HyperlipidemiaPhase 3LAPLACE-2NCT01763866

LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-2

A Phase 3 study testing Evolocumab, Ezetimibe and Atorvastatin in people with Hyperlipidemia, run by Amgen at 244 sites in 21 countries.

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

The primary objective was to evaluate the effect of 12 weeks of evolocumab administered subcutaneously every 2 weeks (Q2W) and monthly (QM) when used in combination with a statin, compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in patients with primary… Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Hyperlipidemia
What is being tested?: Evolocumab, Ezetimibe and Atorvastatin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 2,067 participants
Where: 244 sitesin 21 countries
Study dates: 15 Jan 2013to 4 Dec 2013
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 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female ≥ 18 to ≤ 80 years of age
Subjects not taking a statin must have fasting LDL-C of at least 150 mg/dL (4.0 mmol/L)
Subjects already on a non-intensive statin must have fasting LDL-C at screening ≥ 100 mg/dL (2.6 mmol/L)
Subjects already on a intensive statin must have fasting LDL-C at screening ≥ 80 mg/dL (2.1 mmol/L)
Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

Who cannot join

Statin intolerance
New York Heart association (NYHA) III or IV heart failure
Uncontrolled hypertension
Uncontrolled cardiac arrhythmia
Type 1 diabetes, poorly controlled type 2 diabetes
Uncontrolled hypothyroidism or hyperthyroidism

Trial locations and contacts

244 sites in 21 countries.

Country

City, postcode or hospital

244 sites in 21 countries

United States65 sites

Research Site
Atlanta, Georgia, 30328
Research Site
Atlanta, Georgia, 30342
Research Site
Auburn, Maine, 04210
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Baltimore, Maryland, 21201
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Bangor, Maine, 04401
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Billings, Montana, 59102
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Birmingham, Alabama, 35294
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Boise, Idaho, 83704
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Cadiz, Ohio, 43907
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Canton, Ohio, 44708
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Carmichael, California, 95608
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Cincinnati, Ohio, 45219
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Cincinnati, Ohio, 45227
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Crestview Hills, Kentucky, 41017
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Dallas, Texas, 75231
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Dayton, Ohio, 45414
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Daytona Beach, Florida, 32117
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Duncansville, Pennsylvania, 16635
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Encino, California, 91436
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Florence, South Carolina, 29501
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Glendale, Arizona, 85306
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Hammond, Indiana, 46320
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Houston, Texas, 77074
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Indianapolis, Indiana, 46237
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Iowa City, Iowa, 52242
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Jackson, Tennessee, 38301
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Jackson, Tennessee, 38305
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Jacksonville, Florida, 32223
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Littleton, Colorado, 80120
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Long Beach, California, 90822
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Manlius, New York, 13104
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Mansfield, Ohio, 44906
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Marion, Ohio, 43302
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Melbourne, Florida, 32901
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Miami, Florida, 33173
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Monroe, Louisiana, 71203
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Newport Beach, California, 92663
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Norman, Oklahoma, 73069
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Pittsburgh, Pennsylvania, 15216
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Port Charlotte, Florida, 33952
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Portland, Maine, 04101
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Rapid City, South Dakota, 57701
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Rochester, New York, 14609
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San Antonio, Texas, 78229
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San Diego, California, 92123
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Sandusky, Ohio, 44870
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Santa Ana, California, 92705
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Santa Rosa, California, 95405
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Suffolk, Virginia, 23435
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Syracuse, New York, 13210
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Tacoma, Washington, 98405
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Thousand Oaks, California, 91360
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Torrance, California, 90509
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Tucson, Arizona, 85710
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Tucson, Arizona, 85712
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Tupelo, Mississippi, 38801
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Tustin, California, 92780
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Valparaiso, Indiana, 46383
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Voorhees Township, New Jersey, 08043
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Westlake Village, California, 91361
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Williamsville, New York, 14221
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Winchester, Virginia, 22601
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Winston-Salem, North Carolina, 27103
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York, Pennsylvania, 17405
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Ypsilanti, Michigan, 48197

Other trials in United States

Canada21 sites

Research Site
Brossard, Quebec, J4X 1S4
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Burnaby, British Columbia, V5G 1T4
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Cambridge, Ontario, N1R 6V6
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Greenfield Park, Quebec, J4V 2G8
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Hamilton, Ontario, L8L 2X2
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Kelowna, British Columbia, V1Y 1E4
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Kelowna, British Columbia, V1Y 1V6
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Lachine, Quebec, H8S 2E4
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London, Ontario, N5W 6A2
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Longueuil, Quebec, J4N 0C9
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Montreal, Quebec, H4N 2W2
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Newmarket, Ontario, L3Y 5G8
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Oshawa, Ontario, L1J 2K1
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Pointe-Claire, Quebec, H9R 3J1
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Saint Johnâ€™s, Newfoundland and Labrador, A1A 3R5
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Sarnia, Ontario, N7T 4X3
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Scarborough Village, Ontario, M1P 2T7
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Surrey, British Columbia, V3V 1N1
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Toronto, Ontario, M8V 3X8
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Toronto, Ontario, M9V 4B4
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Woodstock, Ontario, N4S 5P5

Other trials in Canada

United Kingdom18 sites

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Birmingham, B15 2SQ
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Blackpool, FY3 7EN
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Cardiff, CF14 5GJ
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Chesterfield, S40 4TF
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Chorley, PR7 7NA
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Doncaster, DN9 1EP
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Glasgow, G20 0SP
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Glasgow, G45 9AW
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Harrow, HA3 7LT
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Liverpool, L22 0LG
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Liverpool, L7 8XP
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Manchester, M13 9WL
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Manchester, M15 6SX
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Reading, RG2 0FT
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Reading, RG2 0TG
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Scunthorpe, DN15 7BH
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Wakefield, WF1 4DG
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Whitby, YO21 1SD

Other trials in United Kingdom

Czechia13 sites

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Brno, 602 00
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Brno, 603 00
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Kladno, 272 01
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Litoměřice, 412 01
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Moravské Budějovice, 676 02
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Olomouc, 775 20
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Pardubice, 530 02
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Prague, 120 00
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Prague, 130 00
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Prague, 140 21
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Slaný, 274 01
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Svitavy, 568 25
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Ústí nad Orlicí, 562 18

Other trials in Czechia

Germany11 sites

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Bad Krozingen, 79189
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Berlin, 10367
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Berlin, 10787
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Freiburg im Breisgau, 79106
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Heidelberg, 69120
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Hellersdorf, 12627
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Homburg, 66421
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Leipzig, 04103
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Magdeburg, 39104
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Messkirch, 88605
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Witten, 58455

Other trials in Germany

Hungary11 sites

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Baja, 6500
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Berettyóújfalu, 4100
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Dunaújváros, 2400
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Eger, 3300
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Gyöngyös, 3200
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Hódmezővásárhely, 6800
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Jászberény, 5100
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Komárom, 2921
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Marcali, 8700
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Mosonmagyaróvár, 9200
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Pécs, 7624

Other trials in Hungary

Russia11 sites

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Barnaul, 656055
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Kemerovo, 650002
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Moscow, 121002
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Moscow, 121552
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Moscow, 127299
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Novosibirsk, 630047
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Saint Petersburg, 192242
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Saint Petersburg, 194156
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Saint Petersburg, 197022
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Saint Petersburg, 197341
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Saratov, 410054

Other trials in Russia

France10 sites

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Brest, 29200
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Caen, 14033
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Dijon, 21034
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Le Creusot, 71200
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Montpellier, 34295
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Nantes, 44093
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Paris, 75013
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Paris, 75571
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Poitiers, 86000
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Strasbourg, 67091

Other trials in France

Italy10 sites

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Bologna, 40138
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Cagliari, 09134
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Chieti, 66100
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Ferrara, 44124
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Milan, 20162
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Naples, 80131
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Padova, 35128
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Perugia, 06129
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Pisa, 56124
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Trieste, 34149

Other trials in Italy

Netherlands10 sites

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Amsterdam, 1066 EC
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Amsterdam, 1105 AZ
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Den Helder, 1782 GZ
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Groningen, 9728 NT
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Hoogeveen, 7909 AA
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Nieuwegein, 3435 CM
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Nijmegen, 6525 GA
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Rotterdam, 3045 PM
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Waalwijk, 5141 BM
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Zwijndrecht, 3331 LZ

Other trials in Netherlands

Spain10 sites

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AlmerÃ-a, AndalucÃ-a, 04001
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Almería, AndalucÃ-a, 04001
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Barcelona, CataluÃ±a, 08003
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Barcelona, CataluÃ±a, 08036
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L'Hospitalet de Llobregat, CataluÃ±a, 08907
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Madrid, 28007
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Madrid, 28029
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Pozuelo de AlarcÃ³n, Madrid, 28223
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Pozuelo de Alarcón, Madrid, 28223
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Valencia, Valencia, 46010

Other trials in Spain

Mexico9 sites

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Durango, 34270
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Guadalajara, Jalisco, 44100
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Guadalajara, Jalisco, 44130
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León, Guanajuato, 37520
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Mexico City, Mexico City, 03800
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Mexico City, Mexico City, 14000
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Monterrey, Nuevo LeÃ³n, 64460
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San Luis Potosí City, San Luis PotosÃ-, 78240
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Tampico, Tamaulipas, 89000

Other trials in Mexico

South Africa8 sites

Research Site
Alberton, Gauteng, 1449
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Bloemfontein, 9301
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Cape Town, 7405
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Johannesburg, Gauteng, 2196
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Kuils River, Western Cape, 7580
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Lyttelton, Gauteng, 0140
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Pretoria, Gauteng, 0184
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Somerset West, Western Cape, 7130

Other trials in South Africa

Australia6 sites

Research Site
Ashford, South Australia, 5035
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Fitzroy, Victoria, 3065
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Fullarton, South Australia, 5063
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Heidelberg Heights, Victoria, 3081
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Richmond, Victoria, 3121
Research Site
Sydney, New South Wales, 2022

Other trials in Australia

Belgium6 sites

Research Site
Blankenberge, 8370
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ChÃªnÃ©e, 4032
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Hasselt, 3500
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Ostend, 8400
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Tremelo, 3120
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Vilvoorde, 1800

