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

• ClinicalTrials.gov Identifier: NCT02561078
• Recruitment Status: Completed
• First Posted: September 25, 2015
• Results First Posted: May 20, 2020
• Last Update Posted: May 20, 2020
• Sponsor: Eli Lilly and Company
• Collaborator: Insulet Corporation
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus	Drug: Human regular U-500 insulin (CSII); Drug: Human regular U-500 insulin (MDI)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 420 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 20, 2015
• Actual Primary Completion Date: May 9, 2017
• Actual Study Completion Date: May 9, 2017

Arms and Interventions

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 Name: 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 Name: LY041001

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, 26 Weeks ]

   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.

Secondary Outcome Measures :

1. Change From Baseline in Fasting Plasma Glucose (FPG) [ Time Frame: Baseline, 26 Weeks ]
   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.
2. Percentage of Participants With HbA1c <7.0% [ Time Frame: 26 Weeks ]
   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.
3. Percentage of Participants With HbA1c <7.5% [ Time Frame: 26 Weeks ]
   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.
4. Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values [ Time Frame: Baseline, 26 Weeks ]
   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.
5. Change From Baseline in Total Daily Dose (TDD) [ Time Frame: Baseline, 26 Weeks ]
   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.
6. Percentage of Participants With Hypoglycemic Episodes (Documented Hypoglycemia With Blood Glucose <= 70 mg/dL) [ Time Frame: 26 Weeks ]
   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.
7. Rate of Hypoglycemic Episodes (Documented Hypoglycemia With Blood Glucose <= 70 mg/dL) [ Time Frame: Baseline to 26 Weeks ]
   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.
8. Change From Baseline in Body Weight [ Time Frame: Baseline, 26 Weeks ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

Internal Medicine Center LLC

Mobile, Alabama, United States, 36608

United States, California

John Muir Physician Network Clinical Research Center

Concord, California, United States, 94520

Valley Endocrine, Fresno

Fresno, California, United States, 93720

Scripps Whittier Diabetes Institute

La Jolla, California, United States, 92037

Diabetes and Endocrine Associates

La Mesa, California, United States, 91942

First Valley Medical Group

Lancaster, California, United States, 93534

Pacific Research Partners, LLC

Oakland, California, United States, 94607

Inland Empire Liver Foundation

Rialto, California, United States, 92377

NorCal Endocrinology and Internal Medicine - Roseville

Roseville, California, United States, 95661

NorCal Endocrinology and Internal Medicine - Roseville

San Ramon, California, United States, 94583

Olive View Medical Center

Sylmar, California, United States, 91342

United States, Florida

ALL Medical Research, LLC

Cooper City, Florida, United States, 33024

East Coast Institute For Research, LLC

Jacksonville, Florida, United States, 32216

Suncoast Clinical Research

New Port Richey, Florida, United States, 34652

Metabolic Research Institute Inc.

West Palm Beach, Florida, United States, 33401

United States, Georgia

East Coast Institute For Research, LLC

Macon, Georgia, United States, 31210

United States, Idaho

Rocky Mountain Diabetes and Osteoporosis Center

Idaho Falls, Idaho, United States, 83404

United States, Illinois

John H. Stroger Hospital of Cook County

Chicago, Illinois, United States, 60612

Midwest CRC

Crystal Lake, Illinois, United States, 60012

HSHS Medical Group Diabetes Research

Springfield, Illinois, United States, 62711

United States, Iowa

Iderc, P.L.C.

Des Moines, Iowa, United States, 50314

United States, Kansas

Cotton O'Neil Diabetes and Endocrinology Center

Topeka, Kansas, United States, 66606

United States, Kentucky

Kentucky Diabetes Endocrinology Center

Lexington, Kentucky, United States, 40503

United States, Louisiana

The Arthritis & Diabetes Clinic Inc.

Monroe, Louisiana, United States, 71203

United States, Michigan

Grunberger Diabetes Institute

Bloomfield Hills, Michigan, United States, 48302

Adult Endocrinology Consultants, P.C.

Livonia, Michigan, United States, 48154

United States, Missouri

JCMG Clinical Research

Jefferson City, Missouri, United States, 65109

United States, Montana

Billings Clinic Research Center

Billings, Montana, United States, 59101

United States, Nebraska

Diabetes and Endocrinology Associates

Omaha, Nebraska, United States, 68114

United States, Nevada

Palm Research Center

Las Vegas, Nevada, United States, 89128

Palm Research Center

Las Vegas, Nevada, United States, 89148

United States, New Hampshire

Southern New Hampshire Diabetes and Endocrinology

Nashua, New Hampshire, United States, 03063

United States, New York

North Shore Diabetes and Endocrine Assoc

New Hyde Park, New York, United States, 11040

United States, North Carolina

Mountain Diabetes and Endocrine Center

Asheville, North Carolina, United States, 28803

Physicians East

Greenville, North Carolina, United States, 27834

PMG Research of Rocky Mount, LLC

Rocky Mount, North Carolina, United States, 27804

United States, Oklahoma

University of Oklahoma Health Sciences Center-Tulsa

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Portland Diabetes & Endocrine Center

Portland, Oregon, United States, 97210

United States, Pennsylvania

Endocrine Metabolic Associates, P.C.

Philadelphia, Pennsylvania, United States, 19114

Partners in Nephrology & Endocrinology

Pittsburgh, Pennsylvania, United States, 15224

United States, Rhode Island

Sudhir Bansal M.D. Inc.

Warwick, Rhode Island, United States, 02886

United States, Tennessee

AM Diabetes and Endocrinology Center

Bartlett, Tennessee, United States, 38133

University Diabetes and Endocrine Consultants

Chattanooga, Tennessee, United States, 37411

Vanderbilt Univeristy School of Medicine

Nashville, Tennessee, United States, 37232

United States, Texas

Texas Diabetes and Endocrinology-Austin South

Austin, Texas, United States, 78749

Dallas Diabetes Endocrine Center

Dallas, Texas, United States, 75230

Texas Diabetes and Endocrinology, P.A.

Round Rock, Texas, United States, 78681

United States, Utah

Advanced Research Institute

South Ogden, Utah, United States, 84405

United States, Washington

Dr. Larry Stonesifer

Federal Way, Washington, United States, 98003

Rainier Clinical Research Center

Renton, Washington, United States, 98057

Northside Internal Medicine

Spokane, Washington, United States, 99208

Multicare Health System

Tacoma, Washington, United States, 98405

Puerto Rico

Dr Altagracia Aurora Alcantara Gonzalez

Bayamon, Puerto Rico, 00956

Manati Center for Clinical Research Inc

Manati, Puerto Rico, 00674

Endocrine Lipid Diabetes Research Institute

Ponce, Puerto Rico, 00717

American Telemedicine Center

San Juan, Puerto Rico, 00917

Martha Gomez Cuellar M.D.

San Juan, Puerto Rico, 00921

Sponsors and Collaborators

Eli Lilly and Company

Insulet Corporation

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:

Study Protocol: Study Protocol  [PDF] June 11, 2015

Statistical Analysis Plan  [PDF] May 31, 2017

Study Protocol: Study Protocol (a)  [PDF] December 7, 2016

More Information

Additional Information:

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 

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02561078
• Other Study ID Numbers: 14902; B5K-MC-IBHD ( Other Identifier: Eli Lilly and Company )
• First Posted: September 25, 2015
• Results First Posted: May 20, 2020
• Last Update Posted: May 20, 2020
• Last Verified: August 2018

Keywords provided by Eli Lilly and Company:

insulin pumps; concentrated insulin; OmniPod

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Insulin; Insulin, Globin Zinc; Hypoglycemic Agents; Physiological Effects of Drugs