An Administration Method Study of Human Regular U-500 Insulin (LY041001) in Participants With Type 2 Diabetes Mellitus
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Drug: Human regular U-500 insulin (CSII)Drug: Human regular U-500 insulin (MDI)
- Registration Number
- NCT02561078
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 420
-
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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Human regular U-500 insulin administered by CSII Human regular U-500 insulin (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. Human regular U-500 insulin administered by MDI Human regular U-500 insulin (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.
- Primary Outcome Measures
Name Time Method Change From Baseline in Hemoglobin A1c (HbA1c) 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
Name Time Method Percentage of Participants With HbA1c <7.5% 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.
Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values 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.
Change From Baseline in Total Daily Dose (TDD) 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.
Percentage of Participants With Hypoglycemic Episodes (Documented Hypoglycemia With Blood Glucose <= 70 mg/dL) 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.
Rate of Hypoglycemic Episodes (Documented Hypoglycemia With Blood Glucose <= 70 mg/dL) 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.
Change From Baseline in Body Weight 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.
Change From Baseline in Fasting Plasma Glucose (FPG) 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.
Percentage of Participants With HbA1c <7.0% 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.
Trial Locations
- Locations (54)
Endocrine Lipid Diabetes Research Institute
🇵🇷Ponce, Puerto Rico
American Telemedicine Center
🇵🇷San Juan, Puerto Rico
Martha Gomez Cuellar M.D.
🇵🇷San Juan, Puerto Rico
Internal Medicine Center LLC
🇺🇸Mobile, Alabama, United States
East Coast Institute For Research, LLC
🇺🇸Macon, Georgia, United States
Metabolic Research Institute Inc.
🇺🇸West Palm Beach, Florida, United States
Rocky Mountain Diabetes and Osteoporosis Center
🇺🇸Idaho Falls, Idaho, United States
John H. Stroger Hospital of Cook County
🇺🇸Chicago, Illinois, United States
Partners in Nephrology & Endocrinology
🇺🇸Pittsburgh, Pennsylvania, United States
Endocrine Metabolic Associates, P.C.
🇺🇸Philadelphia, Pennsylvania, United States
Cotton O'Neil Diabetes and Endocrinology Center
🇺🇸Topeka, Kansas, United States
University of Oklahoma Health Sciences Center-Tulsa
🇺🇸Oklahoma City, Oklahoma, United States
Grunberger Diabetes Institute
🇺🇸Bloomfield Hills, Michigan, United States
HSHS Medical Group Diabetes Research
🇺🇸Springfield, Illinois, United States
Scripps Whittier Diabetes Institute
🇺🇸La Jolla, California, United States
Inland Empire Liver Foundation
🇺🇸Rialto, California, United States
University Diabetes and Endocrine Consultants
🇺🇸Chattanooga, Tennessee, United States
Sudhir Bansal M.D. Inc.
🇺🇸Warwick, Rhode Island, United States
Southern New Hampshire Diabetes and Endocrinology
🇺🇸Nashua, New Hampshire, United States
PMG Research of Rocky Mount, LLC
🇺🇸Rocky Mount, North Carolina, United States
Mountain Diabetes and Endocrine Center
🇺🇸Asheville, North Carolina, United States
Dallas Diabetes Endocrine Center
🇺🇸Dallas, Texas, United States
Palm Research Center
🇺🇸Las Vegas, Nevada, United States
North Shore Diabetes and Endocrine Assoc
🇺🇸New Hyde Park, New York, United States
Physicians East
🇺🇸Greenville, North Carolina, United States
Manati Center for Clinical Research Inc
🇵🇷Manati, Puerto Rico
Vanderbilt Univeristy School of Medicine
🇺🇸Nashville, Tennessee, United States
AM Diabetes and Endocrinology Center
🇺🇸Bartlett, Tennessee, United States
John Muir Physician Network Clinical Research Center
🇺🇸Concord, California, United States
Valley Endocrine, Fresno
🇺🇸Fresno, California, United States
First Valley Medical Group
🇺🇸Lancaster, California, United States
Pacific Research Partners, LLC
🇺🇸Oakland, California, United States
Diabetes and Endocrine Associates
🇺🇸La Mesa, California, United States
NorCal Endocrinology and Internal Medicine - Roseville
🇺🇸San Ramon, California, United States
Olive View Medical Center
🇺🇸Sylmar, California, United States
ALL Medical Research, LLC
🇺🇸Cooper City, Florida, United States
Suncoast Clinical Research
🇺🇸New Port Richey, Florida, United States
Iderc, P.L.C.
🇺🇸Des Moines, Iowa, United States
Midwest CRC
🇺🇸Crystal Lake, Illinois, United States
Kentucky Diabetes Endocrinology Center
🇺🇸Lexington, Kentucky, United States
The Arthritis & Diabetes Clinic Inc.
🇺🇸Monroe, Louisiana, United States
JCMG Clinical Research
🇺🇸Jefferson City, Missouri, United States
Dr. Larry Stonesifer
🇺🇸Federal Way, Washington, United States
Multicare Health System
🇺🇸Tacoma, Washington, United States
Dr Altagracia Aurora Alcantara Gonzalez
🇵🇷Bayamon, Puerto Rico
Adult Endocrinology Consultants, P.C.
🇺🇸Livonia, Michigan, United States
Texas Diabetes and Endocrinology, P.A.
🇺🇸Round Rock, Texas, United States
Rainier Clinical Research Center
🇺🇸Renton, Washington, United States
Northside Internal Medicine
🇺🇸Spokane, Washington, United States
Portland Diabetes & Endocrine Center
🇺🇸Portland, Oregon, United States
Diabetes and Endocrinology Associates
🇺🇸Omaha, Nebraska, United States
Texas Diabetes and Endocrinology-Austin South
🇺🇸Austin, Texas, United States
Billings Clinic Research Center
🇺🇸Billings, Montana, United States
Advanced Research Institute
🇺🇸South Ogden, Utah, United States