To Evaluate Safety, Pharmacokinetics and Pharmacodynamics of MEDI6012 in Subjects With Stable Coronary Artery Disease

A Phase 2a Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single- Ascending Doses of MEDI6012 in Subjects With Stable Coronary Artery Disease

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02601560

Enrollment

Registered

2015-11-10

Start date

2015-12-03

Completion date

2016-11-03

Last updated

2018-03-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Coronary Artery Disease

Keywords

Coronary Artery Disease, CAD

Brief summary

This is a Phase 2a randomized, double-blind (subject/investigator blinded, MedImmune unblinded), placebo-controlled, dose-escalation study to evaluate the safety, PK/PD, and immunogenicity of single IV and SC MEDI6012 doses in adult subjects with stable CAD.

Interventions

BIOLOGICALPlacebo SC

Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.

BIOLOGICALPlacebo IV

Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.

BIOLOGICALMEDI6012

Participants received a single IV (24, 80, 240, and 800 mg) and SC (80 and 600 mg) MEDI6012 doses on Day 1.

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

40 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Men and women 40 - 75 years old * History of Stable CAD * Currently receiving statin as standard of care

Exclusion criteria

* Severe angina pectoris symptoms * High-risk coronary or carotid artery disease that will likely require surgical or percutaneous intervention during the study period * Hospitalization for heart failure within 12 months prior to screening * Uncontrolled Hypertension * Within 6 months prior to screening, a history of ACS or hospitalization for heart failure * Clinically significant abnormalities in rhythm, conduction or morphology of ECG * Subjects with transplanted heart, left ventricular assist device, implanted pacemaker, implantable cardioverter defibrillator, or cardiac resynchronization therapy * Untreated life-threatening ventricular arrhythmias * History, within 12 months prior to screening, of myocarditis or restrictive pericarditis, or hemodynamically significant valvular hear disease or aortic disease * Undergone major surgery with in 3 months prior to screening or has planned major surgery during the study period

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	Baseline (Day 1) up to Day 57	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was 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 57 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations	Baseline (Day 1) up to Day 57	TEAEs observed in participants with clinically significant ECG abnormalities were assessed. TEAEs are the events between first dose of study drug and up to 57 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
Number of Participants With TEAEs Related to Vital Sign Parameters	Baseline (Day 1) up to Day 57	TEAEs observed in participants with clinically significant vital signs abnormalities were assessed. Vital signs parameters included blood pressure, respiration rate, pulse, pulse oximetry, and body temperature.
Number of Participants With TEAEs Related to Clinical Laboratory Evaluations	Baseline (Day 1) up to Day 57	An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (Hrs) (AUC [0-96 Hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion, 4 and 8 hrs post-dose Day 1 (IV cohorts only)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of HDL-C.

Secondary

Measure	Time frame	Description
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for High-Density Lipoprotein Unesterified Cholesterol	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of high density lipoprotein unesterified cholesterol.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Non-High Density Lipoprotein Cholesteryl Ester	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of non-high density lipoprotein cholesteryl ester.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Non-High Density Lipoprotein Unesterified Cholesterol	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of non-high density lipoprotein unesterified cholesterol.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Low Density Lipoprotein-Cholesterol (Direct)	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of low density lipoprotein cholesterol (direct).
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) Post Dose for Apolipoprotein B	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of apolipoprotein B.
Change From Baseline in Serum Concentration of Pre Beta 1-High Density Lipoprotein at Day 29	Baseline (Day 1) and Day 29	The change from baseline in serum concentration of pre beta 1-high density lipoprotein was estimated.
Change From Baseline in Serum Concentration of Lecithin-Cholesterol Acyltransferase (LCAT) at Day 57	Baseline (Day 1) and Day 57	The change from baseline in serum concentration of lecithin-cholesterol acyltransferase was estimated.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Total Cholesterol	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of total cholesterol.
Time to Reach Concentration Maximum (Tmax) of MEDI6012	Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)	The time at which Cmax of MEDI6012 was observed determined directly from raw concentration time data.
Area Under the Concentration Time Curve From 0 to 168 Hrs (AUC [0-168]) of MEDI6012	Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)	The area under the concentration-time curve from 0 to 168 hrs of MEDI6012.
Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC [0-last]) of MEDI6012	Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUC \[0-last\]) of MEDI6012.
Area Under the Concentration Time Curve to Infinite Time (AUC [0-inf]) of MEDI6012	Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)	The area under the concentration-time curve to infinite time of MEDI6012.
Elimination Half Life (t1/2) of MEDI6012	Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)	The t1/2 is the time measured for the plasma concentration to decrease by one half.
Number of Participants With Positive Anti-Drug Antibodies for MEDI6012	Day 1 (pre-dose), 15, 29 and 57	Participants were tested for immunogenicity to MEDI6012. The neutralization assay measures the capacity of participant's plasma (antibodies) to inhibit the binding of MEDI6012 to its target.
Maximum Observed Serum Concentration (Cmax) of MEDI6012	Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)	The first occurrence of the maximum observed plasma concentration of MEDI6012 determined directly from the raw concentration time data.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Free Cholesterol	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of free cholesterol.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Cholesteryl Ester	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)	The AUC(0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of cholesteryl ester.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for High-Density Lipoprotein Cholesteryl Ester	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)	The AUC (0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of high density lipoprotein cholesteryl ester.
Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Non-High Density Lipoprotein Cholesterol	Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)	The AUC(0-96 hrs) is the area under the concentration-time curve from time 0 to 96 hrs of non-high density lipoprotein cholesterol.

Countries

United States

Participant flow

Recruitment details

A total of 230 participants were screened in the study from 07-Dec-2015 to 13-Jan-2017 at 8 sites in the United States of America.

Pre-assignment details

Out of 230 participants, 182 participants were considered screen failures. The remaining 48 participants were randomized to receive the study drug. The 1600 mg dose was omitted based on a greater than expected pharmacodynamics effects at lower doses.

Participants by arm

Arm	Count
Placebo Intravenous (IV) Participants received a single IV dose of placebo matched to MEDI6012 on Day 1 of the study.	8
MEDI6012 24 Milligram (mg) IV Participants received a single IV dose of 24 mg MEDI6012 on Day 1.	6
MEDI6012 80 mg IV Participants received a single IV dose of 80 mg MEDI6012 on Day 1.	6
MEDI6012 240 mg IV Participants received a single IV dose of 240 mg MEDI6012 on Day 1.	6
MEDI6012 800 mg IV Participants received a single IV dose of 800 mg MEDI6012 on Day 1.	6
Placebo Subcutaneous (SC) Participants received a single SC dose of placebo matched to MEDI6012 on Day 1 of the study.	4
MEDI6012 80 mg SC Participants received a single SC dose of 80 mg MEDI6012 on Day 1.	6
MEDI6012 600 mg SC Participants received a single SC dose of 600 mg MEDI6012 on Day 1.	6
Total	48

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007
Overall Study	Other	0	0	0	0	0	0	1	0

Baseline characteristics

Characteristic	Placebo Intravenous (IV)	MEDI6012 24 Milligram (mg) IV	MEDI6012 80 mg IV	MEDI6012 240 mg IV	MEDI6012 800 mg IV	Placebo Subcutaneous (SC)	MEDI6012 80 mg SC	MEDI6012 600 mg SC	Total
Age, Continuous	62.8 Years STANDARD_DEVIATION 6.5	59.8 Years STANDARD_DEVIATION 7	60.0 Years STANDARD_DEVIATION 6.4	63.5 Years STANDARD_DEVIATION 5.4	65.8 Years STANDARD_DEVIATION 8.2	62.0 Years STANDARD_DEVIATION 9.3	71.3 Years STANDARD_DEVIATION 3.4	66.5 Years STANDARD_DEVIATION 4.7	64.0 Years STANDARD_DEVIATION 6.9
Sex: Female, Male Female	1 Participants	0 Participants	3 Participants	2 Participants	1 Participants	1 Participants	0 Participants	1 Participants	9 Participants
Sex: Female, Male Male	7 Participants	6 Participants	3 Participants	4 Participants	5 Participants	3 Participants	6 Participants	5 Participants	39 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	3 / 8	2 / 6	5 / 6	2 / 6	4 / 6	2 / 4	3 / 6	4 / 6
serious Total, serious adverse events	0 / 8	0 / 6	0 / 6	0 / 6	0 / 6	0 / 4	0 / 6	0 / 6

Outcome results

Primary

Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (Hrs) (AUC [0-96 Hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)

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

Time frame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion, 4 and 8 hrs post-dose Day 1 (IV cohorts only)

Population: As-treated Population.

Arm	Measure	Value (MEAN)	Dispersion
Placebo Intravenous (IV)	Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (Hrs) (AUC [0-96 Hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)	-49.1 milligrams per deciliter (mg/dL)	Standard Deviation 120
MEDI6012 24 Milligram (mg) IV	Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (Hrs) (AUC [0-96 Hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)	728.3 milligrams per deciliter (mg/dL)	Standard Deviation 334.2
MEDI6012 80 mg IV	Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (Hrs) (AUC [0-96 Hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)	1639.9 milligrams per deciliter (mg/dL)	Standard Deviation 631.7
MEDI6012 240 mg IV	Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (Hrs) (AUC [0-96 Hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)	3035.0 milligrams per deciliter (mg/dL)	Standard Deviation 439.1
MEDI6012 800 mg IV	Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (Hrs) (AUC [0-96 Hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)	5318.3 milligrams per deciliter (mg/dL)	Standard Deviation 1674.3
Placebo Subcutaneous (SC)	Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (Hrs) (AUC [0-96 Hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)	-113.5 milligrams per deciliter (mg/dL)	Standard Deviation 289.4
MEDI6012 80 mg SC	Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (Hrs) (AUC [0-96 Hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)	422.4 milligrams per deciliter (mg/dL)	Standard Deviation 395.7
MEDI6012 600 mg SC	Baseline-adjusted Area Under the Curve From Time 0 to 96 Hours (Hrs) (AUC [0-96 Hrs]) for High-Density Lipoprotein-Cholesterol (HDL-C)	2844.7 milligrams per deciliter (mg/dL)	Standard Deviation 1219.1

p-value: 0.095ANCOVA

p-value: <0.001ANCOVA

p-value: 0.44ANCOVA

p-value: <0.001ANCOVA

Primary

Number of Participants With TEAEs Related to Clinical Laboratory Evaluations

An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed.

Time frame: Baseline (Day 1) up to Day 57

Population: As-treated Population

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo Intravenous (IV)	Number of Participants With TEAEs Related to Clinical Laboratory Evaluations	0 Participants
MEDI6012 24 Milligram (mg) IV	Number of Participants With TEAEs Related to Clinical Laboratory Evaluations	0 Participants
MEDI6012 80 mg IV	Number of Participants With TEAEs Related to Clinical Laboratory Evaluations	0 Participants
MEDI6012 240 mg IV	Number of Participants With TEAEs Related to Clinical Laboratory Evaluations	0 Participants
MEDI6012 800 mg IV	Number of Participants With TEAEs Related to Clinical Laboratory Evaluations	0 Participants
Placebo Subcutaneous (SC)	Number of Participants With TEAEs Related to Clinical Laboratory Evaluations	0 Participants
MEDI6012 80 mg SC	Number of Participants With TEAEs Related to Clinical Laboratory Evaluations	1 Participants
MEDI6012 600 mg SC	Number of Participants With TEAEs Related to Clinical Laboratory Evaluations	0 Participants

Primary

Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations

TEAEs observed in participants with clinically significant ECG abnormalities were assessed. TEAEs are the events between first dose of study drug and up to 57 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.

