Clinical trial NCT02189837: Effects on Lipoprotein Metabolism From PCSK9 Inhibition Utilizing a Monoclonal Antibody
Official title: Double-blind, Randomized, Placebo-controlled, Single Site Study to Evaluate the Effects of Evolocumab (AMG 145) Treatment, Alone and in Combination With Atorvastatin, on Lipoprotein Kinetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Hyperlipidemia and Mixed Dyslipidemia
Keywords: Raised cholesterol
Cholesterol
Elevated Cholesterol
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2014-07-15
Enrollment: 89
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo-controlled trial to evaluate the effect of evolocumab, atorvastatin, and combination therapy on lipoprotein kinetics.


Eligibility criteria: Inclusion Criteria:

* Fasting LDL-C at screening ≥ 100 mg/dL and ≤ 190 mg/dL
* Fasting triglycerides ≤ 150 mg/dL
* Body mass index (BMI) between 18.0 and 32.0 kg/m\^2
* Framingham cardiac risk score 10% or less

Exclusion Criteria:

* Treatment with a lipid-regulating drug or over the counter supplement in the last 3 months prior to screening
* History of coronary heart disease (CHD) or CHD equivalent
* Uncontrolled hypertension
* Diabetes mellitus

Primary outcomes:
measure: Percent Change From Baseline in Low-density Lipoprotein (LDL) Apolipoprotein B-100 Fractional Catabolic Rate (FCR)
timeFrame: Baseline (5 days prior to Day 1) and Day 50; plasma samples for fasting lipids were obtained at 0, 5, 10, 20, 30, 40, and 60 min, as well as at 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 10 hours, and 2, 3, 4 and 5 days after D3-leucine administration.
Secondary outcomes:
measure: Percent Change From Baseline in LDL-C at Day 50
timeFrame: Baseline and Day 50
measure: Percent Change From Baseline in LDL Apolipoprotein B-100 Production Rate (PR)
timeFrame: Baseline and Day 50
measure: Percent Change From Baseline in Lipoprotein (a) Fractional Catabolic Rate (FCR)
timeFrame: Baseline (5 days prior to Day 1) and Day 50; plasma samples for fasting lipids were obtained at 0, 5, 10, 20, 30, 40, and 60 min, as well as at 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 10 hours, and 2, 3, 4 and 5 days after D3-leucine administration.
measure: Percent Change From Baseline in Lipoprotein(a) Production Rate (PR)
timeFrame: Baseline and Day 50
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Research Site
state: South Australia
city: Nedlands
country: Australia
facility: Research Site
state: Western Australia
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Watts GF, Chan DC, Dent R, Somaratne R, Wasserman SM, Scott R, Burrows S, R Barrett PH. Factorial Effects of Evolocumab and Atorvastatin on Lipoprotein Metabolism. Circulation. 2017 Jan 24;135(4):338-351. doi: 10.1161/CIRCULATIONAHA.116.025080. Epub 2016 Dec 9.
citation: Watts GF, Chan DC, Somaratne R, Wasserman SM, Scott R, Marcovina SM, Barrett PHR. Controlled study of the effect of proprotein convertase subtilisin-kexin type 9 inhibition with evolocumab on lipoprotein(a) particle kinetics. Eur Heart J. 2018 Jul 14;39(27):2577-2585. doi: 10.1093/eurheartj/ehy122.
citation: Chan DC, Watts GF, Somaratne R, Wasserman SM, Scott R, Barrett PHR. Comparative Effects of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibition and Statins on Postprandial Triglyceride-Rich Lipoprotein Metabolism. Arterioscler Thromb Vasc Biol. 2018 Jul;38(7):1644-1655. doi: 10.1161/ATVBAHA.118.310882. Epub 2018 Jun 7.
citation: Chan DC, Watts GF, Coll B, Wasserman SM, Marcovina SM, Barrett PHR. Lipoprotein(a) Particle Production as a Determinant of Plasma Lipoprotein(a) Concentration Across Varying Apolipoprotein(a) Isoform Sizes and Background Cholesterol-Lowering Therapy. J Am Heart Assoc. 2019 Apr 2;8(7):e011781. doi: 10.1161/JAHA.118.011781.