Other trials in Belgium

Sweden6 sites

Research Site
Ã-rebro, 701 46
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GÃ¶teborg, 413 45
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Lund, 222 21
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Lund, 222 22
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Stockholm, 171 45
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Uddevalla, 451 50

Other trials in Sweden

Switzerland6 sites

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Bellinzona, 6500
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Geneva, 1211
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Lausanne, 1011
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Muensterlingen, 8596
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Sankt Gallen, 9007
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Zurich, 8063

Other trials in Switzerland

South Korea5 sites

Research Site
Seoul, 120-752
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Seoul, 135-710
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Seoul, 138-736
Research Site
Suwon, 443-380
Research Site
Suwon, 443-721

Other trials in South Korea

Denmark3 sites

Research Site
Aalborg, 9000
Research Site
Ballerup Municipality, 2750
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Vejle, 7100

Other trials in Denmark

Taiwan3 sites

Research Site
Kaohsiung City, 807
Research Site
Kaohsiung City, 83301
Research Site
Taipei, 100

Other trials in Taiwan

Hong Kong2 sites

Research Site
Hong Kong
Research Site
New Territories

Other trials in Hong Kong

About this study

Official title: A Double-blind, Randomized, Placebo and Ezetimibe Controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia

Read the detailed description

Prior to the first randomization, participants entered a screening period to determine eligibility. During screening, all participants received subcutaneous placebo corresponding to the once monthly dose volume. Participants who completed the screening period and met eligibility criteria were randomized to 1 of 5 open-label statin cohorts (atorvastatin 10 mg or 80 mg, rosuvastatin 5 mg or 40 mg, or simvastatin 40 mg) for a 4 week lipid stabilization period based on statin therapy at the time of study entry (no statin use vs non-intensive statin use vs intensive statin use).

After the 4-week lipid-stabilization period, eligible patients taking rosuvastatin or simvastatin during the lipid-stabilization phase were then randomized to 1 of 4 treatment groups: evolocumab (140 mg, subcutaneous, every 2 weeks) or matching placebo (subcutaneous, every 2 weeks), or evolocumab (420 mg, subcutaneous, monthly) or matching placebo (subcutaneous, monthly). Patients taking atorvastatin during the lipid-stabilization phase were then randomized to 1 of 6 treatment groups: evolocumab (140 mg, subcutaneous, every 2 weeks) and placebo (oral, daily), evolocumab (420 mg, subcutaneous, monthly) and placebo (oral, daily), placebo (subcutaneous, every 2 weeks) and placebo (oral, daily) or ezetimibe (10 mg, oral, daily), or placebo (subcutaneous, monthly) and placebo (oral, daily) or ezetimibe (10 mg, oral, daily).

A participant was considered randomized into the study after successfully completing the screening period, meeting all inclusion/exclusion criteria, and undergoing both randomization procedures.

Participants randomized to simvastatin who were taking verapamil or diltiazem prior to randomization received simvastatin 10 mg once daily (QD) while participants who were taking amlodipine, amiodarone or ranolazine prior to randomization received simvastatin 20 mg QD. All other participants randomized to simvastatin received simvastatin 40 mg QD.

Conditions: Hyperlipidemia
Being tested: Evolocumab, Ezetimibe, Placebo to Evolocumab, Placebo to Ezetimibe, Atorvastatin
Keywords: High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
Medical subject headings: Hyperlipidemias, Hypercholesterolemia

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
EzetimibeDrug
Also called Zetia
Administered orally once a day
Placebo to EvolocumabDrug
Administered by subcutaneous injection
Placebo to EzetimibeDrug
Administered orally once a day
AtorvastatinDrug
Also called Lipitor
Administered orally once a day
RosuvastatinDrug
Also called Crestor
Administered orally once a day
SimvastatinDrug
Also called Zocor
Administered orally once a day

