A Study of LY900014 Compared to Insulin Lispro (Humalog) in Adults With Type 1 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to see if LY900014 compared to insulin lispro (Humalog), both in combination with insulin glargine or insulin degludec, is safe and effective in participants with type 1 diabetes (T1D).

Official Title
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A Prospective, Randomized, Double-Blind Comparison of LY900014 to Insulin Lispro in Combination With Insulin Glargine or Insulin Degludec in Adults With Type 1 Diabetes

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: LY900014
* Drug: Insulin Lispro
* Drug: Insulin Glargine
* Drug: Insulin Degludec


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have T1D for at least 1 year prior to screening and continuously using insulin for at least 1 year. Participants must have HbA1c of ≥7.0 and ≤10.0%. Participants must have been treated for at least 90 days prior to screening with either multiple daily injection(s) (MDI) or premixed analog/human insulin regimens at least twice daily. Participants must have body mass index (BMI) of ≤35.0 kilograms per square meter (kg/m2). Exclusion Criteria: Participants must not have used other anti-hyperglycemic medications or therapies (inhaled, oral or injectable) except for metformin within 90-days prior to screening. Participants must not have had more than 1 severe hypoglycemic episode within 6 months prior to screening. Participants must not have had more than 1 hospitalization related to hyperglycemia or diabetic ketoacidosis within 6 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY900014<br>Participants received 100 units per milliliter (U/mL) LY900014 subcutaneously (SC) 0-2 minutes before each meal with either basal insulin glargine or insulin degludec given SC once daily. | Drug: LY900014<br>* Administered SC<br>* Other names: Ultra-Rapid Lispro;Drug: Insulin Glargine<br>* Administered SC<br>Drug: Insulin Degludec<br>* Administered SC<br>|
| Active Comparator: Insulin Lispro (Humalog)<br>Participants received 100 U/mL insulin lispro SC 0-2 minutes before each meal with either basal insulin glargine or insulin degludec given SC once daily. | Drug: Insulin Lispro<br>* Administered SC<br>* Other names: Humalog;Drug: Insulin Glargine<br>* Administered SC<br>Drug: Insulin Degludec<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HbA1c) | HbA1c is the glycosylated fraction of hemoglobin A. It 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 Baseline + Pooled Country + Number of Bolus at Study Entry Stratum + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-hour Postprandial Glucose (PPG) Excursion During Mixed-Meal Tolerance Test (MMTT) | 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. LS mean was determined by analysis of covariance (ANCOVA) model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Use of Metformin at Study Entry + Type of Basal at Lead-in Stratum + Treatment (Type III sum of squares) as variables. | Week 26 | 
| 2-hour PPG Excursion During MMTT | 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. LS mean was determined by analysis of covariance (ANCOVA) model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Use of Metformin at Study Entry + Type of Basal at Lead-in Stratum + Treatment (Type III sum of squares) as variables. | Week 26 | 
| Rate of Severe Hypoglycemia | Severe hypoglycemia is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. 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 that treatment group *36525 days. | Baseline through Week 26 | 
| Rate of Documented Symptomatic Post Meal Hypoglycemia | Documented symptomatic post meal hypoglycemia is an event during which typical symptoms of hypoglycemia are accompanied by blood glucose (BG) of ≤70 mg/dL [3.9 millimole per liter (mmol/L)]. The rate of documented symptomatic post meal hypoglycemia per year during a defined period is calculated by the total number of documented symptomatic post meal hypoglycemia events within the period divided by the cumulative days on treatment from all participants within that treatment group *365.25. | Baseline through Week 26 | 
| Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) | 1,5-anhydroglucitol (1,5-AG) is a marker of short-term glycemic control especially postprandial hyperglycemia. It accurately predicts rapid changes in glycemia and is tightly associated with glucose fluctuations and postprandial glucose. LS mean was determined by MMRM model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Use of Metformin at Study Entry + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. | Baseline, Week 26 | 
| Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values | SMBG 10-point profiles were measured at morning (premeal-fasting, 1-hour post meal, 2-hour post meal), midday (premeal, 1-hour post meal, 2-hour post meal), evening (premeal, 1-hour post meal, 2-hour post meal) and bedtime. LS Mean was determined by MMRM model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Use of Metformin at Study Entry + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. | Baseline, Week 26 | 
| Change From Baseline in Daily Insulin Dose | LS mean was determined by MMRM model with Baseline + Pooled Country + Hemoglobin A1c Stratum at Baseline + Use of Metformin at Study Entry + Type of Basal at Lead-in Stratum + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. | Baseline, Week 26 | 
| Percentage of Participants With HbA1c <7% and ≤6.5% | HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. | Week 26 |