Trial Outcomes & Findings for Multiple Ascending Doses of MEDI6012 in Subjects With Stable Atherosclerotic Cardiovascular Disease (NCT NCT03004638)
NCT ID: NCT03004638
Last Updated: 2018-12-19
Results Overview
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. Treatment-emergent are the events between first dose of study drug and up to 56 days after last dose of study drug (Day 66 for Cohort 4 and placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm) that were absent before treatment or that worsened relative to pre-treatment state.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
32 participants
Primary outcome timeframe
From Day 1 to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm)
Results posted on
2018-12-19
Participant Flow
The study was conducted at 4 sites in the USA between 23Jan2017 and 02Nov2017.
A total of 91 participants were screened, of which 32 participants were randomized in a 6:2 ratio to receive MEDI6012 or placebo in 4 cohorts (8 participants in each cohort). For Cohort 4, randomization happened in a 7:1 ratio to receive MEDI6012 or placebo due to an interactive voice/web response system programming issue.
Participant milestones
| Measure |
Placebo
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
MEDI6012 40 mg
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
MEDI6012 120 mg
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
MEDI6012 300 mg
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
MEDI6012 IV Push
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
6
|
1
|
7
|
|
Overall Study
COMPLETED
|
6
|
6
|
6
|
6
|
1
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Multiple Ascending Doses of MEDI6012 in Subjects With Stable Atherosclerotic Cardiovascular Disease
Baseline characteristics by cohort
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=6 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
67.8 Years
STANDARD_DEVIATION 4.8 • n=5 Participants
|
66.7 Years
STANDARD_DEVIATION 3.3 • n=7 Participants
|
68.8 Years
STANDARD_DEVIATION 2.8 • n=5 Participants
|
66.2 Years
STANDARD_DEVIATION 2.6 • n=4 Participants
|
65.0 Years
STANDARD_DEVIATION NA • n=21 Participants
|
71.4 Years
STANDARD_DEVIATION 4.2 • n=10 Participants
|
68.2 Years
STANDARD_DEVIATION 3.9 • n=115 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
9 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
23 Participants
n=115 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
29 Participants
n=115 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
31 Participants
n=115 Participants
|
PRIMARY outcome
Timeframe: From Day 1 to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm)Population: As-treated population included all participants who received at least one dose of study drug.
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. Treatment-emergent are the events between first dose of study drug and up to 56 days after last dose of study drug (Day 66 for Cohort 4 and placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm) that were absent before treatment or that worsened relative to pre-treatment state.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=6 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
TEAEs
|
3 Participants
|
3 Participants
|
3 Participants
|
4 Participants
|
0 Participants
|
3 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
TESAEs
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: From Day 1 to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm)Population: As-treated population included all participants who received at least one dose of study drug.
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator as medically significant was reported as an AE. Laboratory evaluations included haematology, serum chemistry, and urinalysis.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=6 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Abnormal Clinical Laboratory Evaluations Reported as TEAEs
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: From Day 1 to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm)Population: As-treated population included all participants who received at least one dose of study drug.
Treatment-emergent adverse events observed in participants with clinically significant vital signs abnormalities are reported. Vital sign parameters included blood pressure, respiration rate, heart rate, pulse oximetry, and body temperature.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=6 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Hypertension
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Hypotension
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: From Day 1 to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm)Population: As-treated population included all participants who received at least one dose of study drug.
Treatment-emergent adverse events observed in participants with clinically significant ECG abnormalities are reported.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=6 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Abnormal Electrocardiogram Reported as TEAEs
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 15 dose (third dose) for Cohorts 1 to 3 and Placebo arm; Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 10 dose (third dose) for Cohort 4 and Placebo IV push arm.Population: As-treated population included all participants who received at least one dose of study drug. The overall number of participants analyzed denotes the number of participants evaluated specific for this outcome measure.
The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of high-density lipoprotein-cholesterol.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=5 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for High-density Lipoprotein-cholesterol (HDL-C)
|
-6.72 mg*h/dL
Standard Deviation 467.59
|
1355.64 mg*h/dL
Standard Deviation 576.94
|
2874.86 mg*h/dL
Standard Deviation 1232.21
|
6465.05 mg*h/dL
Standard Deviation 2074.77
|
266.68 mg*h/dL
Standard Deviation NA
Standard deviation was not applicable as only one participant was evaluable for this reporting group.
|
1803.12 mg*h/dL
Standard Deviation 1684.32
|
PRIMARY outcome
Timeframe: Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 15 dose (third dose) for Cohorts 1 to 3 and Placebo arm; Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 10 dose (third dose) for Cohort 4 and Placebo IV push arm.Population: As-treated population included all participants who received at least one dose of study drug.The overall number of participants analyzed denotes the number of participants evaluated specific for this outcome measure.
The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of high-density lipoprotein-cholesterol ester.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=5 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for High-density Lipoprotein-cholesterol Ester (HDL-CE)
|
-23.75 mg*h/dL
Standard Deviation 422.76
|
1161.47 mg*h/dL
Standard Deviation 506.67
|
2580.51 mg*h/dL
Standard Deviation 1076.11
|
5710.09 mg*h/dL
Standard Deviation 1622.36
|
273.03 mg*h/dL
Standard Deviation NA
Standard deviation was not applicable as only one participant was evaluable for this reporting group.
|
1597.12 mg*h/dL
Standard Deviation 1531.40
|
PRIMARY outcome
Timeframe: Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 15 dose (third dose) for Cohorts 1 to 3 and Placebo arm; Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 10 dose (third dose) for Cohort 4 and Placebo IV push arm.Population: As-treated population included all participants who received at least one dose of study drug. The overall number of participants analyzed denotes the number of participants evaluated specific for this outcome measure.
The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of cholesterol ester.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=5 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Cholesterol Ester
|
373.04 mg*h/dL
Standard Deviation 1060.76
|
2267.37 mg*h/dL
Standard Deviation 1126.43
|
4047.38 mg*h/dL
Standard Deviation 1314.67
|
9004.31 mg*h/dL
Standard Deviation 2086.47
|
371.75 mg*h/dL
Standard Deviation NA
Standard deviation was not applicable as only one participant was evaluable for this reporting group.
|
2649.56 mg*h/dL
Standard Deviation 3039.83
|
SECONDARY outcome
Timeframe: Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 15 dose (third dose) for Cohorts 1 to 3 and Placebo arm; Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 10 dose (third dose) for Cohort 4 and Placebo IV push arm.Population: As-treated population included all participants who received at least one dose of study drug. The overall number of participants analyzed denotes the number of participants evaluated specific for this outcome measure.
The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of Apolipoprotein A1.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=5 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Apolipoprotein A1
|
821.33 mg*h/dL
Standard Deviation 1465.70
|
2440.48 mg*h/dL
Standard Deviation 1021.34
|
3740.59 mg*h/dL
Standard Deviation 1508.93
|
5302.87 mg*h/dL
Standard Deviation 1739.86
|
-20.42 mg*h/dL
Standard Deviation NA
Standard deviation was not applicable as only one participant was evaluable for this reporting group.
|
2399.42 mg*h/dL
Standard Deviation 2611.21
|
SECONDARY outcome
Timeframe: Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 15 dose (third dose) for Cohorts 1 to 3 and Placebo arm; Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 10 dose (third dose) for Cohort 4 and Placebo IV push arm.Population: As-treated population included all participants who received at least one dose of study drug. The overall number of participants analyzed denotes the number of participants evaluated specific for this outcome measure.
The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of LDL-C.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=5 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Low-density Lipoprotein Cholesterol (LDL-C).
|
-55.96 mg*h/dL
Standard Deviation 886.81
|
1125.45 mg*h/dL
Standard Deviation 872.40
|
1043.39 mg*h/dL
Standard Deviation 700.00
|
3056.76 mg*h/dL
Standard Deviation 1765.33
|
-78.79 mg*h/dL
Standard Deviation NA
Standard deviation was not applicable as only one participant was evaluable for this reporting group.
|
1364.12 mg*h/dL
Standard Deviation 2375.93
|
SECONDARY outcome
Timeframe: Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 15 dose (third dose) for Cohorts 1 to 3 and Placebo arm; Pre-dose, end of infusion, 12, 24, and 96 hrs post Day 10 dose (third dose) for Cohort 4 and Placebo IV push arm.Population: As-treated population included all participants who received at least one dose of study drug. The overall number of participants analyzed denotes the number of participants evaluated specific for this outcome measure.
The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of Apolipoprotein B.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=5 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Apolipoprotein B
|
-82.95 mg*h/dL
Standard Deviation 667.65
|
-40.06 mg*h/dL
Standard Deviation 477.21
|
145.42 mg*h/dL
Standard Deviation 283.62
|
-374.38 mg*h/dL
Standard Deviation 588.54
|
-239.17 mg*h/dL
Standard Deviation NA
Standard deviation was not applicable as only one participant was evaluable for this reporting group.
|
73.01 mg*h/dL
Standard Deviation 864.30
|
SECONDARY outcome
Timeframe: Seven days post-dose following Doses 1 to 3 in Cohorts 1 to 3 and placebo arm (Days 8, 15, 22); 2 days post-dose following Dose 1 (Day 3) and 7 days post-dose following Doses 2 and 3 (Days 10, 17) in Cohort 4 and placbo IV push.Population: Pharmacokinetic (PK) population included all participants in the as-treated population who had at least one detectable lecithin-cholesterol acyltransferase (LCAT) serum concentration measurement. The overall number of participants analyzed denotes the number of participants evaluated specific for this outcome measure.
The trough concentration level of MEDI6012 following each dose is reported (concentration at Days 8, 15, and 22 for Cohorts 1 to 3 and placebo; Concentration at Days 3, 10, and 17 for Cohort 4 and placebo IV push arm).
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=6 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Serum Concentration for MEDI6012 Mass
Day 3
|
—
|
—
|
—
|
—
|
0.0000 μg/mL
Standard Deviation NA
Standard deviation was not applicable as only one participant was evaluable for this reporting group.
|
16.2684 μg/mL
Standard Deviation 4.5094
|
|
Change From Baseline in Serum Concentration for MEDI6012 Mass
Day 8
|
0.0000 μg/mL
Standard Deviation 0.0000
|
0.0000 μg/mL
Standard Deviation 0.0000
|
0.0000 μg/mL
Standard Deviation 0.0000
|
3.8646 μg/mL
Standard Deviation 2.0753
|
—
|
—
|
|
Change From Baseline in Serum Concentration for MEDI6012 Mass
Day 10
|
—
|
—
|
—
|
—
|
0.0000 μg/mL
Standard Deviation NA
Standard deviation was not applicable as only one participant was evaluable for this reporting group.
|
2.4407 μg/mL
Standard Deviation 2.1437
|
|
Change From Baseline in Serum Concentration for MEDI6012 Mass
Day 15
|
0.0000 μg/mL
Standard Deviation 0.0000
|
0.0000 μg/mL
Standard Deviation 0.0000
|
0.0000 μg/mL
Standard Deviation 0.0000
|
5.4320 μg/mL
Standard Deviation 2.6999
|
—
|
—
|
|
Change From Baseline in Serum Concentration for MEDI6012 Mass
Day 17
|
—
|
—
|
—
|
—
|
0.0000 μg/mL
Standard Deviation NA
Standard deviation was not applicable as only one participant was evaluable for this reporting group.
|
0.3980 μg/mL
Standard Deviation 0.8900
|
|
Change From Baseline in Serum Concentration for MEDI6012 Mass
Day 22
|
0.0000 μg/mL
Standard Deviation 0.0000
|
0.0000 μg/mL
Standard Deviation 0.0000
|
0.5478 μg/mL
Standard Deviation 0.8613
|
7.1622 μg/mL
Standard Deviation 2.7936
|
—
|
—
|
SECONDARY outcome
Timeframe: Seven days post-dose following Doses 1 to 3 in Cohorts 1 to 3 and placebo arm (Days 8, 15, 22); 2 days post-dose following Dose 1 (Day 3) and 7 days post-dose following Doses 2 and 3 (Days 10, 17) in Cohort 4 and placbo IV push.Population: PK population included all participants in the as-treated population who had at least one detectable LCAT serum concentration measurement. LCAT activity at Day 3 and Day 17 were not collected for Cohort 4. The overall number of participants analyzed denotes the number of participants evaluated specific for this outcome measure.
Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme secreted by the liver. Serum LCAT activity was estimated to provide an alternative measure to LCAT mass in establishing the relationship between pharmacokinetics and pharmacodynamics of MEDI6012. Change in LCAT activity from baseline (pre-dose of each dose) to post doses was reported (concentration at Days 8, 15, and 22 for Cohorts 1 to 3 and placebo; Concentration at Days 3, 10, and 17 for Cohort 4 and placebo IV push arm).
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=6 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Serum Concentration for Total LCAT Activity
Day 8
|
0.2046 μg/mL
Standard Deviation 0.3035
|
0.0282 μg/mL
Standard Deviation 0.9432
|
0.6710 μg/mL
Standard Deviation 0.8715
|
0.9720 μg/mL
Standard Deviation 0.7029
|
—
|
—
|
|
Change From Baseline in Serum Concentration for Total LCAT Activity
Day 10
|
—
|
—
|
—
|
—
|
0.0000 μg/mL
Standard Deviation NA
Standard deviation was not applicable as only one participant was evaluable for this reporting group.
|
0.5503 μg/mL
Standard Deviation 0.5960
|
|
Change From Baseline in Serum Concentration for Total LCAT Activity
Day 15
|
-0.1467 μg/mL
Standard Deviation 0.8494
|
0.1700 μg/mL
Standard Deviation 0.7582
|
0.2418 μg/mL
Standard Deviation 0.9939
|
1.1188 μg/mL
Standard Deviation 0.7320
|
—
|
—
|
|
Change From Baseline in Serum Concentration for Total LCAT Activity
Day 22
|
0.4983 μg/mL
Standard Deviation 0.3355
|
-0.1617 μg/mL
Standard Deviation 0.7031
|
0.0824 μg/mL
Standard Deviation 1.0816
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 end of infusion to Day 8 predose for Cohorts 1 to 3; Day 1 end of infusion to Day 3 predose for Cohort 4; Cmax following the third dose: Day 15 end of infusion to Day 71 for Cohort 1 to 3; Day 10 end of infusion to Day 65 for Cohort 4.Population: PK population included all participants in the as-treated population who had at least one detectable LCAT serum concentration measurement. The overall number of participants analyzed denotes the number of participants evaluated specific for this outcome measure.
The maximum observed serum concentration following the first and third dose of MEDI6012 was reported.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=5 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=5 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Maximum Observed Serum Concentration (Cmax) of MEDI6012
Dose 1
|
9.17 μg/mL
Standard Deviation 3.27
|
27.5 μg/mL
Standard Deviation 7.78
|
83.7 μg/mL
Standard Deviation 27.7
|
75.1 μg/mL
Standard Deviation 14.6
|
—
|
—
|
|
Maximum Observed Serum Concentration (Cmax) of MEDI6012
Dose 3
|
9.63 μg/mL
Standard Deviation 3.5
|
27.1 μg/mL
Standard Deviation 5.37
|
94.7 μg/mL
Standard Deviation 33.1
|
28.5 μg/mL
Standard Deviation 6.89
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 end of infusion to Day 8 predose for Cohorts 1 to 3; Day 1 end of infusion to Day 3 predose for Cohort 4; Tmax following the third dose: Day 15 end of infusion to Day 71 for Cohort 1 to 3; Day 10 end of infusion to Day 65 for Cohort 4.Population: PK population included all participants in the as-treated population who had at least one detectable LCAT serum concentration measurement. The overall number of participants analyzed denotes the number of participants evaluated specific for this outcome measure.
The time to reach the maximum observed serum concentration following the first and third dose of MEDI6012 was reported.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=5 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI6012
Dose 1
|
0.0417 Hours
Standard Deviation 0.00
|
0.0417 Hours
Standard Deviation 0.00
|
0.0417 Hours
Standard Deviation 0.00
|
0.000696 Hours
Standard Deviation 0.00
|
—
|
—
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI6012
Dose 3
|
14.0417 Hours
Standard Deviation 0.00
|
14.0417 Hours
Standard Deviation 0.00
|
14.0417 Hours
Standard Deviation 0.00
|
9.00070 Hours
Standard Deviation 0.00
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 end of infusion to Day 8 predose for Cohorts 1 to 3; Day 1 end of infusion to Day 3 predose for Cohort 4; The Rac following third dose: Day 15 end of infusion to Day 71 for Cohort 1 to 3; Day 10 end of infusion to Day 65 for Cohort 4.Population: PK population. The Rac was not calculated for Cohort 4 as the first dose regimen (300 mg loading dose follow by 2nd dose given 48 hours later, therefore NCA was not performed for Dose 1) are different from 3rd dose (100 mg). The overall number of participants analyzed denotes the number of participants evaluated specific for this outcome measure.
The accumulation ratio (Rac) is defined as the ratio of accumulation of a study drug going from a single dose to steady state with repeated administration. Accumulation ratio was reported on the basis of maximum concentration (ARC max) and area under the concentration-time curve (ARAUC).
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=7 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Accumulation Ratio (Rac) of MEDI6012
ARCmax
|
1.09 Ratio
Standard Deviation 0.214
|
1.01 Ratio
Standard Deviation 0.112
|
1.02 Ratio
Standard Deviation 0.177
|
—
|
—
|
—
|
|
Accumulation Ratio (Rac) of MEDI6012
ARAUC
|
0.897 Ratio
Standard Deviation NA
Standard deviation was not applicable as only one participant was evaluable for this reporting group.
|
1.16 Ratio
Standard Deviation 0.0982
|
1.21 Ratio
Standard Deviation 0.169
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: The t1/2 following third dose: Day 15 end of infusion to Day 71 for Cohort 1 to 3; Day 10 end of infusion to Day 65 for Cohort 4.Population: PK population included all participants in the as-treated population who had at least one detectable LCAT serum concentration measurement. The overall number of participants analyzed denotes the number of participants evaluated specific for this outcome measure.
The t1/2 is the time measured for the serum concentration to decrease by one half after the third dose of MEDI6012.
Outcome measures
| Measure |
Placebo
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=5 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=5 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=4 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Terminal Half-life (t1/2) of MEDI6012
|
2.7 Days
Standard Deviation NA
Standard deviation was not applicable as only one participant was evaluable for this reporting group.
|
1.79 Days
Standard Deviation 0.374
|
2.52 Days
Standard Deviation 0.702
|
2.6 Days
Standard Deviation 0.942
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 end of infusion to Day 8 predose for Cohorts 1 to 3; Day 1 end of infusion to Day 3 predose for Cohort 4; AUClast following the third dose: Day 15 end of infusion to Day 71 for Cohort 1 to 3; Day 10 end of infusion to Day 65 for Cohort 4.Population: PK population. The AUClast was not reported following first dose in Cohort 4 since NCA was not performed due to dosing period was only 48 hrs. The overall number of participants analyzed denotes the number of participants evaluated specific for this outcome measure.
The area under the concentration time-curve to the last measured concentration after the third dose of MEDI6012 was reported.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=5 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Area Under the Concentration Time Curve to Last Measurable Time Point (AUClast) of MEDI6012
Dose 1
|
10.9 µg*day/mL
Standard Deviation 10.1
|
35.2 µg*day/mL
Standard Deviation 17.8
|
152 µg*day/mL
Standard Deviation 50.5
|
—
|
—
|
—
|
|
Area Under the Concentration Time Curve to Last Measurable Time Point (AUClast) of MEDI6012
Dose 3
|
8.98 µg*day/mL
Standard Deviation 5.61
|
48.3 µg*day/mL
Standard Deviation 23.6
|
205 µg*day/mL
Standard Deviation 63.7
|
38.6 µg*day/mL
Standard Deviation 21.9
|
—
|
—
|
SECONDARY outcome
Timeframe: For Cohorts 1 to 3 and Placebo arm: Pre-dose on Days 1 and 15, and on Days 29, 43, and 71; For Cohort 4 and Placebo IV push arm: Pre-dose on Days 1 and 10, and on Days 24, 38, and 66.Population: Immunogenicity population included all participants in the as-treated population who had at least one serum sample for immunogenicity testing
Participants with positive serum antibodies to MEDI6012 were reported.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
|
Cohort 1: MEDI6012 40 mg
n=6 Participants
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 2: MEDI6012 120 mg
n=6 Participants
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
Cohort 3: MEDI6012 300 mg
n=6 Participants
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 Participants
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
Cohort 4: MEDI6012 IV Push
n=7 Participants
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Positive Anti-Drug Antibodies for MEDI6012
ADA positive at baseline
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Positive Anti-Drug Antibodies for MEDI6012
ADA positive post-baseline
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
MEDI6012 40 mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
MEDI6012 120 mg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
MEDI6012 300 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo IV Push
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
MEDI6012 IV Push
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=6 participants at risk
Description (Arm-group)
|
MEDI6012 40 mg
n=6 participants at risk
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
MEDI6012 120 mg
n=6 participants at risk
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
MEDI6012 300 mg
n=6 participants at risk
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 participants at risk
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
MEDI6012 IV Push
n=7 participants at risk
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
Other adverse events
| Measure |
Placebo
n=6 participants at risk
Description (Arm-group)
|
MEDI6012 40 mg
n=6 participants at risk
Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
|
MEDI6012 120 mg
n=6 participants at risk
Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
|
MEDI6012 300 mg
n=6 participants at risk
Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
|
Placebo IV Push
n=1 participants at risk
Participants received 3 doses of placebo matching with MEDI6012 by IV push. A loading dose on Day 1 and maintenance doses on Days 3 and 10.
|
MEDI6012 IV Push
n=7 participants at risk
Participants received 3 doses of MEDI6012 by IV push as 300 mg loading dose on Day 1, and maintenance doses of 150 mg and 100 mg on Day 3 and Day 10, respectively.
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
33.3%
2/6 • Number of events 3 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
General disorders
Chest discomfort
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
General disorders
Infusion site erythema
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
General disorders
Infusion site pain
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
General disorders
Infusion site induration
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
General disorders
Infusion site reaction
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
14.3%
1/7 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
14.3%
1/7 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Infections and infestations
Epididymitis
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
14.3%
1/7 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
16.7%
1/6 • Number of events 2 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Nervous system disorders
Headache
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Psychiatric disorders
Anxiety
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
14.3%
1/7 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Vascular disorders
Hypertension
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
|
Vascular disorders
Hypotension
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
16.7%
1/6 • Number of events 1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/6 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/1 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
0.00%
0/7 • Adverse events were collected from baseline (Day 1) to Day 56 after last dose of study drug (Day 66 for Cohort 4 and Placebo IV push arm and Day 71 for Cohorts 1 to 3 and placebo arm).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
- Publication restrictions are in place
Restriction type: OTHER