NCT02189837

Brief Summary

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
89

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jul 2014

Shorter than P25 for phase_3

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 8, 2014

Completed
Same day until next milestone

Study Start

First participant enrolled

July 8, 2014

Completed
7 days until next milestone

First Posted

Study publicly available on registry

July 15, 2014

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 13, 2015

Completed
20 days until next milestone

Study Completion

Last participant's last visit for all outcomes

March 5, 2015

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

August 31, 2016

Completed
Last Updated

October 3, 2018

Status Verified

September 1, 2018

Enrollment Period

7 months

First QC Date

July 8, 2014

Results QC Date

June 6, 2016

Last Update Submit

September 6, 2018

Conditions

Primary Hyperlipidemia and Mixed Dyslipidemia

Keywords

Raised cholesterolCholesterolElevated CholesterolHyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic Diseases

Outcome Measures

Primary Outcomes (1)

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

    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 Outcomes (4)

  • Percent Change From Baseline in LDL-C at Day 50

    Baseline and Day 50

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

    Baseline and Day 50

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

    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)

    Baseline and Day 50

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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 EvolocumabDrug: Placebo to Atorvastatin

Atorvastatin

ACTIVE COMPARATOR

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: AtorvastatinDrug: Placebo to Evolocumab

Evolocumab

EXPERIMENTAL

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: EvolocumabDrug: Placebo to Atorvastatin

Evolocumab and Atorvastatin

EXPERIMENTAL

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: EvolocumabDrug: Atorvastatin

Interventions

EvolocumabBIOLOGICAL

Administered by subcutaneous injection

Also known as: AMG 145, Repatha
EvolocumabEvolocumab and Atorvastatin
AtorvastatinDRUG

Administered by mouth

Also known as: LIPITOR®
AtorvastatinEvolocumab and Atorvastatin
Placebo to EvolocumabDRUG

Administered by subcutaneous injection

AtorvastatinPlacebo
Placebo to AtorvastatinDRUG

Administered by mouth

EvolocumabPlacebo

Eligibility Criteria

Age18 Years - 65 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Research Site

Adelaide, South Australia, 5000, Australia

Location

Research Site

Nedlands, Western Australia, 6009, Australia

Location

Related Publications (4)

  • 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.

    PMID: 27941065BACKGROUND

  • 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.

    PMID: 29566128BACKGROUND

  • 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.

    PMID: 29880491BACKGROUND

  • 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.

    PMID: 30897995DERIVED

Related Links

MeSH Terms

Conditions

HypercholesterolemiaHyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic Diseases

Interventions

evolocumabAtorvastatin

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

PyrrolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeptanoic AcidsFatty AcidsLipids

Results Point of Contact

Title
Study Director
Organization
Amgen Inc.
866-572-6436

Study Officials

  • MD

    Amgen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 8, 2014

First Posted

July 15, 2014

Study Start

July 8, 2014

Primary Completion

February 13, 2015

Study Completion

March 5, 2015

Last Updated

October 3, 2018

Results First Posted

August 31, 2016

Record last verified: 2018-09

Locations

AU(2)