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Effects on Lipoprotein Metabolism From PCSK9 Inhibition Utilizing a Monoclonal Antibody (FLOREY)

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ClinicalTrials.gov Identifier: NCT02189837
Recruitment Status : Completed
First Posted : July 15, 2014
Results First Posted : August 31, 2016
Last Update Posted : October 3, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

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

Condition or disease Intervention/treatment Phase
Primary Hyperlipidemia and Mixed Dyslipidemia Biological: Evolocumab Drug: Atorvastatin Drug: Placebo to Evolocumab Drug: Placebo to Atorvastatin Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 89 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : July 8, 2014
Actual Primary Completion Date : February 13, 2015
Actual Study Completion Date : March 5, 2015

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Arms and Interventions
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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.
 Drug: Placebo to Evolocumab
Administered by subcutaneous injection

Drug: Placebo to Atorvastatin
Administered by mouth
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.
 Drug: Atorvastatin
Administered by mouth
Other Name: LIPITOR®

Drug: Placebo to Evolocumab
Administered by subcutaneous injection
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.
 Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • AMG 145
  • Repatha

Drug: Placebo to Atorvastatin
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.
 Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • AMG 145
  • Repatha

Drug: Atorvastatin
Administered by mouth
Other Name: LIPITOR®


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02189837


Locations
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Australia, South Australia
Research Site
Adelaide, South Australia, Australia, 5000
Australia, Western Australia
Research Site
Nedlands, Western Australia, Australia, 6009
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
More Information
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Additional Information:

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02189837    
Other Study ID Numbers: 20130194
FLOREY ( Other Identifier: Amgen )
First Posted: July 15, 2014    Key Record Dates
Results First Posted: August 31, 2016
Last Update Posted: October 3, 2018
Last Verified: September 2018
Keywords provided by Amgen:
Raised cholesterol
Cholesterol
Elevated Cholesterol
Hyperlipidemias
 Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Additional relevant MeSH terms:
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Dyslipidemias
Hyperlipidemias
Hyperlipoproteinemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin
Evolocumab
Antibodies, Monoclonal
Anticholesteremic Agents
 Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs