Clinical trial NCT01499420: A Single Ascending Dose Study Examining the Safety and Pharmacokinetic Profile of Reconstituted High Density Lipoprotein (CSL112) Administered to Patients
Official title: A Phase 2a, Multi-center, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of a Single Intravenous Infusion of CSL112 in Patients With Stable Atherothrombotic Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stable Atherothrombotic Disease
Lead sponsor: CSL Limited
Sponsor class: INDUSTRY
First posted: 2011-12-26
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Reconstituted high density lipoprotein used in patients with acute coronary syndrome (ACS) may reduce atherosclerotic plaque burden, thereby reducing the risk of recurrent cardiovascular events. This study is a multi-center, randomized, placebo-controlled, single ascending dose study in patients with stable atherothrombotic disease in whom the safety and pharmacokinetic profile of CSL112 will be assessed.


Eligibility criteria: Inclusion Criteria:

* Male or female aged 18 years to 80 years.
* Subjects must have documented evidence of a history of atherosclerotic coronary artery disease/surgical revascularization.
* Subjects on a stable medication regimen.
* Body weight 50 kg or greater at screening.

Exclusion Criteria:

* Moderate/severe heart failure or renal impairment.
* Uncontrolled hyperglycemia in subjects with type 1 or type 2 diabetes.
* Receipt of the combination of omeprazole and clopidogrel within 1 month of randomization.
* Subjects whose medical history, condition or medication regimen may interfere with the evaluation of the safety and tolerability of CSL112 (for example significantly altered electrocardiogram (ECG) waveform, hepatobiliary disease, malignancy, thrombocytopenia, etc.)
* Known hypersensitivity to the product components

Primary outcomes:
measure: Safety
timeFrame: 14 days
measure: Clinically significant elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
timeFrame: 14 days
Secondary outcomes:
measure: Pharmacokinetic profile of apolipoprotein A-I (apoA-I)
timeFrame: 9 days
measure: Plasma apoA-I area under the curve (AUC)
timeFrame: 9 days
measure: Plasma apoA-I Cmax
timeFrame: 9 days
measure: Plasma apoA-I Tmax
timeFrame: 9 days
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Study Site
state: California
city: Jacksonville
country: United States
facility: Study Site
state: Florida
city: Miami
country: United States
facility: Study Site
state: Florida
city: Lexington
country: United States
facility: Study Site
state: Kentucky
city: Madisonville
country: United States
facility: Study Site
state: Kentucky
city: Auburn
country: United States
facility: Study Site
state: Maine
city: Baltimore
country: United States
facility: Study Site
state: Maryland
city: Petoskey
country: United States
facility: Study Site
state: Michigan
city: Durham
country: United States
facility: Study Site
state: North Carolina
city: Philadelphia
country: United States
facility: Study Site
state: Pennsylvania
city: Rapid City
country: United States
facility: Study Site
state: South Dakota
Study officials:
affiliation: CSL Limited
name: Dr. Denise D'Andrea
role: STUDY_DIRECTOR
References:
citation: Zheng B, Duffy D, Tricoci P, Kastrissios H, Pfister M, Wright SD, Gille A, Tortorici MA. Pharmacometric analyses to characterize the effect of CSL112 on apolipoprotein A-I and cholesterol efflux capacity in acute myocardial infarction patients. Br J Clin Pharmacol. 2021 Jun;87(6):2558-2571. doi: 10.1111/bcp.14666. Epub 2020 Dec 23.
citation: Tricoci P, D'Andrea DM, Gurbel PA, Yao Z, Cuchel M, Winston B, Schott R, Weiss R, Blazing MA, Cannon L, Bailey A, Angiolillo DJ, Gille A, Shear CL, Wright SD, Alexander JH. Infusion of Reconstituted High-Density Lipoprotein, CSL112, in Patients With Atherosclerosis: Safety and Pharmacokinetic Results From a Phase 2a Randomized Clinical Trial. J Am Heart Assoc. 2015 Aug 25;4(8):e002171. doi: 10.1161/JAHA.115.002171.