Type 1 Diabetes Mellitus
Conditions
Keywords
prandial insulin, multiple daily injections, pediatric patients, postmeal dosing
Brief summary
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).
Interventions
DRUGLY900014
Administered SC
DRUGInsulin Lispro
Administered SC
DRUGInsulin Glargine
Administered SC
DRUGInsulin Degludec
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Years to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26 | Baseline, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (Postprandial) at Week 26 | Baseline, 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. |
| Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | Baseline through Week 26 | Documented post-dose hypoglycemia \<54 milligrams per deciliter (mg/dL) and ≤ 70 mg/dL that occurred 1 and 2 hours after prandial dose. |
| Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | Baseline through Week 26 | 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. |
| Percentage of Participants With Documented Hypoglycemic Events | Baseline through Week 26 | Documented hypoglycemia is defined as \<54 mg/dL and ≤70 mg/dL, respectively. |
| Percentage of Participants With HbA1c < 7.0% and <7.5% | Week 26 | 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. |
| Rate of Severe Hypoglycemia | Week 0 through Week 26 | 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. |
| 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) 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. |
| Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Baseline, 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. |
| Rate of Documented Hypoglycemia Events | Week 0 through Week 26 | 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. |
Countries
Austria, Brazil, China, Czechia, Denmark, France, Germany, Israel, Italy, Japan, Mexico, Poland, Puerto Rico, Russia, Spain, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The study included a 4-week lead-in period using open-label insulin lispro (Humalog) followed by a 26-week double-blind treatment period (LY900014 and Insulin Lispro) and one Open-label treatment arm (LY900014 Postmeal).
Pre-assignment details
The purpose of the lead-in period was to obtain blood glucose (BG) values along with basal and prandial insulin doses to assess basal and mealtime insulin dosing and to determine baseline hypoglycemia rates.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Lispro (Humalog) Participants received 100 U/mL insulin lispro (Humalog) administered 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. | 298 |
| LY900014 Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal. | 280 |
| LY900014 Postmeal Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal. | 138 |
| Total | 716 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Lead-in Period | Due to Coronavirus Disease 2019 (COVID-19) | 18 | 0 | 0 | 0 |
| Lead-in Period | Lab Results Did Not Match Inclusion Criteria | 1 | 0 | 0 | 0 |
| Lead-in Period | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Lead-in Period | Physician Decision | 2 | 0 | 0 | 0 |
| Lead-in Period | Protocol Violation | 1 | 0 | 0 | 0 |
| Lead-in Period | Study Task Too Burdensome | 1 | 0 | 0 | 0 |
| Lead-in Period | Withdrawal by Subject | 10 | 0 | 0 | 0 |
| Lead-in Period | Withdrew Consent Due to Required Procedures | 1 | 0 | 0 | 0 |
| Treatment Period | Adverse Event | 0 | 0 | 2 | 0 |
| Treatment Period | Due to COVID-19 Pandemic | 0 | 0 | 3 | 1 |
| Treatment Period | Failure of Inclusion Criteria | 0 | 0 | 1 | 0 |
| Treatment Period | Insulin Painful to Participant | 0 | 0 | 1 | 0 |
| Treatment Period | Issue with Insulin Pump | 0 | 1 | 0 | 0 |
| Treatment Period | Not Completing Diary | 0 | 0 | 1 | 0 |
| Treatment Period | Protocol Violation | 0 | 1 | 0 | 0 |
| Treatment Period | Terminated by Sponsor | 0 | 1 | 0 | 0 |
| Treatment Period | Withdrawal by Subject | 0 | 7 | 6 | 2 |
Baseline characteristics
| Characteristic | Insulin Lispro (Humalog) | Total | LY900014 Postmeal | LY900014 |
|---|---|---|---|---|
| Age, Continuous | 12.4 years STANDARD_DEVIATION 3.2 | 12.3 years STANDARD_DEVIATION 3.4 | 12.3 years STANDARD_DEVIATION 3.8 | 12.1 years STANDARD_DEVIATION 3.4 |
| HbA1c at Baseline | 7.81 percentage of HbA1c STANDARD_DEVIATION 0.91 | 7.80 percentage of HbA1c STANDARD_DEVIATION 0.88 | 7.77 percentage of HbA1c STANDARD_DEVIATION 0.85 | 7.81 percentage of HbA1c STANDARD_DEVIATION 0.87 |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 12 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 20 Participants | 40 Participants | 7 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 11 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 5 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 8 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 256 Participants | 638 Participants | 126 Participants | 256 Participants |
| Region of Enrollment Austria | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Brazil | 22 Participants | 55 Participants | 13 Participants | 20 Participants |
| Region of Enrollment China | 11 Participants | 22 Participants | 4 Participants | 7 Participants |
| Region of Enrollment Czechia | 26 Participants | 60 Participants | 11 Participants | 23 Participants |
| Region of Enrollment Denmark | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment France | 1 Participants | 4 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Germany | 6 Participants | 17 Participants | 4 Participants | 7 Participants |
| Region of Enrollment Israel | 15 Participants | 35 Participants | 5 Participants | 15 Participants |
| Region of Enrollment Italy | 15 Participants | 36 Participants | 6 Participants | 15 Participants |
| Region of Enrollment Japan | 7 Participants | 12 Participants | 2 Participants | 3 Participants |
| Region of Enrollment Mexico | 25 Participants | 58 Participants | 11 Participants | 22 Participants |
| Region of Enrollment Poland | 14 Participants | 33 Participants | 6 Participants | 13 Participants |
| Region of Enrollment Russia | 23 Participants | 56 Participants | 12 Participants | 21 Participants |
| Region of Enrollment Spain | 21 Participants | 48 Participants | 8 Participants | 19 Participants |
| Region of Enrollment Ukraine | 57 Participants | 137 Participants | 27 Participants | 53 Participants |
| Region of Enrollment United Kingdom | 3 Participants | 10 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 51 Participants | 131 Participants | 25 Participants | 55 Participants |
| Sex: Female, Male Female | 140 Participants | 349 Participants | 65 Participants | 144 Participants |
| Sex: Female, Male Male | 158 Participants | 367 Participants | 73 Participants | 136 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 751 | 0 / 298 | 0 / 280 | 0 / 138 |
| other Total, other adverse events | 39 / 751 | 60 / 298 | 67 / 280 | 21 / 138 |
| serious Total, serious adverse events | 2 / 751 | 12 / 298 | 6 / 280 | 2 / 138 |
Outcome results
Primary
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.
Time frame: Baseline, Week 26
Population: All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug, per protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro (Humalog) | Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26 | 0.09 percentage of HbA1c | Standard Error 0.052 |
| LY900014 | Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26 | 0.06 percentage of HbA1c | Standard Error 0.054 |
p-value: 0.78395% CI: [-0.17, 0.13]Mixed Models Analysis
Secondary
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.
Time frame: Baseline, Week 26
Population: All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro (Humalog) | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Morning 1 hour Postmeal | -3.2 mg/dL | Standard Error 2.92 |
| Insulin Lispro (Humalog) | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Evening Premeal | 1.0 mg/dL | Standard Error 3.18 |
| Insulin Lispro (Humalog) | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Midday 1 hour Postmeal | 0.9 mg/dL | Standard Error 2.99 |
| Insulin Lispro (Humalog) | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Morning Premeal - Fasting | 1.0 mg/dL | Standard Error 2.78 |
| Insulin Lispro (Humalog) | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Bedtime | -1.9 mg/dL | Standard Error 3.03 |
| Insulin Lispro (Humalog) | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Evening 1 hour Postmeal | 6.9 mg/dL | Standard Error 3.22 |
| Insulin Lispro (Humalog) | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Midday Premeal | -3.1 mg/dL | Standard Error 3.06 |
| LY900014 | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Midday 1 hour Postmeal | -5.2 mg/dL | Standard Error 3.14 |
| LY900014 | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Morning Premeal - Fasting | -3.4 mg/dL | Standard Error 2.88 |
| LY900014 | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Morning 1 hour Postmeal | -17.9 mg/dL | Standard Error 3.06 |
| LY900014 | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Midday Premeal | 2.5 mg/dL | Standard Error 3.17 |
| LY900014 | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Evening Premeal | 4.6 mg/dL | Standard Error 3.29 |
| LY900014 | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Evening 1 hour Postmeal | -6.2 mg/dL | Standard Error 3.39 |
| LY900014 | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Bedtime | -2.3 mg/dL | Standard Error 3.14 |
| LY900014 Postmeal | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Evening Premeal | 0.3 mg/dL | Standard Error 4.69 |
| LY900014 Postmeal | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Morning 1 hour Postmeal | -9.8 mg/dL | Standard Error 4.39 |
| LY900014 Postmeal | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Bedtime | -2.7 mg/dL | Standard Error 4.53 |
| LY900014 Postmeal | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Evening 1 hour Postmeal | -3.9 mg/dL | Standard Error 4.79 |
| LY900014 Postmeal | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Midday 1 hour Postmeal | -1.5 mg/dL | Standard Error 4.43 |
| LY900014 Postmeal | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Midday Premeal | -6.0 mg/dL | Standard Error 4.52 |
| LY900014 Postmeal | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 | Morning Premeal - Fasting | -5.9 mg/dL | Standard Error 4.11 |
Secondary
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.
Time frame: Baseline, Week 26
Population: All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug, per protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro (Humalog) | Change From Baseline in HbA1c (Postprandial) at Week 26 | 0.09 percentage of HbA1c | Standard Error 0.052 |
| LY900014 | Change From Baseline in HbA1c (Postprandial) at Week 26 | 0.07 percentage of HbA1c | Standard Error 0.076 |
p-value: 0.86795% CI: [-0.2, 0.17]Mixed Models Analysis
Secondary
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.
Time frame: Baseline, Week 26
Population: All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro (Humalog) | Change From Baseline in Insulin Dose at Week 26 | Total Daily Basal Insulin Dose | 2.3 Unit per day | Standard Error 0.28 |
| Insulin Lispro (Humalog) | Change From Baseline in Insulin Dose at Week 26 | Total Daily Insulin Dose | 5.3 Unit per day | Standard Error 0.66 |
| LY900014 | Change From Baseline in Insulin Dose at Week 26 | Total Daily Basal Insulin Dose | 2.9 Unit per day | Standard Error 0.29 |
| LY900014 | Change From Baseline in Insulin Dose at Week 26 | Total Daily Insulin Dose | 5.8 Unit per day | Standard Error 0.69 |
| LY900014 Postmeal | Change From Baseline in Insulin Dose at Week 26 | Total Daily Basal Insulin Dose | 2.7 Unit per day | Standard Error 0.4 |
| LY900014 Postmeal | Change From Baseline in Insulin Dose at Week 26 | Total Daily Insulin Dose | 5.0 Unit per day | Standard Error 0.96 |
Comparison: Total Daily Basal Insulinp-value: 0.1395% CI: [-0.2, 1.4]Mixed Models Analysis
Comparison: Total Daily Basal Insulinp-value: 0.40495% CI: [-0.5, 1.4]Mixed Models Analysis
Comparison: Total Daily Basal Insulinp-value: 0.69395% CI: [-1.2, 0.8]Mixed Models Analysis
Comparison: Total Daily Insulin Dosep-value: 0.62595% CI: [-1.4, 2.3]Mixed Models Analysis
Comparison: Total Daily Insulin Dosep-value: 0.75895% CI: [-2.6, 1.9]Mixed Models Analysis
Comparison: Total Daily Insulin Dosep-value: 0.48595% CI: [-3.1, 1.5]Mixed Models Analysis
Secondary
Percentage of Participants With Documented Hypoglycemic Events
Documented hypoglycemia is defined as \<54 mg/dL and ≤70 mg/dL, respectively.
