A Study Comparing LY900014 to Insulin Lispro (Humalog) in Adults With Type 1 Diabetes Using Insulin Pump Therapy

Study Overview
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Brief Summary
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The reason for this study is to compare the study drug LY900014 to insulin lispro (Humalog) when both are used in insulin pump therapy in adults with type 1 diabetes (T1D).

Official Title
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A Prospective, Randomized, Double-Blind Comparison of LY900014 to Humalog in Adults With Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Ultra-Rapid Lispro
* Drug: Insulin Lispro


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have been diagnosed with T1D and continuously using insulin for at least 1 year Have been using CSII therapy for a minimum of 6 months Currently treated with <100 Units of one of following rapid-acting analog insulin via CSII for at least the past 30 days: insulin lispro U-100, insulin aspart, fast-acting insulin aspart, insulin glulisine Must be using a MiniMed 530G (US), Paradigm Revel (US), or MiniMed 630G (US and Canada), MiniMed 640G or Paradigm Veo (select countries outside the US), insulin pump for at least the past 90 days Exclusion Criteria: Have hypoglycemia unawareness Have had more than 1 episode of severe hypoglycemia within 6 months prior to screening Have had more than 1 emergency room visit or hospitalization due to poor glucose control (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 |
| --- | --- |
| Active Comparator: Insulin Lispro (Humalog)<br>Participants received individual dose of 100 U/mL insulin lispro (Humalog) by CSII; where mealtime boluses were delivered 0 to 2 minutes prior to the start of each meal, with basal infusion rates 24 hours/day, and correction boluses as necessary. | Drug: Insulin Lispro<br>* Administered SC<br>* Other names: LY275585;|
| Experimental: Ultra-Rapid Lispro<br>Participants received individual dose of 100 units per milliliter (U/mL) ultra rapid lispro by continuous subcutaneous insulin infusion (CSII); where mealtime boluses were delivered 0 to 2 minutes prior to the start of each meal, with basal infusion rates 24 hours/day, and correction boluses as necessary. | Drug: Ultra-Rapid Lispro<br>* Administered SC<br>* Other names: Insulin lispro;|

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) Efficacy Estimand at Week 16 | 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 covariates: Baseline + Pooled Country + Personal continuous glucose Monitor (CGM) or Flash glucose monitor (FGM) use during study flag + Treatment + Time + Treatment*Time (Type III sum of squares). The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug. | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 1-hour Postprandial Glucose (PPG) During Mixed-Meal Tolerance Test (MMTT) Efficacy Estimand at Week 16 | 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. Least Squares (LS) mean was determined by analysis of variance (ANCOVA) model with independent variables: Baseline + Pooled Country + Hemoglobin A1C Stratum + Personal CGM/FGM use during study Flag + Treatment (Type III sum of squares).The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug. | Baseline, Week 16 | 
| Change From Baseline in 2-hour PPG During MMTT Efficacy Estimand at Week 16 | 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. Least Squares (LS) mean was determined by analysis of variance (ANCOVA) model with independent variables: Baseline + Pooled Country + Hemoglobin A1C Stratum + Personal CGM/FGM use during study Flag + Treatment (Type III sum of squares).The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug. | Baseline, Week 16 | 
| Percentage of Time With Sensor Glucose Values Between 70 and 180 mg/dL Efficacy Estimand at Week 16 | Percentage of time with sensor glucose values between 70 and 180 mg/dL using continuous glucose monitoring (CGM). Least square (LS) mean difference will provided for CGM data normalized to a 24hrs period. Daytime: 0600 hours to midnight (06:00:00-23:59:59 on the 24-hour clock). Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates: Baseline + Pooled Country + Hemoglobin A1C Stratum + Personal continuous glucose Monitor (CGM) or Flash glucose monitor (FGM) use during study flag + Treatment + Time + Treatment*Time (Type III sum of squares). | Week 16 | 
| Rate of Severe Hypoglycemia at Week 16 | 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. | Baseline through Week 16 | 
| Rate of Documented Symptomatic Hypoglycemia at Week 16 | 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. | Baseline through Week 16 | 
| Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 16 | 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 + Hemoglobin A1C Stratum + Personal continuous glucose Monitor (CGM) or Flash glucose monitor (FGM) use during study flag), 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. | Baseline, Week 16 | 
| Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 16 | 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, HbA1c stratum : less than or equal to (≤)7.5%, greater than (>)7.5% and participant's personal CGM or FGM use during the study), 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. | Baseline, Week 16 | 
| Change From Baseline in Insulin Dose at Week 16 | LS mean was determined by MMRM model with covariates: Baseline + Pooled Country + + Hemoglobin A1C Stratum + Personal CGM or FGM use during study flag + Treatment + Time + Treatment*Time (Type III sum of squares). The analysis included data prior to permanent discontinuation of study drug. | Baseline, Week 16 | 
| Change From Baseline in Bolus/Total Insulin Dose Ratio at Week 16 | The bolus/total ratio was derived as the bolus dose divided by the total insulin dose at each visit. LS mean was determined by MMRM model with covariates: Baseline + Pooled Country + + Hemoglobin A1C Stratum + Personal CGM or FGM use during study flag + Treatment + Time + Treatment*Time (Type III sum of squares). The analysis included data prior to permanent discontinuation of study drug. | Baseline, Week 16 | 
| Percentage of Participants With HbA1c <7% | Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. | Week 16 | 
| Percentage of Participants With at Least 1 Pump Occlusion Alarm That Leads to an Unplanned Infusion Set Change | Percentage of participants with at least 1 pump occlusion alarm that leads to an unplanned infusion set change was evaluated. | Baseline through Week 16 | 
| Percentage of Participants With at Least 1 Event of Unexplained Hyperglycemia >300 mg/dL Confirmed by SMBG That Leads to an Unplanned Infusion Set Change | Percentage of participants with at least 1 event of unexplained hyperglycemia >300 milligrams per deciliter (mg/dL) confirmed by SMBG that leads to an unplanned infusion set change was evaluated. | Baseline through Week 16 |