Study of the Efficacy and Safety of Alirocumab (REGN727/SAR236553) in Combination With Other Lipid-modifying Treatment (LMT) (ODYSSEY OPTIONS I)

NCT ID: NCT01730040

Last Updated: 2015-08-31

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

355 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-31

Study Completion Date

2014-05-31

Brief Summary

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This is a randomized, double-blind, active-comparator, parallel-group study in patients at high cardiovascular risk with nonfamilial hypercholesterolemia or heterozygous familial hypercholesterolemia (heFH).

Detailed Description

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Conditions

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Hypercholesterolemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Atorvastatin 40 mg

Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received atorvastatin 40 mg over-encapsulated tablets orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablets orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks.

Group Type ACTIVE_COMPARATOR

Atorvastatin

Intervention Type DRUG

Atorvastatin over-encapsulated tablets orally.

Placebo

Intervention Type DRUG

Placebo for alirocumab and ezetimibe.

Ezetimibe 10 mg + Atorvastatin 20 mg

Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.

Group Type ACTIVE_COMPARATOR

Atorvastatin

Intervention Type DRUG

Atorvastatin over-encapsulated tablets orally.

Ezetimibe

Intervention Type DRUG

Ezetimibe over-encapsulated tablet orally.

Placebo

Intervention Type DRUG

Placebo for alirocumab and ezetimibe.

Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg

Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received Alirocumab 75 mg SC injection Q2W, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.

Group Type EXPERIMENTAL

Alirocumab

Intervention Type DRUG

Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

Atorvastatin

Intervention Type DRUG

Atorvastatin over-encapsulated tablets orally.

Placebo

Intervention Type DRUG

Placebo for alirocumab and ezetimibe.

Atorvastatin 80 mg

Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received Atorvastatin 80 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks.

Group Type ACTIVE_COMPARATOR

Atorvastatin

Intervention Type DRUG

Atorvastatin over-encapsulated tablets orally.

Placebo

Intervention Type DRUG

Placebo for alirocumab and ezetimibe.

Rosuvastatin 40 mg

Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received rosuvastatin 40 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks.

Group Type ACTIVE_COMPARATOR

Rosuvastatin

Intervention Type DRUG

Rosuvastatin over-encapsulated tablets orally.

Placebo

Intervention Type DRUG

Placebo for alirocumab and ezetimibe.

Ezetimibe 10 mg + Atorvastatin 40 mg

Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.

Group Type ACTIVE_COMPARATOR

Atorvastatin

Intervention Type DRUG

Atorvastatin over-encapsulated tablets orally.

Ezetimibe

Intervention Type DRUG

Ezetimibe over-encapsulated tablet orally.

Placebo

Intervention Type DRUG

Placebo for alirocumab and ezetimibe.

Alirocumab 75 mg/ up to 150 mg + Atorvastatin 40 mg

Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received alirocumab 75 mg SC injection Q2W, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.

Group Type EXPERIMENTAL

Alirocumab

Intervention Type DRUG

Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

Atorvastatin

Intervention Type DRUG

Atorvastatin over-encapsulated tablets orally.

Placebo

Intervention Type DRUG

Placebo for alirocumab and ezetimibe.

Interventions

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Alirocumab

Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.

Intervention Type DRUG

Atorvastatin

Atorvastatin over-encapsulated tablets orally.

Intervention Type DRUG

Ezetimibe

Ezetimibe over-encapsulated tablet orally.

Intervention Type DRUG

Rosuvastatin

Rosuvastatin over-encapsulated tablets orally.

Intervention Type DRUG

Placebo

Placebo for alirocumab and ezetimibe.

Intervention Type DRUG

Other Intervention Names

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REGN727/SAR236553 Ezetrol Crestor

Eligibility Criteria

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Inclusion Criteria

1. Patients with screening (visit 1) LDL-C greater than or equal to 70 mg/dL with documented CVD, not adequately controlled with a daily dose of atorvastatin. OR
2. Patients with screening (visit 1) LDL-C greater than or equal to 100 mg/dL at high risk for CVD who are not adequately controlled with a daily dose of atorvastatin.

Exclusion Criteria

1. LDL-C greater than 250 mg/dL
2. LDL-C less than 70 mg/dL at the screening visit in patients with history of documented CVD
3. LDL-C less than 100 mg/dL at the screening visit in patients without history of documented CHD or non-CHD CVD, but with other risk factors
4. TG greater than 400 mg/dL
5. Homozygous FH (clinically or previous genotyping)
6. Currently taking a statin that is not atorvastatin
7. Currently taking Ezetimibe (EZE)
8. Not on a stable dose of allowable lipid modifying treatments (LMT)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role collaborator

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

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Mobile, Alabama, United States

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Chandler, Arizona, United States

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Tucson, Arizona, United States

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Anaheim, California, United States

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Beverly Hills, California, United States

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Lakeland Village, California, United States

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Newport Beach, California, United States

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Northridge, California, United States

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Sacramento, California, United States

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Walnut Creek, California, United States

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Milford, Connecticut, United States

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Atlantis, Florida, United States

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Boca Raton, Florida, United States

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Clearwater, Florida, United States

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Jacksonville, Florida, United States

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Miami (2 Locations), Florida, United States

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Oviedo, Florida, United States

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Pinellas Park, Florida, United States

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Port Orange, Florida, United States

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Sarasota, Florida, United States

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Tampa, Florida, United States

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West Palm Beach, Florida, United States

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Boise, Idaho, United States

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Meridian, Idaho, United States

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Chicago, Illinois, United States

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Morton, Illinois, United States

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Indianapolis, Indiana, United States

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Newton, Kansas, United States

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Overland Park, Kansas, United States

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Wichita, Kansas, United States

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Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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Auburn, Maine, United States

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Bethesda, Maryland, United States

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Edina, Minnesota, United States

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Rochester, Minnesota, United States

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Olive Branch, Mississippi, United States

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Port Gibson, Mississippi, United States

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St Louis, Missouri, United States

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Butte, Montana, United States

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Las Vegas, Nevada, United States

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Williamsville, New York, United States

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Winston-Salem, North Carolina, United States

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Cleveland, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Warwick, Rhode Island, United States

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Greer, South Carolina, United States

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Summerville, South Carolina, United States

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Kingsport, Tennessee, United States

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Dallas (2 Locations), Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Bountiful, Utah, United States

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Marion, Utah, United States

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Salt Lake City, Utah, United States

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Renton, Washington, United States

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Herston QLD, , Australia

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New Lambton Heights, , Australia

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Perth, , Australia

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Sherwood, , Australia

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Woolloongabba, , Australia

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Brampton, Ontario, Canada

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Etobicoke, Ontario, Canada

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London, Ontario, Canada

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Newmarke, Ontario, Canada

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Thornhill, Ontario, Canada

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Toronto, Ontario, Canada

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Chicoutimi, Quebec, Canada

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Dijon, , France

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Lille, , France

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Vénissieux, , France

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Bad Oeynhausen, , Germany

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Berlin, , Germany

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Cologne, , Germany

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Munich, , Germany

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Regensburg, , Germany

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Ulm, , Germany

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Chiete, , Italy

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Genova, , Italy

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Napoli, , Italy

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Palermo, , Italy

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Roma (2 Locations), , Italy

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Distrito Federal, , Mexico

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Guadalajara, , Mexico

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Guadalajara, Jalisco, , Mexico

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Monterrey Nuevo Leon, , Mexico

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Tijuana Baja California, , Mexico

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Zapopan Jalisco, , Mexico

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Barcelona (3 Locations), , Spain

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Madrid, , Spain

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Sant Joan Despí, , Spain

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Carmarthen, , United Kingdom

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Chester, , United Kingdom

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Peterborough, , United Kingdom

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Salford, , United Kingdom

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Stevenage, , United Kingdom

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West Bromwich, West Midlands, , United Kingdom

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Countries

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United States Australia Canada France Germany Italy Mexico Spain United Kingdom

References

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Mahmood T, Minnier J, Ito MK, Li QH, Koren A, Kam IW, Fazio S, Shapiro MD. Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies. Eur J Prev Cardiol. 2021 Jul 23;28(8):816-822. doi: 10.1177/2047487320915803. Epub 2020 Apr 10.

Reference Type DERIVED
PMID: 34298554 (View on PubMed)

Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.

Reference Type DERIVED
PMID: 30183102 (View on PubMed)

Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, Eckel RH, Cannon CP. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016 Dec 13;134(24):1931-1943. doi: 10.1161/CIRCULATIONAHA.116.024604. Epub 2016 Oct 24.

Reference Type DERIVED
PMID: 27777279 (View on PubMed)

Bays H, Gaudet D, Weiss R, Ruiz JL, Watts GF, Gouni-Berthold I, Robinson J, Zhao J, Hanotin C, Donahue S. Alirocumab as Add-On to Atorvastatin Versus Other Lipid Treatment Strategies: ODYSSEY OPTIONS I Randomized Trial. J Clin Endocrinol Metab. 2015 Aug;100(8):3140-8. doi: 10.1210/jc.2015-1520. Epub 2015 Jun 1.

Reference Type DERIVED
PMID: 26030325 (View on PubMed)

Robinson JG, Colhoun HM, Bays HE, Jones PH, Du Y, Hanotin C, Donahue S. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies. Clin Cardiol. 2014 Oct;37(10):597-604. doi: 10.1002/clc.22327. Epub 2014 Sep 30.

Reference Type DERIVED
PMID: 25269777 (View on PubMed)

Other Identifiers

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R727-CL-1110

Identifier Type: -

Identifier Source: org_study_id