A Study of LY900014 in Participants With Type 1 Diabetes
- Conditions
- Type 1 Diabetes Mellitus
- Interventions
- Registration Number
- NCT03214367
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The main purpose of this study is to evaluate the efficacy of the study drug LY900014 compared to insulin lispro, both in combination with insulin glargine or insulin degludec, in adults with type 1 diabetes (T1D).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1392
- Have T1D for at least 1 year prior to screening and continuously using insulin for at least 1 year.
- HbA1c of ≥7.0 and ≤9.5%.
- Use insulin lispro, insulin aspart, or insulin glulisine as prandial insulin.
- Use insulin glargine, insulin detemir, insulin degludec, or neutral protamine Hagedorn (NPH) insulin as basal insulin.
- Have used other antihyperglycemic medications or therapies (inhaled, oral or injectable) within 90-days of screening.
- Have had more than 1 severe hypoglycemic episode within 6 months of screening.
- Have had more than 1 hospitalization related to hyperglycemia or diabetic ketoacidosis within 6 months of screening.
- Have clinically significant gastrointestinal disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LY900014 LY900014 LY900014 given subcutaneously (SC) 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 Postmeal (Open Label) LY900014 LY900014 given SC 20 minutes after the start of each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 Postmeal (Open Label) Insulin Glargine LY900014 given SC 20 minutes after the start of each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 - Maximum Extended Enrollment (MEE) Insulin Degludec LY900014 given subcutaneously (SC) 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 Postmeal (Open Label)-MEE LY900014 LY900014 given SC 20 minutes after the start of each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 - Maximum Extended Enrollment (MEE) LY900014 LY900014 given subcutaneously (SC) 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 Insulin Glargine LY900014 given subcutaneously (SC) 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 Insulin Degludec LY900014 given subcutaneously (SC) 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog) Insulin Glargine Insulin lispro given SC 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog) Insulin Lispro Insulin lispro given SC 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog) Insulin Degludec Insulin lispro given SC 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 Postmeal (Open Label) Insulin Degludec LY900014 given SC 20 minutes after the start of each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog)-MEE Insulin Lispro Insulin lispro given SC 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 - Maximum Extended Enrollment (MEE) Insulin Glargine LY900014 given subcutaneously (SC) 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog)-MEE Insulin Glargine Insulin lispro given SC 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog)-MEE Insulin Degludec Insulin lispro given SC 0-2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 Postmeal (Open Label)-MEE Insulin Glargine LY900014 given SC 20 minutes after the start of each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 Postmeal (Open Label)-MEE Insulin Degludec LY900014 given SC 20 minutes after the start of each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets.
- Primary Outcome Measures
Name Time Method Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26 Baseline, Week 26 HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured 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 strata (pooled country, type of basal insulin, prandial insulin dosing plan, and HbA1c stratum) and treatment as fixed effects and baseline as a covariate. The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug.
- Secondary Outcome Measures
Name Time Method Change From Baseline in 1-hour Postprandial Glucose (PPG) Excursion During Mixed-Meal Tolerance Test (MMTT) Efficacy Estimand at Week 26 Baseline, Week 26 A standardized MMTT was used to characterize postprandial glucose control following administration of the study insulin. Serum glucose measured at 1-hour timepoint after the start of meal minus fasting serum glucose. 1-hour PPG excursion during MMTT uses the ANCOVA model with strata (pooled country, type of basal insulin, prandial insulin dosing plan, and HbA1c stratum) and treatment as fixed effects and baseline as a covariate. The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug.
Change From Baseline in 2-hour PPG Excursion During MMTT Efficacy Estimand at Week 26 Baseline, Week 26 A standardized MMTT was used to characterize postprandial glucose control following administration of the study insulin. Serum glucose measured at 2-hour timepoint after the start of meal minus fasting serum glucose. 2-hour PPG excursion during MMTT uses the ANCOVA model with strata (pooled country, type of basal insulin, prandial insulin dosing plan, and HbA1c stratum) and treatment as fixed effects and baseline as a covariate. The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug.
Rate of Severe Hypoglycemia at Week 26 Baseline through Week 26 Severe hypoglycemia is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. During these episodes, the participant has an altered mental status and cannot assist in his or her own care, or may be semiconscious or unconscious, or experience coma with or without seizures, and may require parenteral therapy. Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within a treatment group \*36525.
Rate of Documented Symptomatic Hypoglycemia at Week 26 Baseline through Week 26 Documented symptomatic hypoglycemia is an event during which typical symptoms of hypoglycemia are accompanied by blood glucose (BG) of \<54 mg/dL \[3.0 millimole per liter (mmol/L)\]. The rate of documented symptomatic hypoglycemia was estimated by negative binomial model: number of episodes = treatment with log (treatment exposure in days/365.25) as an offset variable.
Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 26 Baseline, Week 26 1,5-anhydroglucitol (1,5-AG) is a marker of short-term glycemic control especially postprandial hyperglycemia. 1,5-AG accurately predicts rapid changes in glycemia and is tightly associated with glucose fluctuations and postprandial glucose. LS Mean was calculated using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, HbA1c stratum and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The analysis included data collected prior to permanent discontinuation of study drug.
Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 26 Baseline, Week 26 SMBG 10-point profiles were measured at fasting, 1-hour post morning meal, 2-hours post morning meal, pre midday meal, 1-hour post midday meal, 2-hours post midday meal, pre evening meal, 1-hour post evening meal, 2-hours post evening meal, and bedtime. LS Mean was analyzed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, HbA1c stratum and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The efficacy estimand included participant data when baseline and at least one post-baseline measurement prior to permanent discontinuation of study drug.
Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) Regimen Inconvenience Domain Score at Week 26 Baseline, Week 26 ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data presented are the transformed overall score on a scale of 0-100, where higher scores indicate better treatment satisfaction. LS Mean was calculated using the ANCOVA model with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum), and treatment as fixed effects and baseline as covariate. The analysis included data prior to permanent discontinuation of study drug. The analysis included data prior to permanent discontinuation of study drug.
Change From Baseline in ITSQ Lifestyle Flexibility Domain Score at Week 26 Baseline, Week 26 ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data presented are the transformed overall score on a scale of 0-100, where higher scores indicate better treatment satisfaction. LS Mean was calculated using the analysis of covariance (ANCOVA) with strata (pooled country, type of basal insulin, number of prandial doses at study entry, and HbA1c stratum), and treatment as fixed effects and baseline as covariate. The analysis included data prior to permanent discontinuation of study drug. The analysis included data prior to permanent discontinuation of study drug.
Percentage of Participants With HbA1c <7% Week 26 Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Change From Baseline in HbA1c at Week 52 Baseline, Week 52 HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Least Squares (LS) mean was determined by MMRM model with variables of baseline, pooled country, type of basal insulin during lead-in, prandial Insulin Dosing Plan, treatment (Type III sum of squares) as fixed factors. The analysis included data prior to permanent discontinuation of study drug.Change From Baseline in Insulin Dose at Week 26 Baseline, Week 26 LS Mean was analyzed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, HbA1c stratum and number of prandial doses at study entry), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The analysis included data prior to permanent discontinuation of study drug.
Trial Locations
- Locations (51)
Valley Endocrine, Fresno
🇺🇸Fresno, California, United States
Physicians East
🇺🇸Greenville, North Carolina, United States
Diabetes and Endocrine Associates
🇺🇸La Mesa, California, United States
Marin Endocrine Associates
🇺🇸Greenbrae, California, United States
Coastal Metabolic Research Centre
🇺🇸Ventura, California, United States
Sun Coast Clinical Research, Inc
🇺🇸New Port Richey, Florida, United States
Metabolic Research Institute Inc.
🇺🇸West Palm Beach, Florida, United States
Northwest Clinical Trials
🇺🇸Boise, Idaho, United States
Internal Medicine Center LLC
🇺🇸Mobile, Alabama, United States
John Muir Physician Network Clinical Research Center
🇺🇸Concord, California, United States
University Clinical Investigators, Inc.
🇺🇸Tustin, California, United States
Barbara Davis Center for Childhood Diabetes
🇺🇸Aurora, Colorado, United States
The Center For Diabetes & Endocrine Care
🇺🇸Fort Lauderdale, Florida, United States
East Coast Institute For Research
🇺🇸Macon, Georgia, United States
Atlanta Diabetes Associates
🇺🇸Atlanta, Georgia, United States
Endocrine Research Solutions, Inc.
🇺🇸Roswell, Georgia, United States
East West Medical Institute
🇺🇸Honolulu, Hawaii, United States
Rocky Mountain Diabetes and Osteoporosis Center
🇺🇸Idaho Falls, Idaho, United States
Prairie Education and Research Cooperative
🇺🇸Springfield, Illinois, United States
Iderc, P.L.C.
🇺🇸West Des Moines, Iowa, United States
MassResearch
🇺🇸Waltham, Massachusetts, United States
Cotton O'Neil Diabetes and Endocrinology Center
🇺🇸Topeka, Kansas, United States
Kentucky Diabetes Endocrinology Center
🇺🇸Lexington, Kentucky, United States
Palm Research Center
🇺🇸Las Vegas, Nevada, United States
Southern New Hampshire Diabetes and Endocrinology
🇺🇸Nashua, New Hampshire, United States
Manhattan Medical Research
🇺🇸New York, New York, United States
Your Diabetes Endocrine Nutrition Group PC
🇺🇸Mentor, Ohio, United States
Diabetes & Endocrinology Consultants PC
🇺🇸Morehead City, North Carolina, United States
PMG Research of Wilmington, LLC
🇺🇸Wilmington, North Carolina, United States
Partners in Nephrology & Endocrinology
🇺🇸Pittsburgh, Pennsylvania, United States
Lehigh Valley Hospital
🇺🇸Allentown, Pennsylvania, United States
Sudir Bansal M.D. Inc.
🇺🇸Warwick, Rhode Island, United States
Texas Diabetes and Endocrinology
🇺🇸Austin, Texas, United States
Dallas Diabetes Endocrine Center
🇺🇸Dallas, Texas, United States
Texas Diabetes and Endocrinology, P.A.
🇺🇸Round Rock, Texas, United States
Consano Clinical Research
🇺🇸Shavano Park, Texas, United States
Progressive Clinical Research
🇺🇸Bountiful, Utah, United States
Rainier Clinical Research Center
🇺🇸Renton, Washington, United States
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
🇯🇵Ōsaka, Japan
Private: Dr. Larry Stonesifer
🇺🇸Federal Way, Washington, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
🇨🇳Yongkang, Taiwan
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
🇦🇷Córdoba, Argentina
Dr Altagracia Aurora Alcantara Gonzalez
🇵🇷Bayamon, Puerto Rico
Advanced Clinical Research, LLC
🇵🇷Bayamon, Puerto Rico
Manati Center for Clinical Research Inc
🇵🇷Manati, Puerto Rico
Martha Gomez Cuellar M.D.
🇵🇷San Juan, Puerto Rico
Centro de Endocrinologia del Este
🇵🇷Yabucoa, Puerto Rico
AMCR Institute INC
🇺🇸Escondido, California, United States
University Diabetes and Endocrine Consultants
🇺🇸Chattanooga, Tennessee, United States
"For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."
🇪🇸Sevilla, Spain
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States