A Study of LY900014 Compared to Insulin Lispro in Participants With Type 2 Diabetes
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Registration Number
- NCT03214380
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The purpose of this study is to compare LY900014 to insulin lispro, both in combination with insulin glargine or insulin degludec, in participants with type 2 diabetes (T2D).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 933
-
Have been diagnosed (clinically) with T2D, based on the World Health Organization (WHO) classification for at least 1 year prior to screening.
-
Have been treated for at least 90 days prior to screening with:
- Basal insulin (insulin glargine U-100 [Basaglar/Abasaglar or LANTUS] or U-300, insulin detemir, insulin degludec U-100 or U-200, or neutral protamine Hagedorn [NPH] insulin) in combination with at least 1 prandial injection of bolus insulin (insulin lispro U-100 or U-200, insulin aspart, insulin glulisine, or regular insulin) Or
- Premixed analog or human insulin regimens with any basal and bolus insulin combination injected at least twice daily
-
Participants may be treated with up to 3 of the following oral antihyperglycemic medications (OAMs) in accordance with local regulations:
- Metformin
- Dipeptidyl peptidase-4 (DPP-4) inhibitor
- Sodium glucose cotransporter 2 (SGLT2) inhibitor
- Sulfonylurea
- Meglitinide
- Alpha-glucoside inhibitor
-
Have an HbA1c value between ≥7.0 and ≤10.0%, according to the central laboratory at the time of screening.
-
Have a body mass index (BMI) of ≤45.0 kilograms per meter squared at screening.
- Have been diagnosed, at any time, with type 1 diabetes (T1D) or Latent Autoimmune Diabetes in Adults.
- Have hypoglycemia unawareness as judged by the investigator.
- Have had any episode of severe hypoglycemia within the 6 months prior to screening.
- Have had 1 or more episodes of diabetic ketoacidosis or hyperglycemic hyperosmolar state within the 6 months prior to screening.
- Have used thiazolidinediones, Glucagon-Like Peptide 1 (GLP-1) receptor agonist, or pramlintide within 90 days prior to screening.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LY900014 Insulin Glargine LY900014 given subcutaneously (SC) with each meal with either 100 U/mL (U-100) basal insulin glargine given SC once or twice daily or U-100 or 200 U/mL (U-200) insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 SGLT2 inhibitor LY900014 given subcutaneously (SC) with each meal with either 100 U/mL (U-100) basal insulin glargine given SC once or twice daily or U-100 or 200 U/mL (U-200) insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 Maximum Extended Enrollment (MEE) SGLT2 inhibitor LY900014 given subcutaneously (SC) with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog) MEE SGLT2 inhibitor Insulin lispro given SC with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog) SGLT2 inhibitor Insulin lispro given SC with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 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) with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 LY900014 LY900014 given subcutaneously (SC) with each meal with either 100 U/mL (U-100) basal insulin glargine given SC once or twice daily or U-100 or 200 U/mL (U-200) 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) with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog) MEE Insulin Degludec Insulin lispro given SC with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog) MEE Metformin Insulin lispro given SC with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 Insulin Degludec LY900014 given subcutaneously (SC) with each meal with either 100 U/mL (U-100) basal insulin glargine given SC once or twice daily or U-100 or 200 U/mL (U-200) insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 Metformin LY900014 given subcutaneously (SC) with each meal with either 100 U/mL (U-100) basal insulin glargine given SC once or twice daily or U-100 or 200 U/mL (U-200) insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog) Insulin Lispro Insulin lispro given SC with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog) Insulin Glargine Insulin lispro given SC with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog) Insulin Degludec Insulin lispro given SC with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog) Metformin Insulin lispro given SC with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 Maximum Extended Enrollment (MEE) Insulin Glargine LY900014 given subcutaneously (SC) with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 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 with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. LY900014 Maximum Extended Enrollment (MEE) Metformin LY900014 given subcutaneously (SC) with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 insulin degludec given SC once daily. Prandial insulin doses were individualized and titrated according to protocol-defined targets. Insulin Lispro (Humalog) MEE Insulin Glargine Insulin lispro given SC with each meal with either U-100 basal insulin glargine given SC once or twice daily or U-100 or U-200 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 Change from baseline in HbA1c was performed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, type of basal insulin, 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 were available prior to permanent discontinuation of study drug.
- Secondary Outcome Measures
Name Time Method Rate of Documented Symptomatic Hypoglycemia 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 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.
Change from baseline in ITSQ regimen inconvenience domain score 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.Number of Participants With HbA1c <7% Week 26 Number of participants with HbA1c \<7% at Week 26.
1-hour Postprandial Glucose (PPG) Excursion During Mixed-Meal Tolerance Test (MMTT) Efficacy Estimand Week 26 1-hour PPG excursion during MMTT uses the analysis of covariance (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 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 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.
Change from baseline in ITSQ lifestyle flexibility domain score 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.2-hour PPG Excursion During MMTT Efficacy Estimand Week 26 2-hour PPG excursion during MMTT uses 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 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 Baseline through Week 26 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. 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 com with or without seizures, and may require parenteral therapy.
Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 26 Baseline, Week 26 Change from baseline in 1,5-AG 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 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 Change from baseline in 10-point SMBG values 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 Dose at Week 26 Baseline, Week 26 Change from baseline in insulin dose 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 (40)
Rocky Mountain Diabetes and Osteoporosis Center
🇺🇸Idaho Falls, Idaho, United States
Aventiv Research
🇺🇸Columbus, Ohio, United States
Dallas Diabetes Endocrine Center
🇺🇸Dallas, Texas, United States
National Research Institute
🇺🇸Los Angeles, California, United States
Partners in Nephrology & Endocrinology
🇺🇸Pittsburgh, Pennsylvania, United States
Palm Research Center
🇺🇸Las Vegas, Nevada, United States
East West Medical Institute
🇺🇸Honolulu, Hawaii, 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."
🇯🇵Kumamoto, Japan
First Valley Medical Group
🇺🇸Lancaster, California, United States
Iderc, P.L.C.
🇺🇸West Des Moines, Iowa, United States
University Clinical Investigators, Inc.
🇺🇸Tustin, California, United States
Diabetes and Endocrine Associates
🇺🇸La Mesa, California, United States
Care Access Research
🇺🇸Santa Clarita, California, United States
The Center For Diabetes & Endocrine Care
🇺🇸Fort Lauderdale, Florida, United States
Valley Research
🇺🇸Fresno, California, United States
ALL Medical Research, LLC
🇺🇸Cooper City, Florida, United States
Elite Clinical Trials LLLP
🇺🇸Blackfoot, Idaho, United States
Northwest Clinical Trials
🇺🇸Boise, Idaho, United States
Manati Center for Clinical Research Inc
🇵🇷Manati, Puerto Rico
Research and Cardiovascular Corp.
🇵🇷Ponce, Puerto Rico
GCM Medical Group PSC
🇵🇷San Juan, Puerto Rico
Prairie Education and Research Cooperative
🇺🇸Springfield, Illinois, United States
Heritage Valley Medical Group, Inc.
🇺🇸Beaver, Pennsylvania, 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
🇯🇵Hyōgo, Japan
Centro de Endocrinologia y Nutricion del Turabo
🇵🇷Caguas, Puerto Rico
Cotton O'Neil Diabetes and Endocrinology Center
🇺🇸Kansas City, Kansas, United States
Manhattan Medical Research
🇺🇸New York, New York, United States
Texas Diabetes and Endocrinology
🇺🇸Austin, Texas, United States
Private: Dr. Larry Stonesifer
🇺🇸Federal Way, 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
Ponce School of Medicine CAIMED Center
🇵🇷Ponce, Puerto Rico
Sun Coast Clinical Research, Inc
🇺🇸New Port Richey, Florida, United States
Encompass Clinical Research
🇺🇸Spring Valley, California, United States
East Coast Institute For Research
🇺🇸Jacksonville, Florida, United States
Progressive Clinical Research
🇺🇸Bountiful, Utah, United States
Texas Diabetes and Endocrinology-Austin South
🇺🇸Austin, Texas, United States
Consano Clinical Research
🇺🇸Shavano Park, Texas, United States
Rainier Clinical Research Center
🇺🇸Renton, Washington, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States