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

November 19, 2015 updated by: Amgen

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Actual)

409

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Akita
      • Akita-shi, Akita, Japan, 010-1423
        • Research Site
    • Chiba
      • Noda-shi, Chiba, Japan, 278-0004
        • Research Site
    • Fukuoka
      • Fukuoka-shi, Fukuoka, Japan, 810-0014
        • Research Site
      • Fukuoka-shi, Fukuoka, Japan, 810-0066
        • Research Site
      • Fukuoka-shi, Fukuoka, Japan, 819-8551
        • Research Site
      • Kitakyusyu-shi, Fukuoka, Japan, 807-0856
        • Research Site
    • Fukushima
      • Koriyama-shi, Fukushima, Japan, 963-0209
        • Research Site
      • Koriyama-shi, Fukushima, Japan, 963-8026
        • Research Site
      • Koriyama-shi, Fukushima, Japan, 963-8041
        • Research Site
      • Koriyama-shi, Fukushima, Japan, 963-8832
        • Research Site
      • Koriyama-shi, Fukushima, Japan, 963-8862
        • Research Site
    • Gunma
      • Maebashi-shi, Gunma, Japan, 371-0022
        • Research Site
      • Takasaki-shi, Gunma, Japan, 370-3524
        • Research Site
    • Hokkaido
      • Sapporo-shi, Hokkaido, Japan, 060-0063
        • Research Site
      • Sapporo-shi, Hokkaido, Japan, 003-0026
        • Research Site
      • Sapporo-shi, Hokkaido, Japan, 003-0825
        • Research Site
    • Ibaraki
      • Tsuchiura-shi, Ibaraki, Japan, 300-0047
        • Research Site
    • Iwate
      • Hanamaki-shi, Iwate, Japan, 025-0075
        • Research Site
      • Morioka-shi, Iwate, Japan, 020-0066
        • Research Site
    • Kagawa
      • Takamatsu-shi, Kagawa, Japan, 760-0018
        • Research Site
      • Takamatsu-shi, Kagawa, Japan, 760-0076
        • Research Site
    • Kanagawa
      • Yokohama-shi, Kanagawa, Japan, 231-0023
        • Research Site
    • Kyoto
      • Kyoto-shi, Kyoto, Japan, 615-8125
        • Research Site
    • Miyagi
      • Sendai-shi, Miyagi, Japan, 983-0039
        • Research Site
      • Sendai-shi, Miyagi, Japan, 983-0835
        • Research Site
      • Sendai-shi, Miyagi, Japan, 989-3122
        • Research Site
    • Okinawa
      • Tomigusuku-shi, Okinawa, Japan, 901-0243
        • Research Site
      • Urasoe-shi, Okinawa, Japan, 901-2132
        • Research Site
    • Osaka
      • Ibaraki-shi, Osaka, Japan, 567-0876
        • Research Site
      • Osaka-shi, Osaka, Japan, 530-0001
        • Research Site
      • Toyonaka-shi, Osaka, Japan, 560-0082
        • Research Site
    • Saitama
      • Koshigaya-shi, Saitama, Japan, 343-0826
        • Research Site
      • Kumagaya-shi, Saitama, Japan, 360-0816
        • Research Site
      • Niiza-shi, Saitama, Japan, 352-0014
        • Research Site
    • Tokyo
      • Arakawa-ku, Tokyo, Japan, 116-0002
        • Research Site
      • Chiyoda-ku, Tokyo, Japan, 101-0024
        • Research Site
      • Chiyoda-ku, Tokyo, Japan, 101-0041
        • Research Site
      • Chofu-shi, Tokyo, Japan, 182-0006
        • Research Site
      • Chuo-ku, Tokyo, Japan, 103-0027
        • Research Site
      • Edogawa-ku, Tokyo, Japan, 133-0061
        • Research Site
      • Hachioji-shi, Tokyo, Japan, 192-0046
        • Research Site
      • Itabashi-ku, Tokyo, Japan, 173-8610
        • Research Site
      • Katsushika-ku, Tokyo, Japan, 124-0024
        • Research Site
      • Koto-ku, Tokyo, Japan, 135-0011
        • Research Site
      • Minato-ku, Tokyo, Japan, 108-0075
        • Research Site
      • Minato-ku, Tokyo, Japan, 105-7390
        • Research Site
      • Ota-ku, Tokyo, Japan, 144-0034
        • Research Site
      • Setagaya-ku, Tokyo, Japan, 155-0031
        • Research Site
      • Shibuya-ku, Tokyo, Japan, 150-0012
        • Research Site
      • Shinagawa-ku, Tokyo, Japan, 140-0011
        • Research Site
      • Shinagawa-ku, Tokyo, Japan, 141-0001
        • Research Site
      • Shinagawa-ku, Tokyo, Japan, 141-6003
        • Research Site
      • Shinagawa-ku, Tokyo, Japan, 142-0053
        • Research Site
      • Toshima-ku, Tokyo, Japan, 171-0021
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Atorvastatin
Administered orally once a day
Other Names:
  • Lipitor
Other: Placebo to Evolocumab
Administered by subcutaneous injection
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.
Drug: Atorvastatin
Administered orally once a day
Other Names:
  • 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.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • Repatha
  • AMG 145
Drug: Atorvastatin
Administered orally once a day
Other Names:
  • Lipitor
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.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • Repatha
  • AMG 145
Drug: Atorvastatin
Administered orally once a day
Other Names:
  • Lipitor
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 Names:
  • Lipitor
Other: Placebo to Evolocumab
Administered by subcutaneous injection
Other: 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 Names:
  • 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.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • Repatha
  • AMG 145
Drug: Atorvastatin
Administered orally once a day
Other Names:
  • Lipitor
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.
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • Repatha
  • AMG 145
Drug: Atorvastatin
Administered orally once a day
Other Names:
  • Lipitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time Frame: Baseline and Week 12
Baseline and Week 12
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
Baseline and Weeks 10 and 12

Secondary Outcome Measures

Outcome Measure
Time Frame
Percent Change From Baseline in Total Cholesterol at Week 12
Time Frame: Baseline and Week 12
Baseline and Week 12
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time Frame: Baseline and Weeks 10 and 12
Baseline and Weeks 10 and 12
Change From Baseline in LDL-C at Week 12
Time Frame: Baseline and Week 12
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
Weeks 10 and 12
Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12
Time Frame: Week 12
Week 12
Percent Change From Baseline in Non-HDL-C at Week 12
Time Frame: Baseline and Week 12
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
Baseline and Weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B at Week 12
Time Frame: Baseline and Week 12
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
Baseline and Weeks 10 and 12
Percent Change From Baseline in Triglycerides at Week 12
Time Frame: Baseline and Week 12
Baseline and Week 12
Percent Change From Baseline in VLDL-C at Week 12
Time Frame: Baseline and Week 12
Baseline and Week 12
Percent Change From Baseline in HDL-C at Week 12
Time Frame: Baseline and Week 12
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
Baseline and Weeks 10 and 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
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
Baseline and 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
Baseline and Weeks 10 and 12
Percent Change From Baseline in Lipoprotein(a) at Week 12
Time Frame: Baseline and Week 12
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
Baseline and Weeks 10 and 12
Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12
Time Frame: Baseline and Weeks 10 and 12
Baseline and Weeks 10 and 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
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
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
Baseline and Weeks 10 and 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2013

Primary Completion (Actual)

June 1, 2014

Study Completion (Actual)

June 1, 2014

Study Registration Dates

First Submitted

September 26, 2013

First Submitted That Met QC Criteria

September 26, 2013

First Posted (Estimate)

September 30, 2013

Study Record Updates

Last Update Posted (Estimate)

December 23, 2015

Last Update Submitted That Met QC Criteria

November 19, 2015

Last Verified

November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20120122

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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