Obesity
Conditions
Keywords
Obesity
Brief summary
To assess the safety and tolerability of AMG 171 as single or multiple doses in subjects with obesity
Interventions
DRUGAMG 171
2 SAD cohorts of 8 subjects per cohort randomized 3:1 in Part A; 1 cohort of 8 subjects 3:1 ratio in Part B; and 24 subjects enrolled into 1 of 3 cohorts with 8 subjects randomized to receive 2 to 3 consecutive doses (titration) 3:1 ratio in Part C.
DRUGPlacebo
AMG 171 placebo
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Males and females with ages between 18 and 65 years old, inclusive * Except for obesity, otherwise healthy * Body mass index (BMI) greater than or equal to 30.0 kg/m2 and less than or equal to 40.0 kg/m2 at screening * Other Inclusion criteria may apply
Exclusion criteria
* Currently receiving treatment in another investigational device or drug study * Women of childbearing potential * History or evidence of a clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | From first dose of IP to end of study, up to Day 207 | An adverse event (AE) was any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with study treatment. A serious AE (SAE) was an AE meeting at least 1 of the following serious criteria: fatal, life-threatening, required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability; congenital anomaly/birth defect; other medically important serious event. Clinically significant changes from baseline in laboratory safety tests, vital sign assessments, and 12-lead electrocardiogram assessments were included as TEAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax for AMG 171: MAD Cohorts 2 - 5 | Cohort 2: pre-dose Days 1, 15, 29, 43, 57, 71; post-dose Days 5 up to 207; Cohort 3: pre-dose Days 1, 15; post-dose Days 2 up to 85; Cohort 4: pre-dose Days 1, 15, 29; post-dose Days 2 up to 113; Cohort 5: pre-dose Days 1, 8; post-dose Days 2 up to 85 | Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis. |
| Time of Cmax (Tmax) for AMG 171: SAD Cohorts 1 and 1b | Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120 | Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis. |
| Tmax for AMG 171: MAD Cohorts 2 - 5 | Cohort 2: pre-dose Days 1, 15, 29, 43, 57, 71; post-dose Days 5 up to 207; Cohort 3: pre-dose Days 1, 15; post-dose Days 2 up to 85; Cohort 4: pre-dose Days 1, 15, 29; post-dose Days 2 up to 113; Cohort 5: pre-dose Days 1, 8; post-dose Days 2 up to 85 | Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis. |
| Maximum Observed Serum Concentration (Cmax) for AMG 171: SAD Cohorts 1 and 1b | Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120 | Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of pharmacokinetic (PK) parameters. Concentrations below the lower limit of quantification (LLOQ) (50.0 ng/mL) were set to zero before data analysis. |
| AUC From Time 0 to 14 Days (AUC0-14) for AMG 171: MAD Cohorts 2 - 4 | Cohort 2: pre-dose Days 1, 15, 29, 43, 57, 71; post-dose Days 5 up to 207; Cohort 3: pre-dose Days 1, 15; post-dose Days 2 up to 85; Cohort 4: pre-dose Days 1, 15, 29; post-dose Days 2 up to 113 | Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis. |
| AUC From Time 0 to 7 Days (AUC0-7) for AMG 171: MAD Cohort 5 | Cohort 5: pre-dose Days 1, 8; post-dose Days 2 up to 85 | Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis. |
| Number of Participants With Anti-AMG 171 Antibodies | Cohorts 1 and 1b: Day 1 pre-dose, Days 15, 29, 120; Cohort 2: Days 1, 29, 57 pre-dose, Days 15, 85, 207; Cohort 3: Days 1, 15 pre-dose, Days 29, 57, 85; Cohort 4: Days 1, 15, 29 pre-dose, Days 43, 85, 113; Cohort 5: Days 1, 8 pre-dose, Days 29, 57, 85 | Serum samples were tested for binding and neutralizing antibodies against human Growth Differentiation Factor 15. Participants with transiently positive for binding or neutralizing antibodies had a negative result at the participant's last time point tested. bAb = binding antibody; nAb = neutralizing antibody; +ve = positive; -ve = negative; BL = baseline. |
| Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity (AUCinf) for AMG 171: SAD Cohorts 1 and 1b | Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120 | Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 3 study centers in the United States, and participated from 13 December 2019 to 10 September 2021.
