Study of Low-Density Lipoprotein Cholesterol (LDL-C) Reduction Using Evolocumab (AMG 145) in Japanese Patients With Advanced Cardiovascular Risk (AMG145)
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| ClinicalTrials.gov Identifier: NCT01953328 |
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Recruitment Status :
Completed
First Posted : September 30, 2013
Results First Posted : December 23, 2015
Last Update Posted : December 23, 2015
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Sponsor:
Amgen
Information provided by (Responsible Party):
Amgen
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hyperlipidemia or Mixed Dyslipidemia at High Risk for Cardiovascular Events | Drug: Atorvastatin Biological: Evolocumab Other: Placebo to Evolocumab | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 409 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Study Start Date : | October 2013 |
| Actual Primary Completion Date : | June 2014 |
| Actual Study Completion Date : | June 2014 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Atorvastatin
Administered orally once a day
Other Name: Lipitor Other: Placebo to Evolocumab Administered by subcutaneous injection |
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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.
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Drug: Atorvastatin
Administered orally once a day
Other Name: Lipitor Other: Placebo to Evolocumab Administered by subcutaneous injection |
|
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.
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Drug: Atorvastatin
Administered orally once a day
Other Name: Lipitor Biological: Evolocumab Administered by subcutaneous injection
Other Names:
|
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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.
|
Drug: Atorvastatin
Administered orally once a day
Other Name: Lipitor Biological: Evolocumab Administered by subcutaneous injection
Other Names:
|
|
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.
|
Drug: Atorvastatin
Administered orally once a day
Other Name: Lipitor Other: Placebo to Evolocumab Administered by subcutaneous injection |
|
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.
|
Drug: Atorvastatin
Administered orally once a day
Other Name: Lipitor Other: Placebo to Evolocumab Administered by subcutaneous injection |
|
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.
|
Drug: Atorvastatin
Administered orally once a day
Other Name: Lipitor Biological: Evolocumab Administered by subcutaneous injection
Other Names:
|
|
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.
|
Drug: Atorvastatin
Administered orally once a day
Other Name: Lipitor Biological: Evolocumab Administered by subcutaneous injection
Other Names:
|
Primary Outcome Measures :
- 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 ]
- Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ]
Secondary Outcome Measures :
- Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
- Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
- Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
- Percent Change From Baseline in Non-HDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
- Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
- Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ]
- Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
- Percent Change From Baseline in Total Cholesterol at Week 12 [ Time Frame: Baseline and Week 12 ]
- 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 ]
- Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]
- 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 ]
- Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]
- 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 ]
- Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 [ Time Frame: Week 12 ]
- Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
- Percent Change From Baseline in Lipoprotein(a) at Week 12 [ Time Frame: Baseline and Week 12 ]
- Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
- Percent Change From Baseline in Triglycerides at Week 12 [ Time Frame: Baseline and Week 12 ]
- Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
- Percent Change From Baseline in HDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
- Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 [ Time Frame: Baseline and Weeks 10 and 12 ]
- Percent Change From Baseline in VLDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 20 Years to 85 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01953328
Locations
Show 54 study locations
Sponsors and Collaborators
Amgen
Investigators
| Study Director: | MD | Amgen |
Additional Information:
| Responsible Party: | Amgen |
| ClinicalTrials.gov Identifier: | NCT01953328 |
| Other Study ID Numbers: |
20120122 |
| First Posted: | September 30, 2013 Key Record Dates |
| Results First Posted: | December 23, 2015 |
| Last Update Posted: | December 23, 2015 |
| Last Verified: | November 2015 |
Keywords provided by Amgen:
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Japanese, high cholesterol, LDL-C, High Cardiovascular Risk |
Additional relevant MeSH terms:
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Dyslipidemias Hyperlipidemias Hyperlipoproteinemias Lipid Metabolism Disorders Metabolic Diseases Atorvastatin Evolocumab Antibodies, Monoclonal Anticholesteremic Agents |
Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors Immunologic Factors Physiological Effects of Drugs |