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LDL-C Assessment w/ PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-2 (LAPLACE-2)

This study is currently recruiting participants.
Verified June 2013 by Amgen
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01763866
First received: January 7, 2013
Last updated: June 10, 2013
Last verified: June 2013
History of Changes
  Purpose

The primary hypothesis is that both dosing regimens of AMG 145 subcutaneous will be well tolerated and will result in greater reduction of Low Density Lipoprotein-Cholesterol in subjects with primary hypercholesterolemia and mixed dyslipidemia.


Condition Intervention Phase
Hyperlipidemia
 Drug: AMG 145
Other: Ezetimibe
Other: Placebo (administered subcutaneously)
Other: Placebo (administered orally)
Drug: Statin therapy
 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 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

Resource links provided by NLM:

MedlinePlus related topics: Cholesterol Statins
Drug Information available for: Ezetimibe
U.S. FDA Resources

Further study details as provided by Amgen:

Primary Outcome Measures:
  • Mean percent change from baseline in low density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in low density lipoprotein-cholesterol

  • Percent change from baseline in low density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in low density lipoprotein-cholesterol


Secondary Outcome Measures:
  • Mean change from baseline in low density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean change from baseline in low density lipoprotein-cholesterol

  • Change from baseline in low density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Change from baseline in low density lipoprotein-cholesterol

  • Mean percent change from baseline in non-high density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in non-high density lipoprotein-cholesterol

  • Percent change from baseline in non-high density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in non-high density lipoprotein-cholesterol

  • Mean percent change from baseline in apolipoprotein B [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in apolipoprotein B

  • Percent change from baseline in apolipoprotein B [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in apolipoprotein B

  • Mean percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio

  • Percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in the total cholesterol/high density lipoprotein-cholesterol ratio

  • Mean percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio

  • Percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in apolipoprotein B/apolipoprotein A1 ratio

  • Mean low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L])

  • Low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Low density lipoprotein-cholesterol response (low density lipoprotein-cholesterol < 70 mg/dL [1.8 mmol/L])

  • Mean percent change from baseline in lipoprotein (a) [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in lipoprotein (a)

  • Percent change from baseline in lipoprotein (a) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in lipoprotein (a)

  • Mean percent change from baseline in triglycerides [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in triglycerides

  • Percent change from baseline in triglycerides [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in triglycerides

  • Mean percent change from baseline in high density lipoprotein-cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in high density lipoprotein-cholesterol

  • Percent change from baseline in high density lipoprotein-cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in high density lipoprotein-cholesterol

  • Mean percent change from baseline in very low-density lipoprotein cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in very low-density lipoprotein cholesterol

  • Percent change from baseline in very low-density lipoprotein cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in very low-density lipoprotein cholesterol


Estimated Enrollment: 1700
Study Start Date: January 2013
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm 1
Dose 1 of statin therapy and placebo orally/daily and placebo subcutaneously every 2 weeks
 Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Other: Placebo (administered orally)
Subject will receive Placebo daily
Drug: Statin therapy
Subject will receive statin therapy daily
Placebo Comparator: Arm 2
Dose 2 of statin therapy and placebo orally/daily and placebo subcutaneously monthly
 Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Other: Placebo (administered orally)
Subject will receive Placebo daily
Drug: Statin therapy
Subject will receive statin therapy daily
Arm 3
Dose 3 of statin therapy and Ezetimibe orally/daily and placebo subcutaneously every 2 weeks
 Other: Ezetimibe
Subject will receive Ezetimibe daily
Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Drug: Statin therapy
Subject will receive statin therapy daily
Arm 4
Dose 4 of statin therapy and Ezetimibe orally/daily and placebo subcutaneously monthly
 Other: Ezetimibe
Subject will receive Ezetimibe daily
Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Drug: Statin therapy
Subject will receive statin therapy daily
Active Comparator: Arm 5
Dose 5 of statin therapy and placebo orally/daily and AMG 145 subcutaneously every 2 weeks
 Drug: AMG 145
Subject will receive AMG 145 every 2 weeks or monthly
Other: Placebo (administered orally)
Subject will receive Placebo daily
Drug: Statin therapy
Subject will receive statin therapy daily
Active Comparator: Arm 6
Dose 6 of statin therapy and placebo orally/daily and AMG 145 subcutaneously monthly
 Drug: AMG 145
Subject will receive AMG 145 every 2 weeks or monthly
Other: Placebo (administered orally)
Subject will receive Placebo daily
Drug: Statin therapy
Subject will receive statin therapy daily
Placebo Comparator: Arm 7
Dose 7 of statin therapy and placebo orally/daily and placebo subcutaneously every 2 weeks
 Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Other: Placebo (administered orally)
Subject will receive Placebo daily
Drug: Statin therapy
Subject will receive statin therapy daily
Placebo Comparator: Arm 8
Dose 8 of statin therapy and placebo orally/daily and placebo subcutaneously monthly
 Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Other: Placebo (administered orally)
Subject will receive Placebo daily
Drug: Statin therapy
Subject will receive statin therapy daily
Arm 9
Dose 9 of statin therapy and Ezetimibe orally/daily and placebo subcutaneously every 2 weeks
 Other: Ezetimibe
Subject will receive Ezetimibe daily
Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Drug: Statin therapy
Subject will receive statin therapy daily
Arm 10
Dose 10 of statin therapy and Ezetimibe orally/daily and placebo subcutaneously monthly
 Other: Ezetimibe
Subject will receive Ezetimibe daily
Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Drug: Statin therapy
Subject will receive statin therapy daily
Active Comparator: Arm 11
Dose 11 of statin therapy and placebo orally/daily and AMG 145 subcutaneously every 2 weeks
 Drug: AMG 145
Subject will receive AMG 145 every 2 weeks or monthly
Other: Placebo (administered orally)
Subject will receive Placebo daily
Drug: Statin therapy
Subject will receive statin therapy daily
Active Comparator: Arm 12
Dose 12 of statin therapy and placebo orally/daily and AMG 145 subcutaneously monthly
 Drug: AMG 145
Subject will receive AMG 145 every 2 weeks or monthly
Other: Placebo (administered orally)
Subject will receive Placebo daily
Drug: Statin therapy
Subject will receive statin therapy daily
Placebo Comparator: Arm 13
Dose 13 of statin therapy orally/daily and placebo subcutaneously every 2 weeks
 Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Drug: Statin therapy
Subject will receive statin therapy daily
Placebo Comparator: Arm 14
Dose 14 of statin therapy orally/daily and placebo subcutaneously monthly
 Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Drug: Statin therapy
Subject will receive statin therapy daily
Active Comparator: Arm 15
Dose 15 of statin therapy orally/daily and AMG 145 subcutaneously every 2 weeks
 Drug: AMG 145
Subject will receive AMG 145 every 2 weeks or monthly
Drug: Statin therapy
Subject will receive statin therapy daily
Active Comparator: Arm 16
Dose 16 of statin therapy orally/daily and AMG 145 subcutaneously monthly
 Drug: AMG 145
Subject will receive AMG 145 every 2 weeks or monthly
Drug: Statin therapy
Subject will receive statin therapy daily
Placebo Comparator: Arm 17
Dose 17 of statin therapy orally/daily and placebo subcutaneously every 2 weeks.
 Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Drug: Statin therapy
Subject will receive statin therapy daily
Placebo Comparator: Arm 18
Dose 18 of statin therapy orally/daily and placebo subcutaneously monthly
 Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Drug: Statin therapy
Subject will receive statin therapy daily
Active Comparator: Arm 19
Dose 19 of statin therapy orally/daily and AMG 145 subcutaneously every 2 weeks
 Drug: AMG 145
Subject will receive AMG 145 every 2 weeks or monthly
Drug: Statin therapy
Subject will receive statin therapy daily
Active Comparator: Arm 20
Dose 20 of statin therapy orally/daily and AMG 145 subcutaneously monthly
 Drug: AMG 145
Subject will receive AMG 145 every 2 weeks or monthly
Drug: Statin therapy
Subject will receive statin therapy daily
Placebo Comparator: Arm 21
Dose 21 of statin therapy orally/daily and placebo subcutaneously every 2 weeks
 Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Drug: Statin therapy
Subject will receive statin therapy daily
Placebo Comparator: Arm 22
Dose 22 of statin therapy orally/daily and placebo subcutaneously monthly
 Other: Placebo (administered subcutaneously)
Subject will receive Placebo every 2 weeks or monthly. All subjects at screening will participate in the placebo run-in.
Drug: Statin therapy
Subject will receive statin therapy daily
Active Comparator: Arm 23
Dose 23 of statin therapy orally/daily and AMG 145 subcutaneously every 2 weeks
 Drug: AMG 145
Subject will receive AMG 145 every 2 weeks or monthly
Drug: Statin therapy
Subject will receive statin therapy daily
Active Comparator: Arm 24
Dose 24 of statin therapy orally/daily and AMG 145 subcutaneously monthly
 Drug: AMG 145
Subject will receive AMG 145 every 2 weeks or monthly
Drug: Statin therapy
Subject will receive statin therapy daily

  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
  • Subjects not taking a statin with fasting LDL-C of at least 150 mg/dL(4.0 mmol/L)
  • Subjects already on a non-intensive statin with fasting LDL-C at screening of ≥ 100 mg/dL (2.6 mmol/L)
  • Subjects already on a intensive statin with fasting LDL-C at screening of ≥ 80 mg/dL (2.1 mmol/L)
  • Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

Exclusion Criteria:

  • Statin intolerance
  • NYHA III or IV heart failure
  • Uncontrolled hypertension
  • Uncontrolled cardiac arrhythmia
  • Type 1 diabetes, poorly controlled type 2 diabetes
  • Uncontrolled hypothyroidism or hyperthyroidism
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01763866

Contacts
Contact: Amgen Call Center 866-572-6436

  Show 239 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

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01763866     History of Changes
Other Study ID Numbers: 20110115
Study First Received: January 7, 2013
Last Updated: June 10, 2013
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Hong Kong: Department of Health
South Korea: Korea Food and Drug Administration (KFDA)
Czech Republic: State Institute for Drug Control
Russia: Ministry of Health of the Russian Federation
Australia: Department of Health and Ageing Therapeutic Goods Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Health and Medicines Authority
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
South Africa: Medicines Control Council
Sweden: Medical Products Agency
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
United States: Food and Drug Administration
Turkey: Ministry of Health
Brazil: ANVISA (Agencia Nacional de Vigilancia Sanitaria)
Taiwan: Taiwan Food and Drug Administration
Hungary: National Institute of Pharmacy
Italy: Ethics Committee
Mexico: Federal Commission for Protection Against Health Risks

Keywords provided by Amgen:
High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Ezetimibe
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 June 17, 2013