Clinical trial NCT03001297: Phase 1, Single Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of MEDI5884
Official title: A Phase 1 Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses of MEDI5884 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: atherosclerosis; acute coronary syndrome; MEDI5884
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2016-12-23
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase 1, single dose study with 4 cohorts of ascending doses and an optional Japanese cohort designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of MEDI5884 in healthy volunteers

Detailed description: This is a first time in human, phase 1, randomized, blinded, placebo-controlled study to evaluate the safety, pharmacokinetics and pharmacodynamics of single ascending subcutaneous doses of MEDI5884 in healthy volunteers (age 18-55). The study consists of 4 cohorts of increasing doses (8 subjects each) and an optional Japanese American cohort (24 subjects) for a total of 56 healthy subjects. The decision whether or not to dose escalate will be based upon data review by the Dose Escalation Committee. Subjects will be randomized 3:1 to MEDI5884 or placebo. Following screening, the study consists of a 3 day inpatient stay and follow up visits. The number of follow up visits depend on the cohort assigned.

Eligibility criteria: Inclusion Criteria:

* Healthy volunteers aged 18-55 years
* Must provide written informed consent
* Ability and willingness to adhere to the protocol
* BMI 18-30kg/m2
* Females not of childbearing potential
* Males must practice 2 effective contraceptive measures if sexually active
* Japanese descent for the Japanese cohort

Exclusion Criteria:

* Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product
* History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
* Abnormal lab values, physical exam, vital signs
* Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to dosing
* Positive Hepatitis B, Hepatitis C or HIV test
* Receipt of investigational therapy with 4 months from screening
* Current or previous use of systemic corticosteroids 60 days prior to dosing or lipid lowering medications 28 days prior to dosing
* Abnormal ECG
* Recent plasma or blood donation
* Positive drug or alcohol screen.
* Current smoker

Primary outcomes:
measure: Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884
timeFrame: Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.
measure: Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884
timeFrame: Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.
measure: Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884
timeFrame: Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.
measure: Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884
timeFrame: Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.
measure: HDL-Cholesterol over time
timeFrame: Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.
Secondary outcomes:
measure: Lipoprotein particle size
timeFrame: Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
measure: Lipoprotein particle number
timeFrame: Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
measure: Levels of total cholesterol
timeFrame: Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
measure: Non-HDL-Cholesterol
timeFrame: Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
measure: Low-density lipoprotein cholesterol (direct and Friedewald equation)
timeFrame: Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
measure: Very low-density lipoprotein cholesterol
timeFrame: Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
measure: Triglycerides
timeFrame: Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
measure: Apolipoprotein B
timeFrame: Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
measure: Apolipoprotein A1
timeFrame: Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
measure: MEDI5884 serum concentration: maximum observed concentration
timeFrame: Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4)
measure: MEDI5884 serum concentration: time to maximum observed concentration
timeFrame: Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4)
measure: MEDI5884 serum concentration: area under the concentration time curve
timeFrame: Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4)
measure: MEDI5884 serum concentration: terminal half-life
timeFrame: Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4)
measure: Anti-drug antibody
timeFrame: Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
Study officials:
References: