Stable Coronary Heart Disease
Conditions
Keywords
Coronary heart disease, Pharmacokinetic, Pharmacodynamics
Brief summary
A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamic Effects of MEDI5884 in Adults With Stable Coronary Heart Disease.
Detailed description
A Randomized, Double-blind, Placebo-controlled, Parallel-designed Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamic Effects of MEDI5884 in Participants with Stable Coronary Heart Disease.
Interventions
DRUGMEDI5884
Participants will receive SC dose of MEDI5884 50 mg or 100 mg or 200 mg or 350 mg or 500 mg on Days 1, 31, and 61.
DRUGPlacebo
Participants will receive SC dose of placebo (volume matched to MEDI5884) on Days 1, 31, and 61.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of stable coronary heart disease prior to screening * Currently receiving high intensity statin(s)
Exclusion criteria
* Unstable cardiovascular conditions * Any planned arterial revascularizations * Fasting Laboratory values at screening: Triglycerides \> 500 mg/dl, Low Density Lipoprotein-Cholesterol \> 100 mg/dL * Any disease or condition or laboratory value that would place the participant at an unacceptable risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Day 1 (Baseline) through Day 241 | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. |
| Number of Participants With Clinically Important Changes in Electrocardiograms (ECGs) From Baseline | Day 1 (Baseline) through Day 241 | Number of participants with clinically important changes in ECGs from baseline are reported. Clinically important changes in ECGs is defined as any clinical significant difference in heart rate, RR interval, PR interval, QRS, and QT intervals from the primary lead of the digital 12-lead ECG from baseline. |
| Number of Participants With Clinically Important Changes in Vital Signs From Baseline | Day 1 (Baseline) through Day 241 | Number of participants with clinically important changes in vital signs from baseline are reported. Vital signs measurements were obtained after the participant had rested in the supine position for at least 10 minutes at the recording time. Clinically important changes in vital signs from baseline is defined as any clinical significant difference in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate) from baseline. |
| Number of Participants With Clinically Important Changes in Laboratory Parameters From Baseline | Day 1 (Baseline) through Day 241 | Number of participants with clinically important changes in laboratory parameters from baseline are reported. Clinically important changes in laboratory parameters is defined as any clinical significant difference in analysis of serum chemistry, hematology, and urine from baseline. |
| Number of Participants With Clinically Important Changes in Physical Examinations From Baseline | Day 1 (Baseline) through Day 241 | Number of participants with clinically important changes in physical examinations from baseline are reported. Clinically important changes in physical examinations is defined as any clinical significant difference in general appearance, head, ears, eyes, nose, throat, neck, skin, heart, lung, abdomen, musculoskeletal system, endocrine system, nervous system, height, and weight from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Apolipoprotein B | Day 1 (Baseline), and Days 31, 61, and 91 | Change from baseline in apolipoprotein B is reported. |
| Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to MEDI5884 | Day 1 (pre-dose), on Day 8, Day 31 (pre-dose), Day 61 (pre-dose), on Days 151 and 241 | Treatment-emergent ADA is defined as the sum of treatment-induced ADA (post baseline-positive only) and treatment-boosted ADA (baseline ADA titer that was boosted to a 4-fold or higher level following drug administration). |
| Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 1 (Baseline), and Days 31, 61, and 91 | Percent change from baseline in HDL-C is reported. |
| Area Under the Concentration-time Curve for 30 Days (AUC30d) After the Last Dose of MEDI5884 | Day 61 (pre-dose), and on Days 64, 68, 71, and 91 | AUC30d after the last dose of MEDI5884 is reported. |
| Maximum Observed Serum Concentration (Cmax) of MEDI5884 After the Last Dose | Day 61 (pre-dose), and on Days 64, 68, 71, 91, 111, and 151 | Maximum observed serum concentration (Cmax) of MEDI5884 after the last dose is reported. |
| Terminal Elimination Half-life (t½) of MEDI5884 After the Last Dose | Day 61 (pre-dose), and on Days 64, 68, 71, 91, 111, and 151 | Terminal half-life is the time required for the plasma concentration to fall by 50% during the terminal phase. The t½ of MEDI5884 after the last dose is reported. |
Countries
United States
Participant flow
Recruitment details
The study was conducted in the US between 13Dec2017 and 09Nov2018.
Pre-assignment details
A total of 248 participants consented to participate in the study, of which 115 were screen failures. A total of 133 participants were randomized to the study of which only 132 received treatment. One participant was ineligible, being randomized by error but not followed or treated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received subcutaneous (SC) dose of placebo (volume matched to MEDI5884) on Days 1, 31, and 61. | 23 |
| MEDI5884 50 mg Participants received SC dose of MEDI5884 50 mg on Days 1, 31, and 61. | 20 |
| MEDI5884 100 mg Participants received SC dose of MEDI5884 100 mg on Days 1, 31, and 61. | 24 |
| MEDI5884 200 mg Participants received SC dose of MEDI5884 200 mg on Days 1, 31, and 61. | 22 |
| MEDI5884 350 mg Participants received SC dose of MEDI5884 350 mg on Days 1, 31, and 61. | 21 |
| MEDI5884 500 mg Participants received SC dose of MEDI5884 500 mg on Days 1, 31, and 61. | 22 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | MEDI5884 50 mg | MEDI5884 100 mg | MEDI5884 200 mg | MEDI5884 350 mg | MEDI5884 500 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.3 Years STANDARD_DEVIATION 8.4 | 63.8 Years STANDARD_DEVIATION 8.4 | 67.4 Years STANDARD_DEVIATION 5.7 | 64.7 Years STANDARD_DEVIATION 8.9 | 67.5 Years STANDARD_DEVIATION 7.8 | 67.6 Years STANDARD_DEVIATION 8.6 | 66.3 Years STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 19 Participants | 22 Participants | 22 Participants | 20 Participants | 21 Participants | 125 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 17 Participants | 23 Participants | 20 Participants | 20 Participants | 19 Participants | 120 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 1 Participants | 4 Participants | 1 Participants | 4 Participants | 17 Participants |
| Sex: Female, Male Male | 19 Participants | 17 Participants | 23 Participants | 18 Participants | 20 Participants | 18 Participants | 115 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 20 | 0 / 24 | 0 / 22 | 0 / 21 | 0 / 22 |
| other Total, other adverse events | 9 / 23 | 9 / 20 | 6 / 24 | 12 / 22 | 13 / 21 | 13 / 22 |
| serious Total, serious adverse events | 2 / 23 | 2 / 20 | 1 / 24 | 0 / 22 | 4 / 21 | 0 / 22 |
Outcome results
Primary
Number of Participants With Clinically Important Changes in Electrocardiograms (ECGs) From Baseline
Number of participants with clinically important changes in ECGs from baseline are reported. Clinically important changes in ECGs is defined as any clinical significant difference in heart rate, RR interval, PR interval, QRS, and QT intervals from the primary lead of the digital 12-lead ECG from baseline.
Time frame: Day 1 (Baseline) through Day 241
Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. Reported data are through Day 151 for all participants, and Day 241 for participants with elevated ADA, LDL-C, and TG levels at Day 151 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Important Changes in Electrocardiograms (ECGs) From Baseline | 0 Participants |
| MEDI5884 50 mg | Number of Participants With Clinically Important Changes in Electrocardiograms (ECGs) From Baseline | 0 Participants |
| MEDI5884 100 mg | Number of Participants With Clinically Important Changes in Electrocardiograms (ECGs) From Baseline | 0 Participants |
| MEDI5884 200 mg | Number of Participants With Clinically Important Changes in Electrocardiograms (ECGs) From Baseline | 0 Participants |
| MEDI5884 350 mg | Number of Participants With Clinically Important Changes in Electrocardiograms (ECGs) From Baseline | 0 Participants |
| MEDI5884 500 mg | Number of Participants With Clinically Important Changes in Electrocardiograms (ECGs) From Baseline | 0 Participants |
Primary
Number of Participants With Clinically Important Changes in Laboratory Parameters From Baseline
Number of participants with clinically important changes in laboratory parameters from baseline are reported. Clinically important changes in laboratory parameters is defined as any clinical significant difference in analysis of serum chemistry, hematology, and urine from baseline.
Time frame: Day 1 (Baseline) through Day 241
Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. Reported data are through Day 151 for all participants, and Day 241 for participants with elevated ADA, LDL-C, and TG levels at Day 151 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Important Changes in Laboratory Parameters From Baseline | 0 Participants |
| MEDI5884 50 mg | Number of Participants With Clinically Important Changes in Laboratory Parameters From Baseline | 0 Participants |
| MEDI5884 100 mg | Number of Participants With Clinically Important Changes in Laboratory Parameters From Baseline | 0 Participants |
| MEDI5884 200 mg | Number of Participants With Clinically Important Changes in Laboratory Parameters From Baseline | 0 Participants |
| MEDI5884 350 mg | Number of Participants With Clinically Important Changes in Laboratory Parameters From Baseline | 0 Participants |
| MEDI5884 500 mg | Number of Participants With Clinically Important Changes in Laboratory Parameters From Baseline | 0 Participants |
Primary
Number of Participants With Clinically Important Changes in Physical Examinations From Baseline
Number of participants with clinically important changes in physical examinations from baseline are reported. Clinically important changes in physical examinations is defined as any clinical significant difference in general appearance, head, ears, eyes, nose, throat, neck, skin, heart, lung, abdomen, musculoskeletal system, endocrine system, nervous system, height, and weight from baseline.
Time frame: Day 1 (Baseline) through Day 241
Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. Reported data are through Day 151 for all participants, and Day 241 for participants with elevated ADA, LDL-C, and TG levels at Day 151 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Important Changes in Physical Examinations From Baseline | 0 Participants |
| MEDI5884 50 mg | Number of Participants With Clinically Important Changes in Physical Examinations From Baseline | 0 Participants |
| MEDI5884 100 mg | Number of Participants With Clinically Important Changes in Physical Examinations From Baseline | 0 Participants |
| MEDI5884 200 mg | Number of Participants With Clinically Important Changes in Physical Examinations From Baseline | 0 Participants |
| MEDI5884 350 mg | Number of Participants With Clinically Important Changes in Physical Examinations From Baseline | 0 Participants |
| MEDI5884 500 mg | Number of Participants With Clinically Important Changes in Physical Examinations From Baseline | 0 Participants |
Primary
Number of Participants With Clinically Important Changes in Vital Signs From Baseline
Number of participants with clinically important changes in vital signs from baseline are reported. Vital signs measurements were obtained after the participant had rested in the supine position for at least 10 minutes at the recording time. Clinically important changes in vital signs from baseline is defined as any clinical significant difference in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate) from baseline.
Time frame: Day 1 (Baseline) through Day 241
Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. Reported data are through Day 151 for all participants, and Day 241 for participants with elevated ADA, LDL-C, and TG levels at Day 151 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Important Changes in Vital Signs From Baseline | 0 Participants |
| MEDI5884 50 mg | Number of Participants With Clinically Important Changes in Vital Signs From Baseline | 0 Participants |
| MEDI5884 100 mg | Number of Participants With Clinically Important Changes in Vital Signs From Baseline | 0 Participants |
| MEDI5884 200 mg | Number of Participants With Clinically Important Changes in Vital Signs From Baseline | 0 Participants |
| MEDI5884 350 mg | Number of Participants With Clinically Important Changes in Vital Signs From Baseline | 0 Participants |
| MEDI5884 500 mg | Number of Participants With Clinically Important Changes in Vital Signs From Baseline | 0 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time frame: Day 1 (Baseline) through Day 241
Population: As-treated population: All participants who received any dose of study drug and analyzed according to actual treatment they received. Reported data are through Day 151 for all participants, and Day 241 for participants with elevated anti-drug antibodies (ADA), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) levels at Day 151 visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 17 Participants |
| MEDI5884 50 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 2 Participants |
| MEDI5884 50 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 10 Participants |
| MEDI5884 100 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 11 Participants |
| MEDI5884 100 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 1 Participants |
| MEDI5884 200 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| MEDI5884 200 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 12 Participants |
| MEDI5884 350 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 13 Participants |
| MEDI5884 350 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 4 Participants |
| MEDI5884 500 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| MEDI5884 500 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 13 Participants |
Secondary
Area Under the Concentration-time Curve for 30 Days (AUC30d) After the Last Dose of MEDI5884
AUC30d after the last dose of MEDI5884 is reported.