Pre-assignment details
Participants were enrolled into single ascending dose (SAD) cohorts in Part A (Cohorts 1 and 1b), a multiple dosing cohort in Part B (Cohort 2), and step dosing cohorts in Part C (Cohorts 3 - 5). Three doses were given: Dose A (low dose), Dose B (intermediate dose), and Dose C (high dose).
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Cohort 1 and 1b) Participants in Part A Cohorts 1 and 1b were randomized to receive a single SC dose of placebo on Day 1. | 4 |
| Cohort 1 (Part A): AMG 171 Dose A Participants were randomized to receive AMG 171 Dose A as a single SC dose on Day 1. | 7 |
| Cohort 1b (Part A): AMG 171 Dose B Participants were randomized to receive AMG 171 Dose B as a single SC dose on Day 1. | 6 |
| Placebo (Cohort 4 Replaced) Participants enrolled in Part C Cohort 4 received compromised or expired IP. These participants were randomized to receive placebo on Day 1, Day 15, and on Day 29, as SC doses. | 2 |
| Placebo (Cohorts 2-5) Participants in Parts B and C (Cohorts 2-5) were randomized to receive multiple SC doses of placebo. | 8 |
| Cohort 2 (Part B): AMG 171 Dose A Q2W Participants were randomized to receive AMG 171 Dose A Q2W on Days 1, 15, 29, 43, 57, and 71, as SC doses. | 7 |
| Cohort 3 (Part C): AMG 171 Dose A/Dose B Participants were randomized to receive AMG 171 Dose A on Day 1 and Dose B on Day 15, as SC doses. | 8 |
| Cohort 4 (Part C): AMG 171 Dose A/Dose B/Dose C Participants were randomized to receive AMG 171 Dose A on Day 1, Dose B on Day 15, and Dose C on Day 29, as SC doses. | 6 |
| Cohort 5 (Part C): AMG 171 Dose A/Dose B Participants were randomized to receive AMG 171 Dose A on Day 1 and Dose B on Day 8, as SC doses. | 6 |
| Cohort 4 Replaced (Part C): AMG 171 Dose A/Dose B/Dose C Participants enrolled in Part C Cohort 4 received compromised or expired IP. These participants were randomized to receive AMG 171 Dose A on Day 1, Dose B on Day 15, and Dose C on Day 29, as SC doses. | 6 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Decision by sponsor | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 6 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 1 | 4 | 2 | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Placebo (Cohort 1 and 1b) | Cohort 1 (Part A): AMG 171 Dose A | Cohort 1b (Part A): AMG 171 Dose B | Placebo (Cohort 4 Replaced) | Placebo (Cohorts 2-5) | Cohort 2 (Part B): AMG 171 Dose A Q2W | Cohort 3 (Part C): AMG 171 Dose A/Dose B | Cohort 4 (Part C): AMG 171 Dose A/Dose B/Dose C | Cohort 5 (Part C): AMG 171 Dose A/Dose B | Cohort 4 Replaced (Part C): AMG 171 Dose A/Dose B/Dose C | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18 - 64 years | 4 Participants | 7 Participants | 6 Participants | 2 Participants | 8 Participants | 7 Participants | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 60 Participants |
| Age, Customized < 18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized ≥ 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 2 Participants | 6 Participants | 1 Participants | 6 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 3 Participants | 0 Participants | 4 Participants | 4 Participants | 6 Participants | 0 Participants | 5 Participants | 0 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants | 4 Participants | 3 Participants | 0 Participants | 4 Participants | 3 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 6 Participants | 4 Participants | 2 Participants | 3 Participants | 3 Participants | 5 Participants | 6 Participants | 2 Participants | 3 Participants | 38 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 16 Participants |
| Sex: Female, Male Male | 2 Participants | 7 Participants | 5 Participants | 1 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 3 Participants | 4 Participants | 44 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 7 | 0 / 6 | 0 / 2 | 0 / 8 | 0 / 7 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 4 | 5 / 7 | 6 / 6 | 0 / 2 | 3 / 8 | 7 / 7 | 5 / 8 | 5 / 6 | 5 / 6 | 5 / 6 |
| serious Total, serious adverse events | 0 / 4 | 0 / 7 | 0 / 6 | 0 / 2 | 0 / 8 | 0 / 7 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with study treatment. A serious AE (SAE) was an AE meeting at least 1 of the following serious criteria: fatal, life-threatening, required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability; congenital anomaly/birth defect; other medically important serious event. Clinically significant changes from baseline in laboratory safety tests, vital sign assessments, and 12-lead electrocardiogram assessments were included as TEAEs.
Time frame: From first dose of IP to end of study, up to Day 207
Population: The safety analysis set included all participants who received at least 1 dose of IP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Cohort 1 and 1b) | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 0 Participants |
| Placebo (Cohort 1 and 1b) | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAE leading to IP discontinuation | 0 Participants |
| Placebo (Cohort 1 and 1b) | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any SAE | 0 Participants |
| Cohort 1 (Part A): AMG 171 Dose A | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any SAE | 0 Participants |
| Cohort 1 (Part A): AMG 171 Dose A | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAE leading to IP discontinuation | 0 Participants |
| Cohort 1 (Part A): AMG 171 Dose A | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 5 Participants |
| Cohort 1b (Part A): AMG 171 Dose B | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAE leading to IP discontinuation | 0 Participants |
| Cohort 1b (Part A): AMG 171 Dose B | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 6 Participants |
| Cohort 1b (Part A): AMG 171 Dose B | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any SAE | 0 Participants |
| Placebo (Cohort 4 Replaced) | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAE leading to IP discontinuation | 0 Participants |
| Placebo (Cohort 4 Replaced) | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 0 Participants |
| Placebo (Cohort 4 Replaced) | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any SAE | 0 Participants |
| Placebo (Cohorts 2-5) | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 3 Participants |
| Placebo (Cohorts 2-5) | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any SAE | 0 Participants |
| Placebo (Cohorts 2-5) | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAE leading to IP discontinuation | 0 Participants |
| Cohort 2 (Part B): AMG 171 Dose A Q2W | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any SAE | 0 Participants |
| Cohort 2 (Part B): AMG 171 Dose A Q2W | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 7 Participants |
| Cohort 2 (Part B): AMG 171 Dose A Q2W | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAE leading to IP discontinuation | 0 Participants |
| Cohort 3 (Part C): AMG 171 Dose A/Dose B | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 5 Participants |
| Cohort 3 (Part C): AMG 171 Dose A/Dose B | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAE leading to IP discontinuation | 0 Participants |
| Cohort 3 (Part C): AMG 171 Dose A/Dose B | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any SAE | 0 Participants |
| Cohort 4 (Part C): AMG 171 Dose A/Dose B/Dose C | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any SAE | 0 Participants |
| Cohort 4 (Part C): AMG 171 Dose A/Dose B/Dose C | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 5 Participants |
| Cohort 4 (Part C): AMG 171 Dose A/Dose B/Dose C | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAE leading to IP discontinuation | 0 Participants |
| Cohort 5 (Part C): AMG 171 Dose A/Dose B | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any SAE | 0 Participants |
| Cohort 5 (Part C): AMG 171 Dose A/Dose B | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 5 Participants |
| Cohort 5 (Part C): AMG 171 Dose A/Dose B | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAE leading to IP discontinuation | 0 Participants |
| Cohort 4 Replaced (Part C): AMG 171 Dose A/Dose B/Dose C | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 5 Participants |
| Cohort 4 Replaced (Part C): AMG 171 Dose A/Dose B/Dose C | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAE leading to IP discontinuation | 0 Participants |
| Cohort 4 Replaced (Part C): AMG 171 Dose A/Dose B/Dose C | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any SAE | 0 Participants |
Secondary
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity (AUCinf) for AMG 171: SAD Cohorts 1 and 1b
Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis.
Time frame: Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120
Population: The PK analysis set included all participants who received at least 1 dose of AMG 171 for whom at least 1 PK parameter could be adequately estimated. Participants with available data are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Cohort 1 and 1b) | Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity (AUCinf) for AMG 171: SAD Cohorts 1 and 1b | 285000 hours*ng/mL | Standard Deviation 72200 |
| Cohort 1 (Part A): AMG 171 Dose A | Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Infinity (AUCinf) for AMG 171: SAD Cohorts 1 and 1b | 792000 hours*ng/mL | Standard Deviation 324000 |
Secondary
AUC From Time 0 to 14 Days (AUC0-14) for AMG 171: MAD Cohorts 2 - 4
Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis.
Time frame: Cohort 2: pre-dose Days 1, 15, 29, 43, 57, 71; post-dose Days 5 up to 207; Cohort 3: pre-dose Days 1, 15; post-dose Days 2 up to 85; Cohort 4: pre-dose Days 1, 15, 29; post-dose Days 2 up to 113
Population: The PK analysis set included all participants who received at least 1 dose of AMG 171 for whom at least 1 PK parameter could be adequately estimated. Participants with data available are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Cohort 1 and 1b) | AUC From Time 0 to 14 Days (AUC0-14) for AMG 171: MAD Cohorts 2 - 4 | Day 71 | 375000 hours*ng/mL | Standard Deviation 120000 |
| Placebo (Cohort 1 and 1b) | AUC From Time 0 to 14 Days (AUC0-14) for AMG 171: MAD Cohorts 2 - 4 | Day 1 | 201000 hours*ng/mL | Standard Deviation 36400 |
| Cohort 1 (Part A): AMG 171 Dose A | AUC From Time 0 to 14 Days (AUC0-14) for AMG 171: MAD Cohorts 2 - 4 | Day 15 | 362000 hours*ng/mL | Standard Deviation 160000 |
| Cohort 1 (Part A): AMG 171 Dose A | AUC From Time 0 to 14 Days (AUC0-14) for AMG 171: MAD Cohorts 2 - 4 | Day 1 | 205000 hours*ng/mL | Standard Deviation 123000 |
| Cohort 1b (Part A): AMG 171 Dose B | AUC From Time 0 to 14 Days (AUC0-14) for AMG 171: MAD Cohorts 2 - 4 | Day 15 | 440000 hours*ng/mL | Standard Deviation 261000 |
| Cohort 1b (Part A): AMG 171 Dose B | AUC From Time 0 to 14 Days (AUC0-14) for AMG 171: MAD Cohorts 2 - 4 | Day 29 | 1050000 hours*ng/mL | Standard Deviation 429000 |
| Cohort 1b (Part A): AMG 171 Dose B | AUC From Time 0 to 14 Days (AUC0-14) for AMG 171: MAD Cohorts 2 - 4 | Day 1 | 133000 hours*ng/mL | Standard Deviation 74000 |
Secondary
AUC From Time 0 to 7 Days (AUC0-7) for AMG 171: MAD Cohort 5
Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis.
Time frame: Cohort 5: pre-dose Days 1, 8; post-dose Days 2 up to 85
Population: The PK analysis set included all participants who received at least 1 dose of AMG 171 for whom at least 1 PK parameter could be adequately estimated. Participants with data available are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Cohort 1 and 1b) | AUC From Time 0 to 7 Days (AUC0-7) for AMG 171: MAD Cohort 5 | Day 1 | 138000 hours*ng/mL | Standard Deviation 47200 |
| Placebo (Cohort 1 and 1b) | AUC From Time 0 to 7 Days (AUC0-7) for AMG 171: MAD Cohort 5 | Day 8 | 351000 hours*ng/mL | Standard Deviation 272000 |
Secondary
Cmax for AMG 171: MAD Cohorts 2 - 5
Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis.
