Cardiovascular
Conditions
Brief summary
A study to assess the safety and tolerability of AMG 529 following single, ascending doses administered subcutaneously (SC) or intravenously (IV) in healthy adults.
Interventions
DRUGAMG 529
Ascending single doses of AMG 529 by subcutaneous (SC) or intravenous (IV) injection
DRUGPlacebo
Single doses of matching placebo by SC or IV injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Within each dose cohort participants were randomized in a 3:1 ratio to receive either AMG 529 or placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy men and women ≥ 18 to ≤ 55 years old with no history or evidence of clinically relevant medical disorders 2. Body mass index (BMI) between 18 and 32 kg/m², inclusive, at screening 3. Women must be of non-reproductive potential as defined in protocol 4. Other inclusion criteria may apply
Exclusion criteria
1. Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives (whichever is longer), since ending treatment on another investigational device or drug study(s) prior to receiving the first dose of investigational product 2. Women who are lactating/breastfeeding or who plan to breastfeed while on study through 90 days after receiving the dose of investigational product 3. Men with partners who are pregnant or planning to become pregnant while the subject is on study through 90 days after receiving the dose of investigational product 4. Positive pregnancy test at screening or day -1 5. Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | From first dose up to 30 days for participants assigned to the 21 mg or 70 mg dose cohorts and up to 57 days for participants assigned to the 210 mg, 420 mg, or 700 mg dose cohorts. | Determination of the severity of adverse events was according to the following: grade 1 = mild (eg, asymptomatic or mild symptoms); grade 2 = moderate (eg, minimal intervention indicated or interferes with activity); grade 3 = severe (eg, medically significant but not immediately life-threatening, prevents daily activity, or requires treatment); grade 4 = life-threatening (ie, refers to an event in which the participant was, in the view of the investigator, at risk of death at the time of the event); and grade 5 = fatal. A serious adverse event was defined as an adverse event that met at least 1 of the following criteria: * fatal * life threatening * required in patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. |
Secondary
| Measure | Time frame |
|---|---|
| Time to Maximum Observed Concentration (Tmax) of AMG 529 | Predose and at 0.5 and 1 hour postdose (IV cohort only) and 6, 12, 24, 36, 48, 72, 120, 168, 240, 366, 504, and 696 hours postdose (all participants) and additionally at days 43 and 57 for participants assigned to the 210, 420, or 700 mg dose cohorts. |
| Area Under the Curve From Time 0 to the Last Quantifiable Concentration (AUClast) for AMG 529 | Predose and at 0.5 and 1 hour postdose (IV cohort only) and 6, 12, 24, 36, 48, 72, 120, 168, 240, 366, 504, and 696 hours postdose (all participants) and additionally at days 43 and 57 for participants assigned to the 210, 420, or 700 mg dose cohorts. |
| Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Baseline and days 3, 8, and 30 |
| Maximum Observed Concentration (Cmax) of AMG 529 | Predose and at 0.5 and 1 hour postdose (IV cohort only) and 6, 12, 24, 36, 48, 72, 120, 168, 240, 366, 504, and 696 hours postdose (all participants) and additionally at days 43 and 57 for participants assigned to the 210, 420, or 700 mg dose cohorts. |
| Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Baseline and days 3, 6, 11, 22, 30 (all participants), and day 57 for participants assigned to the 210 mg, 420 mg, or 700 mg cohorts. |
| Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Baseline and days 3, 6, 11, 22, 30 (all participants), and day 57 for participants assigned to the 210 mg, 420 mg, or 700 mg cohorts. |
| Change From Baseline in Triglycerides Concentration Over Time | Baseline and days 3, 6, 11, 22, 30 (all participants), and day 57 for participants assigned to the 210 mg, 420 mg, or 700 mg cohorts. |
| Change From Baseline in Total Cholesterol Concentration Over Time | Baseline and days 3, 6, 11, 22, 30 (all participants), and day 57 for participants assigned to the 210 mg, 420 mg, or 700 mg cohorts. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at a single center in the United States. Participants were enrolled from 15 May 2017 to 18 September 2017.
Pre-assignment details
Participants were enrolled into one of six dose cohorts. Within each cohort participants were randomized in a ratio of 3:1 to receive AMG 529 or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single dose of matching placebo by either subcutaneous or intravenous injection. | 12 |
| AMG 529 21 mg SC Participants received a single dose of 21 mg AMG 529 on study day 1 by subcutaneous (SC) injection. | 6 |
| AMG 529 70 mg SC Participants received a single dose of 70 mg AMG 529 on study day 1 by subcutaneous injection. | 6 |
| AMG 529 210 mg SC Participants received a single dose of 210 mg AMG 529 on study day 1 by subcutaneous injection. | 6 |
| AMG 529 420 mg SC Participants received a single dose of 420 mg AMG 529 on study day 1 by subcutaneous injection. | 6 |
| AMG 529 700 mg SC Participants received a single dose of 700 mg AMG 529 on study day 1 by subcutaneous injection. | 6 |
| AMG 529 70 mg IV Participants received a single dose of 70 mg AMG 529 on study day 1 by intravenous (IV) injection. | 6 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | AMG 529 21 mg SC | AMG 529 70 mg SC | AMG 529 210 mg SC | AMG 529 420 mg SC | AMG 529 700 mg SC | AMG 529 70 mg IV | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 35.7 years STANDARD_DEVIATION 10.5 | 33.5 years STANDARD_DEVIATION 12.5 | 32.3 years STANDARD_DEVIATION 11.6 | 45.2 years STANDARD_DEVIATION 11.6 | 35.0 years STANDARD_DEVIATION 11 | 36.5 years STANDARD_DEVIATION 9.6 | 34.7 years STANDARD_DEVIATION 12.7 | 36.1 years STANDARD_DEVIATION 11.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 5 Participants | 5 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 5 Participants | 5 Participants | 5 Participants | 2 Participants | 3 Participants | 4 Participants | 5 Participants | 29 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 1 Participants | 1 Participants | 4 Participants | 3 Participants | 2 Participants | 1 Participants | 19 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 12 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 5 Participants | 46 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 3 / 12 | 0 / 6 | 0 / 6 | 2 / 6 | 2 / 6 | 3 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
Determination of the severity of adverse events was according to the following: grade 1 = mild (eg, asymptomatic or mild symptoms); grade 2 = moderate (eg, minimal intervention indicated or interferes with activity); grade 3 = severe (eg, medically significant but not immediately life-threatening, prevents daily activity, or requires treatment); grade 4 = life-threatening (ie, refers to an event in which the participant was, in the view of the investigator, at risk of death at the time of the event); and grade 5 = fatal. A serious adverse event was defined as an adverse event that met at least 1 of the following criteria: * fatal * life threatening * required in patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event.
Time frame: From first dose up to 30 days for participants assigned to the 21 mg or 70 mg dose cohorts and up to 57 days for participants assigned to the 210 mg, 420 mg, or 700 mg dose cohorts.
Population: Randomized participants who received at least 1 dose of AMG 529 or placebo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 3 | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 2 | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | All adverse events | 3 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 4 | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Serious adverse events | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of study drug | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events | 1 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Fatal adverse events | 0 Participants |
| AMG 529 21 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 2 | 0 Participants |
| AMG 529 21 mg SC | Number of Participants With Adverse Events (AEs) | Fatal adverse events | 0 Participants |
| AMG 529 21 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 3 | 0 Participants |
| AMG 529 21 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 4 | 0 Participants |
| AMG 529 21 mg SC | Number of Participants With Adverse Events (AEs) | Serious adverse events | 0 Participants |
| AMG 529 21 mg SC | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of study drug | 0 Participants |
| AMG 529 21 mg SC | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events | 0 Participants |
| AMG 529 21 mg SC | Number of Participants With Adverse Events (AEs) | All adverse events | 0 Participants |
| AMG 529 70 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 3 | 0 Participants |
| AMG 529 70 mg SC | Number of Participants With Adverse Events (AEs) | Fatal adverse events | 0 Participants |
| AMG 529 70 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 4 | 0 Participants |
| AMG 529 70 mg SC | Number of Participants With Adverse Events (AEs) | Serious adverse events | 0 Participants |
| AMG 529 70 mg SC | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of study drug | 0 Participants |
| AMG 529 70 mg SC | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events | 0 Participants |
| AMG 529 70 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 2 | 0 Participants |
| AMG 529 70 mg SC | Number of Participants With Adverse Events (AEs) | All adverse events | 0 Participants |
| AMG 529 210 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 4 | 0 Participants |
| AMG 529 210 mg SC | Number of Participants With Adverse Events (AEs) | Fatal adverse events | 0 Participants |
