NCT01439880

Brief Summary

The primary clinical hypothesis is that long-term exposure of evolocumab (AMG 145) will be safe and well tolerated in adults with hypercholesterolemia.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
1,324

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Oct 2011

Longer than P75 for phase_2

Geographic Reach
18 countries

187 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 22, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 23, 2011

Completed
14 days until next milestone

Study Start

First participant enrolled

October 7, 2011

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 20, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 20, 2018

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

July 10, 2019

Completed
Last Updated

September 21, 2022

Status Verified

September 1, 2022

Enrollment Period

6.7 years

First QC Date

September 22, 2011

Results QC Date

June 17, 2019

Last Update Submit

September 8, 2022

Conditions

Keywords

High cholesterolRaised cholesterolCholesterolElevated Cholesterol

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Adverse Events

    Adverse event (AE) severity assessments were made using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grading, version 4.03, where grade 1 = mild AE, grade 2 = moderate AE, Grade 3 = severe AE, grade 4 = life-threatening AE and Grade 5 = death due to AE.

    52 weeks in the SOC-controlled period and up to 4 years in the All-IP period; actual median duration of treatment in the All-IP period was 46.9 months.

Secondary Outcomes (5)

  • Low-density Lipoprotein Cholesterol (LDL-C) Level at Week 24 and Week 52

    Baseline of parent study and extension study weeks 24 and 52

  • Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Level at Week 24 and Week 52

    Baseline of parent study and extension study weeks 24 and 52

  • Apolipoprotein B Level at Week 24 and Week 52

    Baseline of parent study and extension study weeks 24 and 52

  • Total Cholesterol/HDL-C Ratio at Week 24 and Week 52

    Baseline of parent study and extension study weeks 24 and 52

  • Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24 and Week 52

    Baseline of parent study and extension study weeks 24 and 52

Study Arms (2)

Standard of Care

ACTIVE COMPARATOR

Participants received standard of care (SOC) treatment for the first year of the study (SOC-controlled period). At week 52 participants began treatment with evolocumab 420 mg once a month (QM) for 4 years during the all-investigational product \[all-IP\] period.

Biological: EvolocumabOther: Standard of care

Evolocumab + SOC

EXPERIMENTAL

Participants received evolocumab 420 mg once a month plus standard of care for the first year of the study (SOC-controlled period). At week 52 participants continued treatment with evolocumab 420 mg QM for another 4 years during the all-IP period.

Biological: Evolocumab

Interventions

EvolocumabBIOLOGICAL

Administered by subcutaneous injection

Also known as: AMG 145, Repatha
Evolocumab + SOCStandard of Care

Standard of care therapy as per local practices. This could include prescribed therapies and/or dietary/exercise regimes

Standard of Care

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Complete a qualifying evolocumab (AMG 145) parent study protocol, including: 20101154 (NCT01375777), 20101155 (NCT01380730), 20090158 (NCT01375751), 20090159 (NCT01375764), and 20110231 (NCT01652703)

You may not qualify if:

  • Experienced a treatment-related serious adverse event that led to investigational product (IP) discontinuation in the parent study
  • Have an unstable medical condition, in the judgment of the investigator
  • Known sensitivity to any of the products to be administered during dosing
  • Currently enrolled in another investigational device or drug study (excluding evolocumab (AMG 145) parent study), or less than 30 days since ending another investigational device or drug study(s),or receiving other investigational agent(s)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (187)

Research Site

Birmingham, Alabama, 35216, United States

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Birmingham, Alabama, 35294, United States

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Tucson, Arizona, 85710, United States

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Little Rock, Arkansas, 72205, United States

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Malvern, Arkansas, 72104, United States

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Anaheim, California, 92801, United States

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Carmichael, California, 95608, United States

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Inglewood, California, 90301, United States

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Mission Viejo, California, 92691, United States

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Newport Beach, California, 92663, United States

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Thousand Oaks, California, 91360, United States

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Tustin, California, 92780, United States

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Colorado Springs, Colorado, 80909, United States

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Littleton, Colorado, 80120, United States

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Daytona Beach, Florida, 32117, United States

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DeLand, Florida, 32720, United States

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Green Cove Springs, Florida, 32043, United States

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Jacksonville, Florida, 32216, United States

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Jacksonville, Florida, 32223, United States

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Melbourne, Florida, 32901, United States

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Miami, Florida, 33144, United States

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Miami, Florida, 33173, United States

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Ponte Vedra, Florida, 32081, United States

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Port Charlotte, Florida, 33952, United States

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Sanford, Florida, 32771, United States

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Atlanta, Georgia, 30338, United States

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Savannah, Georgia, 31406, United States

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Chicago, Illinois, 60654, United States

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Indianapolis, Indiana, 46260, United States

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Munster, Indiana, 46321, United States

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Iowa City, Iowa, 52242, United States

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Louisville, Kentucky, 40213, United States

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Auburn, Maine, 04210, United States

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Portland, Maine, 04101, United States

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Bethesda, Maryland, 20817, United States

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Chevy Chase, Maryland, 20815, United States

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Brockton, Massachusetts, 02301, United States

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Marquette, Michigan, 49855, United States

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Brooklyn Center, Minnesota, 55430, United States

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Tupelo, Mississippi, 38801, United States

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Great Falls, Montana, 59405, United States

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Henderson, Nevada, 89052, United States

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Las Vegas, Nevada, 89117, United States

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Las Vegas, Nevada, 89148, United States

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Cortlandt Manor, New York, 10567, United States

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Endwell, New York, 13760, United States

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New York, New York, 10029, United States

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Williamsville, New York, 14221, United States

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Raleigh, North Carolina, 27609, United States

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Raleigh, North Carolina, 27612, United States

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Winston-Salem, North Carolina, 27103, United States

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Fargo, North Dakota, 58103, United States

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Akron, Ohio, 44311, United States

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Cadiz, Ohio, 43907, United States

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Cincinnati, Ohio, 45219, United States

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Cincinnati, Ohio, 45227, United States

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Cincinnati, Ohio, 45246, United States

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Cleveland, Ohio, 44122, United States

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Dayton, Ohio, 45414, United States

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Norman, Oklahoma, 73069, United States

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Oklahoma City, Oklahoma, 73103, United States

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Camp Hill, Pennsylvania, 17011, United States

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Duncansville, Pennsylvania, 16635, United States

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Pittsburgh, Pennsylvania, 15216, United States

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York, Pennsylvania, 17405, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Rapid City, South Dakota, 57701, United States

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Rapid City, South Dakota, 57702, United States

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Bristol, Tennessee, 37620, United States

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Arlington, Texas, 76018, United States

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Houston, Texas, 77002, United States

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Houston, Texas, 77074, United States

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San Antonio, Texas, 78229, United States

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Norfolk, Virginia, 23502, United States

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Richmond, Virginia, 23294, United States

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Renton, Washington, 98057, United States

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Seattle, Washington, 98122, United States

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Tacoma, Washington, 98405, United States

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Camperdown, New South Wales, 2015, Australia

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Maroubra, New South Wales, 2035, Australia

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Sydney, New South Wales, 2022, Australia

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Perth, Western Australia, 6000, Australia

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Anthée, 5520, Belgium

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Brussels, 1200, Belgium

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Gozée, 6534, Belgium

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Gribomont, 6887, Belgium

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Halen, 3545, Belgium

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Ham, 3945, Belgium

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Linkebeek, 1630, Belgium

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Uccle, 1180, Belgium

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Kelowna, British Columbia, V1Y 1V6, Canada

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Bay Roberts, Newfoundland and Labrador, A0A 1G0, Canada

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Mount Pearl, Newfoundland and Labrador, A1N 1W7, Canada

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St. John's, Newfoundland and Labrador, A1A 3R5, Canada

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Cambridge, Ontario, N1R 6V6, Canada

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Greater Sudbury, Ontario, P3C 5K7, Canada

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London, Ontario, N5W 6A2, Canada

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London, Ontario, N6A 5B7, Canada

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Newmarket, Ontario, L3Y 5G8, Canada

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Sarnia, Ontario, N7T 4X3, Canada

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Toronto, Ontario, M8V 3X8, Canada

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Toronto, Ontario, M9V 4B4, Canada

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Toronto, Ontario, M9W 4L6, Canada

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Woodstock, Ontario, N4S 5P5, Canada

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Chicoutimi, Quebec, G7H 5H6, Canada

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Gatineau, Quebec, J8Y 6S9, Canada

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Granby, Quebec, J2G 8Z9, Canada

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Lachine, Quebec, H8S 2E4, Canada

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Pointe-Claire, Quebec, H9R 3J1, Canada

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Québec, Quebec, G1V 4M6, Canada

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Brno, 601 77, Czechia

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Brno, 603 00, Czechia

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Brno, 625 00, Czechia

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Olomouc, 775 20, Czechia

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Prague, 120 00, Czechia

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Prague, 140 21, Czechia

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Slaný, 274 01, Czechia

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Svitavy, 568 25, Czechia

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Ústí nad Orlicí, 562 18, Czechia

