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

Type 2 Diabetes Mellitus Clinical Trial

— VIVID  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02561078
• Other study ID #: 14902
• Secondary ID: B5K-MC-IBHD
• Status: Completed
• Phase: Phase 3
• Start date: October 20, 2015
• Est. completion date: May 9, 2017

Study information

• Verified date: August 2018
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 420
• Est. completion date: May 9, 2017
• Est. primary completion date: May 9, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Human regular U-500 insulin (CSII)
Administered SC
• Human regular U-500 insulin (MDI)
Administered SC

Locations

Country	Name	City	State
Puerto Rico	Dr Altagracia Aurora Alcantara Gonzalez	Bayamon
Puerto Rico	Manati Center for Clinical Research Inc	Manati
Puerto Rico	Endocrine Lipid Diabetes Research Institute	Ponce
Puerto Rico	American Telemedicine Center	San Juan
Puerto Rico	Martha Gomez Cuellar M.D.	San Juan
United States	Mountain Diabetes and Endocrine Center	Asheville	North Carolina
United States	Texas Diabetes and Endocrinology-Austin South	Austin	Texas
United States	AM Diabetes and Endocrinology Center	Bartlett	Tennessee
United States	Billings Clinic Research Center	Billings	Montana
United States	Grunberger Diabetes Institute	Bloomfield Hills	Michigan
United States	University Diabetes and Endocrine Consultants	Chattanooga	Tennessee
United States	John H. Stroger Hospital of Cook County	Chicago	Illinois
United States	John Muir Physician Network Clinical Research Center	Concord	California
United States	ALL Medical Research, LLC	Cooper City	Florida
United States	Midwest CRC	Crystal Lake	Illinois
United States	Dallas Diabetes Endocrine Center	Dallas	Texas
United States	Iderc, P.L.C.	Des Moines	Iowa
United States	Dr. Larry Stonesifer	Federal Way	Washington
United States	Valley Endocrine, Fresno	Fresno	California
United States	Physicians East	Greenville	North Carolina
United States	Rocky Mountain Diabetes and Osteoporosis Center	Idaho Falls	Idaho
United States	East Coast Institute For Research, LLC	Jacksonville	Florida
United States	JCMG Clinical Research	Jefferson City	Missouri
United States	Scripps Whittier Diabetes Institute	La Jolla	California
United States	Diabetes and Endocrine Associates	La Mesa	California
United States	First Valley Medical Group	Lancaster	California
United States	Palm Research Center	Las Vegas	Nevada
United States	Palm Research Center	Las Vegas	Nevada
United States	Kentucky Diabetes Endocrinology Center	Lexington	Kentucky
United States	Adult Endocrinology Consultants, P.C.	Livonia	Michigan
United States	East Coast Institute For Research, LLC	Macon	Georgia
United States	Internal Medicine Center LLC	Mobile	Alabama
United States	The Arthritis & Diabetes Clinic Inc.	Monroe	Louisiana
United States	Southern New Hampshire Diabetes and Endocrinology	Nashua	New Hampshire
United States	Vanderbilt Univeristy School of Medicine	Nashville	Tennessee
United States	North Shore Diabetes and Endocrine Assoc	New Hyde Park	New York
United States	Suncoast Clinical Research	New Port Richey	Florida
United States	Pacific Research Partners, LLC	Oakland	California
United States	University of Oklahoma Health Sciences Center-Tulsa	Oklahoma City	Oklahoma
United States	Diabetes and Endocrinology Associates	Omaha	Nebraska
United States	Endocrine Metabolic Associates, P.C.	Philadelphia	Pennsylvania
United States	Partners in Nephrology & Endocrinology	Pittsburgh	Pennsylvania
United States	Portland Diabetes & Endocrine Center	Portland	Oregon
United States	Rainier Clinical Research Center	Renton	Washington
United States	Inland Empire Liver Foundation	Rialto	California
United States	PMG Research of Rocky Mount, LLC	Rocky Mount	North Carolina
United States	NorCal Endocrinology and Internal Medicine - Roseville	Roseville	California
United States	Texas Diabetes and Endocrinology, P.A.	Round Rock	Texas
United States	NorCal Endocrinology and Internal Medicine - Roseville	San Ramon	California
United States	Advanced Research Institute	South Ogden	Utah
United States	Northside Internal Medicine	Spokane	Washington
United States	HSHS Medical Group Diabetes Research	Springfield	Illinois
United States	Olive View Medical Center	Sylmar	California
United States	Multicare Health System	Tacoma	Washington
United States	Cotton O'Neil Diabetes and Endocrinology Center	Topeka	Kansas
United States	Sudhir Bansal M.D. Inc.	Warwick	Rhode Island
United States	Metabolic Research Institute Inc.	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Insulet Corporation

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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