Healthy Participants
Conditions
Keywords
Maridebart Cafraglutide, Japanese participants, Caucasian participants, AMG 133
Brief summary
The primary objective of this study is to evaluate the pharmacokinetics (PK) of AMG 133 after single subcutaneous (SC) administration in healthy Japanese and Caucasian participants.
Interventions
DRUGAMG 133
Solution for SC injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: 1. Healthy male or female participants between 18 and 65 years of age (inclusive) at the time of Screening (Japanese participants must be first-generation Japanese) 2. In good health, determined by no clinically significant findings from medical history, physical examination, ECG, vital signs measurements, and clinical laboratory evaluations 3. Body mass index between 18 and 30 kg/m\^2 at the time of Screening 4. Females of nonchildbearing potential Key
Exclusion criteria
1. History or evidence, at Screening or Check-in, of clinically significant disorder, condition, or disease 2. History or current signs or symptoms of cardiovascular disease 3. History or evidence of clinically significant arrhythmia at Screening, including any clinically significant findings on the ECG taken at Check-in 4. History of hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance 5. Positive hepatitis B or hepatitis C panel and/or positive human immunodeficiency virus test at Screening 6. History of alcoholism or drug/chemical abuse within 1 year prior to Check-in 7. Use of tobacco- or nicotine-containing products within 6 months prior to Check-in 8. Positive test for illicit drugs, cotinine (tobacco or nicotine use), and/or alcohol use at Screening or Check-in 9. Female participants with a positive pregnancy test at Screening or Check-in 10. Female participants lactating/breastfeeding or who plans to breastfeed during the study through 90 days after the end of study (EOS) visit 11. Donation of blood from 3 months prior to Check-in, plasma from 2 weeks prior to Check-in, or platelets from 6 weeks prior to Check-in 12. Unwilling to abide with study restrictions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUCinf of Total AMG 133 | Day 1 pre-dose and 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose | Blood samples were collected at specific times during the study for the measurement of plasma concentrations of intact and total AMG 133 by a laboratory. |
| AUClast of Total AMG 133 | Day 1 pre-dose and 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose | Blood samples were collected at specific times during the study for the measurement of plasma concentrations of intact and total AMG 133 by a laboratory. |
| Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Intact AMG 133 | Day 1 pre-dose and 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose | Blood samples were collected at specific times during the study for the measurement of plasma concentrations of intact and total AMG 133 by a laboratory. |
| Maximum Observed Plasma Concentration (Cmax) of Intact AMG 133 | Day 1 pre-dose and 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose | Blood samples were collected at specific times during the study for the measurement of plasma concentrations of intact and total AMG 133 by a laboratory. |
| Cmax of Total AMG 133 | Day 1 pre-dose and 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose | Blood samples were collected at specific times during the study for the measurement of plasma concentrations of intact and total AMG 133 by a laboratory. |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Intact AMG 133 | Day 1 pre-dose and 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose | Blood samples were collected at specific times during the study for the measurement of plasma concentrations of intact and total AMG 133 by a laboratory. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Positive Anti-AMG 133 Binding Antibody Result | Days 1, 15, 29, 57 and 120 | Blood samples were collected at specific times during the study for the measurement of anti-AMG 133 binding antibodies from participants who received AMG 133. |
| Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | Day 1 to Day 120 | A TEAE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with AMG 133 that started during or after dosing, or started prior to dosing and increased in severity after dosing. Clinically significant changes from baseline in clinical laboratory tests, 12-lead electrocardiograms (ECGs) and vital signs were also reported as TEAEs. |
Countries
United States
Participant flow
Recruitment details
Healthy Japanese and Caucasian participants were enrolled at a single center in the United States between 10 September 2021 and 08 April 2022.
Pre-assignment details
A total of 34 participants were enrolled and randomized in the study. All 34 participants were dosed in accordance with the protocol.
Participants by arm
| Arm | Count |
|---|---|
| Japanese Participants: AMG 133 Low Dose Healthy Japanese participants received the low dose of AMG 133 as a SC injection on Day 1 of the study. | 6 |
| Japanese Participants: AMG 133 Medium Dose Healthy Japanese participants received the medium dose of AMG 133 as a SC injection on Day 1 of the study. | 7 |
| Japanese Participants: AMG 133 High Dose Healthy Japanese participants received the high dose of AMG 133 as a SC injection on Day 1 of the study. | 7 |
| Caucasian Participants: AMG 133 Medium Dose Healthy Caucasian participants received the medium dose of AMG 133 as a SC injection on Day 1 of the study. | 7 |
| Caucasian Participants: AMG 133 High Dose Healthy Caucasian participants received the high dose of AMG 133 as a SC injection on Day 1 of the study. | 7 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Caucasian Participants: AMG 133 High Dose | Japanese Participants: AMG 133 Low Dose | Japanese Participants: AMG 133 Medium Dose | Japanese Participants: AMG 133 High Dose | Caucasian Participants: AMG 133 Medium Dose | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 49.0 years STANDARD_DEVIATION 11.93 | 57.3 years STANDARD_DEVIATION 4.8 | 55.0 years STANDARD_DEVIATION 5.35 | 52.9 years STANDARD_DEVIATION 13.9 | 43.0 years STANDARD_DEVIATION 14.59 | 51.3 years STANDARD_DEVIATION 11.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 6 Participants | 7 Participants | 7 Participants | 5 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Japanese | 0 Participants | 6 Participants | 7 Participants | 7 Participants | 0 Participants | 20 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 3 Participants | 4 Participants | 1 Participants | 13 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 4 Participants | 3 Participants | 6 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 6 / 6 | 6 / 7 | 7 / 7 | 7 / 7 | 7 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 | 1 / 7 | 0 / 7 | 0 / 7 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Intact AMG 133
Blood samples were collected at specific times during the study for the measurement of plasma concentrations of intact and total AMG 133 by a laboratory.
