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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01763866
First received: January 7, 2013
Last updated: July 8, 2014
Last verified: July 2014

January 7, 2013
July 8, 2014
January 2013
December 2013   (final data collection date for primary outcome measure)
  • 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
Same as current
Complete list of historical versions of study NCT01763866 on ClinicalTrials.gov Archive Site
  • 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
  • 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 (LDL-C) response (LDL-C < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean Low Density Lipoprotein-Cholesterol (LDL-C) response (LDL-C < 70 mg/dL [1.8 mmol/L])
  • Low Density Lipoprotein-Cholesterol (LDL-C) response (LDL-C < 70 mg/dL [1.8 mmol/L]) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Low Density Lipoprotein-Cholesterol (LDL-C) response (LDL-C < 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
Not Provided
Not Provided
 
LDL-C Assessment w/ PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-2
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

The primary hypothesis is that both dosing regimens of evolocumab (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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hyperlipidemia
  • Biological: evolocumab (AMG 145)
    Subject will receive evolocumab (AMG 145) every 2 weeks or 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.
  • Other: Placebo (administered orally)
    Subject will receive Placebo daily
  • Drug: Atorvastatin
    Subject will receive statin therapy daily
  • Drug: Rosuvastatin
    Subject will receive statin therapy daily
  • Drug: Simvastatin
    Subject will receive statin therapy daily
  • Placebo Comparator: Arm 1
    Dose 1 of statin therapy and placebo orally/daily and placebo subcutaneously every 2 weeks
    Interventions:
    • Other: Placebo (administered subcutaneously)
    • Other: Placebo (administered orally)
    • Drug: Atorvastatin
  • Placebo Comparator: Arm 2
    Dose 2 of statin therapy and placebo orally/daily and placebo subcutaneously monthly
    Interventions:
    • Other: Placebo (administered subcutaneously)
    • Other: Placebo (administered orally)
    • Drug: Atorvastatin
  • Arm 3
    Dose 3 of statin therapy and Ezetimibe orally/daily and placebo subcutaneously every 2 weeks
    Interventions:
    • Other: Ezetimibe
    • Other: Placebo (administered subcutaneously)
    • Drug: Atorvastatin
  • Arm 4
    Dose 4 of statin therapy and Ezetimibe orally/daily and placebo subcutaneously monthly
    Interventions:
    • Other: Ezetimibe
    • Other: Placebo (administered subcutaneously)
    • Drug: Atorvastatin
  • Active Comparator: Arm 5
    Dose 5 of statin therapy and placebo orally/daily and evolocumab (AMG 145) subcutaneously every 2 weeks
    Interventions:
    • Biological: evolocumab (AMG 145)
    • Other: Placebo (administered orally)
    • Drug: Atorvastatin
  • Active Comparator: Arm 6
    Dose 6 of statin therapy and placebo orally/daily and evolocumab (AMG 145) subcutaneously monthly
    Interventions:
    • Biological: evolocumab (AMG 145)
    • Other: Placebo (administered orally)
    • Drug: Atorvastatin
  • Placebo Comparator: Arm 7
    Dose 7 of statin therapy and placebo orally/daily and placebo subcutaneously every 2 weeks
    Interventions:
    • Other: Placebo (administered subcutaneously)
    • Other: Placebo (administered orally)
    • Drug: Atorvastatin
  • Placebo Comparator: Arm 8
    Dose 8 of statin therapy and placebo orally/daily and placebo subcutaneously monthly
    Interventions:
    • Other: Placebo (administered subcutaneously)
    • Other: Placebo (administered orally)
    • Drug: Atorvastatin
  • Arm 9
    Dose 9 of statin therapy and Ezetimibe orally/daily and placebo subcutaneously every 2 weeks
    Interventions:
    • Other: Ezetimibe
    • Other: Placebo (administered subcutaneously)
    • Drug: Atorvastatin
  • Arm 10
    Dose 10 of statin therapy and Ezetimibe orally/daily and placebo subcutaneously monthly
    Interventions:
    • Other: Ezetimibe
    • Other: Placebo (administered subcutaneously)
    • Drug: Atorvastatin
  • Active Comparator: Arm 11
    Dose 11 of statin therapy and placebo orally/daily and evolocumab (AMG 145) subcutaneously every 2 weeks
    Interventions:
    • Biological: evolocumab (AMG 145)
    • Other: Placebo (administered orally)
    • Drug: Atorvastatin
  • Active Comparator: Arm 12
    Dose 12 of statin therapy and placebo orally/daily and evolocumab (AMG 145) subcutaneously monthly
    Interventions:
    • Biological: evolocumab (AMG 145)
    • Other: Placebo (administered orally)
    • Drug: Atorvastatin
  • Placebo Comparator: Arm 13
    Dose 13 of statin therapy orally/daily and placebo subcutaneously every 2 weeks
    Interventions:
    • Other: Placebo (administered subcutaneously)
    • Drug: Rosuvastatin
  • Placebo Comparator: Arm 14
    Dose 14 of statin therapy orally/daily and placebo subcutaneously monthly
    Interventions:
    • Other: Placebo (administered subcutaneously)
    • Drug: Rosuvastatin
  • Active Comparator: Arm 15
    Dose 15 of statin therapy orally/daily and evolocumab (AMG 145) subcutaneously every 2 weeks
    Interventions:
    • Biological: evolocumab (AMG 145)
    • Drug: Rosuvastatin
  • Active Comparator: Arm 16
    Dose 16 of statin therapy orally/daily and evolocumab (AMG 145) subcutaneously monthly
    Interventions:
    • Biological: evolocumab (AMG 145)
    • Drug: Rosuvastatin
  • Placebo Comparator: Arm 17
    Dose 17 of statin therapy orally/daily and placebo subcutaneously every 2 weeks.
    Interventions:
    • Other: Placebo (administered subcutaneously)
    • Drug: Rosuvastatin
  • Placebo Comparator: Arm 18
    Dose 18 of statin therapy orally/daily and placebo subcutaneously monthly
    Interventions:
    • Other: Placebo (administered subcutaneously)
    • Drug: Rosuvastatin
  • Active Comparator: Arm 19
    Dose 19 of statin therapy orally/daily and evolocumab (AMG 145) subcutaneously every 2 weeks
    Interventions:
    • Biological: evolocumab (AMG 145)
    • Drug: Rosuvastatin
  • Active Comparator: Arm 20
    Dose 20 of statin therapy orally/daily and evolocumab (AMG 145) subcutaneously monthly
    Interventions:
    • Biological: evolocumab (AMG 145)
    • Drug: Rosuvastatin
  • Placebo Comparator: Arm 21
    Dose 21 of statin therapy orally/daily and placebo subcutaneously every 2 weeks
    Interventions:
    • Other: Placebo (administered subcutaneously)
    • Drug: Simvastatin
  • Placebo Comparator: Arm 22
    Dose 22 of statin therapy orally/daily and placebo subcutaneously monthly
    Interventions:
    • Other: Placebo (administered subcutaneously)
    • Drug: Simvastatin
  • Active Comparator: Arm 23
    Dose 23 of statin therapy orally/daily and evolocumab (AMG 145) subcutaneously every 2 weeks
    Interventions:
    • Biological: evolocumab (AMG 145)
    • Drug: Simvastatin
  • Active Comparator: Arm 24
    Dose 24 of statin therapy orally/daily and evolocumab (AMG 145) subcutaneously monthly
    Interventions:
    • Biological: evolocumab (AMG 145)
    • Drug: Simvastatin
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1896
January 2014
December 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany,   United States,   Australia,   Belgium,   Canada,   Czech Republic,   Denmark,   France,   United Kingdom,   Hong Kong,   Hungary,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   Russian Federation,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan
 
NCT01763866
20110115
Yes
Amgen
Amgen
Not Provided
Study Director: MD Amgen
Amgen
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP