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Insulin Lispro 6 Days Versus Insulin Aspart 6 Days in Pump Use

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ClinicalTrials.gov Identifier: NCT01134107
Recruitment Status : Completed
First Posted : May 31, 2010
Results First Posted : October 26, 2012
Last Update Posted : April 11, 2013
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 1
Interventions Drug: Insulin Lispro 6 Day (6D)
Drug: Insulin Aspart 6 Day (6D)
Enrollment 133
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Lispro 6D/Aspart 6D Aspart 6D/Lispro 6D
Hide Arm/Group Description Insulin Lispro 6 Day (6D) administered by infusion pump for 12 weeks, followed by Insulin Aspart 6D administered by infusion pump for 12 weeks. Insulin Aspart 6D administered by infusion pump for 12 weeks, followed by Insulin Lispro 6D administered by infusion pump for 12 weeks.
Period Title: Period 1-First Treatment Intervention
Started 67 66
Received at Least One Dose of Study Drug 66 66
Completed 61 61
Not Completed 6 5
Reason Not Completed
Adverse Event             1             0
Entry Criteria Not Met             1             1
Withdrawal by Subject             3             4
Physician Decision             1             0
Period Title: Period 2-Second Treatment Intervention
Started 61 61
Completed 57 61
Not Completed 4 0
Reason Not Completed
Withdrawal by Subject             2             0
Physician Decision             1             0
Sponsor Decision             1             0
Arm/Group Title Lispro 6D/Aspart 6D Aspart 6D/Lispro 6D Total
Hide Arm/Group Description Insulin Lispro 6D administered by infusion pump for 12 weeks, followed by Insulin Aspart 6D administered by infusion pump for 12 weeks. Insulin Aspart 6D administered by infusion pump for 12 weeks, followed by Insulin Lispro 6D administered by infusion pump for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 67 66 133
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 67 participants 66 participants 133 participants
40.71  (11.91) 44.73  (12.96) 42.70  (12.56)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 66 participants 133 participants
Female
48
  71.6%
45
  68.2%
93
  69.9%
Male
19
  28.4%
21
  31.8%
40
  30.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
White Number Analyzed 67 participants 66 participants 133 participants
67 66 133
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 67 participants 66 participants 133 participants
France 15 14 29
Hungary 33 37 70
Germany 19 15 34
1.Primary Outcome
Title Mean of Last Six 7-point Self Monitored Blood Glucose (SMBG) Taken on Day 6 for Insulin Lispro 6D and Insulin Aspart 6D Pump Reservoir In-use
Hide Description [Not Specified]
Time Frame Day 6 of each reservoir cycle for the last 6 weeks of each 12-week treatment period (Week 7 through Week 12)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who completed at least one post-randomization visit. Those included in the primary analysis had to have at least one reservoir in-use cycle with an SMBG measurement on Day 6 during the pre-specified collection period.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 118 118
Mean (Standard Deviation)
Unit of Measure: millimoles per liter (mmol/L)
8.83  (1.55) 8.43  (1.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments This was the primary gated analysis.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority margin of 0.6 mmol/L was used.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
0.06 to 0.66
Estimation Comments Least Squares Mean Difference = Insulin Lispro 6 Day minus Insulin Aspart 6 Day; adjusted for Treatment + Sequence + Period + Baseline HbA1c
2.Secondary Outcome
Title Mean SMBG
Hide Description Mean SMBG for combined periods; all reported SMBG values on Days 1-6, Day 2, and Day 6 for Insulin Lispro 6D and Insulin Aspart 6D.
Time Frame Days 1-6 and Day 2 and Day 6 for each reservoir cycle throughout each 12-week treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who completed at least one post-randomization visit and one SMBG measurement on a Day 6, or Day 2 depending on the analysis, for the respective treatment arm: insulin lispro 6D and insulin aspart 6D.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 126 126
Mean (Standard Deviation)
Unit of Measure: millimoles per liter (mmol/L)
SMBG Days 1-6 (N=124, 124) 8.70  (2.51) 8.47  (2.46)
SMBG Day 2 8.56  (2.51) 8.40  (2.47)
SMBG Day 6 (N=124, 124) 8.93  (2.68) 8.57  (2.64)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority margin of 0.6 mmol/L was used.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.18
Confidence Interval (2-Sided) 95%
-0.10 to 0.47
Estimation Comments Least Squares Mean Difference = Insulin Lispro 6 Day (Day 1-6) minus Insulin Aspart 6 Day (Day 1-6); adjusted for Treatment + Sequence + Period + Baseline HbA1c
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority margin of 0.6 mmol/L was used.
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.25 to 0.58
Estimation Comments Least Squares Mean Difference = Insulin Lispro 6 Day (Day 6) minus Insulin Lispro 6 Day (Day 2); adjusted for DayGroup + Period + Baseline HbA1c
3.Secondary Outcome
Title Mean Daily Insulin Dose (Total, Basal, and Bolus)
Hide Description [Not Specified]
Time Frame Days 1-6 for each reservoir cycle throughout each 12-week treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who completed at least one post-randomization visit. Participants included in insulin analyses are only those for whom data existed regarding insulin dose.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 119 119
Mean (Standard Deviation)
Unit of Measure: Units (U) of insulin
Daily Total Insulin 32.90  (8.43) 32.48  (8.42)
Daily Basal Insulin 17.83  (5.26) 17.71  (5.27)
Daily Bolus Insulin (N=116, 117) 16.26  (6.21) 16.09  (6.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
-0.13 to 0.88
Estimation Comments Daily Total Insulin: Least Squares Mean Difference = Insulin Lispro 6 Day minus Insulin Aspart 6 Day; adjusted for Treatment + Sequence + Period + Baseline Insulin Basal/Bolus/Total Dose
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.26 to 0.31
Estimation Comments Daily Basal Insulin: Least Squares Mean Difference = Insulin Lispro 6 Day minus Insulin Aspart 6 Day; adjusted for Treatment + Sequence + Period + Baseline Insulin Basal/Bolus/Total Dose
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
-0.15 to 0.60
Estimation Comments Daily Bolus Insulin: Least Squares Mean Difference = Insulin Lispro 6 Day minus Insulin Aspart 6 Day; adjusted for Treatment + Sequence + Period + Baseline Insulin Basal/Bolus/Total Dose
4.Secondary Outcome
Title Change From Baseline to 12 Weeks for Each Treatment in Glycated Hemoglobin A1c (HbA1c) Values
Hide Description [Not Specified]
Time Frame Baseline, endpoint for each 12-week treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who completed at least one post-randomization visit, and had a baseline and a post-randomization HbA1c measurement for the respective treatment period. Last Observation Carried Forward (LOCF) method was utilized in this analysis.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 127 126
Mean (Standard Deviation)
Unit of Measure: percentage of HbA1c
-0.16  (0.54) -0.31  (0.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
0.08 to 0.24
Estimation Comments Least Squares Mean Difference = Insulin Lispro 6 Day minus Insulin Aspart 6 Day; adjusted for Treatment + Period + Sequence + Baseline HbA1c
5.Secondary Outcome
Title Number of Participants Who Achieve or Maintain a Glycated Hemoglobin A1c (HbA1c) Less Than or Equal to 6.5% and Less Than 7%
Hide Description [Not Specified]
Time Frame Endpoint for each 12-week treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who completed a post-randomization visit and had an HbA1c measurement for the respective treatment period.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 127 126
Measure Type: Number
Unit of Measure: participants
HbA1c ≤6.5% 18 21
HbA1c <7% 38 56
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.39 to 1.63
Estimation Comments Odds Ratio of HbA1c ≤6.5% for Insulin Lispro 6 Day versus Insulin Aspart 6 Day.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
0.20 to 0.63
Estimation Comments Odds Ratio of HbA1c <7% for Insulin Lispro 6 Day versus Insulin Aspart 6 Day.
6.Other Pre-specified Outcome
Title Change From Baseline to 12 Weeks for Daily Insulin Dose (Total, Basal, and Bolus)
Hide Description [Not Specified]
Time Frame Baseline, endpoint for each 12-week treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who completed at least one post-randomization visit. Participants included in insulin analyses are only those for whom data existed regarding insulin dose.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 119 115
Mean (Standard Deviation)
Unit of Measure: Units (U) of insulin
Total Insulin Dose 5.21  (8.94) 4.97  (7.57)
Basal Insulin Dose 2.34  (3.51) 1.91  (3.80)
Bolus Insulin Dose (N=112, 112) 2.19  (5.58) 1.80  (4.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.595
Comments P-value for Total Insulin Dose computed using Crossover model: Variable = Treatment + Sequence + