A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Tolerability and Efficacy of Evolocumab (AMG 145) in Japanese Subjects (AMG145)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01652703
First received: July 26, 2012
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

Study conducted in Japanese subjects with hypercholesterolemia and high cardiovascular risk. Subjects will receive study drug either every 2 or every 4 weeks for a total of 12 weeks. Subjects will continue on their stable dose of statin +/- ezetimibe.


Condition Intervention Phase
Hypercholesterolemia and High Risk for Cardiovascular Events
Drug: Statin
Drug: Ezetimibe
Biological: Evolocumab (AMG 145)
Other: Placebo
Phase 2

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 Tolerability and Efficacy of Evolocumab (AMG 145) on LDL-C in Combination With Stable Statin Therapy in Japanese Subjects With Hypercholesterolemia and High Cardiovascular Risk

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 week 12 [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in LDL-C at week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • LDL-C response (<70 mg/dL [1.8 mmol/L]) at week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Percent change from baseline to week 12 in the following lipid parameter - non High Density Lipoprotein Cholesterol (non-HDL-C) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Percent change from baseline to week 12 in the following lipid parameter - Apolipoprotein B [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Percent change from baseline to week 12 in the following lipid parameter - Very Low Density Lipoprotein Cholesterol (VLDL-C) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Percent change from baseline to week 12 in the following lipid parameter - total cholesterol/HDL-C ratio [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Percent change from baseline to week 12 in the following lipid parameter - Apolipoprotein B/Apolipoprotein A1 ratio [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Enrollment: 310
Study Start Date: July 2012
Study Completion Date: July 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Dose 1 - Evolocumab (AMG 145), every 2 weeks subcutaneous
Drug: Statin
Statin tablets including atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and other statins used in Japan with or without ezetimibe tablets at dose(s) prescribed by the Investigator and must be sustained greater than or equal to 4 weeks before screening labs and throughout the duration of the study for all arms of the study.
Other Name: Lipid Lowering Medication
Drug: Ezetimibe
Ezetimibe tablets may or may not be taken with statin tablets used in Japan. Doses(s) for ezetimibe and statin tablets are prescribed by the Investigator; regimen must be sustained greater than or equal to 4 weeks before screening labs and throughout the duration of the study for all arms of the study.
Other Name: Cholesterol lowering drug
Biological: Evolocumab (AMG 145)
Dose 1 - Patients will receive evolocumab (AMG 145) every 2 weeks, subcutaneously.
Placebo Comparator: Group 2
Dose 2 - Placebo, every 2 weeks subcutaneous
Drug: Statin
Statin tablets including atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and other statins used in Japan with or without ezetimibe tablets at dose(s) prescribed by the Investigator and must be sustained greater than or equal to 4 weeks before screening labs and throughout the duration of the study for all arms of the study.
Other Name: Lipid Lowering Medication
Drug: Ezetimibe
Ezetimibe tablets may or may not be taken with statin tablets used in Japan. Doses(s) for ezetimibe and statin tablets are prescribed by the Investigator; regimen must be sustained greater than or equal to 4 weeks before screening labs and throughout the duration of the study for all arms of the study.
Other Name: Cholesterol lowering drug
Other: Placebo
Dose 2 - Patients will receive placebo every 2 weeks, subcutaneously. All patients at screening will participate in the placebo run-in.
Experimental: Group 3
Dose 3 - evolocumab (AMG 145), every 2 weeks subcutaneous
Drug: Statin
Statin tablets including atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and other statins used in Japan with or without ezetimibe tablets at dose(s) prescribed by the Investigator and must be sustained greater than or equal to 4 weeks before screening labs and throughout the duration of the study for all arms of the study.
Other Name: Lipid Lowering Medication
Drug: Ezetimibe
Ezetimibe tablets may or may not be taken with statin tablets used in Japan. Doses(s) for ezetimibe and statin tablets are prescribed by the Investigator; regimen must be sustained greater than or equal to 4 weeks before screening labs and throughout the duration of the study for all arms of the study.
Other Name: Cholesterol lowering drug
Biological: Evolocumab (AMG 145)
Dose 3 - Patients will receive evolocumab (AMG 145) every 2 weeks, subcutaneously.
Experimental: Group 4
Dose 4 - evolocumab (AMG 145), every 4 weeks subcutaneous
Drug: Statin
Statin tablets including atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and other statins used in Japan with or without ezetimibe tablets at dose(s) prescribed by the Investigator and must be sustained greater than or equal to 4 weeks before screening labs and throughout the duration of the study for all arms of the study.
Other Name: Lipid Lowering Medication
Drug: Ezetimibe
Ezetimibe tablets may or may not be taken with statin tablets used in Japan. Doses(s) for ezetimibe and statin tablets are prescribed by the Investigator; regimen must be sustained greater than or equal to 4 weeks before screening labs and throughout the duration of the study for all arms of the study.
Other Name: Cholesterol lowering drug
Biological: Evolocumab (AMG 145)
Dose 4 - Patients will receive evolocumab (AMG 145) every 4 weeks, subcutaneously.
Experimental: Group 5
Dose 5 - evolocumab (AMG 145), every 4 weeks subcutaneous
Drug: Statin
Statin tablets including atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and other statins used in Japan with or without ezetimibe tablets at dose(s) prescribed by the Investigator and must be sustained greater than or equal to 4 weeks before screening labs and throughout the duration of the study for all arms of the study.
Other Name: Lipid Lowering Medication
Drug: Ezetimibe
Ezetimibe tablets may or may not be taken with statin tablets used in Japan. Doses(s) for ezetimibe and statin tablets are prescribed by the Investigator; regimen must be sustained greater than or equal to 4 weeks before screening labs and throughout the duration of the study for all arms of the study.
Other Name: Cholesterol lowering drug
Biological: Evolocumab (AMG 145)
Dose 5 - Patients will receive evolocumab (AMG 145) every 4 weeks, subcutaneously.
Placebo Comparator: Group 6
Dose 6 - Placebo, every 4 weeks subcutaneous
Drug: Statin
Statin tablets including atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and other statins used in Japan with or without ezetimibe tablets at dose(s) prescribed by the Investigator and must be sustained greater than or equal to 4 weeks before screening labs and throughout the duration of the study for all arms of the study.
Other Name: Lipid Lowering Medication
Drug: Ezetimibe
Ezetimibe tablets may or may not be taken with statin tablets used in Japan. Doses(s) for ezetimibe and statin tablets are prescribed by the Investigator; regimen must be sustained greater than or equal to 4 weeks before screening labs and throughout the duration of the study for all arms of the study.
Other Name: Cholesterol lowering drug
Other: Placebo
Dose 6 - Patients will receive placebo every 4 weeks, subcutaneously. All patients at screening will participate in the placebo run-in.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Japanese adult, on statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks, fasting LDL-C greater than or equal to 115 mg/dL (3.0 mmol/L), fasting triglycerides less than or equal to 400 mg/dL (4.5 mmol/L); Exclusion Criteria: New York Heart Association (NYHA) class III or IV, poorly controlled hypertension, recently diagnosed or poorly controlled type 2 diabetes, last known left ventricular ejection fraction < 30%, myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), stroke, planned cardiac surgery or revascularization within 6 months of randomization, uncontrolled cardiac arrhythmia

  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: NCT01652703

Locations
Japan
Research Site
Nagoya-shi, Aichi, Japan, 455-8530
Research Site
Nagoya-shi, Aichi, Japan, 462-0825
Research Site
Nagoya-shi, Aichi, Japan, 454-0933
Research Site
Fukui-shi, Fukui, Japan, 910-0067
Research Site
Fukui-shi, Fukui, Japan, 910-0803
Research Site
Fukui-shi, Fukui, Japan, 910-0837
Research Site
Kasuga-shi, Fukuoka, Japan, 816-0864
Research Site
Gifu-shi, Gifu, Japan, 500-8384
Research Site
Fujioka-shi, Gunma, Japan, 375-0015
Research Site
Maebashi-shi, Gunma, Japan, 371-0022
Research Site
Maebashi-shi, Gunma, Japan, 371-0046
Research Site
Takasaki-shi, Gunma, Japan, 370-0829
Research Site
Kawani-shi, Hyogo, Japan, 666-0125
Research Site
Kobe-shi, Hyogo, Japan, 657-0068
Research Site
Hitachi-shi, Ibaraki, Japan, 317-0077
Research Site
Koga-shi, Ibaraki, Japan, 306-0041
Research Site
Mito-shi, Ibaraki, Japan, 311-4198
Research Site
Komatsu-shi, Ishikawa, Japan, 923-8560
Research Site
Takamatsu-shi, Kagawa, Japan, 760-8557
Research Site
Kochi-shi, Kochi, Japan, 781-8555
Research Site
Kumamoto-shi, Kumamoto, Japan, 860-8556
Research Site
Kyoto-shi, Kyoto, Japan, 615-8125
Research Site
Kyoto-shi, Kyoto, Japan, 613-0911
Research Site
Ina-shi, Nagano, Japan, 396-8555
Research Site
Matsumoto-shi, Nagano, Japan, 390-0848
Research Site
Suwa-shi, Nagano, Japan, 392-8510
Research Site
Ibaraki-shi, Osaka, Japan, 567-0876
Research Site
Suita-shi, Osaka, Japan, 565-0871
Research Site
Toyonaka-shi, Osaka, Japan, 560-0082
Research Site
Hanyu-shi, Saitama, Japan, 348-8505
Research Site
Sayama-shi, Saitama, Japan, 350-1305
Research Site
Toda-shi, Saitama, Japan, 335-0023
Research Site
Otsu-shi, Shiga, Japan, 520-0113
Research Site
Bunkyo-ku, Tokyo, Japan, 113-8421
Research Site
Bunkyo-ku, Tokyo, Japan, 113-8519
Research Site
Chiyoda-ku, Tokyo, Japan, 101-0041
Research Site
Chuo-ku, Tokyo, Japan, 103-0027
Research Site
Hachioji-shi, Tokyo, Japan, 192-0918
Research Site
Itabashi-ku, Tokyo, Japan, 173-8610
Research Site
Shinagawa-ku, Tokyo, Japan, 141-0001
Research Site
Taito-ku, Tokyo, Japan, 111-0052
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: NCT01652703     History of Changes
Other Study ID Numbers: 20110231
Study First Received: July 26, 2012
Last Updated: July 21, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency
United States: Food and Drug Administration

Keywords provided by Amgen:
Japanese, hypercholesterolemia, high risk for cardiovascular events

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

ClinicalTrials.gov processed this record on September 29, 2014