Time frame: Cohort 2: pre-dose Days 1, 15, 29, 43, 57, 71; post-dose Days 5 up to 207; Cohort 3: pre-dose Days 1, 15; post-dose Days 2 up to 85; Cohort 4: pre-dose Days 1, 15, 29; post-dose Days 2 up to 113; Cohort 5: pre-dose Days 1, 8; post-dose Days 2 up to 85
Population: The PK analysis set included all participants who received at least 1 dose of AMG 171 for whom at least 1 PK parameter could be adequately estimated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Cohort 1 and 1b) | Cmax for AMG 171: MAD Cohorts 2 - 5 | Day 1 | 695 ng/mL | Standard Deviation 229 |
| Placebo (Cohort 1 and 1b) | Cmax for AMG 171: MAD Cohorts 2 - 5 | Day 71 | 1490 ng/mL | Standard Deviation 702 |
| Cohort 1 (Part A): AMG 171 Dose A | Cmax for AMG 171: MAD Cohorts 2 - 5 | Day 15 | 1350 ng/mL | Standard Deviation 670 |
| Cohort 1 (Part A): AMG 171 Dose A | Cmax for AMG 171: MAD Cohorts 2 - 5 | Day 1 | 847 ng/mL | Standard Deviation 522 |
| Cohort 1b (Part A): AMG 171 Dose B | Cmax for AMG 171: MAD Cohorts 2 - 5 | Day 1 | 455 ng/mL | Standard Deviation 335 |
| Cohort 1b (Part A): AMG 171 Dose B | Cmax for AMG 171: MAD Cohorts 2 - 5 | Day 15 | 1760 ng/mL | Standard Deviation 1080 |
| Cohort 1b (Part A): AMG 171 Dose B | Cmax for AMG 171: MAD Cohorts 2 - 5 | Day 29 | 3960 ng/mL | Standard Deviation 1600 |
| Placebo (Cohort 4 Replaced) | Cmax for AMG 171: MAD Cohorts 2 - 5 | Day 8 | 2550 ng/mL | Standard Deviation 1820 |
| Placebo (Cohort 4 Replaced) | Cmax for AMG 171: MAD Cohorts 2 - 5 | Day 1 | 769 ng/mL | Standard Deviation 470 |
Secondary
Maximum Observed Serum Concentration (Cmax) for AMG 171: SAD Cohorts 1 and 1b
Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of pharmacokinetic (PK) parameters. Concentrations below the lower limit of quantification (LLOQ) (50.0 ng/mL) were set to zero before data analysis.
Time frame: Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120
Population: The PK analysis set included all participants who received at least 1 dose of AMG 171 for whom at least 1 PK parameter could be adequately estimated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Cohort 1 and 1b) | Maximum Observed Serum Concentration (Cmax) for AMG 171: SAD Cohorts 1 and 1b | 697 ng/mL | Standard Deviation 405 |
| Cohort 1 (Part A): AMG 171 Dose A | Maximum Observed Serum Concentration (Cmax) for AMG 171: SAD Cohorts 1 and 1b | 1740 ng/mL | Standard Deviation 759 |
Secondary
Number of Participants With Anti-AMG 171 Antibodies
Serum samples were tested for binding and neutralizing antibodies against human Growth Differentiation Factor 15. Participants with transiently positive for binding or neutralizing antibodies had a negative result at the participant's last time point tested. bAb = binding antibody; nAb = neutralizing antibody; +ve = positive; -ve = negative; BL = baseline.
Time frame: Cohorts 1 and 1b: Day 1 pre-dose, Days 15, 29, 120; Cohort 2: Days 1, 29, 57 pre-dose, Days 15, 85, 207; Cohort 3: Days 1, 15 pre-dose, Days 29, 57, 85; Cohort 4: Days 1, 15, 29 pre-dose, Days 43, 85, 113; Cohort 5: Days 1, 8 pre-dose, Days 29, 57, 85
Population: The safety analysis set included all participants who received at least 1 dose of IP. Data for participants with an on-study result are included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Cohort 1 and 1b) | Number of Participants With Anti-AMG 171 Antibodies | Transient nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Placebo (Cohort 1 and 1b) | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve at/before BL | 0 Participants |
| Placebo (Cohort 1 and 1b) | Number of Participants With Anti-AMG 171 Antibodies | Transient bAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Placebo (Cohort 1 and 1b) | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve at/before BL | 1 Participants |
| Placebo (Cohort 1 and 1b) | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Placebo (Cohort 1 and 1b) | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 1 (Part A): AMG 171 Dose A | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve at/before BL | 1 Participants |
| Cohort 1 (Part A): AMG 171 Dose A | Number of Participants With Anti-AMG 171 Antibodies | Transient bAb +ve post-BL with -ve/no result at BL | 1 Participants |
| Cohort 1 (Part A): AMG 171 Dose A | Number of Participants With Anti-AMG 171 Antibodies | Transient nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 1 (Part A): AMG 171 Dose A | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve at/before BL | 0 Participants |
| Cohort 1 (Part A): AMG 171 Dose A | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 1 (Part A): AMG 171 Dose A | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve post-BL with -ve/no result at BL | 1 Participants |
| Cohort 1b (Part A): AMG 171 Dose B | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 1b (Part A): AMG 171 Dose B | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve post-BL with -ve/no result at BL | 2 Participants |
| Cohort 1b (Part A): AMG 171 Dose B | Number of Participants With Anti-AMG 171 Antibodies | Transient nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 1b (Part A): AMG 171 Dose B | Number of Participants With Anti-AMG 171 Antibodies | Transient bAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 1b (Part A): AMG 171 Dose B | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve at/before BL | 0 Participants |
| Cohort 1b (Part A): AMG 171 Dose B | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve at/before BL | 0 Participants |
| Cohort 2 (Part B): AMG 171 Dose A Q2W | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 2 (Part B): AMG 171 Dose A Q2W | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve at/before BL | 0 Participants |
| Cohort 2 (Part B): AMG 171 Dose A Q2W | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve at/before BL | 0 Participants |
| Cohort 2 (Part B): AMG 171 Dose A Q2W | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve post-BL with -ve/no result at BL | 1 Participants |
| Cohort 2 (Part B): AMG 171 Dose A Q2W | Number of Participants With Anti-AMG 171 Antibodies | Transient bAb +ve post-BL with -ve/no result at BL | 1 Participants |
| Cohort 2 (Part B): AMG 171 Dose A Q2W | Number of Participants With Anti-AMG 171 Antibodies | Transient nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 3 (Part C): AMG 171 Dose A/Dose B | Number of Participants With Anti-AMG 171 Antibodies | Transient bAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 3 (Part C): AMG 171 Dose A/Dose B | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve at/before BL | 0 Participants |
| Cohort 3 (Part C): AMG 171 Dose A/Dose B | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 3 (Part C): AMG 171 Dose A/Dose B | Number of Participants With Anti-AMG 171 Antibodies | Transient nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 3 (Part C): AMG 171 Dose A/Dose B | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 3 (Part C): AMG 171 Dose A/Dose B | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve at/before BL | 0 Participants |