| AMG 529 210 mg SC | Number of Participants With Adverse Events (AEs) | Serious adverse events | 0 Participants |
| AMG 529 210 mg SC | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of study drug | 0 Participants |
| AMG 529 210 mg SC | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events | 2 Participants |
| AMG 529 210 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 3 | 0 Participants |
| AMG 529 210 mg SC | Number of Participants With Adverse Events (AEs) | All adverse events | 2 Participants |
| AMG 529 210 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 2 | 1 Participants |
| AMG 529 420 mg SC | Number of Participants With Adverse Events (AEs) | Serious adverse events | 0 Participants |
| AMG 529 420 mg SC | Number of Participants With Adverse Events (AEs) | Fatal adverse events | 0 Participants |
| AMG 529 420 mg SC | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of study drug | 0 Participants |
| AMG 529 420 mg SC | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events | 2 Participants |
| AMG 529 420 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 4 | 0 Participants |
| AMG 529 420 mg SC | Number of Participants With Adverse Events (AEs) | All adverse events | 2 Participants |
| AMG 529 420 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 2 | 0 Participants |
| AMG 529 420 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 3 | 0 Participants |
| AMG 529 700 mg SC | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of study drug | 0 Participants |
| AMG 529 700 mg SC | Number of Participants With Adverse Events (AEs) | Fatal adverse events | 0 Participants |
| AMG 529 700 mg SC | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events | 0 Participants |
| AMG 529 700 mg SC | Number of Participants With Adverse Events (AEs) | Serious adverse events | 0 Participants |
| AMG 529 700 mg SC | Number of Participants With Adverse Events (AEs) | All adverse events | 3 Participants |
| AMG 529 700 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 2 | 0 Participants |
| AMG 529 700 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 3 | 0 Participants |
| AMG 529 700 mg SC | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 4 | 0 Participants |
| AMG 529 70 mg IV | Number of Participants With Adverse Events (AEs) | Treatment-related adverse events | 2 Participants |
| AMG 529 70 mg IV | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation of study drug | 0 Participants |
| AMG 529 70 mg IV | Number of Participants With Adverse Events (AEs) | Fatal adverse events | 0 Participants |
| AMG 529 70 mg IV | Number of Participants With Adverse Events (AEs) | All adverse events | 2 Participants |
| AMG 529 70 mg IV | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 2 | 1 Participants |
| AMG 529 70 mg IV | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 3 | 0 Participants |
| AMG 529 70 mg IV | Number of Participants With Adverse Events (AEs) | Adverse events Grade ≥ 4 | 0 Participants |
| AMG 529 70 mg IV | Number of Participants With Adverse Events (AEs) | Serious adverse events | 0 Participants |
Secondary
Area Under the Curve From Time 0 to the Last Quantifiable Concentration (AUClast) for AMG 529
Time frame: Predose and at 0.5 and 1 hour postdose (IV cohort only) and 6, 12, 24, 36, 48, 72, 120, 168, 240, 366, 504, and 696 hours postdose (all participants) and additionally at days 43 and 57 for participants assigned to the 210, 420, or 700 mg dose cohorts.
Population: Participants who received AMG 529 for whom at least 1 PK parameter or endpoint was reliably estimated. Four participants were excluded from PK analyses as their profiles had \< 2 samples that were above the lower limit of quantification.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time 0 to the Last Quantifiable Concentration (AUClast) for AMG 529 | 5.99 days*ng/mL | Standard Deviation 2.9 |
| AMG 529 21 mg SC | Area Under the Curve From Time 0 to the Last Quantifiable Concentration (AUClast) for AMG 529 | 46.0 days*ng/mL | Standard Deviation 47.4 |
| AMG 529 70 mg SC | Area Under the Curve From Time 0 to the Last Quantifiable Concentration (AUClast) for AMG 529 | 5370 days*ng/mL | Standard Deviation 8520 |
| AMG 529 210 mg SC | Area Under the Curve From Time 0 to the Last Quantifiable Concentration (AUClast) for AMG 529 | 41800 days*ng/mL | Standard Deviation 51000 |
| AMG 529 420 mg SC | Area Under the Curve From Time 0 to the Last Quantifiable Concentration (AUClast) for AMG 529 | 289000 days*ng/mL | Standard Deviation 330000 |
| AMG 529 700 mg SC | Area Under the Curve From Time 0 to the Last Quantifiable Concentration (AUClast) for AMG 529 | 766 days*ng/mL | Standard Deviation 1240 |
Secondary
Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time
Time frame: Baseline and days 3, 8, and 30
Population: Participants who received at least 1 dose of study drug and with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Baseline | 62.0 units/liter | Standard Deviation 13.8 |
| Placebo | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 3 | -0.3 units/liter | Standard Deviation 4.2 |
| Placebo | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 8 | 2.3 units/liter | Standard Deviation 6 |
| Placebo | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 30 | 3.5 units/liter | Standard Deviation 8.5 |
| AMG 529 21 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 30 | -1.4 units/liter | Standard Deviation 4 |
| AMG 529 21 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 8 | 3.2 units/liter | Standard Deviation 7.5 |
