Obesity
Conditions
Brief summary
The main objective of this study is to assess the safety and tolerability of multiple doses of AMG 598 administered alone or in combination with liraglutide in adults with obesity.
Interventions
DRUGAMG 598
AMG 598 administered by subcutaneous injection
DRUGPlacebo
Placebo matching to AMG 598 administered by subcutaneous injection
DRUGLiraglutide
Liraglutide administered by subcutaneous injection. The starting dose is 0.6 mg/day, and increased by 0.6 mg/day dose increment every 7 days, up to the full dosage of 3.0 mg/day by week 5.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind study
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Men and women with ages between 18 and 65 years old, inclusive, at time of signing consent * Body mass index (BMI) between greater than or equal to 30.0 kg/m\^2 and less than or equal to 40.0 kg/m\^2 at screening * Except for obesity, otherwise healthy or medically stable per protocol * Have a stable body weight defined as less than 5 kg self-reported change during the previous 8 weeks prior to screening * Other Inclusion criteria may apply * Stable on liraglutide, depending on cohort
Exclusion criteria
* History or clinical evidence of diabetes * Inadequate organ function at screening * Currently receiving treatment in another investigational device or drug study * Women who are pregnant/lactating/breastfeeding or who plan to become pregnant/breastfeed while on study through 5 months after receiving the last dose of investigational product * 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 * A family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2; a personal history of non-familial medullary thyroid carcinoma; confirmed chronic pancreatitis or idiopathic acute pancreatitis, or gallbladder disease (ie, cholelithiasis or cholecystitis) not treated with cholecystectomy, for cohorts receiving liraglutide * History of major depressive disorder * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events | 207 days | The investigator assessed the severity of each adverse event reported during the study. The assessment was based on the Amgen Standard Grading Scale: Mild: Aware of sign or symptom, but easily tolerated. Moderate: Discomfort enough to cause interference with usual activity. Severe: Incapacitating with inability to work or do usual activity. A Serious adverse event is defined as any untoward medical occurrence that, met at least 1 of the following serious criteria * Death; * Was life-threatening; * Required in-patient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Other medically important serious event. The investigator also assessed whether each adverse event was related to study drug administration based on clinical judgement. |
| Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | 207 days | TEAEs due to laboratory, electrocardiogram (ECG) and vital sign findings include any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or electrocardiogram, or vital signs measurements, including those that worsened from baseline, that were considered clinically significant in the medical and scientific judgment of the investigator (ie, not related to progression of underlying disease). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207 | Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL. |
| Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85 | Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL. |
| Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85 | Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL. |
| Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207 | Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL. |
| Accumulation Ratio (AR) for Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207 | Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL. Accumulation ratio for Cmax = Day 57 Cmax / Day 1 Cmax. |
| Accumulation Ratio of AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85 | Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL. The accumulation ratio for AUC0-28 = Day 57 AUC0-28 / Day 1 AUC0-28. |
| Terminal Half-life (T1/2,z) of AMG 598 After Subcutaneous Injection on Day 57 | Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207 | Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL. |
| Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of AMG 598 After Subcutaneous Injection on Day 57 | Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207 | Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL. |
| Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207 | Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 2 centers in the United States.
