An Administration Method Study of Human Regular U-500 Insulin (LY041001) in Participants With Type 2 Diabetes Mellitus (VIVID)

Safety and Efficacy of Human Regular U-500 Insulin Administered by Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections in Subjects With Type 2 Diabetes Mellitus: A Randomized, Open-Label, Parallel Clinical Trial

The main purpose of this study is to evaluate the efficacy and safety of the study drug known as human regular U-500 insulin (U-500R) administered by continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) in participants with type 2 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Human regular U-500 insulin (CSII); Drug: Human regular U-500 insulin (MDI)

• Study Type: Interventional
• Enrollment (Actual): 420
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Bayamon, Puerto Rico, 00956
    • Dr Altagracia Aurora Alcantara Gonzalez
  • Manati, Puerto Rico, 00674
    • Manati Center for Clinical Research Inc
  • Ponce, Puerto Rico, 00717
    • Endocrine Lipid Diabetes Research Institute
  • San Juan, Puerto Rico, 00921
    • Martha Gomez Cuellar M.D.
  • San Juan, Puerto Rico, 00917
    • American Telemedicine Center
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Internal Medicine Center LLC
  • California
    • Concord, California, United States, 94520
      • John Muir Physician Network Clinical Research Center
    • Fresno, California, United States, 93720
      • Valley Endocrine, Fresno
    • La Jolla, California, United States, 92037
      • Scripps Whittier Diabetes Institute
    • La Mesa, California, United States, 91942
      • Diabetes and Endocrine Associates
    • Lancaster, California, United States, 93534
      • First Valley Medical Group
    • Oakland, California, United States, 94607
      • Pacific Research Partners, LLC
    • Rialto, California, United States, 92377
      • Inland Empire Liver Foundation
    • Roseville, California, United States, 95661
      • NorCal Endocrinology and Internal Medicine - Roseville
    • San Ramon, California, United States, 94583
      • NorCal Endocrinology and Internal Medicine - Roseville
    • Sylmar, California, United States, 91342
      • Olive View Medical Center
  • Florida
    • Cooper City, Florida, United States, 33024
      • ALL Medical Research, LLC
    • Jacksonville, Florida, United States, 32216
      • East Coast Institute for Research, LLC
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute Inc.
  • Georgia
    • Macon, Georgia, United States, 31210
      • East Coast Institute for Research, LLC
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Diabetes and Osteoporosis Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • John H. Stroger Hospital of Cook County
    • Crystal Lake, Illinois, United States, 60012
      • Midwest CRC
    • Springfield, Illinois, United States, 62711
      • HSHS Medical Group Diabetes Research
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Iderc, P.L.C.
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Diabetes and Endocrinology Center
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Kentucky Diabetes Endocrinology Center
  • Louisiana
    • Monroe, Louisiana, United States, 71203
      • The Arthritis & Diabetes Clinic Inc.
  • Michigan
    • Bloomfield Hills, Michigan, United States, 48302
      • Grunberger Diabetes Institute
    • Livonia, Michigan, United States, 48154
      • Adult Endocrinology Consultants, P.C.
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • JCMG Clinical Research
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Research Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Diabetes and Endocrinology Associates
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Research Center
    • Las Vegas, Nevada, United States, 89128
      • Palm Research Center
  • New Hampshire
    • Nashua, New Hampshire, United States, 03063
      • Southern New Hampshire Diabetes and Endocrinology
  • New York
    • New Hyde Park, New York, United States, 11040
      • North Shore Diabetes and Endocrine Assoc
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Mountain Diabetes and Endocrine Center
    • Greenville, North Carolina, United States, 27834
      • Physicians East
    • Rocky Mount, North Carolina, United States, 27804
      • PMG Research of Rocky Mount, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center-Tulsa
  • Oregon
    • Portland, Oregon, United States, 97210
      • Portland Diabetes & Endocrine Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Endocrine Metabolic Associates, P.C.
    • Pittsburgh, Pennsylvania, United States, 15224
      • Partners in Nephrology & Endocrinology
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Sudhir Bansal M.D. Inc.
  • Tennessee
    • Bartlett, Tennessee, United States, 38133
      • AM Diabetes And Endocrinology Center
    • Chattanooga, Tennessee, United States, 37411
      • University Diabetes and Endocrine Consultants
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Univeristy School of Medicine
  • Texas
    • Austin, Texas, United States, 78749
      • Texas Diabetes and Endocrinology-Austin South
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes Endocrine Center
    • Round Rock, Texas, United States, 78681
      • Texas Diabetes and Endocrinology, P.A.
  • Utah
    • South Ogden, Utah, United States, 84405
      • Advanced Research Institute
  • Washington
    • Federal Way, Washington, United States, 98003
      • Dr. Larry Stonesifer
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center
    • Spokane, Washington, United States, 99208
      • Northside Internal Medicine
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed with type 2 diabetes mellitus (T2DM).

• Current TDD >200 but ≤600 units of non U-500R insulin (MDI or CSII) and/or U-500R by MDI with syringe and vial for ≥3 months at entry.

  • If TDD of U-500R and other insulins are combined, then insulin other than U-500R not to exceed 25% of TDD.
• HbA1c ≥7.5% and ≤12.0%.
• Body mass index ≥25 but ≤50 kilograms per meter squared.
• Have a history of stable body weight.

• Concomitant antihyperglycemic agent (AHA) therapy may include metformin (MET), dipeptidyl peptidase-4 inhibitors and/or pioglitazone.

  • Approximately 64 to 96 subjects using glucagon-like peptide-1 (GLP-1) receptor agonists or sodium-glucose cotransporter 2 (SGLT2) inhibitors will be enrolled in Study Group B.

Exclusion Criteria:

• Diagnosed with type 1 diabetes mellitus (T1DM) or other types of diabetes apart from T2DM.
• Have obvious clinical or radiographic signs or symptoms of liver disease (except nonalcoholic fatty liver disease), cirrhosis, acute or chronic hepatitis, or alanine aminotransferase (ALT/SGPT) and/or aspartate aminotransferase (AST/SGOT) levels ≥2.5X upper limit of normal (ULN), alkaline phosphatase ≥2X ULN or total bilirubin ≥2X ULN.
• Have chronic kidney disease Stage 4 and higher or history of renal transplantation.
• Have history of more than 1 episode of severe hypoglycemia within the 6 months prior to screening.
• Have received U-500R insulin by CSII in the 3 months prior to screening.
• Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia.
• Are taking chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy.
• Have an irregular sleep/wake cycle.
• Have used any weight loss drugs in the 3 months prior to screening.
• Have a history of bariatric surgery including Roux-en-Y gastric bypass surgery, gastric banding, and/or gastric sleeve.
• Have a history of an active or untreated malignancy, or in remission from a clinically significant malignancy during the last 5 years before screening.
• Significant hearing loss and/or vision impairment deemed by the investigator to interfere with the safe use of OmniPod U-500 system.
• Have cardiac disease with functional status that is New York Heart Association (NYHA) Class III or IV per New York Heart Association Cardiac Disease Functional Classification or have congestive heart failure requiring pharmacologic treatment.
• Are women breastfeeding or pregnant, or intend to become pregnant during the course of the study; are men who intend to impregnate their partners; or are sexually active of procreation potential not actively practicing birth control by a method determined by the investigator to be medically acceptable. Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Human regular U-500 insulin administered by CSII; Human regular U-500 insulin administered by CSII and titrated based on blood glucose readings for 26 weeks with a 2-week MDI lead-in.	Drug: Human regular U-500 insulin (CSII); Administered SC; Other Names: LY041001
Active Comparator: Human regular U-500 insulin administered by MDI; Human regular U-500 insulin administered subcutaneously (SC) by MDI three times a day and titrated based on blood glucose readings for 26 weeks.	Drug: Human regular U-500 insulin (MDI); Administered SC; Other Names: LY041001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c)	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline of response, glucagon-like peptide-1 (GLP-1) or sodium-glucose cotransporter 2 (SGLT2) use, U-500R at entry, treatment, time and treatment by time interaction.	Baseline, 26 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG)	Fasting plasma glucose (FPG) is a test to determine how much glucose (sugar) is in a plasma sample after an overnight fast. Least Squares (LS) means was determined by MMRM methodology with baseline of response, glucagon-like peptide-1 (GLP-1) or sodium-glucose cotransporter 2 (SGLT2) use, U-500R at entry, treatment, time and treatment by time interaction.	Baseline, 26 Weeks
Percentage of Participants With HbA1c <7.0%	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Longitudinal logistic regression was used to model the likelihood of having hbA1c<7.0% at Week 26 with baseline of response, glucagon-like peptide-1 (GLP-1) or sodium-glucose cotransporter 2 (SGLT2) use, U-500R at entry, treatment, time and treatment by time interaction.	26 Weeks
Percentage of Participants With HbA1c <7.5%	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Longitudinal logistic regression was used to model the likelihood of having hbA1c<7.5% at Week 26 with baseline of response, glucagon-like peptide-1 (GLP-1) or sodium-glucose cotransporter 2 (SGLT2) use, U-500R at entry, treatment, time and treatment by time interaction.	26 Weeks
Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Seven-point SMBG are completed at the following timepoints: Before Morning Meal, 2 Hours After Morning Meal, Before Mid-Day Meal, 2 Hours After Mid-Day Meal, Before Evening Meal, Bed Time and 03:00 AM hours. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with baseline of response, GLP-1 or SGLT2 use, U-500R at entry, baseline HbA1C group, treatment, time and treatment by time interaction.	Baseline, 26 Weeks
Change From Baseline in Total Daily Dose (TDD)	Baseline TDD was defined as the last prestudy insulin TDD prior to randomization to receiving the first dose of U-500 insulin post randomization. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with baseline of response, GLP-1 or SGLT2 use, U-500R at entry, baseline HbA1C group, treatment, time and treatment by time interaction.	Baseline, 26 Weeks
Percentage of Participants With Hypoglycemic Episodes (Documented Hypoglycemia With Blood Glucose <= 70 mg/dL)	The percentage of participants with hypoglycemic episodes (documented hypoglycemia) was calculated by dividing the number of participants with at least 1 hypoglycemic episode (documented hypoglycemia) over the 26-week treatment period by the total number of participants analyzed, multiplied by 100%. Logistic regression was used to estimate the odds ratio between the two treatments of at least 1 hypoglycemic episode (documented hypoglycemia) over 26 week treatment period adjusted for baseline documented hypoglycemia rate, GLP-1 or SGLT2 use, U-500R at entry, baseline HbA1C group, treatment, time and treatment by time interaction.	26 Weeks
Rate of Hypoglycemic Episodes (Documented Hypoglycemia With Blood Glucose <= 70 mg/dL)	Documented Hypoglycemic episodes with blood glucose<=70mg/dL was used in this outcome measure. Hypoglycemia rate (documented hypoglycemia) per 30 days was summarized at each visit by treatment group. The rate of hypoglycemia (documented hypoglycemia) was analyzed using a generalized estimation equations model with a negative binomial distribution and a Log link. LS mean was determined by MMRM methodology with baseline documented hypoglycemia rate, GLP-1 or SGLT2 use, U-500R at entry, baseline HbA1C group, with log of exposure in days divided by 30 as the offset, treatment, visit, and visit by treatment interaction.	Baseline to 26 Weeks
Change From Baseline in Body Weight	Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with baseline of response, GLP-1 or SGLT2 use, U-500R at entry, baseline HbA1C group, treatment, treatment by time interaction.	Baseline, 26 Weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Insulet Corporation

Publications and helpful links

Helpful Links

• Click here for more information about this study: An Administration Method Study of Human Regular U-500 Insulin (LY041001) in Participants With Type 2 Diabetes Mellitus

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2015
• Primary Completion (Actual): May 9, 2017
• Study Completion (Actual): May 9, 2017

Study Registration Dates

• First Submitted: September 23, 2015
• First Submitted That Met QC Criteria: September 24, 2015
• First Posted (Estimate): September 25, 2015

Study Record Updates

• Last Update Posted (Actual): May 20, 2020
• Last Update Submitted That Met QC Criteria: May 5, 2020
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: OmniPod; insulin pumps; concentrated insulin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: 14902; B5K-MC-IBHD (Other Identifier: Eli Lilly and Company)