| AMG 529 21 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Baseline | 69.0 units/liter | Standard Deviation 21.2 |
| AMG 529 21 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 3 | 4.7 units/liter | Standard Deviation 4.7 |
| AMG 529 70 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 8 | 17.0 units/liter | Standard Deviation 10.4 |
| AMG 529 70 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 3 | 7.0 units/liter | Standard Deviation 7 |
| AMG 529 70 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Baseline | 56.0 units/liter | Standard Deviation 10.8 |
| AMG 529 70 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 30 | 1.8 units/liter | Standard Deviation 5.3 |
| AMG 529 210 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Baseline | 68.0 units/liter | Standard Deviation 12.2 |
| AMG 529 210 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 3 | 57.0 units/liter | Standard Deviation 51.7 |
| AMG 529 210 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 8 | 102.6 units/liter | Standard Deviation 70.8 |
| AMG 529 210 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 30 | -0.8 units/liter | Standard Deviation 4 |
| AMG 529 420 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Baseline | 57.7 units/liter | Standard Deviation 9 |
| AMG 529 420 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 30 | 11.8 units/liter | Standard Deviation 5.9 |
| AMG 529 420 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 3 | 76.7 units/liter | Standard Deviation 76.9 |
| AMG 529 420 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 8 | 199.3 units/liter | Standard Deviation 256.1 |
| AMG 529 700 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 3 | 88.2 units/liter | Standard Deviation 33.5 |
| AMG 529 700 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Baseline | 57.5 units/liter | Standard Deviation 18 |
| AMG 529 700 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 8 | 155.8 units/liter | Standard Deviation 34.8 |
| AMG 529 700 mg SC | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 30 | 14.6 units/liter | Standard Deviation 6.5 |
| AMG 529 70 mg IV | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 8 | 8.8 units/liter | Standard Deviation 5.8 |
| AMG 529 70 mg IV | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Baseline | 58.0 units/liter | Standard Deviation 8.1 |
| AMG 529 70 mg IV | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 3 | 28.7 units/liter | Standard Deviation 14.7 |
| AMG 529 70 mg IV | Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time | Change from baseline to day 30 | 2.0 units/liter | Standard Deviation 7.8 |
Secondary
Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time
Time frame: Baseline and days 3, 6, 11, 22, 30 (all participants), and day 57 for participants assigned to the 210 mg, 420 mg, or 700 mg cohorts.
Population: Randomized participants who received study drug with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 3 | -0.0592 mmol/L | Standard Deviation 0.1094 |
| Placebo | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 6 | -0.0975 mmol/L | Standard Deviation 0.1096 |
| Placebo | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 11 | -0.0133 mmol/L | Standard Deviation 0.1224 |
| Placebo | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Baseline | 1.1775 mmol/L | Standard Deviation 0.2932 |
| Placebo | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 30 | 0.0473 mmol/L | Standard Deviation 0.1769 |
| Placebo | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 22 | 0.0208 mmol/L | Standard Deviation 0.1468 |
| Placebo | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 57 | -0.0540 mmol/L | Standard Deviation 0.1549 |
| AMG 529 21 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Baseline | 1.3783 mmol/L | Standard Deviation 0.2928 |
| AMG 529 21 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 6 | -0.1617 mmol/L | Standard Deviation 0.1254 |
| AMG 529 21 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 11 | -0.2080 mmol/L | Standard Deviation 0.1854 |
| AMG 529 21 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 30 | -0.0760 mmol/L | Standard Deviation 0.0853 |
| AMG 529 21 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 3 | -0.0100 mmol/L | Standard Deviation 0.1092 |
| AMG 529 21 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 22 | -0.0580 mmol/L | Standard Deviation 0.1644 |
| AMG 529 70 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 3 | -0.1267 mmol/L | Standard Deviation 0.0935 |
| AMG 529 70 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 30 | -0.0400 mmol/L | Standard Deviation 0.3107 |
| AMG 529 70 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 11 | -0.1600 mmol/L | Standard Deviation 0.1689 |
| AMG 529 70 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 22 | -0.0417 mmol/L | Standard Deviation 0.1815 |
| AMG 529 70 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 6 | -0.2083 mmol/L | Standard Deviation 0.143 |
| AMG 529 70 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Baseline | 1.3950 mmol/L | Standard Deviation 0.2626 |
| AMG 529 210 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 3 | 0.0417 mmol/L | Standard Deviation 0.1032 |
| AMG 529 210 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Baseline | 1.4133 mmol/L | Standard Deviation 0.4968 |
| AMG 529 210 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 6 | -0.0980 mmol/L | Standard Deviation 0.1417 |
| AMG 529 210 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 11 | -0.0960 mmol/L | Standard Deviation 0.1318 |