Time frame: Baseline (Day 1) up to Day 57

Population: As-treated Population

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo Intravenous (IV)	Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations	0 Participants
MEDI6012 24 Milligram (mg) IV	Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations	0 Participants
MEDI6012 80 mg IV	Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations	0 Participants
MEDI6012 240 mg IV	Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations	0 Participants
MEDI6012 800 mg IV	Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations	0 Participants
Placebo Subcutaneous (SC)	Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations	0 Participants
MEDI6012 80 mg SC	Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations	0 Participants
MEDI6012 600 mg SC	Number of Participants With TEAEs Related to Electrocardiogram (ECG) Evaluations	0 Participants

Primary

Number of Participants With TEAEs Related to Vital Sign Parameters

TEAEs observed in participants with clinically significant vital signs abnormalities were assessed. Vital signs parameters included blood pressure, respiration rate, pulse, pulse oximetry, and body temperature.

Time frame: Baseline (Day 1) up to Day 57

Population: As-treated Population

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo Intravenous (IV)	Number of Participants With TEAEs Related to Vital Sign Parameters	0 Participants
MEDI6012 24 Milligram (mg) IV	Number of Participants With TEAEs Related to Vital Sign Parameters	0 Participants
MEDI6012 80 mg IV	Number of Participants With TEAEs Related to Vital Sign Parameters	0 Participants
MEDI6012 240 mg IV	Number of Participants With TEAEs Related to Vital Sign Parameters	0 Participants
MEDI6012 800 mg IV	Number of Participants With TEAEs Related to Vital Sign Parameters	0 Participants
Placebo Subcutaneous (SC)	Number of Participants With TEAEs Related to Vital Sign Parameters	0 Participants
MEDI6012 80 mg SC	Number of Participants With TEAEs Related to Vital Sign Parameters	0 Participants
MEDI6012 600 mg SC	Number of Participants With TEAEs Related to Vital Sign Parameters	0 Participants

Primary

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was 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 57 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.

Time frame: Baseline (Day 1) up to Day 57

Population: As-treated Population: All participants who received any amount of study drug were included in this population.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo Intravenous (IV)	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TESAEs	0 Participants
Placebo Intravenous (IV)	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TEAEs	3 Participants
MEDI6012 24 Milligram (mg) IV	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TESAEs	0 Participants
MEDI6012 24 Milligram (mg) IV	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TEAEs	2 Participants
MEDI6012 80 mg IV	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TESAEs	0 Participants
MEDI6012 80 mg IV	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TEAEs	5 Participants
MEDI6012 240 mg IV	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TEAEs	2 Participants
MEDI6012 240 mg IV	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TESAEs	0 Participants
MEDI6012 800 mg IV	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TEAEs	4 Participants
MEDI6012 800 mg IV	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TESAEs	0 Participants
Placebo Subcutaneous (SC)	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TESAEs	0 Participants
Placebo Subcutaneous (SC)	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TEAEs	2 Participants
MEDI6012 80 mg SC	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TESAEs	0 Participants
MEDI6012 80 mg SC	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TEAEs	3 Participants
MEDI6012 600 mg SC	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TEAEs	4 Participants
MEDI6012 600 mg SC	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	TESAEs	0 Participants

Secondary

Area Under the Concentration Time Curve From 0 to 168 Hrs (AUC [0-168]) of MEDI6012

The area under the concentration-time curve from 0 to 168 hrs of MEDI6012.

Time frame: Pre-dose and within 5 minutes; 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 168 hrs post-dose Day 1 for IV and SC dose, Day 15 and Day 29; additional 30 min after start of 1-hour infusion (IV cohorts only)

Population: PK population. PK data of MEDI6012 80 mg SC dose group was not interpretable as concentration levels were predominantly beneath the limit of quantitation (\<2.5 mcg/mL).

Arm	Measure	Value (MEAN)	Dispersion
Placebo Intravenous (IV)	Area Under the Concentration Time Curve From 0 to 168 Hrs (AUC [0-168]) of MEDI6012	137 mcg*hr/mL	Standard Deviation 55
MEDI6012 24 Milligram (mg) IV	Area Under the Concentration Time Curve From 0 to 168 Hrs (AUC [0-168]) of MEDI6012	805 mcg*hr/mL	Standard Deviation 265
MEDI6012 80 mg IV	Area Under the Concentration Time Curve From 0 to 168 Hrs (AUC [0-168]) of MEDI6012	2760 mcg*hr/mL	Standard Deviation 249
MEDI6012 240 mg IV	Area Under the Concentration Time Curve From 0 to 168 Hrs (AUC [0-168]) of MEDI6012	8470 mcg*hr/mL	Standard Deviation 2000
MEDI6012 800 mg IV	Area Under the Concentration Time Curve From 0 to 168 Hrs (AUC [0-168]) of MEDI6012	2460 mcg*hr/mL	Standard Deviation 824

Secondary

Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC [0-last]) of MEDI6012

Area under the plasma concentration time-curve from zero to the last measured concentration (AUC \[0-last\]) of MEDI6012.

Population: PK population. PK data of MEDI6012 80 mg SC dose group was not interpretable as concentration levels were predominantly beneath the limit of quantitation (\<2.5 mcg/mL).

Arm	Measure	Value (MEAN)	Dispersion
Placebo Intravenous (IV)	Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC [0-last]) of MEDI6012	46.8 mcg*hr/mL	Standard Deviation 42.7
MEDI6012 24 Milligram (mg) IV	Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC [0-last]) of MEDI6012	683 mcg*hr/mL	Standard Deviation 267
MEDI6012 80 mg IV	Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC [0-last]) of MEDI6012	2760 mcg*hr/mL	Standard Deviation 249
MEDI6012 240 mg IV	Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC [0-last]) of MEDI6012	9020 mcg*hr/mL	Standard Deviation 2760
MEDI6012 800 mg IV	Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Concentration (AUC [0-last]) of MEDI6012	2460 mcg*hr/mL	Standard Deviation 824

Secondary

Area Under the Concentration Time Curve to Infinite Time (AUC [0-inf]) of MEDI6012

The area under the concentration-time curve to infinite time of MEDI6012.

Population: PK population. PK data of MEDI6012 80 mg SC dose group was not interpretable as concentration levels were predominantly beneath the limit of quantitation (\<2.5 mcg/mL).

Arm	Measure	Value (MEAN)	Dispersion
Placebo Intravenous (IV)	Area Under the Concentration Time Curve to Infinite Time (AUC [0-inf]) of MEDI6012	137 mcg*hr/mL	Standard Deviation 56.1
MEDI6012 24 Milligram (mg) IV	Area Under the Concentration Time Curve to Infinite Time (AUC [0-inf]) of MEDI6012	887 mcg*hr/mL	Standard Deviation 308
MEDI6012 80 mg IV	Area Under the Concentration Time Curve to Infinite Time (AUC [0-inf]) of MEDI6012	3030 mcg*hr/mL	Standard Deviation 298
MEDI6012 240 mg IV	Area Under the Concentration Time Curve to Infinite Time (AUC [0-inf]) of MEDI6012	9510 mcg*hr/mL	Standard Deviation 2720
MEDI6012 800 mg IV	Area Under the Concentration Time Curve to Infinite Time (AUC [0-inf]) of MEDI6012	3560 mcg*hr/mL	Standard Deviation 732

Secondary

Baseline-adjusted Area Under the Curve From Time 0 to 96 Hrs (AUC [0-96 Hrs]) for Cholesteryl Ester

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

Time frame: Pre-dose, 12, 24, 48, 72 and 96 hrs post-dose Day 1 for IV and SC dose; additional within 5 minutes after completion of infusion and 4 and 8 hrs post-dose Day 1 (IV cohorts only)