Evaluation of Evolocumab (AMG 145) Efficacy in Diabetic Adults With Hypercholesterolemia/Mixed Dyslipidemia (BANTING)

A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Evolocumab (AMG 145) on LDL-C in Subjects With Type 2 Diabetes Mellitus and Hypercholesterolemia/Mixed Dyslipidemia

The purpose of this study is to evaluate the effect of 12 weeks of subcutaneous evolocumab taken monthly compared with subcutaneous placebo taken monthly on low density lipoprotein cholesterol (LDL-C) in adults with type 2 diabetes mellitus and high blood cholesterol on a maximally tolerated oral dose of statin of at least moderate-intensity.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Hypercholesterolemia; Mixed Dyslipidemia
• Intervention / Treatment: Drug: Placebo to Evolocumab; Biological: Evolocumab

Detailed Description

This study will enroll adults with type 2 diabetes mellitus and elevated LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) levels on a stable, maximally tolerated statin dose of at least moderate-intensity at signing of the informed consent; statin therapy must remain unchanged during screening and the remainder of the study.

• Study Type: Interventional
• Enrollment (Actual): 424
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Liege, Belgium, 4000
    • Research Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Y 3W2
      • Research Site
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 6S8
      • Research Site
    • Montreal, Quebec, Canada, H1Y 3L1
      • Research Site
    • St-Jérôme, Quebec, Canada, J7Z 5T3
      • Research Site
• Italy
  • Roma, Italy, 00128
    • Research Site
  • Roma, Italy, 00133
    • Research Site
  • Verona, Italy, 37126
    • Research Site
• Mexico
  • Chihuahua, Mexico, 31217
    • Research Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44600
      • Research Site
• Poland
  • Katowice, Poland, 40-040
    • Research Site
  • Krakow, Poland, 31-315
    • Research Site
  • Warszawa, Poland, 02-018
    • Research Site
  • Wroclaw, Poland, 50-306
    • Research Site
• Spain
  • Andalucía
    • Almeria, Andalucía, Spain, 04001
      • Research Site
    • Granada, Andalucía, Spain, 18016
      • Research Site
  • Cataluña
    • Badalona, Cataluña, Spain, 08916
      • Research Site
    • Barcelona, Cataluña, Spain, 08036
      • Research Site
• United States
  • Alabama
    • Tuscumbia, Alabama, United States, 35674
      • Research Site
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Research Site
  • California
    • Lomita, California, United States, 90717
      • Research Site
    • Los Angeles, California, United States, 90057
      • Research Site
    • Roseville, California, United States, 95661
      • Research Site
    • San Ramon, California, United States, 94583
      • Research Site
    • Spring Valley, California, United States, 91978
      • Research Site
    • Tarzana, California, United States, 91356
      • Research Site
    • Walnut Creek, California, United States, 94598
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80246
      • Research Site
    • Lakewood, Colorado, United States, 80227
      • Research Site
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Research Site
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Research Site
    • Coral Gables, Florida, United States, 33134
      • Research Site
    • Daytona Beach, Florida, United States, 32117
      • Research Site
    • Fleming Island, Florida, United States, 32003
      • Research Site
    • Hollywood, Florida, United States, 33021
      • Research Site
    • Inverness, Florida, United States, 34452
      • Research Site
    • Jacksonville, Florida, United States, 32216
      • Research Site
    • Miami, Florida, United States, 33136
      • Research Site
    • Miami, Florida, United States, 33135
      • Research Site
    • West Palm Beach, Florida, United States, 33401
      • Research Site
  • Georgia
    • Dunwoody, Georgia, United States, 30338
      • Research Site
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Research Site
    • Chicago, Illinois, United States, 60611
      • Research Site
    • Chicago, Illinois, United States, 60616
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • Research Site
  • Maine
    • Auburn, Maine, United States, 04210
      • Research Site
    • Scarborough, Maine, United States, 04074
      • Research Site
  • Maryland
    • Salisbury, Maryland, United States, 21804
      • Research Site
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • Research Site
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Research Site
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Research Site
  • New York
    • New Windsor, New York, United States, 12553
      • Research Site
    • New York, New York, United States, 10016
      • Research Site
    • New York, New York, United States, 10029
      • Research Site
  • North Carolina
    • Shelby, North Carolina, United States, 28150
      • Research Site
    • Tabor City, North Carolina, United States, 28463
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43203
      • Research Site
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Research Site
  • Texas
    • Austin, Texas, United States, 78749
      • Research Site
    • Houston, Texas, United States, 77070
      • Research Site
  • Virginia
    • Suffolk, Virginia, United States, 23435
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female ≥ 18 years
• Type 2 Diabetes Mellitus
• Hemoglobin A1c < 10%
• Stable diabetes therapy
• Must be on maximally tolerated dose of statin of at least moderate Intensity
• Fasting triglycerides ≤ 600 mg/dL
• Not at LDL-C or Non-HDL-C goal.

Exclusion Criteria:

• Moderate to severe renal dysfunction
• Uncontrolled hypertension
• Persistent active liver disease or hepatic dysfunction
• Has taken a cholesterylester transfer protein inhibitor in the last 12 months,
• Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft or stroke within 3 months prior to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Participants received placebo subcutaneous injection once every month (QM) for 12 weeks.	Drug: Placebo to Evolocumab; Administered by subcutaneous injection with an automated mini doser
EXPERIMENTAL: Evolocumab; Participants received 420 mg evolocumab subcutaneous injection once every month (QM) for 12 weeks.	Biological: Evolocumab; Administered by subcutaneous injection with an automated mini doser; Other Names: Repatha; AMG 145

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12	Baseline and Weeks 10 and 12
Percent Change From Baseline in LDL-C at Week 12	Baseline and week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Change From Baseline in LDL-C at Week 12	Baseline and week 12
Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Non-HDL-C at Week 12	Baseline and week 12
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B at Week 12	Baseline and week 12
Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Total Cholesterol at Week 12	Baseline and week 12
Percentage of Participants With Mean LDL-C at Weeks 10 and 12 Less Than 70 mg/dL (1.8 mmol/L)	Weeks 10 and 12
Percentage of Participants With LDL-C at Week 12 Less Than 70 mg/dL (1.8 mmol/L)	Week 12
Percentage of Participants With at Least a 50% Reduction From Baseline in Mean LDL-C at Weeks 10 and 12	Baseline and weeks 10 and 12
Percentage of Participants With at Least a 50% Reduction From Baseline in LDL-C at Week 12	Baseline and Week 12
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Lipoprotein(a) at Week 12	Baseline and week 12
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in Triglycerides at Week 12	Baseline and week 12
Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in HDL-C at Week 12	Baseline and week 12
Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12	Baseline and weeks 10 and 12
Percent Change From Baseline in VLDL-C at Week 12	Baseline and week 12

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Rosenson RS, Daviglus ML, Handelsman Y, Pozzilli P, Bays H, Monsalvo ML, Elliott-Davey M, Somaratne R, Reaven P. Efficacy and safety of evolocumab in individuals with type 2 diabetes mellitus: primary results of the randomised controlled BANTING study. Diabetologia. 2019 Jun;62(6):948-958. doi: 10.1007/s00125-019-4856-7. Epub 2019 Apr 5.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 17, 2016
• Primary Completion (ACTUAL): August 3, 2017
• Study Completion (ACTUAL): August 3, 2017

Study Registration Dates

• First Submitted: April 12, 2016
• First Submitted That Met QC Criteria: April 12, 2016
• First Posted (ESTIMATE): April 15, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 2, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: diabetes; type 2 diabetes; hypercholesterolemia; high cholesterol; mixed dyslipidemia; high blood cholesterol; statin intolerant
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Lipid Metabolism Disorders; Hyperlipidemias; Diabetes Mellitus, Type 2; Dyslipidemias; Hypercholesterolemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Immunologic Factors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Antibodies, Monoclonal; Evolocumab
• Other Study ID Numbers: 20130287; 2015-004711-21 (EUDRACT_NUMBER)