A Study Comparing LY900014 to Insulin Lispro (Humalog) in Children and Adolescents With Type 1 Diabetes

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) in children and adolescents with type 1 diabetes (T1D).

Official Title
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A Prospective, Randomized, Double-Blind Comparison of LY900014 to Humalog With an Open-Label Postprandial LY900014 Treatment Group in Children and Adolescents 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: T1D for at least 6 months at the screening visit. Have been treated with only one of the following rapid-acting insulin analogs as part of an multiple daily injection regimen for at least the last 90 days prior to the screening visit: insulin lispro U-100, or insulin aspart insulin glulisine or fast acting insulin aspart Have been treated with only one of the following basal insulins for at least the last 90 days prior to the screening visit: insulin glargine U-100 (once a day [QD] or twice a day [BID]), or insulin detemir U-100 (QD or BID), or insulin degludec U-100 (QD) Have a HbA1c value ≤ 9.9% at the screening visit. Exclusion Criteria: Have current hypoglycemic unawareness or have had more than 1 episode of severe hypoglycemia within 6 months prior to the screening visit. Have had more than 1 emergency room visit or hospitalization due to poor glucose control within 6 months prior to the screening visit. Have been on a treatment regimen that includes regular human insulin, neutral protamine Hagedorn (NPH), Afrezza® (insulin human) inhalation powder, any premixed insulins or use of diluted insulins within 90 days prior to the screening visit.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 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 100 units per milliliter (U/mL) insulin lispro (Humalog) administered subcutaneously (SC), 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets. | Drug: Insulin Lispro<br>* Administered SC<br>* Other names: LY275585;Drug: Insulin Glargine<br>* Administered SC<br>Drug: Insulin Degludec<br>* Administered SC<br>|
| Experimental: LY900014<br>Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal. | Drug: LY900014<br>* Administered SC<br>* Other names: Ultra-Rapid Lispro;|
| Experimental: LY900014 Postmeal<br>Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal. | Drug: LY900014<br>* Administered SC<br>* Other names: Ultra-Rapid 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 26 | Change from baseline in HbA1c was analyzed using mixed model repeated measures (MMRM) and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. An unstructured covariance structure will be used to model the within-participant errors. The Efficacy estimand included data collected prior to permanent discontinuation of study drug through Week 26. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (Postprandial) at Week 26 | Change from baseline in HbA1c postprandial was analyzed using (MMRM and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. An unstructured covariance structure will be used to model the within-participant errors. The Efficacy estimand included data collected prior to permanent discontinuation of study drug through Week 26. | Baseline, Week 26 | 
| Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | Documented post-dose hypoglycemia <54 milligrams per deciliter (mg/dL) and ≤ 70 mg/dL that occurred 1 and 2 hours after prandial dose. | Baseline through Week 26 | 
| Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | Documented post-dose hypoglycemia event is an event of blood glucose of < 54 mg/dL and ≤70 mg/dL that occurred within 1 and 2 hours after the prandial dose. The rate of documented hypoglycemia was estimated by a negative binomial regression including treatment and age group as independent variable and number of episodes as dependent variables with log (exposure/365.25 days) as the offset in the model. | Baseline through Week 26 | 
| Percentage of Participants With Documented Hypoglycemic Events | Documented hypoglycemia is defined as <54 mg/dL and ≤70 mg/dL, respectively. | Baseline through Week 26 | 
| Rate of Documented Hypoglycemia Events | Documented hypoglycemia is defined as a hypoglycemic event of blood glucose of ≤70 mg/dL or <54 mg/dL. The rate of documented hypoglycemia was estimated by negative binomial regression including treatment and age group as independent variables and number of episodes as dependent variable with log (exposure/365.25 days) as the offset in the model. | Week 0 through Week 26 | 
| Rate of Severe Hypoglycemia | Severe hypoglycemia: during these episodes, participants have an altered mental status and cannot assist in their own care, may be semiconscious or unconscious, or experience coma with or without seizures, and require assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. The rate of severe hypoglycemia per 100 years was calculated as: 100 times the total number of severe hypoglycemia episodes within the period divided by total exposure (in year) for all participants within the treatment group. | Week 0 through Week 26 | 
| Change From Baseline in Insulin Dose at Week 26 | Change from baseline in insulin dose was analyzed using mixed model repeated measures (MMRM) and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, age group, and HbA1c stratum (≤8.0%, >8.0%)), baseline value, visit and treatment-by-visit interaction. An unstructured covariance structure was used to model the within-participant errors. | Baseline, Week 26 | 
| Percentage of Participants With HbA1c < 7.0% and <7.5% | Percentage of participants with HbA1c < 7.0% and <7.5% was analyzed using a longitudinal logistic regression with repeated measurements conducted by a generalized linear mixed model including independent variables of treatment, baseline HbA1c value, visit, baseline HbA1c-by-visit interaction, and treatment-by-visit interaction. An unstructured covariance structure was used. | Week 26 | 
| Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Change from baseline in 7-point SMBG values were analyzed using MMRM and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group, and HbA1c stratum (≤8.0%, >8.0%)) baseline value, visit, and treatment-by-visit interaction. An unstructured covariance structure was used to model the within-participant errors. | Baseline, Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prandial insulin, multiple daily injections, pediatric patients, postmeal dosing