Study groups in NCT01763866
Study group	Role	What they receive
A10 PBO Q2W	Placebo comparator	Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Receives: Drug: Placebo to Evolocumab; Drug: Placebo to Ezetimibe; Drug: Atorvastatin
A10 PBO QM	Placebo comparator	Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Receives: Drug: Placebo to Evolocumab; Drug: Placebo to Ezetimibe; Drug: Atorvastatin
A10 EZE (Q2W)	Active comparator	Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once a day for up to 12 weeks. Receives: Drug: Ezetimibe; Drug: Placebo to Evolocumab; Drug: Atorvastatin
A10 EZE (QM)	Active comparator	Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Receives: Drug: Ezetimibe; Drug: Placebo to Evolocumab; Drug: Atorvastatin
A10 EvoMab Q2W	Experimental	Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Receives: Biological: Evolocumab; Drug: Placebo to Ezetimibe; Drug: Atorvastatin
A10 EvoMab QM	Experimental	Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks Receives: Biological: Evolocumab; Drug: Placebo to Ezetimibe; Drug: Atorvastatin
A80 PBO Q2W	Placebo comparator	Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Receives: Drug: Placebo to Evolocumab; Drug: Placebo to Ezetimibe; Drug: Atorvastatin
A80 PBO QM	Placebo comparator	Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month and placebo tablets once a day for up to 12 weeks. Receives: Drug: Placebo to Evolocumab; Drug: Placebo to Ezetimibe; Drug: Atorvastatin
A80 EZE (Q2W)	Active comparator	Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Receives: Drug: Ezetimibe; Drug: Placebo to Evolocumab; Drug: Atorvastatin
A80 EZE (QM)	Active comparator	Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Receives: Drug: Ezetimibe; Drug: Placebo to Evolocumab; Drug: Atorvastatin
A80 EvoMab Q2W	Experimental	Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Receives: Biological: Evolocumab; Drug: Placebo to Ezetimibe; Drug: Atorvastatin
A80 EvoMab QM	Experimental	Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks. Receives: Biological: Evolocumab; Drug: Placebo to Ezetimibe; Drug: Atorvastatin
R5 PBO Q2W	Placebo comparator	Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Receives: Drug: Placebo to Evolocumab; Drug: Rosuvastatin
R5 PBO QM	Placebo comparator	Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks. Receives: Drug: Placebo to Evolocumab; Drug: Rosuvastatin
R5 EvoMab Q2W	Experimental	Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Receives: Biological: Evolocumab; Drug: Rosuvastatin
R5 EvoMab QM	Experimental	Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Receives: Biological: Evolocumab; Drug: Rosuvastatin
R40 PBO Q2W	Placebo comparator	Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Receives: Drug: Placebo to Evolocumab; Drug: Rosuvastatin
R40 PBO QM	Placebo comparator	Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks. Receives: Drug: Placebo to Evolocumab; Drug: Rosuvastatin
R40 EvoMab Q2W	Experimental	Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Receives: Biological: Evolocumab; Drug: Rosuvastatin
R40 EvoMab QM	Experimental	Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Receives: Biological: Evolocumab; Drug: Rosuvastatin
S40 PBO Q2W	Placebo comparator	Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Receives: Drug: Placebo to Evolocumab; Drug: Simvastatin
S40 PBO QM	Placebo comparator	Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks. Receives: Drug: Placebo to Evolocumab; Drug: Simvastatin
S40 EvoMab Q2W	Experimental	Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Receives: Biological: Evolocumab; Drug: Simvastatin
S40 EvoMab QM	Experimental	Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Receives: Biological: Evolocumab; Drug: Simvastatin

What is being measured

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

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12

Secondary outcomes (20)

Change From Baseline in LDL-C at at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Change From Baseline in LDL-C at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Non-HDL-C at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Measured: Baseline and Week 12
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL
Measured: Weeks 10 and 12
Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12
Measured: Week 12
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Lipoprotein(a) at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Triglycerides at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Very Low-Density Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Very Low-Density Cholesterol (VLDL-C) at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in HDL-C at Week 12
Measured: Baseline and Week 12

Timeline

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

15 Jan 20134 Dec 2013

First posted9 Jan 2013 (estimated)
Study start15 Jan 2013
Primary completion12 Nov 2013
Study completion4 Dec 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (12)Papers the sponsor has linked to this study.
Other trials for HyperlipidemiaStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 2,067 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01763866
Sponsor's protocol ID: 20110115
Other IDs: 2012-001363-70
Acronym: LAPLACE-2
Status last verified: Nov 2022
First submitted: 7 Jan 2013
Last updated: 8 Nov 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Robinson JG, Nedergaard BS, Rogers WJ, Fialkow J, Neutel JM, Ramstad D, Somaratne R, Legg JC, Nelson P, Scott R, Wasserman SM, Weiss R; LAPLACE-2 Investigators. Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial. JAMA. 2014 May 14;311(18):1870-82. doi: 10.1001/jama.2014.4030.
PubMed 24825642
Robinson JG, Rogers WJ, Nedergaard BS, Fialkow J, Neutel JM, Ramstad D, Somaratne R, Legg JC, Nelson P, Scott R, Wasserman SM, Weiss R. Rationale and design of LAPLACE-2: a phase 3, randomized, double-blind, placebo- and ezetimibe-controlled trial evaluating the efficacy and safety of evolocumab in subjects with hypercholesterolemia on background statin therapy. Clin Cardiol. 2014 Apr;37(4):195-203. doi: 10.1002/clc.22252. Epub 2014 Jan 30.
PubMed 24481874
Daviglus ML, Ferdinand KC, Lopez JAG, Wu Y, Monsalvo ML, Rodriguez CJ. Effects of Evolocumab on Low-Density Lipoprotein Cholesterol, Non-High Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a) by Race and Ethnicity: A Meta-Analysis of Individual Participant Data From Double-Blind and Open-Label Extension Studies. J Am Heart Assoc. 2021 Jan 5;10(1):e016839. doi: 10.1161/JAHA.120.016839. Epub 2020 Dec 16.
PubMed 33325247
Koren MJ, Jones PH, Robinson JG, Sullivan D, Cho L, Hucko T, Lopez JAG, Fleishman AN, Somaratne R, Stroes E. A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies. Cardiol Ther. 2020 Dec;9(2):447-465. doi: 10.1007/s40119-020-00181-8. Epub 2020 Jun 20.
PubMed 32564340
Kuchimanchi M, Grover A, Emery MG, Somaratne R, Wasserman SM, Gibbs JP, Doshi S. Population pharmacokinetics and exposure-response modeling and simulation for evolocumab in healthy volunteers and patients with hypercholesterolemia. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):505-522. doi: 10.1007/s10928-018-9592-y. Epub 2018 May 7.
PubMed 29736889
Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.
PubMed 29353350
Shapiro MD, Minnier J, Tavori H, Kassahun H, Flower A, Somaratne R, Fazio S. Relationship Between Low-Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab. J Am Heart Assoc. 2019 Feb 19;8(4):e010932. doi: 10.1161/JAHA.118.010932.
PubMed 30755061
Stroes E, Robinson JG, Raal FJ, Dufour R, Sullivan D, Kassahun H, Ma Y, Wasserman SM, Koren MJ. Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies. Clin Cardiol. 2018 Oct;41(10):1328-1335. doi: 10.1002/clc.23049. Epub 2018 Oct 21.
PubMed 30120772
Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1.
PubMed 28249876
Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, Lopez JAG, Banach M. Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies. J Am Heart Assoc. 2020 Mar 3;9(5):e014129. doi: 10.1161/JAHA.119.014129. Epub 2020 Mar 2.
PubMed 32114889
Wasserman SM, Sabatine MS, Koren MJ, Giugliano RP, Legg JC, Emery MG, Doshi S, Liu T, Somaratne R, Gibbs JP. Comparison of LDL-C Reduction Using Different Evolocumab Doses and Intervals: Biological Insights and Treatment Implications. J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):423-432. doi: 10.1177/1074248418774043. Epub 2018 May 16.
PubMed 29768954
May HT, Muhlestein JB, Ma Y, Lopez JAG, Coll B, Nelson J. Effects of Evolocumab on the ApoA1 Remnant Ratio: A Pooled Analysis of Phase 3 Studies. Cardiol Ther. 2019 Jun;8(1):91-102. doi: 10.1007/s40119-019-0133-6. Epub 2019 Mar 9.
PubMed 30852766

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Study at a glance

From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-blind, Randomized, Placebo and Ezetimibe Controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia
ClinicalTrials.gov ID: NCT01763866
Acronym / sponsor ID: LAPLACE-2 / 20110115
Conditions: Hyperlipidemia
Keywords: High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 2,067 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 15 Jan 2013 (actual)
Primary completion: 12 Nov 2013 (actual)
Study completion: 4 Dec 2013 (actual)
First posted: 9 Jan 2013 (estimated)
Results: Posted 22 Dec 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

A participant was considered randomized into the study after successfully completing the screening period, meeting all inclusion/exclusion criteria, and undergoing both randomization procedures.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 24

Arm	Type	Receives
A10 PBO Q2W	Placebo comparator	Drug: Placebo to Evolocumab, Drug: Placebo to Ezetimibe, Drug: AtorvastatinParticipants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks.
A10 PBO QM	Placebo comparator	Drug: Placebo to Evolocumab, Drug: Placebo to Ezetimibe, Drug: AtorvastatinParticipants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
A10 EZE (Q2W)	Active comparator	Drug: Ezetimibe, Drug: Placebo to Evolocumab, Drug: AtorvastatinParticipants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once a day for up to 12 weeks.
A10 EZE (QM)	Active comparator	Drug: Ezetimibe, Drug: Placebo to Evolocumab, Drug: AtorvastatinParticipants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
A10 EvoMab Q2W	Experimental	Biological: Evolocumab, Drug: Placebo to Ezetimibe, Drug: AtorvastatinParticipants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
A10 EvoMab QM	Experimental	Biological: Evolocumab, Drug: Placebo to Ezetimibe, Drug: AtorvastatinParticipants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks
A80 PBO Q2W	Placebo comparator	Drug: Placebo to Evolocumab, Drug: Placebo to Ezetimibe, Drug: AtorvastatinParticipants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
A80 PBO QM	Placebo comparator	Drug: Placebo to Evolocumab, Drug: Placebo to Ezetimibe, Drug: AtorvastatinParticipants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month and placebo tablets once a day for up to 12 weeks.
A80 EZE (Q2W)	Active comparator	Drug: Ezetimibe, Drug: Placebo to Evolocumab, Drug: AtorvastatinParticipants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
A80 EZE (QM)	Active comparator	Drug: Ezetimibe, Drug: Placebo to Evolocumab, Drug: AtorvastatinParticipants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
A80 EvoMab Q2W	Experimental	Biological: Evolocumab, Drug: Placebo to Ezetimibe, Drug: AtorvastatinParticipants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
A80 EvoMab QM	Experimental	Biological: Evolocumab, Drug: Placebo to Ezetimibe, Drug: AtorvastatinParticipants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
R5 PBO Q2W	Placebo comparator	Drug: Placebo to Evolocumab, Drug: RosuvastatinParticipants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.
R5 PBO QM	Placebo comparator	Drug: Placebo to Evolocumab, Drug: RosuvastatinParticipants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks.
R5 EvoMab Q2W	Experimental	Biological: Evolocumab, Drug: RosuvastatinParticipants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
R5 EvoMab QM	Experimental	Biological: Evolocumab, Drug: RosuvastatinParticipants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
R40 PBO Q2W	Placebo comparator	Drug: Placebo to Evolocumab, Drug: RosuvastatinParticipants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.
R40 PBO QM	Placebo comparator	Drug: Placebo to Evolocumab, Drug: RosuvastatinParticipants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks.
R40 EvoMab Q2W	Experimental	Biological: Evolocumab, Drug: RosuvastatinParticipants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
R40 EvoMab QM	Experimental	Biological: Evolocumab, Drug: RosuvastatinParticipants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
S40 PBO Q2W	Placebo comparator	Drug: Placebo to Evolocumab, Drug: SimvastatinParticipants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.
S40 PBO QM	Placebo comparator	Drug: Placebo to Evolocumab, Drug: SimvastatinParticipants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks.
S40 EvoMab Q2W	Experimental	Biological: Evolocumab, Drug: SimvastatinParticipants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.
S40 EvoMab QM	Experimental	Biological: Evolocumab, Drug: SimvastatinParticipants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Male or female ≥ 18 to ≤ 80 years of age
Subjects not taking a statin must have fasting LDL-C of at least 150 mg/dL (4.0 mmol/L)
Subjects already on a non-intensive statin must have fasting LDL-C at screening ≥ 100 mg/dL (2.6 mmol/L)
Subjects already on a intensive statin must have fasting LDL-C at screening ≥ 80 mg/dL (2.1 mmol/L)
Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

Key exclusion criteria (6 listed)

Statin intolerance
New York Heart association (NYHA) III or IV heart failure
Uncontrolled hypertension
Uncontrolled cardiac arrhythmia
Type 1 diabetes, poorly controlled type 2 diabetes

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EvolocumabAlso: AMG 145, RepathaAdministered by subcutaneous injection	Biological	A10 EvoMab Q2W, A10 EvoMab QM, A80 EvoMab Q2W, A80 EvoMab QM, R40 EvoMab Q2W, R40 EvoMab QM, R5 EvoMab Q2W, R5 EvoMab QM, S40 EvoMab Q2W, S40 EvoMab QM
EzetimibeAlso: ZetiaAdministered orally once a day	Drug	A10 EZE (Q2W), A10 EZE (QM), A80 EZE (Q2W), A80 EZE (QM)
Placebo to EvolocumabAdministered by subcutaneous injection	Drug	A10 EZE (Q2W), A10 EZE (QM), A10 PBO Q2W, A10 PBO QM, A80 EZE (Q2W), A80 EZE (QM), A80 PBO Q2W, A80 PBO QM, R40 PBO Q2W, R40 PBO QM, R5 PBO Q2W, R5 PBO QM, S40 PBO Q2W, S40 PBO QM
Placebo to EzetimibeAdministered orally once a day	Drug	A10 EvoMab Q2W, A10 EvoMab QM, A10 PBO Q2W, A10 PBO QM, A80 EvoMab Q2W, A80 EvoMab QM, A80 PBO Q2W, A80 PBO QM
AtorvastatinAlso: LipitorAdministered orally once a day	Drug	A10 EZE (Q2W), A10 EZE (QM), A10 EvoMab Q2W, A10 EvoMab QM, A10 PBO Q2W, A10 PBO QM, A80 EZE (Q2W), A80 EZE (QM), A80 EvoMab Q2W, A80 EvoMab QM, A80 PBO Q2W, A80 PBO QM
RosuvastatinAlso: CrestorAdministered orally once a day	Drug	R40 EvoMab Q2W, R40 EvoMab QM, R40 PBO Q2W, R40 PBO QM, R5 EvoMab Q2W, R5 EvoMab QM, R5 PBO Q2W, R5 PBO QM
SimvastatinAlso: ZocorAdministered orally once a day	Drug	S40 EvoMab Q2W, S40 EvoMab QM, S40 PBO Q2W, S40 PBO QM

Primary outcome

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12

20 secondary outcomes

Change From Baseline in LDL-C at at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Change From Baseline in LDL-C at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Non-HDL-C at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Time frame: Baseline and Week 12
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL
Time frame: Weeks 10 and 12
Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12
Time frame: Week 12
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Lipoprotein(a) at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Triglycerides at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Very Low-Density Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Very Low-Density Cholesterol (VLDL-C) at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in HDL-C at Week 12
Time frame: Baseline and Week 12

Results and safety

Results posted to the registry on 22 Dec 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
A10 PBO Q2W	56	54
A10 PBO QM	55	54
A10 EZE (Q2W)	56	51
A10 EZE (QM)	55	55
A10 EvoMab Q2W	110	108
A10 EvoMab QM	110	107
A80 PBO Q2W	55	48
A80 PBO QM	55	55
A80 EZE (Q2W)	56	53
A80 EZE (QM)	54	53
A80 EvoMab Q2W	110	102
A80 EvoMab QM	110	108
R5 PBO Q2W	58	54
R5 PBO QM	57	57
R5 EvoMab Q2W	114	102
R5 EvoMab QM	115	112
R40 PBO Q2W	56	55
R40 PBO QM	56	55
R40 EvoMab Q2W	111	105
R40 EvoMab QM	112	110
S40 PBO Q2W	56	52
S40 PBO QM	55	54
S40 EvoMab Q2W	112	109
S40 EvoMab QM	115	113

Primary outcome: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12

Time frame: Baseline and Week 12. Least squares mean (Standard Error). Unit: percent change