| Cohort 4 (Part C): AMG 171 Dose A/Dose B/Dose C | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 4 (Part C): AMG 171 Dose A/Dose B/Dose C | Number of Participants With Anti-AMG 171 Antibodies | Transient bAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 4 (Part C): AMG 171 Dose A/Dose B/Dose C | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve at/before BL | 0 Participants |
| Cohort 4 (Part C): AMG 171 Dose A/Dose B/Dose C | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 4 (Part C): AMG 171 Dose A/Dose B/Dose C | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve at/before BL | 0 Participants |
| Cohort 4 (Part C): AMG 171 Dose A/Dose B/Dose C | Number of Participants With Anti-AMG 171 Antibodies | Transient nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 5 (Part C): AMG 171 Dose A/Dose B | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve post-BL with -ve/no result at BL | 1 Participants |
| Cohort 5 (Part C): AMG 171 Dose A/Dose B | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve at/before BL | 0 Participants |
| Cohort 5 (Part C): AMG 171 Dose A/Dose B | Number of Participants With Anti-AMG 171 Antibodies | Transient nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 5 (Part C): AMG 171 Dose A/Dose B | Number of Participants With Anti-AMG 171 Antibodies | Transient bAb +ve post-BL with -ve/no result at BL | 1 Participants |
| Cohort 5 (Part C): AMG 171 Dose A/Dose B | Number of Participants With Anti-AMG 171 Antibodies | nAb +ve post-BL with -ve/no result at BL | 0 Participants |
| Cohort 5 (Part C): AMG 171 Dose A/Dose B | Number of Participants With Anti-AMG 171 Antibodies | bAb +ve at/before BL | 0 Participants |
Secondary
Time of Cmax (Tmax) for AMG 171: SAD Cohorts 1 and 1b
Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis.
Time frame: Cohorts 1 and 1b: pre-dose Day 1; 1, 2, 4, and 8 hours post-dose Day 1, Days 2 up to Day 120
Population: The PK analysis set included all participants who received at least 1 dose of AMG 171 for whom at least 1 PK parameter could be adequately estimated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Cohort 1 and 1b) | Time of Cmax (Tmax) for AMG 171: SAD Cohorts 1 and 1b | 120 hours |
| Cohort 1 (Part A): AMG 171 Dose A | Time of Cmax (Tmax) for AMG 171: SAD Cohorts 1 and 1b | 120 hours |
Secondary
Tmax for AMG 171: MAD Cohorts 2 - 5
Serum concentrations of AMG 171 were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (50.0 ng/mL) were set to zero before data analysis.
Time frame: Cohort 2: pre-dose Days 1, 15, 29, 43, 57, 71; post-dose Days 5 up to 207; Cohort 3: pre-dose Days 1, 15; post-dose Days 2 up to 85; Cohort 4: pre-dose Days 1, 15, 29; post-dose Days 2 up to 113; Cohort 5: pre-dose Days 1, 8; post-dose Days 2 up to 85
Population: The PK analysis set included all participants who received at least 1 dose of AMG 171 for whom at least 1 PK parameter could be adequately estimated.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo (Cohort 1 and 1b) | Tmax for AMG 171: MAD Cohorts 2 - 5 | Day 1 | 93 hours |
| Placebo (Cohort 1 and 1b) | Tmax for AMG 171: MAD Cohorts 2 - 5 | Day 71 | 72 hours |
| Cohort 1 (Part A): AMG 171 Dose A | Tmax for AMG 171: MAD Cohorts 2 - 5 | Day 15 | 72 hours |
| Cohort 1 (Part A): AMG 171 Dose A | Tmax for AMG 171: MAD Cohorts 2 - 5 | Day 1 | 60 hours |
| Cohort 1b (Part A): AMG 171 Dose B | Tmax for AMG 171: MAD Cohorts 2 - 5 | Day 1 | 84 hours |
| Cohort 1b (Part A): AMG 171 Dose B | Tmax for AMG 171: MAD Cohorts 2 - 5 | Day 15 | 96 hours |
| Cohort 1b (Part A): AMG 171 Dose B | Tmax for AMG 171: MAD Cohorts 2 - 5 | Day 29 | 110 hours |
| Placebo (Cohort 4 Replaced) | Tmax for AMG 171: MAD Cohorts 2 - 5 | Day 8 | 82 hours |
| Placebo (Cohort 4 Replaced) | Tmax for AMG 171: MAD Cohorts 2 - 5 | Day 1 | 58 hours |