Time frame: Baseline through Week 26
Population: All randomized participants who received at least one dose of the randomly assigned study drug with non-missing baseline value and at least one non-missing post-baseline value of the response variable.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro (Humalog) | Percentage of Participants With Documented Hypoglycemic Events | ≤70 mg/dL | 93.98 percentage of participants | Standard Error 1.375 |
| Insulin Lispro (Humalog) | Percentage of Participants With Documented Hypoglycemic Events | <54 mg/dL | 80.81 percentage of participants | Standard Error 2.283 |
| LY900014 | Percentage of Participants With Documented Hypoglycemic Events | <54 mg/dL | 81.37 percentage of participants | Standard Error 2.329 |
| LY900014 | Percentage of Participants With Documented Hypoglycemic Events | ≤70 mg/dL | 92.55 percentage of participants | Standard Error 1.569 |
| LY900014 Postmeal | Percentage of Participants With Documented Hypoglycemic Events | <54 mg/dL | 74.45 percentage of participants | Standard Error 3.718 |
| LY900014 Postmeal | Percentage of Participants With Documented Hypoglycemic Events | ≤70 mg/dL | 87.62 percentage of participants | Standard Error 2.806 |
Comparison: \<54 mg/dLp-value: 0.86495% CI: [0.68, 1.57]Regression, Logistic
Comparison: \<54 mg/dLp-value: 0.13295% CI: [0.43, 1.12]Regression, Logistic
p-value: 0.10495% CI: [0.41, 1.09]Regression, Logistic
Comparison: ≤70 mg/dLp-value: 0.48995% CI: [0.42, 1.52]Regression, Logistic
Comparison: ≤70 mg/dLp-value: 0.02595% CI: [0.23, 0.9]Regression, Logistic
Comparison: ≤70 mg/dLp-value: 0.09995% CI: [0.29, 1.11]Regression, Logistic
Secondary
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.
Time frame: Baseline through Week 26
Population: All randomized participants who received at least one dose of the randomly assigned study drug with non-missing baseline value and at least one non-missing post-baseline value of the response variable.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro (Humalog) | Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | <54 mg/dL 1 Hour Post Dose | 26.50 percentage of participants | Standard Error 2.563 |
| Insulin Lispro (Humalog) | Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | <54 mg/dL 2 Hour Post Dose | 54.04 percentage of participants | Standard Error 2.896 |
| Insulin Lispro (Humalog) | Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | ≤70 mg/dL 1 Hour Post Dose | 49.67 percentage of participants | Standard Error 2.901 |
| Insulin Lispro (Humalog) | Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | ≤70 mg/dL 2 Hour Post Dose | 77.03 percentage of participants | Standard Error 2.449 |
| LY900014 | Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | ≤70 mg/dL 2 Hour Post Dose | 82.67 percentage of participants | Standard Error 2.267 |
| LY900014 | Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | <54 mg/dL 1 Hour Post Dose | 36.79 percentage of participants | Standard Error 2.891 |
| LY900014 | Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | ≤70 mg/dL 1 Hour Post Dose | 63.92 percentage of participants | Standard Error 2.874 |
| LY900014 | Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | <54 mg/dL 2 Hour Post Dose | 63.61 percentage of participants | Standard Error 2.883 |
| LY900014 Postmeal | Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | ≤70 mg/dL 2 Hour Post Dose | 70.29 percentage of participants | Standard Error 3.912 |
| LY900014 Postmeal | Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | <54 mg/dL 2 Hour Post Dose | 57.88 percentage of participants | Standard Error 4.216 |
| LY900014 Postmeal | Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | ≤70 mg/dL 1 Hour Post Dose | 48.51 percentage of participants | Standard Error 4.261 |
| LY900014 Postmeal | Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | <54 mg/dL 1 Hour Post Dose | 29.70 percentage of participants | Standard Error 3.897 |
Comparison: \< 54 mg/dL 1 hour post-dosep-value: 0.00895% CI: [1.13, 2.3]Regression, Logistic
Comparison: \< 54 mg/dL 1 hour post-dosep-value: 0.48795% CI: [0.75, 1.83]Regression, Logistic
Comparison: \< 54 mg/dL 1 hour post-dosep-value: 0.15395% CI: [0.47, 1.13]Regression, Logistic
Comparison: \< 54 mg/dL 2 hour post-dosep-value: 0.0295% CI: [1.06, 2.08]Regression, Logistic
Comparison: \< 54 mg/dL 2 hour post-dosep-value: 0.45595% CI: [0.78, 1.76]Regression, Logistic
Comparison: \< 54 mg/dL 2 hour post-dosep-value: 0.25995% CI: [0.52, 1.19]Regression, Logistic
Comparison: ≤ 70 mg/dL 1 hour post-dosep-value: <0.00195% CI: [1.29, 2.51]Regression, Logistic
Comparison: ≤ 70 mg/dL 1 hour post-dosep-value: 0.82295% CI: [0.64, 1.43]Regression, Logistic
Comparison: ≤ 70 mg/dL 1 hour post-dosep-value: 0.00395% CI: [0.35, 0.8]Regression, Logistic
Comparison: ≤ 70 mg/dL 2 hour post-dosep-value: 0.09295% CI: [0.94, 2.14]Regression, Logistic
Comparison: ≤ 70 mg/dL 2 hour post-dosep-value: 0.13395% CI: [0.45, 1.11]Regression, Logistic
Comparison: ≤ 70 mg/dL 2 hour post-dosep-value: 0.00495% CI: [0.31, 0.8]Regression, Logistic
Secondary
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.
Time frame: Week 26
Population: All participants who were randomly assigned to study drug and had non-missing baseline value and at least one non-missing post-baseline value of the response variable.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Lispro (Humalog) | Percentage of Participants With HbA1c < 7.0% and <7.5% | HbA1c <7% | 20.00 percentage of participants |
| Insulin Lispro (Humalog) | Percentage of Participants With HbA1c < 7.0% and <7.5% | HbA1c < 7.5% | 40.00 percentage of participants |
| LY900014 | Percentage of Participants With HbA1c < 7.0% and <7.5% | HbA1c <7% | 21.92 percentage of participants |
| LY900014 | Percentage of Participants With HbA1c < 7.0% and <7.5% | HbA1c < 7.5% | 37.31 percentage of participants |
| LY900014 Postmeal | Percentage of Participants With HbA1c < 7.0% and <7.5% | HbA1c <7% | 19.08 percentage of participants |
| LY900014 Postmeal | Percentage of Participants With HbA1c < 7.0% and <7.5% | HbA1c < 7.5% | 32.82 percentage of participants |
Comparison: HbA1c \< 7%p-value: 0.39695% CI: [0.76, 2]Regression, Logistic
Comparison: HbA1c \< 7%p-value: 0.81495% CI: [0.49, 1.75]Regression, Logistic
Comparison: HbA1c \< 7%p-value: 0.38495% CI: [0.39, 1.43]Regression, Logistic
Comparison: HbA1c \< 7.5%p-value: 0.495% CI: [0.55, 1.27]Regression, Logistic
Comparison: HbA1c \< 7.5%p-value: 0.09495% CI: [0.36, 1.08]Regression, Logistic
Comparison: HbA1c \< 7.5%p-value: 0.30695% CI: [0.43, 1.31]Regression, Logistic
Secondary
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.
Time frame: Week 0 through Week 26
Population: All randomized participants who received at least one dose of the randomly assigned study drug with non-missing baseline value and at least one non-missing post-baseline value of the response variable.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro (Humalog) | Rate of Documented Hypoglycemia Events | < 54 mg/dL | 16.6 events per participant per year | Standard Error 1.23 |
| Insulin Lispro (Humalog) | Rate of Documented Hypoglycemia Events | ≤70 mg/dL | 78.0 events per participant per year | Standard Error 4.23 |
| LY900014 | Rate of Documented Hypoglycemia Events | < 54 mg/dL | 16.1 events per participant per year | Standard Error 1.2 |
| LY900014 | Rate of Documented Hypoglycemia Events | ≤70 mg/dL | 75.1 events per participant per year | Standard Error 4.44 |
| LY900014 Postmeal | Rate of Documented Hypoglycemia Events | < 54 mg/dL | 17.7 events per participant per year | Standard Error 1.99 |
| LY900014 Postmeal | Rate of Documented Hypoglycemia Events | ≤70 mg/dL | 76.1 events per participant per year | Standard Error 6.1 |
Comparison: \< 54 mg/dLp-value: 0.732Negative binomial regression
Comparison: \< 54 mg/dLp-value: 0.638Negative binomial regression
Comparison: \<54 mg/dLp-value: 0.462Negative binomial regression
Comparison: ≤ 70 mg/dLp-value: 0.632Negative binomial regression
Comparison: ≤ 70 mg/dLp-value: 0.8Negative binomial regression
Comparison: ≤ 70 mg/dLp-value: 0.889Negative binomial regression
Secondary
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.
Time frame: Baseline through Week 26
Population: All randomized participants who received at least one dose of the randomly assigned study drug with non-missing baseline value and at least one non-missing post-baseline value of the response variable.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro (Humalog) | Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | < 54mg/dL 1 Hour Post Dose | 1.59 Events per participant per year | Standard Error 0.251 |
| Insulin Lispro (Humalog) | Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | < 54 mg/dL 2 Hour Post Dose | 4.48 Events per participant per year | Standard Error 0.454 |
| Insulin Lispro (Humalog) | Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | ≤70 mg/dL 1 Hour Post Dose | 6.54 Events per participant per year | Standard Error 1.036 |
| Insulin Lispro (Humalog) | Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | ≤70 mg/dL 2 Hour Post Dose | 19.0 Events per participant per year | Standard Error 1.58 |
| LY900014 | Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | ≤70 mg/dL 2 Hour Post Dose | 23.7 Events per participant per year | Standard Error 1.86 |
| LY900014 | Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | < 54mg/dL 1 Hour Post Dose | 2.04 Events per participant per year | Standard Error 0.262 |
| LY900014 | Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | ≤70 mg/dL 1 Hour Post Dose | 8.46 Events per participant per year | Standard Error 0.992 |
| LY900014 | Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | < 54 mg/dL 2 Hour Post Dose | 5.95 Events per participant per year | Standard Error 0.51 |
| LY900014 Postmeal | Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | ≤70 mg/dL 2 Hour Post Dose | 21.1 Events per participant per year | Standard Error 2.31 |
| LY900014 Postmeal | Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | < 54 mg/dL 2 Hour Post Dose | 6.17 Events per participant per year | Standard Error 0.816 |
| LY900014 Postmeal | Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | ≤70 mg/dL 1 Hour Post Dose | 5.29 Events per participant per year | Standard Error 1.145 |
| LY900014 Postmeal | Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose | < 54mg/dL 1 Hour Post Dose | 1.38 Events per participant per year | Standard Error 0.287 |
Comparison: \< 54 mg/dL 1 hour post-dosep-value: 0.599Negative binomial regression
Comparison: \< 54 mg/dL 1 hour post-dosep-value: 0.112Negative binomial regression
Comparison: \< 54 mg/dL 2 hour post-dosep-value: 0.034Negative binomial regression
Comparison: \< 54 mg/dL 2 hour post-dosep-value: 0.055Negative binomial regression
Comparison: \< 54 mg/dL 2 hour post-dosep-value: 0.814Negative binomial regression
Comparison: ≤70 mg/dL 1 hour post-dosep-value: 0.194Negative binomial regression
Comparison: \< 54 mg/dL 1 hour post-dosep-value: 0.22Negative binomial regression
Comparison: ≤70 mg/dL 1 hour post-dosep-value: 0.428Negative binomial regression
Comparison: ≤70 mg/dL 1 hour post-dosep-value: 0.057Negative binomial regression
Comparison: ≤70 mg/dL 2 hour post-dosep-value: 0.056Negative binomial regression
Comparison: ≤70 mg/dL 2 hour post-dosep-value: 0.435Negative binomial regression
Comparison: ≤70 mg/dL 2 hour post-dosep-value: 0.404Negative binomial regression
Secondary
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.
Time frame: Week 0 through Week 26
Population: All randomized participants who received at least one dose of the randomly assigned study drug with non-missing baseline value and at least one non-missing post-baseline value of the response variable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Lispro (Humalog) | Rate of Severe Hypoglycemia | 2.05 Events per participant per 100 years |
| LY900014 | Rate of Severe Hypoglycemia | 2.20 Events per participant per 100 years |
| LY900014 Postmeal | Rate of Severe Hypoglycemia | 0.00 Events per participant per 100 years |