| AMG 529 210 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 22 | 0.0220 mmol/L | Standard Deviation 0.1026 |
| AMG 529 210 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 30 | 0.1380 mmol/L | Standard Deviation 0.1644 |
| AMG 529 210 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 57 | 0.1160 mmol/L | Standard Deviation 0.1595 |
| AMG 529 420 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Baseline | 1.2633 mmol/L | Standard Deviation 0.2202 |
| AMG 529 420 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 30 | 0.0667 mmol/L | Standard Deviation 0.206 |
| AMG 529 420 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 3 | -0.0600 mmol/L | Standard Deviation 0.1373 |
| AMG 529 420 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 57 | 0.1483 mmol/L | Standard Deviation 0.1113 |
| AMG 529 420 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 11 | -0.0800 mmol/L | Standard Deviation 0.0812 |
| AMG 529 420 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 6 | -0.1100 mmol/L | Standard Deviation 0.2028 |
| AMG 529 420 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 22 | 0.0583 mmol/L | Standard Deviation 0.1533 |
| AMG 529 700 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 11 | 0.0475 mmol/L | Standard Deviation 0.0768 |
| AMG 529 700 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 3 | 0.0783 mmol/L | Standard Deviation 0.0981 |
| AMG 529 700 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 57 | 0.2633 mmol/L | Standard Deviation 0.247 |
| AMG 529 700 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 22 | 0.2860 mmol/L | Standard Deviation 0.1704 |
| AMG 529 700 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Baseline | 1.0700 mmol/L | Standard Deviation 0.4527 |
| AMG 529 700 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 30 | 0.2480 mmol/L | Standard Deviation 0.0944 |
| AMG 529 700 mg SC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 6 | 0.0350 mmol/L | Standard Deviation 0.1816 |
| AMG 529 70 mg IV | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 3 | -0.0383 mmol/L | Standard Deviation 0.1118 |
| AMG 529 70 mg IV | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 30 | 0.1340 mmol/L | Standard Deviation 0.1396 |
| AMG 529 70 mg IV | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 6 | -0.0767 mmol/L | Standard Deviation 0.1402 |
| AMG 529 70 mg IV | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 11 | -0.0060 mmol/L | Standard Deviation 0.1809 |
| AMG 529 70 mg IV | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Baseline | 1.4417 mmol/L | Standard Deviation 0.5517 |
| AMG 529 70 mg IV | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time | Change from baseline to day 22 | 0.0320 mmol/L | Standard Deviation 0.1583 |
Secondary
Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time
Time frame: Baseline and days 3, 6, 11, 22, 30 (all participants), and day 57 for participants assigned to the 210 mg, 420 mg, or 700 mg cohorts.
Population: Randomized participants who received study drug with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 57 | 0.0500 mmol/L | Standard Deviation 0.7559 |
| Placebo | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 3 | 0.1608 mmol/L | Standard Deviation 0.2423 |
| Placebo | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 22 | 0.0117 mmol/L | Standard Deviation 0.4577 |
| Placebo | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 11 | -0.3367 mmol/L | Standard Deviation 0.4298 |
| Placebo | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 30 | -0.1018 mmol/L | Standard Deviation 0.6698 |
| Placebo | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Baseline | 2.8317 mmol/L | Standard Deviation 0.8071 |
| Placebo | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 6 | 0.1400 mmol/L | Standard Deviation 0.2992 |
| AMG 529 21 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 3 | 0.1383 mmol/L | Standard Deviation 0.3271 |
| AMG 529 21 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 30 | -0.4260 mmol/L | Standard Deviation 0.4258 |
| AMG 529 21 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 11 | -0.7600 mmol/L | Standard Deviation 0.4464 |
| AMG 529 21 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Baseline | 3.2683 mmol/L | Standard Deviation 1.0026 |
| AMG 529 21 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 22 | -0.5240 mmol/L | Standard Deviation 0.8043 |
| AMG 529 21 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 6 | 0.0417 mmol/L | Standard Deviation 0.3547 |
| AMG 529 70 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 6 | 0.1050 mmol/L | Standard Deviation 0.1549 |
| AMG 529 70 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 30 | -0.0767 mmol/L | Standard Deviation 0.4002 |
| AMG 529 70 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 22 | -0.0600 mmol/L | Standard Deviation 0.3205 |
| AMG 529 70 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 3 | 0.2150 mmol/L | Standard Deviation 0.1571 |
| AMG 529 70 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Baseline | 2.8400 mmol/L | Standard Deviation 0.7687 |
| AMG 529 70 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 11 | -0.3900 mmol/L | Standard Deviation 0.2912 |
| AMG 529 210 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 11 | -0.7920 mmol/L | Standard Deviation 0.4873 |
| AMG 529 210 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 22 | -0.2860 mmol/L | Standard Deviation 0.4116 |
| AMG 529 210 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 57 | 0.0520 mmol/L | Standard Deviation 0.6514 |
| AMG 529 210 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 3 | -0.0867 mmol/L | Standard Deviation 0.328 |
| AMG 529 210 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 30 | -0.4020 mmol/L | Standard Deviation 0.4773 |
| AMG 529 210 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 6 | -0.5860 mmol/L | Standard Deviation 0.518 |
| AMG 529 210 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Baseline | 3.4017 mmol/L | Standard Deviation 1.2875 |
| AMG 529 420 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 57 | 0.1283 mmol/L | Standard Deviation 0.3075 |
| AMG 529 420 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Baseline | 2.4633 mmol/L | Standard Deviation 0.5727 |
| AMG 529 420 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 3 | 0.2650 mmol/L | Standard Deviation 0.1401 |
| AMG 529 420 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 6 | -0.0967 mmol/L | Standard Deviation 0.2708 |
| AMG 529 420 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 11 | -0.7333 mmol/L | Standard Deviation 0.5 |
| AMG 529 420 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 22 | -0.3517 mmol/L | Standard Deviation 0.3969 |
| AMG 529 420 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 30 | 0.2667 mmol/L | Standard Deviation 0.3768 |
| AMG 529 700 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 11 | -0.5850 mmol/L | Standard Deviation 0.2204 |
| AMG 529 700 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 22 | -0.3960 mmol/L | Standard Deviation 0.1521 |
| AMG 529 700 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 6 | -0.0967 mmol/L | Standard Deviation 0.1975 |
| AMG 529 700 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 3 | 0.3350 mmol/L | Standard Deviation 0.2482 |
| AMG 529 700 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 57 | -0.1617 mmol/L | Standard Deviation 0.8583 |
| AMG 529 700 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 30 | -0.0740 mmol/L | Standard Deviation 0.4999 |
| AMG 529 700 mg SC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Baseline | 3.2267 mmol/L | Standard Deviation 0.7112 |
| AMG 529 70 mg IV | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Baseline | 3.1583 mmol/L | Standard Deviation 1.1382 |
| AMG 529 70 mg IV | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 22 | -0.2780 mmol/L | Standard Deviation 0.7706 |
| AMG 529 70 mg IV | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 6 | 0.1650 mmol/L | Standard Deviation 0.5853 |
| AMG 529 70 mg IV | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 11 | -0.0520 mmol/L | Standard Deviation 0.5955 |
| AMG 529 70 mg IV | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 3 | 0.3350 mmol/L | Standard Deviation 0.2874 |
| AMG 529 70 mg IV | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time | Change from baseline to day 30 | -0.2680 mmol/L | Standard Deviation 0.9091 |
Secondary
Change From Baseline in Total Cholesterol Concentration Over Time
Time frame: Baseline and days 3, 6, 11, 22, 30 (all participants), and day 57 for participants assigned to the 210 mg, 420 mg, or 700 mg cohorts.
Population: Randomized participants who received study drug with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 3 | 0.0692 mmol/L | Standard Deviation 0.2381 |
| Placebo | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 6 | 0.0867 mmol/L | Standard Deviation 0.4151 |
| Placebo | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 11 | -0.4625 mmol/L | Standard Deviation 0.411 |
| Placebo | Change From Baseline in Total Cholesterol Concentration Over Time | Baseline | 4.5817 mmol/L | Standard Deviation 0.8204 |
| Placebo | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 30 | -0.0936 mmol/L | Standard Deviation 0.788 |
| Placebo | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 22 | -0.0300 mmol/L | Standard Deviation 0.5567 |
| Placebo | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 57 | 0.1840 mmol/L | Standard Deviation 0.7451 |
| AMG 529 21 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Baseline | 5.3567 mmol/L | Standard Deviation 0.9662 |
| AMG 529 21 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 6 | -0.3317 mmol/L | Standard Deviation 0.1997 |
| AMG 529 21 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 11 | -1.0620 mmol/L | Standard Deviation 0.5976 |
| AMG 529 21 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 30 | -0.6780 mmol/L | Standard Deviation 0.3467 |
| AMG 529 21 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 3 | -0.1583 mmol/L | Standard Deviation 0.1347 |
| AMG 529 21 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 22 | -0.7480 mmol/L | Standard Deviation 0.8825 |
| AMG 529 70 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 3 | -0.0200 mmol/L | Standard Deviation 0.2254 |
| AMG 529 70 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 30 | -0.1933 mmol/L | Standard Deviation 0.4376 |
| AMG 529 70 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 11 | -0.6933 mmol/L | Standard Deviation 0.4763 |
| AMG 529 70 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 22 | -0.2550 mmol/L | Standard Deviation 0.5021 |
| AMG 529 70 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 6 | -0.3533 mmol/L | Standard Deviation 0.3426 |
| AMG 529 70 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Baseline | 4.8383 mmol/L | Standard Deviation 1.0789 |
| AMG 529 210 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 3 | 0.0800 mmol/L | Standard Deviation 0.2224 |
| AMG 529 210 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Baseline | 5.3417 mmol/L | Standard Deviation 0.9771 |
| AMG 529 210 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 6 | -0.2520 mmol/L | Standard Deviation 0.6208 |
| AMG 529 210 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 11 | -0.6700 mmol/L | Standard Deviation 0.577 |
| AMG 529 210 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 22 | -0.1640 mmol/L | Standard Deviation 0.3092 |
| AMG 529 210 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 30 | 0.1300 mmol/L | Standard Deviation 0.0919 |
| AMG 529 210 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 57 | 0.5120 mmol/L | Standard Deviation 0.8889 |
| AMG 529 420 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Baseline | 4.2483 mmol/L | Standard Deviation 0.6335 |
| AMG 529 420 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 30 | 0.2583 mmol/L | Standard Deviation 0.4088 |
| AMG 529 420 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 3 | 0.1617 mmol/L | Standard Deviation 0.2375 |
| AMG 529 420 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 57 | 0.2383 mmol/L | Standard Deviation 0.4896 |
| AMG 529 420 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 11 | -0.8500 mmol/L | Standard Deviation 0.6339 |
| AMG 529 420 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 6 | -0.3267 mmol/L | Standard Deviation 0.314 |
| AMG 529 420 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 22 | -0.2183 mmol/L | Standard Deviation 0.41 |
| AMG 529 700 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 11 | -0.7600 mmol/L | Standard Deviation 0.5306 |
| AMG 529 700 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 3 | 0.2350 mmol/L | Standard Deviation 0.1299 |
| AMG 529 700 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 57 | -0.0033 mmol/L | Standard Deviation 0.9705 |
| AMG 529 700 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 22 | -0.2040 mmol/L | Standard Deviation 0.5358 |
| AMG 529 700 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Baseline | 4.8533 mmol/L | Standard Deviation 0.8125 |
| AMG 529 700 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 30 | 0.1380 mmol/L | Standard Deviation 0.4964 |
| AMG 529 700 mg SC | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 6 | -0.1667 mmol/L | Standard Deviation 0.2614 |
| AMG 529 70 mg IV | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 3 | 0.3400 mmol/L | Standard Deviation 0.3428 |
| AMG 529 70 mg IV | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 30 | -0.1140 mmol/L | Standard Deviation 0.9209 |
| AMG 529 70 mg IV | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 6 | 0.3350 mmol/L | Standard Deviation 0.5461 |
| AMG 529 70 mg IV | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 11 | -0.0340 mmol/L | Standard Deviation 0.8344 |
| AMG 529 70 mg IV | Change From Baseline in Total Cholesterol Concentration Over Time | Baseline | 5.0633 mmol/L | Standard Deviation 1.5937 |
| AMG 529 70 mg IV | Change From Baseline in Total Cholesterol Concentration Over Time | Change from baseline to day 22 | -0.3200 mmol/L | Standard Deviation 0.9193 |
Secondary
Change From Baseline in Triglycerides Concentration Over Time
Time frame: Baseline and days 3, 6, 11, 22, 30 (all participants), and day 57 for participants assigned to the 210 mg, 420 mg, or 700 mg cohorts.
Population: Randomized participants who received study drug with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 22 | 0.0475 mmol/L | Standard Deviation 0.5965 |
| Placebo | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 6 | -0.0525 mmol/L | Standard Deviation 0.3015 |
| Placebo | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 11 | -0.0975 mmol/L | Standard Deviation 0.347 |
| Placebo | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 3 | -0.0942 mmol/L | Standard Deviation 0.288 |
| Placebo | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 30 | 0.0991 mmol/L | Standard Deviation 0.4538 |
| Placebo | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 57 | 0.4580 mmol/L | Standard Deviation 0.5334 |
| Placebo | Change From Baseline in Triglycerides Concentration Over Time | Baseline | 1.2292 mmol/L | Standard Deviation 0.508 |
| AMG 529 21 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 22 | 0.0920 mmol/L | Standard Deviation 0.2212 |
| AMG 529 21 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 30 | 0.2320 mmol/L | Standard Deviation 0.3214 |
| AMG 529 21 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Baseline | 1.1100 mmol/L | Standard Deviation 0.5588 |
| AMG 529 21 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 6 | -0.0450 mmol/L | Standard Deviation 0.1148 |
| AMG 529 21 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 11 | 0.2040 mmol/L | Standard Deviation 0.7577 |
| AMG 529 21 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 3 | -0.1283 mmol/L | Standard Deviation 0.1379 |
| AMG 529 70 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Baseline | 1.0050 mmol/L | Standard Deviation 0.5478 |
| AMG 529 70 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 3 | -0.0633 mmol/L | Standard Deviation 0.2366 |
| AMG 529 70 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 6 | -0.0583 mmol/L | Standard Deviation 0.1932 |
| AMG 529 70 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 11 | 0.1400 mmol/L | Standard Deviation 0.4963 |
| AMG 529 70 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 22 | 0.5800 mmol/L | Standard Deviation 0.6549 |
| AMG 529 70 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 30 | 0.5533 mmol/L | Standard Deviation 0.7672 |
| AMG 529 210 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 11 | 0.1840 mmol/L | Standard Deviation 0.4797 |
| AMG 529 210 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 30 | 0.2600 mmol/L | Standard Deviation 0.5742 |
| AMG 529 210 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 3 | -0.0183 mmol/L | Standard Deviation 0.3725 |
| AMG 529 210 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Baseline | 1.3750 mmol/L | Standard Deviation 0.977 |
| AMG 529 210 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 6 | 0.4580 mmol/L | Standard Deviation 1.2469 |
| AMG 529 210 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 22 | 0.1780 mmol/L | Standard Deviation 0.4043 |
| AMG 529 210 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 57 | 0.4900 mmol/L | Standard Deviation 0.7883 |
| AMG 529 420 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 22 | 0.2183 mmol/L | Standard Deviation 0.2193 |
| AMG 529 420 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 6 | -0.2900 mmol/L | Standard Deviation 0.2521 |
| AMG 529 420 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 11 | -0.1167 mmol/L | Standard Deviation 0.4131 |
| AMG 529 420 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Baseline | 1.0533 mmol/L | Standard Deviation 0.3525 |
| AMG 529 420 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 57 | 0.0533 mmol/L | Standard Deviation 0.3663 |
| AMG 529 420 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 30 | 0.0533 mmol/L | Standard Deviation 0.432 |
| AMG 529 420 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 3 | -0.1833 mmol/L | Standard Deviation 0.0993 |
| AMG 529 700 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 30 | -0.0360 mmol/L | Standard Deviation 0.533 |
| AMG 529 700 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 57 | -0.3283 mmol/L | Standard Deviation 0.5669 |
| AMG 529 700 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 6 | -0.5783 mmol/L | Standard Deviation 0.5958 |
| AMG 529 700 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 3 | -0.5600 mmol/L | Standard Deviation 0.6615 |
| AMG 529 700 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Baseline | 1.5067 mmol/L | Standard Deviation 1.0848 |
| AMG 529 700 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 22 | -0.4360 mmol/L | Standard Deviation 0.9239 |
| AMG 529 700 mg SC | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 11 | -0.5925 mmol/L | Standard Deviation 1.0357 |
| AMG 529 70 mg IV | Change From Baseline in Triglycerides Concentration Over Time | Baseline | 0.8317 mmol/L | Standard Deviation 0.3036 |
| AMG 529 70 mg IV | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 22 | 0.3340 mmol/L | Standard Deviation 0.4185 |
| AMG 529 70 mg IV | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 6 | 0.3133 mmol/L | Standard Deviation 0.3102 |
| AMG 529 70 mg IV | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 11 | 0.3320 mmol/L | Standard Deviation 0.5496 |
| AMG 529 70 mg IV | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 30 | 0.2220 mmol/L | Standard Deviation 0.158 |
| AMG 529 70 mg IV | Change From Baseline in Triglycerides Concentration Over Time | Change from baseline to day 3 | 0.0750 mmol/L | Standard Deviation 0.1244 |
Secondary
Maximum Observed Concentration (Cmax) of AMG 529
Time frame: Predose and at 0.5 and 1 hour postdose (IV cohort only) and 6, 12, 24, 36, 48, 72, 120, 168, 240, 366, 504, and 696 hours postdose (all participants) and additionally at days 43 and 57 for participants assigned to the 210, 420, or 700 mg dose cohorts.
Population: Participants who received AMG 529 for whom at least 1 PK parameter or endpoint was reliably estimated. Four participants were excluded from PK analyses as their profiles had \< 2 samples that were above the lower limit of quantification.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Concentration (Cmax) of AMG 529 | 6.90 ng/mL | Standard Deviation 1.73 |
| AMG 529 21 mg SC | Maximum Observed Concentration (Cmax) of AMG 529 | 23.8 ng/mL | Standard Deviation 13.4 |
| AMG 529 70 mg SC | Maximum Observed Concentration (Cmax) of AMG 529 | 2010 ng/mL | Standard Deviation 3120 |
| AMG 529 210 mg SC | Maximum Observed Concentration (Cmax) of AMG 529 | 9370 ng/mL | Standard Deviation 10800 |
| AMG 529 420 mg SC | Maximum Observed Concentration (Cmax) of AMG 529 | 35600 ng/mL | Standard Deviation 32700 |
| AMG 529 700 mg SC | Maximum Observed Concentration (Cmax) of AMG 529 | 3460 ng/mL | Standard Deviation 4430 |
Secondary
Time to Maximum Observed Concentration (Tmax) of AMG 529
Time frame: Predose and at 0.5 and 1 hour postdose (IV cohort only) and 6, 12, 24, 36, 48, 72, 120, 168, 240, 366, 504, and 696 hours postdose (all participants) and additionally at days 43 and 57 for participants assigned to the 210, 420, or 700 mg dose cohorts.
Population: Participants who received AMG 529 for whom at least 1 PK parameter or endpoint was reliably estimated. Four participants were excluded from PK analyses as their profiles had \< 2 samples that were above the lower limit of quantification.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Maximum Observed Concentration (Tmax) of AMG 529 | 24 hours |
| AMG 529 21 mg SC | Time to Maximum Observed Concentration (Tmax) of AMG 529 | 5.8 hours |
| AMG 529 70 mg SC | Time to Maximum Observed Concentration (Tmax) of AMG 529 | 72 hours |
| AMG 529 210 mg SC | Time to Maximum Observed Concentration (Tmax) of AMG 529 | 72 hours |
| AMG 529 420 mg SC | Time to Maximum Observed Concentration (Tmax) of AMG 529 | 96 hours |
| AMG 529 700 mg SC | Time to Maximum Observed Concentration (Tmax) of AMG 529 | 0.5 hours |