Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study Comparing LY900014 to Insulin Lispro (Humalog) in Adults With Type 1 Diabetes Using Insulin Pump Therapy (PRONTO-Pump-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03830281
Recruitment Status : Completed
First Posted : February 5, 2019
Results First Posted : January 22, 2021
Last Update Posted : January 22, 2021
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Type 1 Diabetes Mellitus
Interventions Drug: Ultra-Rapid Lispro
Drug: Insulin Lispro
Enrollment 471
Recruitment Details  
Pre-assignment Details The purpose of the lead-in period was to assess basal rates and bolus calculator settings and adjust if needed prior to randomization. Participants (Pts) were then randomized to insulin lispro (Humalog) or ultra-rapid lispro as both basal and bolus insulin and delivered bolus doses 0 to 2 minutes prior to each meal (pre-meal).
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description Participants received individual dose of 100 units per milliliter (U/mL) insulin lispro (Humalog) 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. Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Period Title: Lead-in Period (2 Weeks)
Started 471 0
Completed 432 0
Not Completed 39 0
Reason Not Completed
Adverse Event             2             0
Not Met Eligibility Criteria             6             0
Physician Decision             2             0
Withdrawal by Subject             29             0
Period Title: Treatment Period (16 Weeks)
Started 217 [1] 215 [1]
Completed 205 198
Not Completed 12 17
Reason Not Completed
Adverse Event             1             7
Lost to Follow-up             4             3
Sponsor Decision             1             1
Physician Decision             1             0
Withdrawal by Subject             5             6
[1]
Pts who completed lead-in period randomized to Humalog or Ultra-Rapid Lispro in treatment period.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro Total
Hide Arm/Group Description 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. Participants received individual dose of 100 U/mL ultra rapid lispro 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. Total of all reporting groups
Overall Number of Baseline Participants 217 215 432
Hide Baseline Analysis Population Description
All randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 217 participants 215 participants 432 participants
44.7  (14.9) 48.2  (15.4) 46.4  (15.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 217 participants 215 participants 432 participants
Female 119 120 239
Male 98 95 193
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 217 participants 215 participants 432 participants
Hispanic or Latino 17 18 35
Not Hispanic or Latino 180 178 358
Unknown or Not Reported 20 19 39
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 217 participants 215 participants 432 participants
American Indian or Alaska Native 0 2 2
Asian 0 2 2
Native Hawaiian or Other Pacific Islander 1 0 1
Black or African American 6 7 13
White 207 202 409
More than one race 1 0 1
Unknown or Not Reported 2 2 4
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 217 participants 215 participants 432 participants
Canada 11 11 22
Puerto Rico 2 3 5
Austria 8 8 16
Hungary 24 24 48
United States 86 84 170
Italy 9 9 18
Israel 22 19 41
Australia 15 15 30
France 7 7 14
Germany 17 19 36
Spain 16 16 32
Hemoglobin A1c  
Mean (Standard Deviation)
Unit of measure:  Percentage of HbA1c
Number Analyzed 217 participants 215 participants 432 participants
7.54  (0.58) 7.56  (0.59) 7.55  (0.58)
1.Primary Outcome
Title Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 16
Hide Description

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.

Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and at least one post-baseline HbA1c data.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description:
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.
Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Overall Number of Participants Analyzed 207 191
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of HbA1c
-0.09  (0.030) -0.06  (0.031)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro (Humalog), Ultra-Rapid Lispro
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Noninferiority margin = 0.4% for HbA1c
Statistical Test of Hypothesis P-Value 0.565
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.06 to 0.11
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in 1-hour Postprandial Glucose (PPG) During Mixed-Meal Tolerance Test (MMTT) Efficacy Estimand at Week 16
Hide Description 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.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and at least one post-baseline 1-hour PPG data.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description:
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.
Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Overall Number of Participants Analyzed 193 182
Least Squares Mean (Standard Error)
Unit of Measure: milligrams per deciliter (mg/dL)
-2.2  (5.02) -26.3  (5.33)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro (Humalog), Ultra-Rapid Lispro
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -24.1
Confidence Interval (2-Sided) 95%
-36.0 to -12.2
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in 2-hour PPG During MMTT Efficacy Estimand at Week 16
Hide Description 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.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and at least one post-baseline 2-hour PPG data.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description:
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.
Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Overall Number of Participants Analyzed 192 183
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-4.2  (6.27) -32.0  (6.59)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro (Humalog), Ultra-Rapid Lispro
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -27.8
Confidence Interval (2-Sided) 95%
-42.6 to -13.0
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Time With Sensor Glucose Values Between 70 and 180 mg/dL Efficacy Estimand at Week 16
Hide Description 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).
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing baseline value and at least one non-missing post-baseline value.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description:
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.
Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Overall Number of Participants Analyzed 181 172
Least Squares Mean (Standard Error)
Unit of Measure: percentage of time
Daytime Number Analyzed 181 participants 172 participants
58.6  (0.75) 59.3  (0.77)
24-Hour Number Analyzed 181 participants 171 participants
57.5  (0.76) 57.9  (0.79)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro (Humalog), Ultra-Rapid Lispro
Comments Statistical analysis during daytime is reported.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.532
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-1.4 to 2.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin Lispro (Humalog), Ultra-Rapid Lispro
Comments Statistical analysis during 24-hour period is reported.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.738
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-1.8 to 2.5
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Rate of Severe Hypoglycemia at Week 16
Hide Description 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.
Time Frame Baseline through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable hypoglycemic data.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description:
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.
Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Overall Number of Participants Analyzed 217 214
Measure Type: Number
Unit of Measure: Events per 100 participant years
2.95 6.36
6.Secondary Outcome
Title Rate of Documented Symptomatic Hypoglycemia at Week 16
Hide Description 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.
Time Frame Baseline through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable hypoglycemic data.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description:
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.
Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Overall Number of Participants Analyzed 217 214
Least Squares Mean (Standard Error)
Unit of Measure: Events per participant per year
30.7  (2.48) 24.6  (1.88)
7.Secondary Outcome
Title Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 16
Hide Description 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.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and at least one post-baseline 1,5-AG data.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description:
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.
Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Overall Number of Participants Analyzed 202 185
Least Squares Mean (Standard Error)
Unit of Measure: milligram per liter (mg/L)
0.16  (0.116) 0.11  (0.121)
8.Secondary Outcome
Title Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 16
Hide Description 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.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and at least one post-baseline SMBG data.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description:
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.
Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Overall Number of Participants Analyzed 195 178
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Morning Premeal Number Analyzed 195 participants 178 participants
0.2  (2.76) 0.5  (2.89)
Morning 1-hour Postmeal Number Analyzed 189 participants 172 participants
-3.1  (3.15) -12.9  (3.31)
Morning 2-hour Postmeal Number Analyzed 192 participants 172 participants
-2.7  (3.04) -2.9  (3.21)
Midday Premeal Number Analyzed 195 participants 175 participants
-0.6  (2.82) 4.9  (2.98)
Midday 1-hour Postmeal Number Analyzed 188 participants 166 participants
-4.2  (2.85) -6.3  (3.03)
Midday 2-hour Postmeal Number Analyzed 191 participants 171 participants
-0.2  (3.14) 4.4  (3.31)
Evening Premeal Number Analyzed 193 participants 178 participants
3.8  (3.28) 17.5  (3.41)
Evening 1-hour Postmeal Number Analyzed 189 participants 167 participants
2.6  (3.21) 8.6  (3.41)
Evening 2-hour Postmeal Number Analyzed 190 participants 171 participants
6.3  (3.36) 12.2  (3.54)
Bedtime Number Analyzed 180 participants 169 participants
8.6  (6.37) 19.0  (6.58)
9.Secondary Outcome
Title Change From Baseline in Insulin Dose at Week 16
Hide Description 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.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and at least one post-baseline basal insulin dose data.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description:
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.
Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Overall Number of Participants Analyzed 199 186
Least Squares Mean (Standard Error)
Unit of Measure: units per day (U/day)
Daily Basal Insulin Dose Number Analyzed 199 participants 186 participants
-0.2  (0.43) -0.1  (0.44)
Daily Bolus Insulin Dose Number Analyzed 197 participants 183 participants
0.8  (0.66) -1.0  (0.68)
Total Daily Insulin Dose Number Analyzed 195 participants 183 participants
0.6  (0.80) -1.1  (0.82)
10.Secondary Outcome
Title Change From Baseline in Bolus/Total Insulin Dose Ratio at Week 16
Hide Description 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.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with non-missing baseline value and at least one non-missing post-baseline value.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description:
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.
Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Overall Number of Participants Analyzed 195 183
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of bolus/total insulin dose
0.6  (0.66) -1.3  (0.68)
11.Secondary Outcome
Title Percentage of Participants With HbA1c <7%
Hide Description Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and at least one post-baseline HbA1c <7% data. Missing endpoints were imputed by applying the Last Observation Carried Forward (LOCF) method to the post-baseline data.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description:
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.
Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Overall Number of Participants Analyzed 207 191
Measure Type: Number
Unit of Measure: Percentage of participants
20.77 18.85
12.Secondary Outcome
Title Percentage of Participants With at Least 1 Pump Occlusion Alarm That Leads to an Unplanned Infusion Set Change
Hide Description Percentage of participants with at least 1 pump occlusion alarm that leads to an unplanned infusion set change was evaluated.
Time Frame Baseline through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and at least one post-baseline value.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description:
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.
Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Overall Number of Participants Analyzed 212 210
Measure Type: Number
Unit of Measure: Percentage of participants
12.7 14.8
13.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and at least one post-baseline value.
Arm/Group Title Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description:
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.
Participants received individual dose of 100 U/mL ultra rapid lispro 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.
Overall Number of Participants Analyzed 217 215
Measure Type: Number
Unit of Measure: Percentage of participants
18.4 16.3
Time Frame Up to 20 Weeks
Adverse Event Reporting Description All randomized participants. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
 
Arm/Group Title Insulin Lispro (Humalog) Lead-in Insulin Lispro (Humalog) Ultra-Rapid Lispro
Hide Arm/Group Description 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. 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. Participants received individual dose of 100 U/mL ultra rapid lispro 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.
All-Cause Mortality
Insulin Lispro (Humalog) Lead-in Insulin Lispro (Humalog) Ultra-Rapid Lispro
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/471 (0.00%)      0/217 (0.00%)      0/215 (0.00%)    
Hide Serious Adverse Events
Insulin Lispro (Humalog) Lead-in Insulin Lispro (Humalog) Ultra-Rapid Lispro
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/471 (0.85%)      10/217 (4.61%)      17/215 (7.91%)    
Cardiac disorders       
Acute myocardial infarction  1  0/471 (0.00%)  0 0/217 (0.00%)  0 1/215 (0.47%)  1
Myocardial infarction  1  0/471 (0.00%)  0 0/217 (0.00%)  0 2/215 (0.93%)  2
Stress cardiomyopathy  1  0/471 (0.00%)  0 0/217 (0.00%)  0 1/215 (0.47%)  1
Eye disorders       
Vitreous haemorrhage  1  1/471 (0.21%)  1 0/217 (0.00%)  0 0/215 (0.00%)  0
Gastrointestinal disorders       
Hiatus hernia  1  0/471 (0.00%)  0 1/217 (0.46%)  1 0/215 (0.00%)  0
Intestinal dilatation  1  0/471 (0.00%)  0 1/217 (0.46%)  1 0/215 (0.00%)  0
Intestinal obstruction  1  1/471 (0.21%)  1 0/217 (0.00%)  0 0/215 (0.00%)  0
General disorders       
Impaired healing  1  1/471 (0.21%)  1 0/217 (0.00%)  0 0/215 (0.00%)  0
Infections and infestations       
Abscess limb  1  1/471 (0.21%)  1 0/217 (0.00%)  0 0/215 (0.00%)  0
Gastroenteritis viral  1  0/471 (0.00%)  0 1/217 (0.46%)  1 0/215 (0.00%)  0
Herpes zoster oticus  1  0/471 (0.00%)  0 1/217 (0.46%)  1 0/215 (0.00%)  0
Pneumonia  1  1/471 (0.21%)  1 0/217 (0.00%)  0 0/215 (0.00%)  0
Injury, poisoning and procedural complications       
Fibula fracture  1  0/471 (0.00%)  0 0/217 (0.00%)  0 1/215 (0.47%)  1
Foreign body in respiratory tract  1  0/471 (0.00%)  0 0/217 (0.00%)  0 1/215 (0.47%)  1
Humerus fracture  1  0/471 (0.00%)  0 0/217 (0.00%)  0 1/215 (0.47%)  1
Maternal exposure during pregnancy  1  0/261 (0.00%)  0 1/119 (0.84%)  1 0/120 (0.00%)  0
Patella fracture  1  0/471 (0.00%)  0 1/217 (0.46%)  1 0/215 (0.00%)  0
Tibia fracture  1  0/471 (0.00%)  0 0/217 (0.00%)  0 1/215 (0.47%)  1
Investigations       
Intraocular pressure increased  1  1/471 (0.21%)  1 0/217 (0.00%)  0 0/215 (0.00%)  0
Metabolism and nutrition disorders       
Diabetic ketoacidosis  1  0/471 (0.00%)  0 3/217 (1.38%)  3 3/215 (1.40%)  3
Hypoglycaemia  1  0/471 (0.00%)  0 2/217 (0.92%)  2 5/215 (2.33%)  6
Ketosis  1  0/471 (0.00%)  0 0/217 (0.00%)  0 1/215 (0.47%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer  1  0/471 (0.00%)  0 0/217 (0.00%)  0 1/215 (0.47%)  1
Malignant melanoma  1  0/471 (0.00%)  0 1/217 (0.46%)  1 0/215 (0.00%)  0
Nervous system disorders       
Cerebrovascular accident  1  0/471 (0.00%)  0 0/217 (0.00%)  0 1/215 (0.47%)  1
Facial paralysis  1  0/471 (0.00%)  0 1/217 (0.46%)  1 0/215 (0.00%)  0
Renal and urinary disorders       
Acute kidney injury  1  0/471 (0.00%)  0 1/217 (0.46%)  1 0/215 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Respiratory failure  1  0/471 (0.00%)  0 0/217 (0.00%)  0 1/215 (0.47%)  1
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Insulin Lispro (Humalog) Lead-in Insulin Lispro (Humalog) Ultra-Rapid Lispro
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/471 (3.18%)      31/217 (14.29%)      90/215 (41.86%)    
General disorders       
Infusion site pain  1  3/471 (0.64%)  3 6/217 (2.76%)  6 35/215 (16.28%)  41
Infusion site reaction  1  6/471 (1.27%)  6 16/217 (7.37%)  16 47/215 (21.86%)  60
Infections and infestations       
Nasopharyngitis  1  6/471 (1.27%)  6 13/217 (5.99%)  14 13/215 (6.05%)  15
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
EMail: ClinicalTrials.gov@lilly.com
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT03830281    
Other Study ID Numbers: 16315
I8B-MC-ITRO ( Other Identifier: Eli Lilly and Company )
2015-005358-36 ( EudraCT Number )
First Submitted: February 4, 2019
First Posted: February 5, 2019
Results First Submitted: January 4, 2021
Results First Posted: January 22, 2021
Last Update Posted: January 22, 2021