Multiple Ascending Doses of MEDI6012 in Subjects With Sta... | NCT03004638

NCT03004638

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
MEDI6012 40 mg	Experimental	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.	Drug: MEDI6012 40 mg
Placebo	Placebo Comparator	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.	Drug: Placebo
MEDI6012 120 mg	Experimental	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.	Drug: MEDI6012 120 mg
MEDI6012 300 mg	Experimental	Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.	Drug: MEDI6012 300 mg
MEDI6012 IV Push	Experimental	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.	Drug: MEDI6012 IV Push
Placebo IV Push	Placebo Comparator

Name	Type	Description	Arm Group Labels	Other Names
MEDI6012 40 mg	Drug	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.	MEDI6012 40 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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. 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.	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)
Number of Participants With Abnormal Clinical Laboratory Evaluations Reported as TEAEs	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.	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)
Number of Participants With Abnormal Vital Signs Reported as TEAEs	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.	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)
Number of Participants With Abnormal Electrocardiogram Reported as TEAEs

Secondary Outcomes

Measure	Description	Time Frame
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Apolipoprotein A1	The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of Apolipoprotein A1.	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.

Eligibility Module

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Anniston	Alabama	36207	United States
Research Site

References Module

Label	URL
D5780C00005-CSP-amendment-1\_REDACTED\_16Jul2017\_PDF-A	View source
5780C00005 MEDI6012 Statistical Analysis Plan\_21Jul2017\_Version2\_Redacted\_PDF-A.pdf	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
FG001	MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 16, 2017	Oct 31, 2018

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Treatment-emergent adverse events observed in participants with clinically significant ECG abnormalities are reported.

As-treated population included all participants who received at least one dose of study drug.

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
BG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
BG002	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
BG003	Cohort 3: MEDI6012 300 mg	Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
BG004	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.
BG005	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.
BG006	Total	Total of all reporting groups

Units	Counts
Participants	BG0006 BG0016 BG0026 BG0036 BG0041 BG0057 BG00632

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00067.8± 4.8 BG00166.7± 3.3 BG00268.8± 2.8 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0002 BG0012 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0001 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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. 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.

As-treated population included all participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
OG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
OG003	Cohort 3: MEDI6012 300 mg	Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
OG004	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.
OG005	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.

Units	Counts
Participants	OG0006 OG0016 OG0026 OG003

Title

Denominators

Categories

TEAEs

Title	Measurements
	OG0003 OG0013 OG0023 OG003

Primary

Number of Participants With Abnormal Clinical Laboratory Evaluations Reported as TEAEs

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.

As-treated population included all participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
OG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
OG003	Cohort 3: MEDI6012 300 mg

Primary

Number of Participants With Abnormal Vital Signs Reported as TEAEs

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.

As-treated population included all participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
OG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
OG003	Cohort 3: MEDI6012 300 mg

Primary

Number of Participants With Abnormal Electrocardiogram Reported as TEAEs

Treatment-emergent adverse events observed in participants with clinically significant ECG abnormalities are reported.

As-treated population included all participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
OG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
OG003	Cohort 3: MEDI6012 300 mg	Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.

Primary

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)

The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of high-density lipoprotein-cholesterol.

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.

Posted

Mean

Standard Deviation

mg*h/dL

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.

ID	Title	Description
OG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
OG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.

Primary

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)

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.

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.

Posted

Mean

Standard Deviation

mg*h/dL

ID	Title	Description
OG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
OG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.

Primary

Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Cholesterol Ester

The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of cholesterol ester.

Posted

Mean

Standard Deviation

mg*h/dL

ID	Title	Description
OG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
OG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
OG003

Secondary

Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Apolipoprotein A1

The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of Apolipoprotein A1.

Posted

Mean

Standard Deviation

mg*h/dL

ID	Title	Description
OG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
OG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
OG003

Secondary

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).

The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of LDL-C.

Posted

Mean

Standard Deviation

mg*h/dL

ID	Title	Description
OG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
OG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.

Secondary

Baseline-adjusted Area Under the Curve From Time 0 to 96 Hour (hr) (AUC [0-96 hr]) Post Dose 3 for Apolipoprotein B

The AUC (0-96 hr) is the area under the concentration-time curve from time 0 to 96 hrs of Apolipoprotein B.

Posted

Mean

Standard Deviation

mg*h/dL

ID	Title	Description
OG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
OG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
OG003

Secondary

Change From Baseline in Serum Concentration for MEDI6012 Mass

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).

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.

Posted

Mean

Standard Deviation

μg/mL

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.

ID	Title	Description
OG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
OG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.

Secondary

Change From Baseline in Serum Concentration for Total LCAT Activity

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).

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.

Posted

Mean

Standard Deviation

μg/mL

ID	Title	Description
OG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
OG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.

Secondary

Maximum Observed Serum Concentration (Cmax) of MEDI6012

The maximum observed serum concentration following the first and third dose of MEDI6012 was reported.

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.

Posted

Mean

Standard Deviation

μg/mL

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.

ID	Title	Description
OG000	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG001	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 3: MEDI6012 300 mg	Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
OG003

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI6012

The time to reach the maximum observed serum concentration following the first and third dose of MEDI6012 was reported.

Posted

Mean

Standard Deviation

Hours

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.

ID	Title	Description
OG000	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG001	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 3: MEDI6012 300 mg	Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
OG003

Secondary

Accumulation Ratio (Rac) of MEDI6012

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).

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.

Posted

Mean

Standard Deviation

Ratio

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.

ID	Title	Description
OG000	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG001	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 3: MEDI6012 300 mg

Secondary

Terminal Half-life (t1/2) of MEDI6012

The t1/2 is the time measured for the serum concentration to decrease by one half after the third dose of MEDI6012.

Posted

Mean

Standard Deviation

Days

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.

ID	Title	Description
OG000	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG001	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 3: MEDI6012 300 mg	Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.
OG003	Cohort 4: MEDI6012 IV Push

Secondary

Area Under the Concentration Time Curve to Last Measurable Time Point (AUClast) of MEDI6012

The area under the concentration time-curve to the last measured concentration after the third dose of MEDI6012 was reported.

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.

Posted

Mean

Standard Deviation

µg*day/mL

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.

ID	Title	Description
OG000	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG001	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 3: MEDI6012 300 mg	Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.

Secondary

Number of Participants With Positive Anti-Drug Antibodies for MEDI6012

Participants with positive serum antibodies to MEDI6012 were reported.

Immunogenicity population included all participants in the as-treated population who had at least one serum sample for immunogenicity testing

Posted

Count of Participants

Participants

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.

ID	Title	Description
OG000	Placebo	Participants received 3 doses of placebo matching with MEDI6012 intravenously (IV) on Days 1, 8, and 15.
OG001	Cohort 1: MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.
OG002	Cohort 2: MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.
OG003	Cohort 3: MEDI6012 300 mg	Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Description (Arm-group)	6	0	6	3	6
EG001	MEDI6012 40 mg	Participants received 3 doses of 40 milligram (mg) MEDI6012 IV on Days 1, 8, and 15.	6	0	6	3	6
EG002	MEDI6012 120 mg	Participants received 3 doses of 120 mg MEDI6012 IV on Days 1, 8, and 15.	6	1	6	3	6
EG003	MEDI6012 300 mg	Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.	6	0	6	4	6
EG004	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.	1	0	1	0	1
EG005	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.	7	0	7	3	7

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA 20.0	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected6 at risk EG0030 events0 affected6 at risk EG0040 events0 affected1 at risk EG0050 events0 affected7 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG0033 events2 affected6 at risk EG0040 events0 affected1 at risk EG0050 events0 affected7 at risk
Chest discomfort	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Infusion site erythema	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Infusion site pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Infusion site induration	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Infusion site reaction	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Epididymitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected6 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Dizziness	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected6 at risk EG003
Hypertension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Hypotension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected6 at risk EG003

ID	Term
D050197	Atherosclerosis
D002318	Cardiovascular Diseases

BG00465.0± NAStandard deviation was not applicable as only one participant was evaluable for this reporting group.

Participants received 3 doses of 300 mg MEDI6012 IV on Days 1, 8, and 15.

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.