Clinical trial NCT01380730: LAPLACE-TIMI 57: Low-density Lipoprotein Cholesterol (LDL-C) Assessment With PCSK9 monoclonaL Antibody Inhibition Combined With Statin thErapy
Official title: LAPLACE TIMI 57 - A Double-blind, Randomized, Placebo-controlled, Multicenter, Dose-ranging Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Combination With HMG-CoA Reductase Inhibitors in Hypercholesterolemic Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hyperlipidemia
Keywords: Hypercholesterolemia
Proprotein convertase subtilisin/kexin type 9 (PCSK9)
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: The TIMI Study Group
First posted: 2011-06-27
Enrollment: 631
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab (AMG 145) administered every 2 weeks (Q2W) or every 4 weeks (Q4W), compared with placebo, on percent change from baseline in LDL-C when used in addition to a statin in adults with hypercholesterolemia.


Eligibility criteria: Inclusion Criteria:

* Male or female ≥ 18 to ≤ 80 years of age
* On an approved statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks
* Fasting LDL-C ≥ 85 mg/dL
* Fasting triglycerides ≤ 400 mg/dL

Exclusion Criteria:

* Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization
* Type 1 diabetes; newly diagnosed or poorly controlled type 2 diabetes (Glycosyated Hemoglobin (HbA1c) \> 8.5%)
* Uncontrolled hypertension
* New York Heart Association (NYHA) III or IV heart failure, or known left ventricular ejection fraction \< 30%
* Uncontrolled cardiac arrhythmia

Primary outcomes:
measure: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline in LDL-C at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in Apolipoprotein B at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12
timeFrame: Baseline and Week 12
measure: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Malvern
country: United States
facility: Research Site
state: Arkansas
city: Anaheim
country: United States
facility: Research Site
state: California
city: Carmichael
country: United States
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state: California
city: Newport Beach
country: United States
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state: California
city: Roseville
country: United States
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state: California
city: Westlake Village
country: United States
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state: California
city: Colorado Springs
country: United States
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state: Colorado
city: Littleton
country: United States
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state: Colorado
city: Daytona Beach
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state: Florida
city: Green Cove Springs
country: United States
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city: Melbourne
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city: Miami
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city: Miami
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city: Port Charlotte
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city: Hammond
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city: Indianapolis
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city: Valparaiso
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city: Iowa City
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city: Lexington
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city: Auburn
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state: Maine
city: Bangor
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city: Portland
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city: Kalamazoo
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state: Michigan
city: Marquette
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city: Ypsilanti
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city: Tupelo
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city: Great Falls
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city: Voorhees
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city: Cortlandt Manor
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city: Williamsville
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city: Smithfield
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state: North Carolina
city: Winston-Salem
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city: Cincinnati
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city: Cincinnati
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city: Dayton
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city: Mansfield
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city: Marion
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city: Philadelphia
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city: Pittsburgh
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city: York
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city: Florence
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state: South Carolina
city: Spartanburg
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state: South Carolina
city: Rapid City
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state: South Dakota
city: Jackson
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state: Tennessee
city: Jackson
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city: Houston
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city: Houston
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state: Washington
city: Madison
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state: Wisconsin
city: Burnaby
country: Canada
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state: British Columbia
city: Kelowna
country: Canada
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state: British Columbia
city: Vancouver
country: Canada
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state: British Columbia
city: Victoria
country: Canada
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state: British Columbia
city: Cambridge
country: Canada
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state: Ontario
city: Hamilton
country: Canada
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state: Ontario
city: London
country: Canada
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state: Ontario
city: London
country: Canada
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state: Ontario
city: Newmarket
country: Canada
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state: Ontario
city: Oshawa
country: Canada
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state: Ontario
city: Oshawa
country: Canada
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state: Ontario
city: Sarnia
country: Canada
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state: Ontario
city: Scarborough
country: Canada
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state: Ontario
city: Sudbury
country: Canada
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state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Woodstock
country: Canada
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state: Ontario
city: Gatineau
country: Canada
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state: Quebec
city: Lachine
country: Canada
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state: Quebec
city: Longueuil
country: Canada
facility: Research Site
state: Quebec
city: Pointe-Claire
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Slany
country: Czechia
facility: Research Site
city: Svitavy
country: Czechia
facility: Research Site
city: Usti nad Orlici
country: Czechia
facility: Research Site
city: Znojmo
country: Czechia
facility: Research Site
city: Aalborg
country: Denmark
facility: Research Site
city: Ballerup
country: Denmark
facility: Research Site
city: Vejle
country: Denmark
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Dunaujvaros
country: Hungary
facility: Research Site
city: Eger
country: Hungary
facility: Research Site
city: Gyula
country: Hungary
facility: Research Site
city: Kecskemet
country: Hungary
facility: Research Site
city: Komarom
country: Hungary
facility: Research Site
city: Mosonmagyarovar
country: Hungary
facility: Research Site
city: Szolnok
country: Hungary
facility: Research Site
city: Zalaegerszeg
country: Hungary
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Giugliano RP, Desai NR, Kohli P, Rogers WJ, Somaratne R, Huang F, Liu T, Mohanavelu S, Hoffman EB, McDonald ST, Abrahamsen TE, Wasserman SM, Scott R, Sabatine MS; LAPLACE-TIMI 57 Investigators. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet. 2012 Dec 8;380(9858):2007-17. doi: 10.1016/S0140-6736(12)61770-X. Epub 2012 Nov 6.
citation: Kohli P, Desai NR, Giugliano RP, Kim JB, Somaratne R, Huang F, Knusel B, McDonald S, Abrahamsen T, Wasserman SM, Scott R, Sabatine MS. Design and rationale of the LAPLACE-TIMI 57 trial: a phase II, double-blind, placebo-controlled study of the efficacy and tolerability of a monoclonal antibody inhibitor of PCSK9 in subjects with hypercholesterolemia on background statin therapy. Clin Cardiol. 2012;35(7):385-91. doi: 10.1002/clc.22014. Epub 2012 Jun 19.
citation: Desai NR, Kohli P, Giugliano RP, O'Donoghue ML, Somaratne R, Zhou J, Hoffman EB, Huang F, Rogers WJ, Wasserman SM, Scott R, Sabatine MS. AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9, significantly reduces lipoprotein(a) in hypercholesterolemic patients receiving statin therapy: an analysis from the LDL-C Assessment with Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined with Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57 trial. Circulation. 2013 Aug 27;128(9):962-9. doi: 10.1161/CIRCULATIONAHA.113.001969. Epub 2013 Jul 24.