Clinical trial NCT02100839: Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of AEM-28 in Healthy Subjects and Patients With Refractory Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hypercholesterolemia
Hyperlipoproteinemia Type II
Keywords: hypercholesterolemia
apolipoprotein E
First in Human
Apolipoprotein E (ApoE)
Apolipoprotein E Mimetic (AEM)
Lead sponsor: LipimetiX Development, LLC
Sponsor class: INDUSTRY
First posted: 2014-04-01
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the first part of this study is to determine the safety and tolerability of a single dose of AEM-28, an apolipoprotein E mimetic, in subjects with high total cholesterol who are otherwise healthy subjects. The pharmacokinetics and pharmacodynamics of AEM-28 will also be evaluated.

The second part of this study will be a multiple ascending dose evaluation of AEM-28 in patients with refractory hypercholesterolemia.

AEM-28 has demonstrated significant lipid lowering activity and positive effects on the artery wall. AEM-28 is being developed for the treatment of homozygous familial hypercholesterolemia.


Eligibility criteria: Inclusion Criteria:

Single Ascending Dose (SAD) Study:

* Male or female non-smoker, ≥18 and ≤55 years of age, with BMI \>18.5 and \< 32.0 kg/m²
* Total cholesterol greater or equal to 5.0 mmol/L (≥194 mg/dL) at screening

Multiple Ascending Dose (MAD) Study:

* Male or female non-smoker, ≥18 and ≤75 years of age, with BMI \>18.5 and \< 35.0 kg/m²
* Diagnosis of refractory hypercholesterolemia with LDL cholesterol levels \> 2.5 mmol/L (97 mg/mL) at screening.
* On stable lipid lowering therapy for ≥ 8 weeks
* On stable diet for ≥ 12 weeks.

Exclusion Criteria:

SAD Study:

* Any clinically significant abnormality or abnormal laboratory test results found during medical screening or positive test for hepatitis B, hepatitis C, or HIV found during medical screening.
* History of allergic reactions to diphenhydramine, ranitidine, methylprednisone or other related drugs, or history of significant allergic or hypersensitivity reaction (e.g. angioedema) to any substance.

MAD Study:

* Significant health problems within 6 months prior to screening, which in the opinion of the Medical Sub-Investigator would prevent the subject from participating in the study, including but not limited to: unstable coronary heart disease; transient ischemic attack; stroke; revascularization procedure; uncontrolled hyperthyroidism; coagulation disorder; peptic ulcers or GI bleeding; significant disease of the central nervous system; liver or renal disease.
* History of allergic reactions to diphenhydramine, ranitidine, methylprednisone or other related drugs, or history of significant allergic or hypersensitivity reaction (e.g. angioedema) to any substance.

Primary outcomes:
measure: Number of Participants Who Incurred at Least One Treatment Emergent Event
timeFrame: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57
measure: Number of Participants Who Incurred Mild Treatment Emergent Adverse Events
timeFrame: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57
measure: Number of Participants Who Incurred Moderate Treatment Emergent Events
timeFrame: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57
Secondary outcomes:
measure: Very Low Density Lipoprotein Cholesterol (VLDL-C) Percent Change
timeFrame: Part A (SAD): Day 1 to Day 15; Part B (MAD): Day 1 to Day 57
Other outcomes:
Locations:
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd.
state: Western Australia
Study officials:
affiliation: Linear Clinical Research
name: Janakan Krishnarajah, MBBS, FRACP
role: PRINCIPAL_INVESTIGATOR
References: