Durable Effect of PCSK9 Antibody CompARed wiTh placEbo Study - Full Text View

Purpose

To evaluate the efficacy, safety, and tolerability of 52 weeks of subcutaneous (SC) evolocumab (AMG 145) compared with placebo when added to assigned background lipid-lowering therapy.

Condition	Intervention	Phase
Hypercholesterolemia	Biological: Evolocumab (AMG 145) + background lipid lowering therapy Biological: Placebo + background lipid lowering therapy Drug: Atorvastatin 10 mg Drug: Atorvastatin 80 mg Drug: Atorvastatin 80 mg + Ezetimibe 10 mg Other: Diet Only (no drug)	Phase 3


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:	A Double-Blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Long-Term Tolerability and Durable Efficacy of AMG 145 (Evolocumab) on LDL-C in Hyperlipidemic Subjects

Resource links provided by NLM:

MedlinePlus related topics: Cholesterol

Drug Information available for: Atorvastatin Atorvastatin calcium Ezetimibe

Genetic and Rare Diseases Information Center resources: Sphingolipidosis

U.S. FDA Resources

Further study details as provided by Amgen:

Primary Outcome Measures:

Percent change from baseline in LDL-C at week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in LDL-C at week 52

Secondary Outcome Measures:

Percent change from baseline in LDL-C at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in LDL-C at week 12
Percent change from week 12 in LDL-C at week 52 [ Time Frame: 40 weeks ] [ Designated as safety issue: No ]
Percent change from week 12 in LDL-C at week 52
Absolute change from baseline in LDL-C at week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Absolute change from baseline in LDL-C at week 52
Percent change from baseline in non-HDL-C at week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in non-HDL-C at week 52
Percent change from baseline in ApoB at week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in ApoB at week 52
Percent change from baseline in the total cholesterol/HDL-C ratio at week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in the total cholesterol/HDL-C ratio at week 52
Percent change from baseline in ApoB/ApoA1 ratio at week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in ApoB/ApoA1 ratio at week 52
LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L]) at week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L]) at week 52
Percent change from baseline in TC at week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in TC at week 12
Percent change from baseline in TC at week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in TC at week 52
Percent change from baseline in Lp(a) at week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in Lp(a) at week 52
Percent change from baseline in triglycerides at week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in triglycerides at week 52
Percent change from baseline in HDL-C at week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in HDL-C at week 52
Percent change from baseline in VLDL-C at week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Percent change from baseline in VLDL-C at week 52


Enrollment:	901
Study Start Date:	January 2012
Study Completion Date:	December 2013
Primary Completion Date:	October 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Evolocumab (AMG 145) Evolocumab (AMG 145) 420mg subcutaneous QM.	Biological: Evolocumab (AMG 145) + background lipid lowering therapy Subjects randomized to the evolocumab (AMG 145) arm will receive evolocumab (AMG 145) 420 mg subcutaneously every 4 weeks plus diet (no drug), atorvastatin 10 mg, atorvastatin 80 mg or combination atorvastatin 80 mg plus exetimibe 10 mg. Drug: Atorvastatin 10 mg Background lipid lowering therapy Drug: Atorvastatin 80 mg Background lipid lowering therapy Drug: Atorvastatin 80 mg + Ezetimibe 10 mg Background lipid lowering therapy Other: Diet Only (no drug) Diet only, no lipid lowering background drug given
Placebo Comparator: Placebo Placebo QM	Biological: Placebo + background lipid lowering therapy Subjects randomized to the placebo arm will receive Placebo 6 ml subcutaneously every 4 weeks + diet (no drug), atorvastatin 10 mg, atorvastatin 80 mg, or combination atorvastatin 80 mg plus ezetimibe 10 mg. Drug: Atorvastatin 10 mg Background lipid lowering therapy Drug: Atorvastatin 80 mg Background lipid lowering therapy Drug: Atorvastatin 80 mg + Ezetimibe 10 mg Background lipid lowering therapy Other: Diet Only (no drug) Diet only, no lipid lowering background drug given

Arms

Assigned Interventions

Experimental: Evolocumab (AMG 145)

Evolocumab (AMG 145) 420mg subcutaneous QM.

Biological: Evolocumab (AMG 145) + background lipid lowering therapy

Subjects randomized to the evolocumab (AMG 145) arm will receive evolocumab (AMG 145) 420 mg subcutaneously every 4 weeks plus diet (no drug), atorvastatin 10 mg, atorvastatin 80 mg or combination atorvastatin 80 mg plus exetimibe 10 mg.

Drug: Atorvastatin 10 mg

Background lipid lowering therapy

Drug: Atorvastatin 80 mg

Background lipid lowering therapy

Drug: Atorvastatin 80 mg + Ezetimibe 10 mg

Background lipid lowering therapy

Other: Diet Only (no drug)

Diet only, no lipid lowering background drug given

Placebo Comparator: Placebo

Placebo QM

Biological: Placebo + background lipid lowering therapy

Subjects randomized to the placebo arm will receive Placebo 6 ml subcutaneously every 4 weeks + diet (no drug), atorvastatin 10 mg, atorvastatin 80 mg, or combination atorvastatin 80 mg plus ezetimibe 10 mg.

Drug: Atorvastatin 10 mg

Background lipid lowering therapy

Drug: Atorvastatin 80 mg

Background lipid lowering therapy

Drug: Atorvastatin 80 mg + Ezetimibe 10 mg

Background lipid lowering therapy

Other: Diet Only (no drug)

Diet only, no lipid lowering background drug given

Eligibility


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

Criteria

Inclusion Criteria:

Subject has provided informed consent.
Fasting LDL-C ≥ 75 mg/dL and meeting the following LDL-C values on background lipid-lowering therapy:
- < 100 mg/dL for subjects with diagnosed CHD or CHD risk equivalent
- < 130 mg/dL for subjects without diagnosed CHD or CHD risk equivalent
- OR on maximal background lipid-lowering therapy defined as atorvastatin 80 mg PO QD and ezetimibe 10 mg PO QD
Fasting triglycerides ≤ 400 mg/dL

Exclusion Criteria:

NYHA II-IV heart failure, or last known left ventricular ejection fraction < 30%
Uncontrolled cardiac arrhythmia
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
Uncontrolled hypertension

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01516879

Show 96 Study Locations

Sponsors and Collaborators

Amgen

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):

Blom DJ, Hala T, Bolognese M, Lillestol MJ, Toth PD, Burgess L, Ceska R, Roth E, Koren MJ, Ballantyne CM, Monsalvo ML, Tsirtsonis K, Kim JB, Scott R, Wasserman SM, Stein EA; DESCARTES Investigators. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014 May 8;370(19):1809-19. doi: 10.1056/NEJMoa1316222. Epub 2014 Mar 29.


Responsible Party:	Amgen
ClinicalTrials.gov Identifier:	NCT01516879 History of Changes
Other Study ID Numbers:	20110109
Study First Received:	January 18, 2012
Last Updated:	July 14, 2014
Health Authority:	United States: Food and Drug Administration Austria: Agency for Health and Food Safety Canada: Health Canada Belgium: Federal Agency for Medicines and Health Products, FAMHP Denmark: Danish Medicines Agency South Africa: Medicines Control Council Hungary: National Institute of Pharmacy Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Amgen:


Cholesterol High Cholesterol Elevated Cholesterol Raised Cholesterol

Additional relevant MeSH terms:


Hypercholesterolemia Dyslipidemias Hyperlipidemias Lipid Metabolism Disorders Metabolic Diseases Atorvastatin Anticholesteremic Agents Antimetabolites	Enzyme Inhibitors Hydroxymethylglutaryl-CoA Reductase Inhibitors Hypolipidemic Agents Lipid Regulating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015

Durable Effect of PCSK9 Antibody CompARed wiTh placEbo Study (DESCARTES)