Measure	A10 PBO Q2W n = 56	A10 PBO QM n = 55	A10 EZE (Q2W) n = 56	A10 EZE (QM) n = 55	A10 EvoMab Q2W n = 110	A10 EvoMab QM n = 110	A80 PBO Q2W n = 55	A80 PBO QM n = 55	A80 EZE (Q2W) n = 56	A80 EZE (QM) n = 54	A80 EvoMab Q2W n = 109	A80 EvoMab QM n = 110	R5 PBO Q2W n = 58	R5 PBO QM n = 57	R5 EvoMab Q2W n = 113	R5 EvoMab QM n = 115	R40 PBO Q2W n = 56	R40 PBO QM n = 55	R40 EvoMab Q2W n = 111	R40 EvoMab QM n = 112	S40 PBO Q2W n = 56	S40 PBO QM n = 55	S40 EvoMab Q2W n = 112	S40 EvoMab QM n = 115
Value	9.86 (2.53)	0.97 (2.82)	-21.96 (2.63)	-17.08 (2.78)	-61.56 (1.81)	-58.19 (1.99)	14.49 (4.42)	11.83 (3.85)	-14.60 (4.29)	-19.80 (3.85)	-61.80 (3.04)	-58.68 (2.74)	8.12 (2.68)	5.10 (2.62)	-60.09 (1.94)	-59.40 (1.87)	9.42 (3.60)	2.59 (4.30)	-58.89 (2.58)	-52.40 (2.98)	4.70 (3.61)	3.40 (4.94)	-65.86 (3.05)	-57.02 (3.93)

A10 PBO Q2W vs A10 EvoMab Q2W: LS Mean Treatment Difference: -71.42 (95% CI -77.55 to -65.29), p <0.001, Repeated measures linear effects model
A10 PBO QM vs A10 EvoMab QM: LS Mean Treatment Difference: -59.16 (95% CI -65.94 to -52.38), p <0.001, Repeated measures linear effects model
A10 EZE (Q2W) vs A10 EvoMab Q2W: LS Mean Treatment Difference: -39.60 (95% CI -45.81 to -33.40), p <0.001, Repeated measures linear effects model

Population analysed: Full analysis set

Primary outcome: Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

Time frame: Baseline and Weeks 10 and 12. Least squares mean (Standard Error). Unit: percent change

Measure	A10 PBO Q2W n = 56	A10 PBO QM n = 55	A10 EZE (Q2W) n = 56	A10 EZE (QM) n = 55	A10 EvoMab Q2W n = 110	A10 EvoMab QM n = 110	A80 PBO Q2W n = 55	A80 PBO QM n = 55	A80 EZE (Q2W) n = 56	A80 EZE (QM) n = 54	A80 EvoMab Q2W n = 109	A80 EvoMab QM n = 110	R5 PBO Q2W n = 58	R5 PBO QM n = 57	R5 EvoMab Q2W n = 113	R5 EvoMab QM n = 115	R40 PBO Q2W n = 56	R40 PBO QM n = 55	R40 EvoMab Q2W n = 111	R40 EvoMab QM n = 112	S40 PBO Q2W n = 56	S40 PBO QM n = 55	S40 EvoMab Q2W n = 112	S40 EvoMab QM n = 115
Value	8.54 (2.24)	0.35 (2.60)	-23.88 (2.34)	-18.98 (2.57)	-61.41 (1.61)	-62.47 (1.83)	13.12 (3.99)	9.76 (3.39)	-16.85 (3.88)	-21.25 (3.42)	-61.80 (2.77)	-65.05 (2.42)	7.55 (2.39)	2.79 (2.50)	-59.33 (1.74)	-63.79 (1.76)	6.57 (3.11)	-0.02 (3.51)	-59.08 (2.23)	-62.94 (2.44)	3.26 (3.40)	6.00 (4.80)

20 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first dose of blinded investigational product until the end of the study (up to 14 weeks).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
A10 PBO Q2W	1 of 56 (1.8%)	5 of 56 (8.9%)	Not reported
A10 PBO QM	2 of 55 (3.6%)	3 of 55 (5.5%)	Not reported
A10 EZE (Q2W)	0 of 56 (0%)	9 of 56 (16.1%)	Not reported
A10 EZE (QM)	0 of 55 (0%)	6 of 55 (10.9%)	Not reported
A10 EvoMab Q2W	4 of 110 (3.6%)	9 of 110 (8.2%)	Not reported
A10 EvoMab QM	2 of 110 (1.8%)	7 of 110 (6.4%)	Not reported
A80 PBO Q2W	2 of 55 (3.6%)	7 of 55 (12.7%)	Not reported
A80 PBO QM	1 of 55 (1.8%)	13 of 55 (23.6%)	Not reported
A80 EZE (Q2W)	1 of 56 (1.8%)	8 of 56 (14.3%)	Not reported
A80 EZE (QM)	1 of 54 (1.9%)	2 of 54 (3.7%)	Not reported
A80 EvoMab Q2W	3 of 109 (2.8%)	11 of 109 (10.1%)	Not reported
A80 EvoMab QM	1 of 110 (0.9%)	9 of 110 (8.2%)	Not reported
R5 PBO Q2W	1 of 58 (1.7%)	11 of 58 (19%)	Not reported
R5 PBO QM	2 of 57 (3.5%)	1 of 57 (1.8%)	Not reported
R5 EvoMab Q2W	3 of 113 (2.7%)	6 of 113 (5.3%)	Not reported
R5 EvoMab QM	3 of 115 (2.6%)	9 of 115 (7.8%)	Not reported
R40 PBO Q2W	2 of 56 (3.6%)	3 of 56 (5.4%)	Not reported
R40 PBO QM	1 of 55 (1.8%)	8 of 55 (14.5%)	Not reported
R40 EvoMab Q2W	1 of 111 (0.9%)	5 of 111 (4.5%)	Not reported
R40 EvoMab QM

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 24825642Robinson JG, Nedergaard BS, Rogers WJ, Fialkow J, Neutel JM, Ramstad D, Somaratne R, Legg JC, Nelson P, Scott R, Wasserman SM, Weiss R; LAPLACE-2 Investigators. Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial. JAMA. 2014 May 14;311(18):1870-82. doi: 10.1001/jama.2014.4030.
Background: PubMed 24481874Robinson JG, Rogers WJ, Nedergaard BS, Fialkow J, Neutel JM, Ramstad D, Somaratne R, Legg JC, Nelson P, Scott R, Wasserman SM, Weiss R. Rationale and design of LAPLACE-2: a phase 3, randomized, double-blind, placebo- and ezetimibe-controlled trial evaluating the efficacy and safety of evolocumab in subjects with hypercholesterolemia on background statin therapy. Clin Cardiol. 2014 Apr;37(4):195-203. doi: 10.1002/clc.22252. Epub 2014 Jan 30.
Background: PubMed 33325247Daviglus ML, Ferdinand KC, Lopez JAG, Wu Y, Monsalvo ML, Rodriguez CJ. Effects of Evolocumab on Low-Density Lipoprotein Cholesterol, Non-High Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a) by Race and Ethnicity: A Meta-Analysis of Individual Participant Data From Double-Blind and Open-Label Extension Studies. J Am Heart Assoc. 2021 Jan 5;10(1):e016839. doi: 10.1161/JAHA.120.016839. Epub 2020 Dec 16.
Background: PubMed 32564340Koren MJ, Jones PH, Robinson JG, Sullivan D, Cho L, Hucko T, Lopez JAG, Fleishman AN, Somaratne R, Stroes E. A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies. Cardiol Ther. 2020 Dec;9(2):447-465. doi: 10.1007/s40119-020-00181-8. Epub 2020 Jun 20.
Background: PubMed 29736889Kuchimanchi M, Grover A, Emery MG, Somaratne R, Wasserman SM, Gibbs JP, Doshi S. Population pharmacokinetics and exposure-response modeling and simulation for evolocumab in healthy volunteers and patients with hypercholesterolemia. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):505-522. doi: 10.1007/s10928-018-9592-y. Epub 2018 May 7.
Background: PubMed 29353350Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.
Background: PubMed 30755061Shapiro MD, Minnier J, Tavori H, Kassahun H, Flower A, Somaratne R, Fazio S. Relationship Between Low-Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab. J Am Heart Assoc. 2019 Feb 19;8(4):e010932. doi: 10.1161/JAHA.118.010932.
Background: PubMed 30120772Stroes E, Robinson JG, Raal FJ, Dufour R, Sullivan D, Kassahun H, Ma Y, Wasserman SM, Koren MJ. Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies. Clin Cardiol. 2018 Oct;41(10):1328-1335. doi: 10.1002/clc.23049. Epub 2018 Oct 21.
Background: PubMed 28249876Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1.
Background: PubMed 32114889Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, Lopez JAG, Banach M. Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies. J Am Heart Assoc. 2020 Mar 3;9(5):e014129. doi: 10.1161/JAHA.119.014129. Epub 2020 Mar 2.
Background: PubMed 29768954Wasserman SM, Sabatine MS, Koren MJ, Giugliano RP, Legg JC, Emery MG, Doshi S, Liu T, Somaratne R, Gibbs JP. Comparison of LDL-C Reduction Using Different Evolocumab Doses and Intervals: Biological Insights and Treatment Implications. J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):423-432. doi: 10.1177/1074248418774043. Epub 2018 May 16.
Background: PubMed 30852766May HT, Muhlestein JB, Ma Y, Lopez JAG, Coll B, Nelson J. Effects of Evolocumab on the ApoA1 Remnant Ratio: A Pooled Analysis of Phase 3 Studies. Cardiol Ther. 2019 Jun;8(1):91-102. doi: 10.1007/s40119-019-0133-6. Epub 2019 Mar 9.
AmgenTrials clinical trials websiteLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

244 sites in 21 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Evolocumab, Ezetimibe and Atorvastatin in people with Hyperlipidemia, run by Amgen at 244 sites in 21 countries.

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 5 inclusion and 6 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 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 244 sites in United States, Canada, United Kingdom, Czechia, Germany and 16 more countries. 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 22 Dec 2015). 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 Cholesterol (LDL-C) at Week 12 (time frame: Baseline and Week 12). The study lists 2 primary outcomes in all. 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 NCT01763866, which also lists 12 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 8 Nov 2022.