Time frame: Day 1 pre-dose and 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose
Population: PK Population: Included all participants who received at least 1 dose of AMG 133 and had evaluable PK data. Only participants with available data are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese Participants: AMG 133 Low Dose | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Intact AMG 133 | 10700 h*ug/mL | Geometric Coefficient of Variation 44.9 |
| Japanese Participants: AMG 133 Medium Dose | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Intact AMG 133 | 19600 h*ug/mL | Geometric Coefficient of Variation 36.4 |
| Japanese Participants: AMG 133 High Dose | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Intact AMG 133 | 33900 h*ug/mL | Geometric Coefficient of Variation 20.4 |
| Caucasian Participants: AMG 133 Medium Dose | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Intact AMG 133 | 17300 h*ug/mL | Geometric Coefficient of Variation 43.3 |
| Caucasian Participants: AMG 133 High Dose | Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Intact AMG 133 | 36000 h*ug/mL | Geometric Coefficient of Variation 31.6 |
Primary
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Intact AMG 133
Blood samples were collected at specific times during the study for the measurement of plasma concentrations of intact and total AMG 133 by a laboratory.
Time frame: Day 1 pre-dose and 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose
Population: PK Population: Included all participants who received at least 1 dose of AMG 133 and had evaluable PK data. Only participants with available data are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese Participants: AMG 133 Low Dose | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Intact AMG 133 | 10600 h*ug/mL | Geometric Coefficient of Variation 45.2 |
| Japanese Participants: AMG 133 Medium Dose | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Intact AMG 133 | 19400 h*ug/mL | Geometric Coefficient of Variation 36 |
| Japanese Participants: AMG 133 High Dose | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Intact AMG 133 | 33500 h*ug/mL | Geometric Coefficient of Variation 20.5 |
| Caucasian Participants: AMG 133 Medium Dose | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Intact AMG 133 | 17200 h*ug/mL | Geometric Coefficient of Variation 42.4 |
| Caucasian Participants: AMG 133 High Dose | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Intact AMG 133 | 35700 h*ug/mL | Geometric Coefficient of Variation 31.1 |
Primary
AUCinf of Total AMG 133
Blood samples were collected at specific times during the study for the measurement of plasma concentrations of intact and total AMG 133 by a laboratory.
Time frame: Day 1 pre-dose and 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose
Population: PK Population: Included all participants who received at least 1 dose of AMG 133 and had evaluable PK data. Only participants with available data are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese Participants: AMG 133 Low Dose | AUCinf of Total AMG 133 | 15600 h*ug/mL | Geometric Coefficient of Variation 40.5 |
| Japanese Participants: AMG 133 Medium Dose | AUCinf of Total AMG 133 | 30100 h*ug/mL | Geometric Coefficient of Variation 39.2 |
| Japanese Participants: AMG 133 High Dose | AUCinf of Total AMG 133 | 50100 h*ug/mL | Geometric Coefficient of Variation 21.8 |
| Caucasian Participants: AMG 133 Medium Dose | AUCinf of Total AMG 133 | 21800 h*ug/mL | Geometric Coefficient of Variation 45.4 |
| Caucasian Participants: AMG 133 High Dose | AUCinf of Total AMG 133 | 51500 h*ug/mL | Geometric Coefficient of Variation 32.5 |
Primary
AUClast of Total AMG 133
Blood samples were collected at specific times during the study for the measurement of plasma concentrations of intact and total AMG 133 by a laboratory.
Time frame: Day 1 pre-dose and 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose
Population: PK Population: Included all participants who received at least 1 dose of AMG 133 and had evaluable PK data. Only participants with available data are included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese Participants: AMG 133 Low Dose | AUClast of Total AMG 133 | 14800 h*ug/mL | Geometric Coefficient of Variation 41.8 |
| Japanese Participants: AMG 133 Medium Dose | AUClast of Total AMG 133 | 28300 h*ug/mL | Geometric Coefficient of Variation 37.2 |
| Japanese Participants: AMG 133 High Dose | AUClast of Total AMG 133 | 47700 h*ug/mL | Geometric Coefficient of Variation 21.1 |
| Caucasian Participants: AMG 133 Medium Dose | AUClast of Total AMG 133 | 20800 h*ug/mL | Geometric Coefficient of Variation 41.4 |
| Caucasian Participants: AMG 133 High Dose | AUClast of Total AMG 133 | 49600 h*ug/mL | Geometric Coefficient of Variation 30.9 |
Primary
Cmax of Total AMG 133
Blood samples were collected at specific times during the study for the measurement of plasma concentrations of intact and total AMG 133 by a laboratory.
Time frame: Day 1 pre-dose and 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose
Population: PK Population: Included all participants who received at least 1 dose of AMG 133 and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese Participants: AMG 133 Low Dose | Cmax of Total AMG 133 | 13.2 μg/mL | Geometric Coefficient of Variation 56.3 |
| Japanese Participants: AMG 133 Medium Dose | Cmax of Total AMG 133 | 24.8 μg/mL | Geometric Coefficient of Variation 25.6 |
| Japanese Participants: AMG 133 High Dose | Cmax of Total AMG 133 | 48.4 μg/mL | Geometric Coefficient of Variation 32 |
| Caucasian Participants: AMG 133 Medium Dose | Cmax of Total AMG 133 | 20.8 μg/mL | Geometric Coefficient of Variation 24.5 |
| Caucasian Participants: AMG 133 High Dose | Cmax of Total AMG 133 | 58.7 μg/mL | Geometric Coefficient of Variation 24.8 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Intact AMG 133
Blood samples were collected at specific times during the study for the measurement of plasma concentrations of intact and total AMG 133 by a laboratory.
Time frame: Day 1 pre-dose and 24, 48, 72, 96, 120, 144, 168, 336, 504, 672, 1008, 1344, 1680, 2184, and 2856 hours post-dose
Population: Pharmacokinetic (PK) Population: Included all participants who received at least 1 dose of AMG 133 and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese Participants: AMG 133 Low Dose | Maximum Observed Plasma Concentration (Cmax) of Intact AMG 133 | 12.3 μg/mL | Geometric Coefficient of Variation 57.3 |
| Japanese Participants: AMG 133 Medium Dose | Maximum Observed Plasma Concentration (Cmax) of Intact AMG 133 | 22.7 μg/mL | Geometric Coefficient of Variation 24.1 |
| Japanese Participants: AMG 133 High Dose | Maximum Observed Plasma Concentration (Cmax) of Intact AMG 133 | 44.9 μg/mL | Geometric Coefficient of Variation 34.6 |
| Caucasian Participants: AMG 133 Medium Dose | Maximum Observed Plasma Concentration (Cmax) of Intact AMG 133 | 22.5 μg/mL | Geometric Coefficient of Variation 33.9 |
| Caucasian Participants: AMG 133 High Dose | Maximum Observed Plasma Concentration (Cmax) of Intact AMG 133 | 55.0 μg/mL | Geometric Coefficient of Variation 26.7 |
Secondary
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
A TEAE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with AMG 133 that started during or after dosing, or started prior to dosing and increased in severity after dosing. Clinically significant changes from baseline in clinical laboratory tests, 12-lead electrocardiograms (ECGs) and vital signs were also reported as TEAEs.
Time frame: Day 1 to Day 120
Population: Safety Population: Included all participants who received at least 1 dose of AMG 133.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Japanese Participants: AMG 133 Low Dose | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 6 Participants |
| Japanese Participants: AMG 133 Medium Dose | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 6 Participants |
| Japanese Participants: AMG 133 High Dose | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 7 Participants |
| Caucasian Participants: AMG 133 Medium Dose | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 7 Participants |
| Caucasian Participants: AMG 133 High Dose | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 7 Participants |
Secondary
Number of Participants With a Positive Anti-AMG 133 Binding Antibody Result
Blood samples were collected at specific times during the study for the measurement of anti-AMG 133 binding antibodies from participants who received AMG 133.
Time frame: Days 1, 15, 29, 57 and 120
Population: Safety Population: Included all participants who received at least 1 dose of AMG 133.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Japanese Participants: AMG 133 Low Dose | Number of Participants With a Positive Anti-AMG 133 Binding Antibody Result | 3 Participants |
| Japanese Participants: AMG 133 Medium Dose | Number of Participants With a Positive Anti-AMG 133 Binding Antibody Result | 3 Participants |
| Japanese Participants: AMG 133 High Dose | Number of Participants With a Positive Anti-AMG 133 Binding Antibody Result | 3 Participants |
| Caucasian Participants: AMG 133 Medium Dose | Number of Participants With a Positive Anti-AMG 133 Binding Antibody Result | 1 Participants |
| Caucasian Participants: AMG 133 High Dose | Number of Participants With a Positive Anti-AMG 133 Binding Antibody Result | 0 Participants |