Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02100839
• Other study ID #: LPMX-112
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 27, 2014
• Last updated: November 23, 2015
• Start date: March 2014
• Est. completion date: December 2014

Study information

• Verified date: March 2015
• Source: LipimetiX Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: December 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia
• Hyperlipoproteinemia Type II
• Hyperlipoproteinemias

Intervention

Drug:
• AEM-28
Solution for injection
• Normal Saline
0.9% saline for injection

Locations

Country	Name	City	State
Australia	Linear Clinical Research Ltd.	Nedlands	Western Australia

Sponsors (1)

Lead Sponsor	Collaborator
LipimetiX Development, LLC

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Incurred at Least One Treatment Emergent Event	Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated.; Safety and tolerability data were reported using descriptive statistics.	Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57	Yes
Primary	Number of Participants Who Incurred Mild Treatment Emergent Adverse Events	Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated.; Safety and tolerability data were reported using descriptive statistics.	Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57	Yes
Primary	Number of Participants Who Incurred Moderate Treatment Emergent Events	Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated.; Safety and tolerability data were reported using descriptive statistics.	Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57	Yes
Secondary	Very Low Density Lipoprotein Cholesterol (VLDL-C) Percent Change	Maximum observed percentage change in VLDL-C level relative to baseline for all time points measured in Parts A or Part B with highest dose, i.e. 3.54 mg/kg.	Part A (SAD): Day 1 to Day 15; Part B (MAD): Day 1 to Day 57	No