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
  Purpose
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 Intervention Phase
Hyperlipidemia or Mixed Dyslipidemia at High Risk for Cardiovascular Events
Drug: Atorvastatin
Biological: Evolocumab
Other: Placebo to Evolocumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Amgen:

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 ] [ 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 ]

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 ] [ 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 ]

Enrollment: 409
Study Start Date: October 2013
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 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.
Drug: Atorvastatin
Administered orally once a day
Other Name: Lipitor
Biological: Evolocumab
Administered by subcutaneous injection
Other Names:
  • AMG 145
  • Repatha
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:
  • AMG 145
  • Repatha
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:
  • AMG 145
  • Repatha
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:
  • AMG 145
  • Repatha

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.
  Eligibility

Ages Eligible for Study:   20 Years to 85 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01953328

  Hide Study Locations
Locations
Japan
Research Site
Akita-shi, Akita, Japan, 010-1423
Research Site
Noda-shi, Chiba, Japan, 278-0004
Research Site
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
Koriyama-shi, Fukushima, Japan, 963-8862
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, 963-0209
Research Site
Maebashi-shi, Gunma, Japan, 371-0022
Research Site
Takasaki-shi, Gunma, Japan, 370-3524
Research Site
Sapporo-shi, Hokkaido, Japan, 003-0026
Research Site
Sapporo-shi, Hokkaido, Japan, 003-0825
Research Site
Sapporo-shi, Hokkaido, Japan, 060-0063
Research Site
Tsuchiura-shi, Ibaraki, Japan, 300-0047
Research Site
Hanamaki-shi, Iwate, Japan, 025-0075
Research Site
Morioka-shi, Iwate, Japan, 020-0066
Research Site
Takamatsu-shi, Kagawa, Japan, 760-0018
Research Site
Takamatsu-shi, Kagawa, Japan, 760-0076
Research Site
Yokohama-shi, Kanagawa, Japan, 231-0023
Research Site
Kyoto-shi, Kyoto, Japan, 615-8125
Research Site
Sendai-shi, Miyagi, Japan, 983-0039
Research Site
Sendai-shi, Miyagi, Japan, 983-0835
Research Site
Sendai-shi, Miyagi, Japan, 989-3122
Research Site
Tomigusuku-shi, Okinawa, Japan, 901-0243
Research Site
Urasoe-shi, Okinawa, Japan, 901-2132
Research Site
Ibaraki-shi, Osaka, Japan, 567-0876
Research Site
Osaka-shi, Osaka, Japan, 530-0001
Research Site
Toyonaka-shi, Osaka, Japan, 560-0082
Research Site
Koshigaya-shi, Saitama, Japan, 343-0826
Research Site
Kumagaya-shi, Saitama, Japan, 360-0816
Research Site
Niiza-shi, Saitama, Japan, 352-0014
Research Site
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, 105-7390
Research Site
Minato-ku, Tokyo, Japan, 108-0075
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
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01953328     History of Changes
Other Study ID Numbers: 20120122 
Study First Received: September 26, 2013
Results First Received: September 23, 2015
Last Updated: November 19, 2015
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Amgen:
Japanese, high cholesterol, LDL-C, High Cardiovascular Risk

Additional relevant MeSH terms:
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on February 08, 2016