or diarrhea within 24 hours of dosing.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Maximum Observed Plasma Concentration (Cmax) of Sotorasib for Treatments A and B | 6650 ng/mL | Geometric Coefficient of Variation 41.3 |
| Treatment B | Maximum Observed Plasma Concentration (Cmax) of Sotorasib for Treatments A and B | 6540 ng/mL | Geometric Coefficient of Variation 37.3 |
90% CI: [0.98, 1.04]
Secondary
Food Effect: AUCinf of Sotorasib
Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib.
Time frame: Predose (Hour 0), 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 Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3)
Population: The PK population included all participants who received at least 1 dose of sotorasib in Period 3 and had evaluable PK data. A participant may have been excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 times median tmax or diarrhea within 24 hours of dosing.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Food Effect: AUCinf of Sotorasib | 23500 h*ng/mL | Geometric Coefficient of Variation 41 |
| Treatment B | Food Effect: AUCinf of Sotorasib | 26500 h*ng/mL | Geometric Coefficient of Variation 30.3 |
| Treatment C | Food Effect: AUCinf of Sotorasib | 34700 h*ng/mL | Geometric Coefficient of Variation 19.2 |
90% CI: [1.236, 1.783]
Secondary
Food Effect: AUClast of Sotorasib
Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib.
Time frame: Predose (Hour 0), 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 Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3)
Population: The PK population included all participants who received at least 1 dose of sotorasib in Period 3 and had evaluable PK data. A participant may have been excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 times median tmax or diarrhea within 24 hours of dosing.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Food Effect: AUClast of Sotorasib | 23900 h*ng/mL | Geometric Coefficient of Variation 40.8 |
| Treatment B | Food Effect: AUClast of Sotorasib | 26100 h*ng/mL | Geometric Coefficient of Variation 31.1 |
| Treatment C | Food Effect: AUClast of Sotorasib | 34500 h*ng/mL | Geometric Coefficient of Variation 19.2 |
90% CI: [1.2, 1.745]
Secondary
Food Effect: Cmax of Sotorasib
Blood samples were collected by venipuncture or cannulation for measurement of plasma concentrations of sotorasib.
Time frame: Predose (Hour 0), 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 Day 1 (Period 1), Day 4 (Period 2), and Day 7 (Period 3)
Population: The PK population included all participants who received at least 1 dose of sotorasib in Period 3 and had evaluable PK data. A participant may have been excluded from the PK summary statistics and statistical analysis if the participant had an AE of vomiting that occurred at or before 2 times median tmax or diarrhea within 24 hours of dosing.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Food Effect: Cmax of Sotorasib | 6390 ng/mL | Geometric Coefficient of Variation 34.6 |
| Treatment B | Food Effect: Cmax of Sotorasib | 6790 ng/mL | Geometric Coefficient of Variation 28.9 |
| Treatment C | Food Effect: Cmax of Sotorasib | 6400 ng/mL | Geometric Coefficient of Variation 19 |
90% CI: [0.836, 1.199]
Secondary
Number of Participants Who Experienced a Treatment-emergent AE (TEAE)
An AE is any untoward medical occurrence in a participant irrespective of a causal relationship with the study treatment. Any abnormal clinical laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety assessments (e.g., 12-lead electrocardiogram or vital signs measurements), including those that worsen from baseline, that are considered clinically significant in the medical and scientific judgment of the Investigator (i.e., not related to progression of underlying disease) were considered AEs.
Time frame: Day 1 to Day 9
Population: The safety population included all participants who received at least 1 dose of sotorasib and had at least 1 postdose safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A | Number of Participants Who Experienced a Treatment-emergent AE (TEAE) | 8 Participants |
| Treatment B | Number of Participants Who Experienced a Treatment-emergent AE (TEAE) | 10 Participants |
| Treatment C | Number of Participants Who Experienced a Treatment-emergent AE (TEAE) | 0 Participants |