- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02189837
Effects on Lipoprotein Metabolism From PCSK9 Inhibition Utilizing a Monoclonal Antibody (FLOREY)
September 6, 2018 updated by: Amgen
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
This is a randomized, double-blind, placebo-controlled trial to evaluate the effect of evolocumab, atorvastatin, and combination therapy on lipoprotein kinetics.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
89
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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South Australia
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Adelaide, South Australia, Australia, 5000
- Research Site
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Western Australia
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Nedlands, Western Australia, Australia, 6009
- Research Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
Male
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks.
|
Administered by subcutaneous injection
Administered by mouth
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Active Comparator: Atorvastatin
Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
|
Administered by subcutaneous injection
Administered by mouth
Other Names:
|
Experimental: Evolocumab
Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks.
|
Administered by subcutaneous injection
Other Names:
Administered by mouth
|
Experimental: Evolocumab and Atorvastatin
Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
|
Administered by subcutaneous injection
Other Names:
Administered by mouth
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline in LDL-C at Day 50
Time Frame: Baseline and Day 50
|
LDL-C was measured using ultrcentrifugation.
|
Baseline and Day 50
|
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.
|
Baseline and Day 50
|
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.
|
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.
|
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.
|
Baseline and Day 50
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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. Erratum In: Eur Heart J. 2019 Jan 1;40(1):58.
- 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.
- 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.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 8, 2014
Primary Completion (Actual)
February 13, 2015
Study Completion (Actual)
March 5, 2015
Study Registration Dates
First Submitted
July 8, 2014
First Submitted That Met QC Criteria
July 11, 2014
First Posted (Estimate)
July 15, 2014
Study Record Updates
Last Update Posted (Actual)
October 3, 2018
Last Update Submitted That Met QC Criteria
September 6, 2018
Last Verified
September 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Lipid Metabolism Disorders
- Dyslipidemias
- Hyperlipidemias
- Hyperlipoproteinemias
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Immunologic Factors
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Atorvastatin
- Antibodies, Monoclonal
- Evolocumab
Other Study ID Numbers
- 20130194
- FLOREY (Other Identifier: Amgen)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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