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Completed

NCT Number: NCT02189837

Effects on Lipoprotein Metabolism From PCSK9 Inhibition Utilizing a Monoclonal Antibody

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

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Key information

Conditions

Primary Hyperlipidemia and Mixed Dyslipidemia Dyslipidemias Hypercholesterolemia Hyperlipidemias Lipid Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–65 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Adelaide, South Australia, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Evolocumab

Biological

Administered by subcutaneous injection

Other names: AMG 145, Repatha

atorvastatin

Drug

Administered by mouth

Other names: LIPITOR®

Placebo to Evolocumab

Drug

Administered by subcutaneous injection

Placebo to atorvastatin

Drug

Administered by mouth

Primary outcomes

  1. Percent Change From Baseline in Low-density Lipoprotein (LDL) Apolipoprotein B-100 Fractional Catabolic Rate (FCR)

    Time frame: 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.

    The fractional catabolic rate (the percentage of apolipoprotein B-100 in LDL which is replaced, transferred or lost per unit of time) was measured at Baseline and Day 50 over 5 consecutive days using the stable isotope tracer, D3-leucine. LDL particles were isolated from plasma by sequential ultracentrifugation, and isotopic enrichment was determined using gas chromatography-mass spectrometry. Mathematical modelling of the protein enrichment data was used to estimate protein catabolism.

Secondary outcomes

  1. Percent Change From Baseline in LDL-C at Day 50

    Time frame: Baseline and Day 50

    LDL-C was measured using ultrcentrifugation.

  2. Percent Change From Baseline in LDL Apolipoprotein B-100 Production Rate (PR)

    Time frame: Baseline and Day 50

    The production rate of apolipoprotein B-100 in LDL was measured at Baseline and Day 50 over 5 consecutive days using the stable isotope tracer, D3-leucine. LDL particles were isolated from plasma by sequential ultracentrifugation and isotopic enrichment was determined using gas chromatography-mass spectrometry. Mathematical modelling of the protein enrichment data was used to estimate the production rate.

  3. Percent Change From Baseline in Lipoprotein (a) Fractional Catabolic Rate (FCR)

    Time frame: 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.

    The fractional catabolic rate (the percentage of lipoprotein(a) (Lp[a]) which is replaced, transferred or lost per unit of time) was measured at Baseline and Day 50 over 5 consecutive days using the stable isotope tracer, D3-leucine. Lp(a) was isolated from plasma using an immunoprecipitation method employing immunomagnetic beads and polyacrylamide gel electrophoresis. Isotopic enrichment was determined using gas chromatography-mass spectrometry. Mathematical modelling of the protein enrichment data was used to estimate protein catabolism.

  4. Percent Change From Baseline in Lipoprotein(a) Production Rate (PR)

    Time frame: Baseline and Day 50

    The production rate of lipoprotein(a) was measured at Baseline and Day 50 over 5 consecutive days using the stable isotope tracer, D3-leucine. Lp(a) was isolated from plasma using an immunoprecipitation method employing immunomagnetic beads and polyacrylamide gel electrophoresis. Isotopic enrichment was determined using gas chromatography-mass spectrometry. Mathematical modelling of the protein enrichment data was used to estimate protein catabolism.

Sponsors and collaborators

Lead sponsor

Amgen

Industry

Registry information

Official study 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

Acronym: FLOREY

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Jul 15, 2014
Registry last updated
Oct 3, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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