LAPLACE-TIMI 57: LDL-C Assessment Wtih PCSK9 monoclonaL Antibody Inhibition Combined With Statin thErapy - Full Text View

Purpose

To evaluate the effect of 12 weeks of subcutaneous (SC) AMG 145 every 2 weeks (Q2W) or every 4 weeks (Q4W), compared with placebo, or percent change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) when used in addition to a statin in subjects with hypercholesterolemia.

Condition	Intervention	Phase
Hyperlipidemia	Drug: AMG 145 Drug: PLACEBO	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	TIMI-57 - A Double-blind, Randomized, Placebo-controlled, Multicenter, Dose-ranging Study to Evaluate Tolerability and Efficacy of AMG 145 on Low-Density Lipoprotein Cholesterol (LDL-C) in Combination With HMG-CoA Reductase Inhibitors in Hypercholesterolemic Subjects

Resource links provided by NLM:

MedlinePlus related topics: Cholesterol Statins

U.S. FDA Resources

Further study details as provided by Amgen:

Primary Outcome Measures:

The primary endpoint is the percent change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Absolute change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in non-High Density Lipoprotein Cholesterol (HDL-C) at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in Apolipoprotein B (ApoB) at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in the total cholesterol/High Density Lipoprotein Cholesterol (HDL-C) ratio at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in Apolipoprotein B (ApoB)/Apolipoprotein A-1 (ApoA1) ratio at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment:	631
Study Start Date:	July 2011
Study Completion Date:	May 2012
Primary Completion Date:	May 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group 4 AMG 145	Drug: AMG 145 Dose 4 - every 4 weeks
Placebo Comparator: Group 7 Placebo	Drug: PLACEBO Dose 7 - every 2 weeks
Experimental: Group 1 AMG 145	Drug: AMG 145 Dose 1 - every 2 weeks
Experimental: Group 5 AMG 145	Drug: AMG 145 Dose 5 - every 4 weeks
Experimental: Group 3 AMG 145	Drug: AMG 145 Dose 3 - every 2 weeks
Experimental: Group 6 AMG 145	Drug: AMG 145 Dose 6 - every 4 weeks
Placebo Comparator: Group 8 Placebo	Drug: PLACEBO Dose 8 - every 4 weeks
Experimental: Group 2 AMG 145	Drug: AMG 145 Dose 2 - every 2 weeks

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 Low-Density Lipoprotein Cholesterol (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 (Glycated Hemoglobin (HbA1c) > 8.5%)
Uncontrolled hypertension defined
New York Heart Association (NYHA) III or IV heart failure, or known left ventricular ejection fraction < 30%
Uncontrolled cardiac arrhythmia

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01380730

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Sponsors and Collaborators

Amgen

TIMI Study Group

Investigators

Study Director:

MD

Amgen

More Information

Additional Information:

AmgenTrials clinical trials website This link exits the ClinicalTrials.gov site

No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

Responsible Party:	Amgen
ClinicalTrials.gov Identifier:	NCT01380730 History of Changes
Other Study ID Numbers:	20101155
Study First Received:	June 23, 2011
Last Updated:	April 2, 2013
Health Authority:	Canada: Health Canada Czech Republic: Statni ustav pro kontrolu leciv Denmark: Laegemiddelstyrelsen Hungary: National Institute of Pharmacy United States: Food and Drug Administration

Keywords provided by Amgen:

Hypercholesterolemia

Additional relevant MeSH terms:

Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents

Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 19, 2013