A Study of Mealtime Insulin LY900014 in Participants With Type 2 Diabetes Using Continuous Glucose Monitoring (PRONTO-Time in Range)

Study Overview
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Brief Summary
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This study is being done to evaluate glycemic control in participants with type 2 diabetes who are taking mealtime insulin LY900014 in combination with long-acting insulin glargine. Participants will use continuous glucose monitoring (CGM) (Freestyle Libre 14-day system) during the study.

Official Title
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A Study of LY900014 in Participants With Type 2 Diabetes Using Continuous Glucose Monitoring

Conditions
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Type 2 Diabetes

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants diagnosed (clinically) with type 2 diabetes mellitus (T2D) for at least 1 year prior to screening. Have been treated with basal-bolus multiple daily injection (MDI) therapy for at least 90 days prior to screening including: Basal insulin glargine U-100, in combination with bolus insulin analog (insulin lispro, insulin aspart, or insulin glulisine) with meals. Participant must have been treated with the same type of allowed bolus insulin analog for at least 30 days prior to screening. Participants may be treated with up to 3 of the following oral antihyperglycemic medications (OAMs) for T2D in accordance with local regulations: Metformin Dipeptidyl peptidase-4 (DPP-4) inhibitor sodium glucose cotransporter 2 (SGLT2) inhibitor oral glucagon-like peptide 1 (GLP-1) agonist Doses of OAMs are required to have been stable for at least 90 days prior to screening. Participants may be treated with injectable GLP-1 receptor agonist for T2D in accordance with local regulations. The GLP-1 receptor agonist dose is required to have been stable for at least 90 days prior to screening. Have an HbA1c value ≥7.5% and ≤10% according to the central laboratory at screening. Exclusion Criteria: Have been diagnosed at any time with type 1 diabetes mellitus or latent autoimmune diabetes in adults. Have had any episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia) within 6 months prior to screening. Have had any episode of hyperglycemic hyperosmolar state or diabetic ketoacidosis within 6 months prior to screening. Have hypoglycemia unawareness as judged by the investigator.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY900014<br>LY900014 (100 units/milliliter (U/mL)) is a mealtime insulin administered subcutaneously (SC) 0-2 minutes prior to each meal in combination with insulin glargine (100 U/mL) SC as long-acting insulin. Mealtime (bolus) and long-acting (basal) insulin doses were titrated to achieve glucose targets during the study. | Drug: LY900014<br>* Administered SC<br>Drug: Insulin Glargine<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 Percentage of Time With Continuous Glucose Monitoring (CGM) Sensor Glucose Values Between 70-180 Milligrams/Deciliter (mg/dL) (3.9-10.0 Millimoles/Liter [mmol/L]) (Both Inclusive) During Daytime Period at Week 12 | Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Time as variables. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 | HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model with Baseline + Time as variables. | Baseline, Week 12 | 
| Change From Baseline in Percentage of Time With CGM Sensor Glucose Values Between 70-180 mg/dL (3.9-10.0 mmol/L) (Both Inclusive) During the 24-hour Period at Week 12 | LS mean was determined by MMRM model with Baseline + Time as variables. | Baseline, Week 12 | 
| Change From Baseline in Percentage of Time With CGM Sensor Glucose Values <54 mg/dL (<3.0 mmol/L) During Daytime and 24-hour Periods at Week 12 | LS mean was determined by MMRM model with Baseline + Time as variables. | Baseline, Week 12 | 
| Change From Baseline in Percentage of Time With CGM Sensor Glucose Values >180 mg/dL (>10.0 mmol/L) During Daytime and 24-hour Period at Week 12 | LS mean was determined by MMRM model with Baseline + Time as variables. | Baseline, Week 12 | 
| Change From Baseline in Percentage of Time With CGM Sensor Glucose Value >250 mg/dL (>13.9 mmol/L) During Daytime and 24-hour Period at Week 12 | LS mean was determined by MMRM model with Baseline + Time as variables. | Baseline, Week 12 | 
| Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12 | iAUC reflects the metabolic control and is calculated using the standard trapezoidal rule from Glucose measures taken every 15 minutes from 0 to 1 hour after meal using CGM sensor (i.e., 0, 15, 30, 45, 60 minutes after meal). LS mean was determined by ANCOVA (analysis of covariance) with Baseline as covariate. | Baseline, Week 12 | 
| Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-2 Hour at Week 12 | iAUC reflects the metabolic control and is calculated using the standard trapezoidal rule from glucose measures taken every 15 minutes from 0 to 2 hours after meal using CGM sensor (i.e., 0, 15, 30, 45, 60, 75, 90, 105, 120 minutes after meal). LS mean was determined by ANCOVA (analysis of covariance) with Baseline as covariate. | Baseline, Week 12 | 
| 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 12 | 
| Change From Baseline in Daily Insulin Dose at Week 12 | LS mean was determined by MMRM model with Baseline + Time as variables. | Baseline, Week 12 | 
| Change From Baseline in Bolus/Total Insulin Dose Percentage at Week 12 | LS mean was determined by MMRM model with Baseline + Time as variables. | Baseline, Week 12 | 
| Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) - Glycemic Control Domain Score at Week 12 | The ITSQ is a 22-item questionnaire that assesses treatment satisfaction for subjects taking insulin under 5 domains: Inconvenience of Regimen [IR - 5 items], Lifestyle Flexibility [LF - 3 items], Glycemic Control [GC - 3 items], Hypoglycemic Control [HC - 5 items], Insulin Delivery Device [IDD - 6 items]. Each Item is measured on a 7-point scale, with scores ranging for IR from 5 to 35, LF from 3 to 21, GC from 3 to 21, HC from 5 to 35, IDD from 6 to 42. Lower scores reflect better outcomes. Data presented are for Glycemic Control Domain Scores transformed on a 0-100 scale, where transformed domain score = 100×[(7-raw domain score)/6]. Higher scores indicate better glycemic control. Least squares (LS) mean estimated from analysis of covariance (ANCOVA) model that included baseline score as a covariate. | Baseline, Week 12 |