Pre-assignment details
Eligible participants were randomized to one of six treatment cohorts. Within each cohort participants were randomly assigned in a 3:1 ratio to receive either AMG 598 or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for a total of 3 doses. | 6 |
| Placebo + Liraglutide Participants received placebo subcutaneous injection once every 4 weeks for a total of 3 doses in addition to liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5. | 6 |
| AMG 598 70 mg Participants received 70 mg AMG 598 by subcutaneous injection once every 4 weeks (Q4W) for a total of 3 doses. | 6 |
| AMG 598 70 mg + Liraglutide Participants received 70 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses in addition liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5. | 8 |
| AMG 598 210 mg Participants received 210 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses. | 6 |
| AMG 598 210 mg + Liraglutide Participants received 210 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses in addition to liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5. | 6 |
| AMG 598 420 mg Participants received 420 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses. | 6 |
| AMG 598 420 mg + Liraglutide Participants received 420 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses in addition to liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5. | 6 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo + Liraglutide | AMG 598 70 mg | AMG 598 70 mg + Liraglutide | AMG 598 210 mg | Placebo | AMG 598 210 mg + Liraglutide | AMG 598 420 mg | AMG 598 420 mg + Liraglutide | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 41.8 years STANDARD_DEVIATION 7.6 | 41.7 years STANDARD_DEVIATION 11.3 | 46.1 years STANDARD_DEVIATION 14.2 | 50.3 years STANDARD_DEVIATION 7.8 | 47.2 years STANDARD_DEVIATION 11 | 51.5 years STANDARD_DEVIATION 8.5 | 44.5 years STANDARD_DEVIATION 10.9 | 49.2 years STANDARD_DEVIATION 11.7 | 46.5 years STANDARD_DEVIATION 10.6 |
| Age, Customized < 40 years | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 14 Participants |
| Age, Customized ≥ 40 years | 4 Participants | 3 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 4 Participants | 5 Participants | 36 Participants |
| Body Mass Index (BMI) | 33.20 kg/m² STANDARD_DEVIATION 2.1 | 34.62 kg/m² STANDARD_DEVIATION 2.92 | 35.46 kg/m² STANDARD_DEVIATION 2.19 | 34.43 kg/m² STANDARD_DEVIATION 3.37 | 34.22 kg/m² STANDARD_DEVIATION 2.61 | 34.42 kg/m² STANDARD_DEVIATION 3.24 | 32.77 kg/m² STANDARD_DEVIATION 3.04 | 36.00 kg/m² STANDARD_DEVIATION 4.04 | 34.43 kg/m² STANDARD_DEVIATION 2.92 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 8 Participants | 6 Participants | 4 Participants | 6 Participants | 3 Participants | 5 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 1 Participants | 9 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 |
| 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 |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 10 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 |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 7 Participants | 5 Participants | 5 Participants | 3 Participants | 5 Participants | 5 Participants | 39 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 1 Participants | 15 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 5 Participants | 5 Participants | 35 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 6 | 6 / 6 | 4 / 6 | 7 / 8 | 5 / 6 | 6 / 6 | 0 / 6 | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings
TEAEs due to laboratory, electrocardiogram (ECG) and vital sign findings include any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or electrocardiogram, or vital signs measurements, including those that worsened from baseline, that were considered clinically significant in the medical and scientific judgment of the investigator (ie, not related to progression of underlying disease).
Time frame: 207 days
Population: All participants who received at least 1 dose of study drug (AMG 598 or placebo) on day 1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Blood creatine phosphokinase increased | 0 Participants |
| Placebo | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hypertension | 0 Participants |
| Placebo | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Lipase increased | 0 Participants |
| Placebo | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hepatic enzyme increased | 0 Participants |
| Placebo | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Electrocardiogram T wave abnormal | 0 Participants |
| Placebo + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Electrocardiogram T wave abnormal | 0 Participants |
| Placebo + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Lipase increased | 1 Participants |
| Placebo + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hypertension | 0 Participants |
| Placebo + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hepatic enzyme increased | 0 Participants |
| Placebo + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Blood creatine phosphokinase increased | 0 Participants |
| AMG 598 70 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Electrocardiogram T wave abnormal | 0 Participants |
| AMG 598 70 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hypertension | 1 Participants |
| AMG 598 70 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Blood creatine phosphokinase increased | 0 Participants |
| AMG 598 70 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Lipase increased | 0 Participants |
| AMG 598 70 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hepatic enzyme increased | 0 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hepatic enzyme increased | 0 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hypertension | 0 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Blood creatine phosphokinase increased | 0 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Electrocardiogram T wave abnormal | 0 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Lipase increased | 3 Participants |
| AMG 598 210 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hepatic enzyme increased | 0 Participants |
| AMG 598 210 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Blood creatine phosphokinase increased | 1 Participants |
| AMG 598 210 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Electrocardiogram T wave abnormal | 0 Participants |
| AMG 598 210 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Lipase increased | 0 Participants |
| AMG 598 210 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hypertension | 0 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hepatic enzyme increased | 0 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Lipase increased | 1 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Electrocardiogram T wave abnormal | 0 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Blood creatine phosphokinase increased | 0 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hypertension | 0 Participants |
| AMG 598 420 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hepatic enzyme increased | 0 Participants |
| AMG 598 420 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Blood creatine phosphokinase increased | 0 Participants |
| AMG 598 420 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Electrocardiogram T wave abnormal | 0 Participants |
| AMG 598 420 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hypertension | 0 Participants |
| AMG 598 420 mg | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Lipase increased | 0 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hypertension | 0 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Lipase increased | 1 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Blood creatine phosphokinase increased | 0 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Hepatic enzyme increased | 1 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings | Electrocardiogram T wave abnormal | 1 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events
The investigator assessed the severity of each adverse event reported during the study. The assessment was based on the Amgen Standard Grading Scale: Mild: Aware of sign or symptom, but easily tolerated. Moderate: Discomfort enough to cause interference with usual activity. Severe: Incapacitating with inability to work or do usual activity. A Serious adverse event is defined as any untoward medical occurrence that, met at least 1 of the following serious criteria * Death; * Was life-threatening; * Required in-patient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Other medically important serious event. The investigator also assessed whether each adverse event was related to study drug administration based on clinical judgement.
Time frame: 207 days
Population: All participants who received at least 1 dose of study drug (AMG 598 or placebo) on day 1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Mild TEAEs | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Severe TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of liraglutide | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Serious TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Fatal TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | All treatment-emergent adverse events (TEAEs) | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of AMG 598 | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Moderate TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events | Life-threatening TEAEs | 0 Participants |
| Placebo + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Moderate TEAEs | 1 Participants |
| Placebo + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Severe TEAEs | 0 Participants |
| Placebo + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Life-threatening TEAEs | 0 Participants |
| Placebo + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Serious TEAEs | 0 Participants |
| Placebo + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Fatal TEAEs | 0 Participants |
| Placebo + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of AMG 598 | 0 Participants |
| Placebo + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | All treatment-emergent adverse events (TEAEs) | 6 Participants |
| Placebo + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of liraglutide | 1 Participants |
| Placebo + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Mild TEAEs | 6 Participants |
| AMG 598 70 mg | Number of Participants With Treatment-emergent Adverse Events | Moderate TEAEs | 0 Participants |
| AMG 598 70 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of AMG 598 | 0 Participants |
| AMG 598 70 mg | Number of Participants With Treatment-emergent Adverse Events | Fatal TEAEs | 0 Participants |
| AMG 598 70 mg | Number of Participants With Treatment-emergent Adverse Events | Mild TEAEs | 4 Participants |
| AMG 598 70 mg | Number of Participants With Treatment-emergent Adverse Events | Life-threatening TEAEs | 0 Participants |
| AMG 598 70 mg | Number of Participants With Treatment-emergent Adverse Events | All treatment-emergent adverse events (TEAEs) | 4 Participants |
| AMG 598 70 mg | Number of Participants With Treatment-emergent Adverse Events | Severe TEAEs | 0 Participants |
| AMG 598 70 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of liraglutide | 0 Participants |
| AMG 598 70 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAEs | 0 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Severe TEAEs | 0 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | All treatment-emergent adverse events (TEAEs) | 7 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Serious TEAEs | 0 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Life-threatening TEAEs | 0 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Mild TEAEs | 7 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Fatal TEAEs | 0 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of liraglutide | 1 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Moderate TEAEs | 2 Participants |
| AMG 598 70 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of AMG 598 | 0 Participants |
| AMG 598 210 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAEs | 0 Participants |
| AMG 598 210 mg | Number of Participants With Treatment-emergent Adverse Events | All treatment-emergent adverse events (TEAEs) | 5 Participants |
| AMG 598 210 mg | Number of Participants With Treatment-emergent Adverse Events | Mild TEAEs | 5 Participants |
| AMG 598 210 mg | Number of Participants With Treatment-emergent Adverse Events | Moderate TEAEs | 0 Participants |
| AMG 598 210 mg | Number of Participants With Treatment-emergent Adverse Events | Severe TEAEs | 0 Participants |
| AMG 598 210 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of AMG 598 | 0 Participants |
| AMG 598 210 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of liraglutide | 0 Participants |
| AMG 598 210 mg | Number of Participants With Treatment-emergent Adverse Events | Life-threatening TEAEs | 0 Participants |
| AMG 598 210 mg | Number of Participants With Treatment-emergent Adverse Events | Fatal TEAEs | 0 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Mild TEAEs | 6 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | All treatment-emergent adverse events (TEAEs) | 6 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of liraglutide | 0 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Moderate TEAEs | 0 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Severe TEAEs | 0 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Fatal TEAEs | 0 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Serious TEAEs | 0 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Life-threatening TEAEs | 0 Participants |
| AMG 598 210 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of AMG 598 | 0 Participants |
| AMG 598 420 mg | Number of Participants With Treatment-emergent Adverse Events | Life-threatening TEAEs | 0 Participants |
| AMG 598 420 mg | Number of Participants With Treatment-emergent Adverse Events | All treatment-emergent adverse events (TEAEs) | 0 Participants |
| AMG 598 420 mg | Number of Participants With Treatment-emergent Adverse Events | Serious TEAEs | 0 Participants |
| AMG 598 420 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of liraglutide | 0 Participants |
| AMG 598 420 mg | Number of Participants With Treatment-emergent Adverse Events | Severe TEAEs | 0 Participants |
| AMG 598 420 mg | Number of Participants With Treatment-emergent Adverse Events | Moderate TEAEs | 0 Participants |
| AMG 598 420 mg | Number of Participants With Treatment-emergent Adverse Events | Mild TEAEs | 0 Participants |
| AMG 598 420 mg | Number of Participants With Treatment-emergent Adverse Events | Fatal TEAEs | 0 Participants |
| AMG 598 420 mg | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of AMG 598 | 0 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Fatal TEAEs | 0 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of AMG 598 | 1 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Severe TEAEs | 0 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Moderate TEAEs | 1 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of liraglutide | 2 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Mild TEAEs | 4 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Life-threatening TEAEs | 0 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | All treatment-emergent adverse events (TEAEs) | 4 Participants |
| AMG 598 420 mg + Liraglutide | Number of Participants With Treatment-emergent Adverse Events | Serious TEAEs | 0 Participants |
Secondary
Accumulation Ratio (AR) for Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL. Accumulation ratio for Cmax = Day 57 Cmax / Day 1 Cmax.
Time frame: Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Population: The PK analysis set; participants with available data at both time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Accumulation Ratio (AR) for Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | 1.62 ratio | Standard Deviation 0.394 |
| Placebo + Liraglutide | Accumulation Ratio (AR) for Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | 1.70 ratio | Standard Deviation 0.237 |
| AMG 598 70 mg | Accumulation Ratio (AR) for Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | 2.12 ratio | Standard Deviation 0.251 |
| AMG 598 70 mg + Liraglutide | Accumulation Ratio (AR) for Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | 1.92 ratio | Standard Deviation 0.207 |
| AMG 598 210 mg | Accumulation Ratio (AR) for Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | 1.83 ratio | Standard Deviation 0.138 |
| AMG 598 210 mg + Liraglutide | Accumulation Ratio (AR) for Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | 2.13 ratio | Standard Deviation 0.418 |
Secondary
Accumulation Ratio of AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL. The accumulation ratio for AUC0-28 = Day 57 AUC0-28 / Day 1 AUC0-28.
Time frame: Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85
Population: The PK analysis set; participants with available data at both time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Accumulation Ratio of AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | 1.74 ratio | Standard Deviation 0.48 |
| Placebo + Liraglutide | Accumulation Ratio of AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | 1.84 ratio | Standard Deviation 0.223 |
| AMG 598 70 mg | Accumulation Ratio of AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | 2.09 ratio | Standard Deviation 0.254 |
| AMG 598 70 mg + Liraglutide | Accumulation Ratio of AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | 1.86 ratio | Standard Deviation 0.186 |
| AMG 598 210 mg | Accumulation Ratio of AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | 1.96 ratio | Standard Deviation 0.177 |
| AMG 598 210 mg + Liraglutide | Accumulation Ratio of AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | 2.17 ratio | Standard Deviation 0.291 |
Secondary
Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time frame: Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85
Population: The PK analysis set; participants with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 139 days*µg/mL | Standard Deviation 19.6 |
| Placebo | Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 215 days*µg/mL | Standard Deviation 45.3 |
| Placebo + Liraglutide | Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 147 days*µg/mL | Standard Deviation 21.8 |
| Placebo + Liraglutide | Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 276 days*µg/mL | Standard Deviation 57.6 |
| AMG 598 70 mg | Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 495 days*µg/mL | Standard Deviation 72.7 |
| AMG 598 70 mg | Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 964 days*µg/mL | Standard Deviation 203 |
| AMG 598 70 mg + Liraglutide | Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 366 days*µg/mL | Standard Deviation 101 |
| AMG 598 70 mg + Liraglutide | Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 749 days*µg/mL | Standard Deviation 254 |
| AMG 598 210 mg | Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 1080 days*µg/mL | Standard Deviation 225 |
| AMG 598 210 mg | Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 1990 days*µg/mL | Standard Deviation 341 |
| AMG 598 210 mg + Liraglutide | Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 763 days*µg/mL | Standard Deviation 285 |
| AMG 598 210 mg + Liraglutide | Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 1610 days*µg/mL | Standard Deviation 511 |
Secondary
Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of AMG 598 After Subcutaneous Injection on Day 57
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time frame: Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Population: The PK analysis set; participants with available data for AUClast.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of AMG 598 After Subcutaneous Injection on Day 57 | 458 days*µg/mL | Standard Deviation 102 |
| Placebo + Liraglutide | Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of AMG 598 After Subcutaneous Injection on Day 57 | 612 days*µg/mL | Standard Deviation 129 |
| AMG 598 70 mg | Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of AMG 598 After Subcutaneous Injection on Day 57 | 2130 days*µg/mL | Standard Deviation 334 |
| AMG 598 70 mg + Liraglutide | Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of AMG 598 After Subcutaneous Injection on Day 57 | 1570 days*µg/mL | Standard Deviation 462 |
| AMG 598 210 mg | Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of AMG 598 After Subcutaneous Injection on Day 57 | 4060 days*µg/mL | Standard Deviation 1610 |
| AMG 598 210 mg + Liraglutide | Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of AMG 598 After Subcutaneous Injection on Day 57 | 3060 days*µg/mL | Standard Deviation 920 |
Secondary
Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time frame: Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85
Population: The PK analysis set; participants with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 1.98 days*µg/mL/mg | Standard Deviation 0.279 |
| Placebo | Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 3.07 days*µg/mL/mg | Standard Deviation 0.647 |
| Placebo + Liraglutide | Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 2.10 days*µg/mL/mg | Standard Deviation 0.311 |
| Placebo + Liraglutide | Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 3.94 days*µg/mL/mg | Standard Deviation 0.823 |
| AMG 598 70 mg | Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 2.36 days*µg/mL/mg | Standard Deviation 0.346 |
| AMG 598 70 mg | Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 4.59 days*µg/mL/mg | Standard Deviation 0.966 |
| AMG 598 70 mg + Liraglutide | Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 1.74 days*µg/mL/mg | Standard Deviation 0.48 |
| AMG 598 70 mg + Liraglutide | Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 3.57 days*µg/mL/mg | Standard Deviation 1.21 |
| AMG 598 210 mg | Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 2.57 days*µg/mL/mg | Standard Deviation 0.535 |
| AMG 598 210 mg | Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 4.75 days*µg/mL/mg | Standard Deviation 0.812 |
| AMG 598 210 mg + Liraglutide | Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 1.82 days*µg/mL/mg | Standard Deviation 0.68 |
| AMG 598 210 mg + Liraglutide | Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 3.84 days*µg/mL/mg | Standard Deviation 1.22 |
Secondary
Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time frame: Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Population: The PK analysis set; participants with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 0.0833 µg/mL/mg | Standard Deviation 0.0239 |
| Placebo | Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 0.130 µg/mL/mg | Standard Deviation 0.0272 |
| Placebo + Liraglutide | Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 0.107 µg/mL/mg | Standard Deviation 0.0167 |
| Placebo + Liraglutide | Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 0.172 µg/mL/mg | Standard Deviation 0.0366 |
| AMG 598 70 mg | Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 0.102 µg/mL/mg | Standard Deviation 0.0258 |
| AMG 598 70 mg | Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 0.216 µg/mL/mg | Standard Deviation 0.0593 |
| AMG 598 70 mg + Liraglutide | Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 0.0856 µg/mL/mg | Standard Deviation 0.0274 |
| AMG 598 70 mg + Liraglutide | Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 0.168 µg/mL/mg | Standard Deviation 0.0572 |
| AMG 598 210 mg | Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 0.122 µg/mL/mg | Standard Deviation 0.0231 |
| AMG 598 210 mg | Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 0.222 µg/mL/mg | Standard Deviation 0.0433 |
| AMG 598 210 mg + Liraglutide | Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 0.0879 µg/mL/mg | Standard Deviation 0.0327 |
| AMG 598 210 mg + Liraglutide | Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 0.172 µg/mL/mg | Standard Deviation 0.05949 |
Secondary
Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time frame: Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Population: The pharmacokinetic (PK) analysis set included all participants for whom at least 1 PK parameter or endpoint could be adequately estimated. Participants with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 5.83 µg/mL | Standard Deviation 1.67 |
| Placebo | Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 9.07 µg/mL | Standard Deviation 1.91 |
| Placebo + Liraglutide | Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 7.49 µg/mL | Standard Deviation 1.17 |
| Placebo + Liraglutide | Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 12.0 µg/mL | Standard Deviation 2.56 |
| AMG 598 70 mg | Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 21.5 µg/mL | Standard Deviation 5.43 |
| AMG 598 70 mg | Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 45.4 µg/mL | Standard Deviation 12.5 |
| AMG 598 70 mg + Liraglutide | Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 18.0 µg/mL | Standard Deviation 5.76 |
| AMG 598 70 mg + Liraglutide | Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 34.8 µg/mL | Standard Deviation 12 |
| AMG 598 210 mg | Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 51.1 µg/mL | Standard Deviation 9.7 |
| AMG 598 210 mg | Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 93.2 µg/mL | Standard Deviation 18.2 |
| AMG 598 210 mg + Liraglutide | Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 36.9 µg/mL | Standard Deviation 13.7 |
| AMG 598 210 mg + Liraglutide | Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 72.4 µg/mL | Standard Deviation 23 |
Secondary
Terminal Half-life (T1/2,z) of AMG 598 After Subcutaneous Injection on Day 57
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time frame: Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Population: The PK analysis set; participants with available data for T1/2,z
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Terminal Half-life (T1/2,z) of AMG 598 After Subcutaneous Injection on Day 57 | 28.2 days | Standard Deviation 3.04 |
| Placebo + Liraglutide | Terminal Half-life (T1/2,z) of AMG 598 After Subcutaneous Injection on Day 57 | 31.5 days | Standard Deviation 6.05 |
| AMG 598 70 mg | Terminal Half-life (T1/2,z) of AMG 598 After Subcutaneous Injection on Day 57 | 35.2 days | Standard Deviation 5.86 |
| AMG 598 70 mg + Liraglutide | Terminal Half-life (T1/2,z) of AMG 598 After Subcutaneous Injection on Day 57 | 29.1 days | Standard Deviation 3.02 |
| AMG 598 210 mg | Terminal Half-life (T1/2,z) of AMG 598 After Subcutaneous Injection on Day 57 | 35.8 days | Standard Deviation 3.21 |
| AMG 598 210 mg + Liraglutide | Terminal Half-life (T1/2,z) of AMG 598 After Subcutaneous Injection on Day 57 | 29.8 days | Standard Deviation 6.72 |
Secondary
Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57
Serum concentrations of AMG 598 were determined using a validated electrochemiluminescence-based method. The lower limit of quantitation was 50.0 ng/mL.
Time frame: Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207
Population: The PK analysis set; participants with available data at each time point
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 7.1 days |
| Placebo | Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 7.0 days |
| Placebo + Liraglutide | Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 7.0 days |
| Placebo + Liraglutide | Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 7.0 days |
| AMG 598 70 mg | Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 7.1 days |
| AMG 598 70 mg | Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 6.1 days |
| AMG 598 70 mg + Liraglutide | Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 7.0 days |
| AMG 598 70 mg + Liraglutide | Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 6.5 days |
| AMG 598 210 mg | Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 6.9 days |
| AMG 598 210 mg | Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 5.3 days |
| AMG 598 210 mg + Liraglutide | Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 1 | 7.0 days |
| AMG 598 210 mg + Liraglutide | Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57 | Day 57 | 7.0 days |