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Primary Hyperlipidemia and Mixed DyslipidemiaPhase 3FLOREYNCT02189837

Effects on Lipoprotein Metabolism From PCSK9 Inhibition Utilizing a Monoclonal Antibody

A Phase 3 study testing Evolocumab and Atorvastatin in people with Primary Hyperlipidemia and Mixed Dyslipidemia, run by Amgen at 2 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 65 years, men onlyHealthy volunteers can take part
What is being tested?
Evolocumab and Atorvastatin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
89 participants
Where
2 sitesAustralia
Study dates
8 Jul 2014to 5 Mar 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • Men only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

Australia2 sites
  • Research Site

    Adelaide, South Australia, 5000

  • Research Site

    Nedlands, Western Australia, 6009

Other trials in Australia

About this study

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

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

Being tested
Evolocumab, Atorvastatin, Placebo to Evolocumab, Placebo to Atorvastatin
Keywords
Raised cholesterol, Cholesterol, Elevated Cholesterol, Hyperlipidemias, Dyslipidemias, Lipid Metabolism Disorders, Metabolic Diseases
Medical subject headings
Hypercholesterolemia, Hyperlipidemias, Dyslipidemias, Lipid Metabolism Disorders, Metabolic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EvolocumabBiological

    Also called AMG 145, Repatha

    Administered by subcutaneous injection

  • AtorvastatinDrug

    Also called LIPITOR®

    Administered by mouth

  • Placebo to EvolocumabDrug

    Administered by subcutaneous injection

  • Placebo to AtorvastatinDrug

    Administered by mouth

Study groups in NCT02189837
Study groupRoleWhat they receive
PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: Placebo to Evolocumab; Drug: Placebo to Atorvastatin
AtorvastatinActive comparatorParticipants 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.
Receives: Drug: Atorvastatin; Drug: Placebo to Evolocumab
EvolocumabExperimentalParticipants 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.
Receives: Biological: Evolocumab; Drug: Placebo to Atorvastatin
Evolocumab and AtorvastatinExperimentalParticipants 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.
Receives: Biological: Evolocumab; Drug: Atorvastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

    LDL-C was measured using ultrcentrifugation.

    Measured: Baseline and Day 50

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

    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.

    Measured: Baseline and Day 50

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

    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.

    Measured: 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.

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

    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.

    Measured: Baseline and Day 50

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jul 2014 (estimated)
  2. Study start8 Jul 2014
  3. Primary completion13 Feb 2015
  4. Study completion5 Mar 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
89 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02189837
Sponsor's protocol ID
20130194
Other IDs
FLOREY
Acronym
FLOREY
Status last verified
Sep 2018
First submitted
8 Jul 2014
Last updated
3 Oct 2018
Data monitoring committee
No

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.

    PubMed 27941065
  • 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.

    PubMed 29566128
  • 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.

    PubMed 29880491
  • 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.

    PubMed 30897995

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Evolocumab and Atorvastatin in people with Primary Hyperlipidemia and Mixed Dyslipidemia, run by Amgen at 2 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02189837, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2018.

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