Time frame: Day 61 (pre-dose), and on Days 64, 68, 71, and 91
Population: Pharmacokinetic (PK) evaluable population included all participants who received any dose of MEDI5884 with at least one detectable post treatment serum concentration measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve for 30 Days (AUC30d) After the Last Dose of MEDI5884 | 14.6 μg⋅day/mL | Standard Deviation 27.3 |
| MEDI5884 50 mg | Area Under the Concentration-time Curve for 30 Days (AUC30d) After the Last Dose of MEDI5884 | 51.8 μg⋅day/mL | Standard Deviation 54.8 |
| MEDI5884 100 mg | Area Under the Concentration-time Curve for 30 Days (AUC30d) After the Last Dose of MEDI5884 | 191 μg⋅day/mL | Standard Deviation 176 |
| MEDI5884 200 mg | Area Under the Concentration-time Curve for 30 Days (AUC30d) After the Last Dose of MEDI5884 | 584 μg⋅day/mL | Standard Deviation 294 |
| MEDI5884 350 mg | Area Under the Concentration-time Curve for 30 Days (AUC30d) After the Last Dose of MEDI5884 | 1020 μg⋅day/mL | Standard Deviation 643 |
Secondary
Change From Baseline in Apolipoprotein B
Change from baseline in apolipoprotein B is reported.
Time frame: Day 1 (Baseline), and Days 31, 61, and 91
Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. Here, number analyzed signifies number of participants analyzed for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Apolipoprotein B | Day 31 | 3.3 mg/dL | Standard Deviation 8.5 |
| Placebo | Change From Baseline in Apolipoprotein B | Day 61 | 1.2 mg/dL | Standard Deviation 13.9 |
| Placebo | Change From Baseline in Apolipoprotein B | Day 91 | -0.5 mg/dL | Standard Deviation 10.7 |
| MEDI5884 50 mg | Change From Baseline in Apolipoprotein B | Day 31 | 0.5 mg/dL | Standard Deviation 12.2 |
| MEDI5884 50 mg | Change From Baseline in Apolipoprotein B | Day 91 | 3.6 mg/dL | Standard Deviation 29.3 |
| MEDI5884 50 mg | Change From Baseline in Apolipoprotein B | Day 61 | -1.2 mg/dL | Standard Deviation 14.1 |
| MEDI5884 100 mg | Change From Baseline in Apolipoprotein B | Day 91 | 2.3 mg/dL | Standard Deviation 10.7 |
| MEDI5884 100 mg | Change From Baseline in Apolipoprotein B | Day 31 | 5.1 mg/dL | Standard Deviation 10.6 |
| MEDI5884 100 mg | Change From Baseline in Apolipoprotein B | Day 61 | 3.5 mg/dL | Standard Deviation 10.8 |
| MEDI5884 200 mg | Change From Baseline in Apolipoprotein B | Day 91 | 2.0 mg/dL | Standard Deviation 8.3 |
| MEDI5884 200 mg | Change From Baseline in Apolipoprotein B | Day 61 | 2.6 mg/dL | Standard Deviation 15.3 |
| MEDI5884 200 mg | Change From Baseline in Apolipoprotein B | Day 31 | 2.2 mg/dL | Standard Deviation 9.4 |
| MEDI5884 350 mg | Change From Baseline in Apolipoprotein B | Day 61 | 3.7 mg/dL | Standard Deviation 11.7 |
| MEDI5884 350 mg | Change From Baseline in Apolipoprotein B | Day 91 | 2.9 mg/dL | Standard Deviation 9.4 |
| MEDI5884 350 mg | Change From Baseline in Apolipoprotein B | Day 31 | 7.1 mg/dL | Standard Deviation 10.6 |
| MEDI5884 500 mg | Change From Baseline in Apolipoprotein B | Day 91 | 7.8 mg/dL | Standard Deviation 13.4 |
| MEDI5884 500 mg | Change From Baseline in Apolipoprotein B | Day 31 | 7.1 mg/dL | Standard Deviation 14.3 |
| MEDI5884 500 mg | Change From Baseline in Apolipoprotein B | Day 61 | 6.2 mg/dL | Standard Deviation 9.6 |
Secondary
Maximum Observed Serum Concentration (Cmax) of MEDI5884 After the Last Dose
Maximum observed serum concentration (Cmax) of MEDI5884 after the last dose is reported.
Time frame: Day 61 (pre-dose), and on Days 64, 68, 71, 91, 111, and 151
Population: The PK evaluable population included all participants who received any dose of MEDI5884 with at least one detectable post treatment serum concentration measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Serum Concentration (Cmax) of MEDI5884 After the Last Dose | 1.01 μg/mL | Standard Deviation 1.34 |
| MEDI5884 50 mg | Maximum Observed Serum Concentration (Cmax) of MEDI5884 After the Last Dose | 4.63 μg/mL | Standard Deviation 2.95 |
| MEDI5884 100 mg | Maximum Observed Serum Concentration (Cmax) of MEDI5884 After the Last Dose | 11.9 μg/mL | Standard Deviation 7.77 |
| MEDI5884 200 mg | Maximum Observed Serum Concentration (Cmax) of MEDI5884 After the Last Dose | 28.5 μg/mL | Standard Deviation 13 |
| MEDI5884 350 mg | Maximum Observed Serum Concentration (Cmax) of MEDI5884 After the Last Dose | 46.3 μg/mL | Standard Deviation 24.6 |
Secondary
Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to MEDI5884
Treatment-emergent ADA is defined as the sum of treatment-induced ADA (post baseline-positive only) and treatment-boosted ADA (baseline ADA titer that was boosted to a 4-fold or higher level following drug administration).
Time frame: Day 1 (pre-dose), on Day 8, Day 31 (pre-dose), Day 61 (pre-dose), on Days 151 and 241
Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to MEDI5884 | 1 Participants |
| MEDI5884 50 mg | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to MEDI5884 | 1 Participants |
| MEDI5884 100 mg | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to MEDI5884 | 1 Participants |
| MEDI5884 200 mg | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to MEDI5884 | 3 Participants |
| MEDI5884 350 mg | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to MEDI5884 | 3 Participants |
| MEDI5884 500 mg | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) to MEDI5884 | 3 Participants |
Secondary
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C)
Percent change from baseline in HDL-C is reported.
Time frame: Day 1 (Baseline), and Days 31, 61, and 91
Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. Here, number analyzed signifies number of participants analyzed for the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 61 | -4.69 Percent change | Standard Deviation 9.45 |
| Placebo | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 31 | -3.08 Percent change | Standard Deviation 10.28 |
| Placebo | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 91 | -3.62 Percent change | Standard Deviation 13.41 |
| MEDI5884 50 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 61 | 4.58 Percent change | Standard Deviation 12.45 |
| MEDI5884 50 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 31 | 7.37 Percent change | Standard Deviation 13.52 |
| MEDI5884 50 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 91 | 1.98 Percent change | Standard Deviation 14.69 |
| MEDI5884 100 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 61 | 28.28 Percent change | Standard Deviation 32.19 |
| MEDI5884 100 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 31 | 22.95 Percent change | Standard Deviation 25.04 |
| MEDI5884 100 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 91 | 21.82 Percent change | Standard Deviation 30.66 |
| MEDI5884 200 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 61 | 37.65 Percent change | Standard Deviation 22.76 |
| MEDI5884 200 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 31 | 27.25 Percent change | Standard Deviation 19.37 |
| MEDI5884 200 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 91 | 35.63 Percent change | Standard Deviation 35.27 |
| MEDI5884 350 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 61 | 39.74 Percent change | Standard Deviation 22.74 |
| MEDI5884 350 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 31 | 44.12 Percent change | Standard Deviation 24.74 |
| MEDI5884 350 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 91 | 43.29 Percent change | Standard Deviation 31.09 |
| MEDI5884 500 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 31 | 55.80 Percent change | Standard Deviation 25.97 |
| MEDI5884 500 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 91 | 48.31 Percent change | Standard Deviation 25.63 |
| MEDI5884 500 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Day 61 | 49.58 Percent change | Standard Deviation 21.46 |
Secondary
Terminal Elimination Half-life (t½) of MEDI5884 After the Last Dose
Terminal half-life is the time required for the plasma concentration to fall by 50% during the terminal phase. The t½ of MEDI5884 after the last dose is reported.
Time frame: Day 61 (pre-dose), and on Days 64, 68, 71, 91, 111, and 151
Population: The PK evaluable population included all participants who received any dose of MEDI5884 with at least one detectable post treatment serum concentration measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MEDI5884 50 mg | Terminal Elimination Half-life (t½) of MEDI5884 After the Last Dose | 7.56 Days | Standard Deviation 6.4 |
| MEDI5884 100 mg | Terminal Elimination Half-life (t½) of MEDI5884 After the Last Dose | 8.09 Days | Standard Deviation 2.8 |
| MEDI5884 200 mg | Terminal Elimination Half-life (t½) of MEDI5884 After the Last Dose | 10.3 Days | Standard Deviation 3.53 |
| MEDI5884 350 mg | Terminal Elimination Half-life (t½) of MEDI5884 After the Last Dose | 13.7 Days | Standard Deviation 5.86 |