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Znojmo, 669 02, Czechia

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Aalborg, 9000, Denmark

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Ballerup Municipality, 2750, Denmark

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Vejle, 7100, Denmark

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Helsinki, 00290, Finland

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OYS, 90029, Finland

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Berlin, 13353, Germany

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Cologne, 50937, Germany

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New Territories, Hong Kong

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Budapest, 1096, Hungary

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Debrecen, 4032, Hungary

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Dunaújváros, 2400, Hungary

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Gyula, 5700, Hungary

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Kecskemét, 6000, Hungary

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Komárom, 2921, Hungary

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Szolnok, 5004, Hungary

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Zalaegerszeg, 8900, Hungary

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Nagoya, Aichi-ken, 454-0933, Japan

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Nagoya, Aichi-ken, 455-8530, Japan

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Nagoya, Aichi-ken, 462-0825, Japan

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Fukui-shi, Fukui, 910-0837, Japan

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Kasuga-shi, Fukuoka, 816-0864, Japan

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Fujioka-shi, Gunma, 375-0015, Japan

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Maebashi, Gunma, 371-0022, Japan

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Maebashi, Gunma, 371-0046, Japan

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Takasaki-shi, Gunma, 370-0829, Japan

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Kawanishi-shi, Hyōgo, 666-0125, Japan

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Kobe, Hyōgo, 657-0068, Japan

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Hitachi-shi, Ibaraki, 317-0077, Japan

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Koga-shi, Ibaraki, 306-0041, Japan

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Mito, Ibaraki, 311-4198, Japan

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Komatsu-shi, Ishikawa-ken, 923-8560, Japan

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Takamatsu, Kagawa-ken, 760-8557, Japan

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Kochi, Kochi, 781-8555, Japan

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Kyoto, Kyoto, 613-0911, Japan

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Kyoto, Kyoto, 615-8125, Japan

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Ina-shi, Nagano, 396-8555, Japan

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Matsumoto-shi, Nagano, 390-0848, Japan

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Suwa-shi, Nagano, 392-8510, Japan

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Ibaraki-shi, Osaka, 567-0876, Japan

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Toyonaka-shi, Osaka, 560-0082, Japan

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Hanyu-shi, Saitama, 348-8505, Japan

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Sayama-shi, Saitama, 350-1305, Japan

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Toda-shi, Saitama, 335-0023, Japan

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Chiyoda-ku, Tokyo, 101-0041, Japan

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Hachioji-shi, Tokyo, 192-0918, Japan

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Itabashi-ku, Tokyo, 173-8610, Japan

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Shinagawa-ku, Tokyo, 141-0001, Japan

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Toshima-ku, Tokyo, 171-0021, Japan

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Amsterdam, 1105 AZ, Netherlands

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Hoorn, 1625 HV, Netherlands

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Utrecht, 3584 CX, Netherlands

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Oslo, 0373, Norway

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Singapore, 169609, Singapore

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Johannesburg, Gauteng, 2193, South Africa

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Midrand, Gauteng, 1685, South Africa

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Observatory, Western Cape, 7925, South Africa

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Parow, Western Cape, 7505, South Africa

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Córdoba, Andalusia, 14004, Spain

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Zaragoza, Aragon, 50009, Spain

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Barcelona, Catalonia, 08036, Spain

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Reus, Catalonia, 43204, Spain

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Madrid, 28040, Spain

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Gothenburg, 412 63, Sweden

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Lund, 222 21, Sweden

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Stockholm, 111 35, Sweden

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Stockholm, 141 86, Sweden

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London, SW10 9NH, United Kingdom

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Related Publications (11)

  • Koren MJ, Sabatine MS, Giugliano RP, Langslet G, Wiviott SD, Kassahun H, Ruzza A, Ma Y, Somaratne R, Raal FJ. Long-term Low-Density Lipoprotein Cholesterol-Lowering Efficacy, Persistence, and Safety of Evolocumab in Treatment of Hypercholesterolemia: Results Up to 4 Years From the Open-Label OSLER-1 Extension Study. JAMA Cardiol. 2017 Jun 1;2(6):598-607. doi: 10.1001/jamacardio.2017.0747.

    PMID: 28291870BACKGROUND
  • Koren MJ, Giugliano RP, Raal FJ, Sullivan D, Bolognese M, Langslet G, Civeira F, Somaratne R, Nelson P, Liu T, Scott R, Wasserman SM, Sabatine MS; OSLER Investigators. Efficacy and safety of longer-term administration of evolocumab (AMG 145) in patients with hypercholesterolemia: 52-week results from the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) randomized trial. Circulation. 2014 Jan 14;129(2):234-43. doi: 10.1161/CIRCULATIONAHA.113.007012. Epub 2013 Nov 19.

    PMID: 24255061BACKGROUND
  • Daviglus ML, Ferdinand KC, Lopez JAG, Wu Y, Monsalvo ML, Rodriguez CJ. Effects of Evolocumab on Low-Density Lipoprotein Cholesterol, Non-High Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a) by Race and Ethnicity: A Meta-Analysis of Individual Participant Data From Double-Blind and Open-Label Extension Studies. J Am Heart Assoc. 2021 Jan 5;10(1):e016839. doi: 10.1161/JAHA.120.016839. Epub 2020 Dec 16.

    PMID: 33325247BACKGROUND
  • Hovingh GK, Raal FJ, Dent R, Stefanutti C, Descamps O, Masana L, Lira A, Bridges I, Coll B, Sullivan D. Long-term safety, tolerability, and efficacy of evolocumab in patients with heterozygous familial hypercholesterolemia. J Clin Lipidol. 2017 Nov-Dec;11(6):1448-1457. doi: 10.1016/j.jacl.2017.09.003. Epub 2017 Sep 22.

    PMID: 29066265BACKGROUND
  • Koren MJ, Sabatine MS, Giugliano RP, Langslet G, Wiviott SD, Ruzza A, Ma Y, Hamer AW, Wasserman SM, Raal FJ. Long-Term Efficacy and Safety of Evolocumab in Patients With Hypercholesterolemia. J Am Coll Cardiol. 2019 Oct 29;74(17):2132-2146. doi: 10.1016/j.jacc.2019.08.1024.

    PMID: 31648705BACKGROUND
  • Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.

    PMID: 29353350BACKGROUND
  • Sattar N, Toth PP, Blom DJ, Koren MJ, Soran H, Uhart M, Elliott M, Cyrille M, Somaratne R, Preiss D. Effect of the Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Evolocumab on Glycemia, Body Weight, and New-Onset Diabetes Mellitus. Am J Cardiol. 2017 Nov 1;120(9):1521-1527. doi: 10.1016/j.amjcard.2017.07.047. Epub 2017 Jul 31.

    PMID: 28844508BACKGROUND
  • Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, Lopez JAG, Banach M. Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies. J Am Heart Assoc. 2020 Mar 3;9(5):e014129. doi: 10.1161/JAHA.119.014129. Epub 2020 Mar 2.

    PMID: 32114889BACKGROUND
  • Schludi B, Giugliano RP, Sabatine MS, Raal FJ, Teramoto T, Koren MJ, Stein EA, Wang H, Monsalvo ML. Time-averaged low-density lipoprotein cholesterol lowering with evolocumab: Pooled analysis of phase 2 trials. J Clin Lipidol. 2022 Jul-Aug;16(4):538-543. doi: 10.1016/j.jacl.2022.05.069. Epub 2022 Jun 6.

    PMID: 35760720BACKGROUND
  • Hirayama A, Yamashita S, Ruzza A, Inomata H, Cyrille M, Lu C, Hamer AW, Yoshida M, Kiyosue A, Teramoto T. Long-Term Treatment With Evolocumab Among Japanese Patients - Final Report of the OSLER Open-Label Extension Studies. Circ J. 2019 Apr 25;83(5):971-977. doi: 10.1253/circj.CJ-19-0139. Epub 2019 Mar 29.

    PMID: 30930429BACKGROUND
  • Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, Ballantyne CM, Somaratne R, Legg J, Wasserman SM, Scott R, Koren MJ, Stein EA; Open-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015 Apr 16;372(16):1500-9. doi: 10.1056/NEJMoa1500858. Epub 2015 Mar 15.

Related Links

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

evolocumabStandard of Care

Condition Hierarchy (Ancestors)

HyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health CareQuality of Health CareHealth Services AdministrationHealth Care Quality, Access, and Evaluation

Results Point of Contact

Title
Study Director
Organization
Amgen Inc.

Study Officials

  • MD

    Amgen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 22, 2011

First Posted

September 23, 2011

Study Start

October 7, 2011

Primary Completion

June 20, 2018

Study Completion

June 20, 2018

Last Updated

September 21, 2022

Results First Posted

July 10, 2019

Record last verified: 2022-09

Locations