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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE July 8, 2014
First Posted Date  ICMJE July 15, 2014
Results First Submitted Date  ICMJE June 6, 2016
Results First Posted Date  ICMJE August 31, 2016
Last Update Posted Date October 3, 2018
Actual Study Start Date  ICMJE July 8, 2014
Actual Primary Completion Date February 13, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 1, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 11, 2014)
Percent change from baseline in LDL apoB-100 Fractional Catabolic Rate (FCR) [ Time Frame: 60 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2017)
  • Percent Change From Baseline in LDL-C at Day 50 [ Time Frame: Baseline and Day 50 ]
    LDL-C was measured using ultrcentrifugation.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2014)
  • Percent change from baseline of lipid turnover parameters in isolated Very Low Density Lipoproteins (VLDL), Intermediate Density Lipoproteins (IDL), Low Density Lipoproteins (LDL) and High Density Lipoproteins (HDL) [ Time Frame: 60 days ]
  • Change in lipids and lipoproteins in plasma lipid panel [ Time Frame: 60 days ]
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 73 days ]
  • Assessment of safety parameters including labs and vital signs [ Time Frame: 73 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects on Lipoprotein Metabolism From PCSK9 Inhibition Utilizing a Monoclonal Antibody
Official Title  ICMJE 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
Brief Summary This is a randomized, double-blind, placebo-controlled trial to evaluate the effect of evolocumab, atorvastatin, and combination therapy on lipoprotein kinetics.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Primary Hyperlipidemia and Mixed Dyslipidemia
Intervention  ICMJE
  • Biological: Evolocumab
    Administered by subcutaneous injection
    Other Names:
    • AMG 145
    • Repatha
  • Drug: Atorvastatin
    Administered by mouth
    Other Name: LIPITOR®
  • Drug: Placebo to Evolocumab
    Administered by subcutaneous injection
  • Drug: Placebo to Atorvastatin
    Administered by mouth
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Placebo to Evolocumab
    • Drug: Placebo to Atorvastatin
  • 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.
    Interventions:
    • Drug: Atorvastatin
    • Drug: Placebo to Evolocumab
  • 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.
    Interventions:
    • Biological: Evolocumab
    • Drug: Placebo to Atorvastatin
  • 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.
    Interventions:
    • Biological: Evolocumab
    • Drug: Atorvastatin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 12, 2015)
89
Original Estimated Enrollment  ICMJE
 (submitted: July 11, 2014)
80
Actual Study Completion Date  ICMJE March 5, 2015
Actual Primary Completion Date February 13, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02189837
Other Study ID Numbers  ICMJE 20130194
FLOREY ( Other Identifier: Amgen )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP