Study of Low-Density Lipoprotein Cholesterol (LDL-C) Reduction Using Evolocumab (AMG 145) in Japanese Patients With Advanced Cardiovascular Risk (AMG145)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01953328
First received: September 26, 2013
Last updated: November 19, 2015
Last verified: November 2015

September 26, 2013
November 19, 2015
October 2013
June 2014   (final data collection date for primary outcome measure)
  • Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Mean percent change from baseline in Low Density Lipoprotein Cholesterol (LDL-C) [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in Low Density Lipoprotein Cholesterol (LDL-C)
  • Percent change from baseline in Low Density Lipoprotein Cholesterol (LDL-C) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in Low Density Lipoprotein Cholesterol (LDL-C)
Complete list of historical versions of study NCT01953328 on ClinicalTrials.gov Archive Site
  • Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Non-HDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Cholesterol at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL [ Time Frame: Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Lipoprotein(a) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Triglycerides at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in HDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in VLDL-C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • 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 total cholesterol [ Time Frame: 10 and 12 Weeks ] [ Designated as safety issue: No ]
    Mean percent change from baseline in total cholesterol
  • Percent change from baseline in total cholesterol [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Percent change from baseline in total cholesterol
  • 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
Not Provided
Not Provided
 
Study of Low-Density Lipoprotein Cholesterol (LDL-C) Reduction Using Evolocumab (AMG 145) in Japanese Patients With Advanced Cardiovascular Risk
A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of Evolocumab (AMG 145) on LDL-C in Combination With Statin Therapy in Japanese Subjects With High Cardiovascular Risk and With Hyperlipidemia or Mixed Dyslipidemia
The primary objective of the study was to evaluate the effect of 12 weeks of subcutaneous evolocumab administered every 2 weeks and once a month, compared with placebo, on percent change from baseline in LDL-C when used in combination with statin therapy in adults with high cardiovascular risk and with hyperlipidemia or mixed dyslipidemia.

After a screening and placebo run-in period, eligible patients were randomized in a 1:1 ratio to 1 of 2 open-label background statin treatments (atorvastatin 5 mg or 20 mg daily [QD]) and entered a 4-week lipid stabilization period. After the lipid stabilization period, eligible patients were randomized in a 1:1:1:1 ratio to investigational product (evolocumab or placebo) for the 12-week treatment period.

Both randomizations were stratified by subject diagnosis and lipid-lowering therapy as follows:

  • current or prior diagnosis of heterozygous familial hypercholesterolemia (HeFH)
  • no diagnosis of HeFH and receiving intensive lipid-lowering therapy
  • no diagnosis of HeFH and receiving non-intensive lipid-lowering therapy. A participant was considered randomized into the study after successfully completing the screening period, meeting all inclusion/exclusion criteria including meeting final laboratory safety criteria, and undergoing both randomization procedures.
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Hyperlipidemia or Mixed Dyslipidemia at High Risk for Cardiovascular Events
  • Drug: Atorvastatin
    Administered orally once a day
    Other Name: Lipitor
  • Biological: Evolocumab
    Administered by subcutaneous injection
    Other Names:
    • AMG 145
    • Repatha
  • Other: Placebo to Evolocumab
    Administered by subcutaneous injection
  • Placebo Comparator: A5 Placebo Q2W
    Participants received atorvastatin 5 mg (A5) once daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
    Interventions:
    • Drug: Atorvastatin
    • Other: Placebo to Evolocumab
  • Placebo Comparator: A5 Placebo QM
    Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month (QM) for 12 weeks.
    Interventions:
    • Drug: Atorvastatin
    • Other: Placebo to Evolocumab
  • Experimental: A5 Evolocumab Q2W
    Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
    Interventions:
    • Drug: Atorvastatin
    • Biological: Evolocumab
  • Experimental: A5 Evolocumab QM
    Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks.
    Interventions:
    • Drug: Atorvastatin
    • Biological: Evolocumab
  • Placebo Comparator: A20 Placebo Q2W
    Participants received atorvastatin 20 mg (A20) once daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for 12 weeks.
    Interventions:
    • Drug: Atorvastatin
    • Other: Placebo to Evolocumab
  • A20 Placebo QM
    Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for 12 weeks.
    Interventions:
    • Drug: Atorvastatin
    • Other: Placebo to Evolocumab
  • Experimental: A20 Evolocumab Q2W
    Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
    Interventions:
    • Drug: Atorvastatin
    • Biological: Evolocumab
  • Experimental: A20 Evolocumab QM
    Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks.
    Interventions:
    • Drug: Atorvastatin
    • Biological: Evolocumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
409
June 2014
June 2014   (final data collection date for primary outcome measure)
Inclusion Criteria: Male or female, Japanese adult, 20-85 years of age; Subjects on stable dose of statin for greater than equal to 4 weeks; Fasting LDL-C greater than equal to 100 mg/dL; Fasting triglycerides less than equal to 400 mg/dL; Subject is at high risk for cardiovascular events. Exclusion Criteria: New York heart Association (NYHA) III or IV - heart failure; Uncontrolled cardiac arrhythmia; Uncontrolled hypertension; Type 1 diabetes, poorly controlled type 2 diabetes; Uncontrolled hypothyroidism or hyperthyroidism
Both
20 Years to 85 Years
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT01953328
20120122
Yes
Not Provided
Not Provided
Amgen
Amgen
Not Provided
Study Director: MD Amgen
Amgen
November 2015

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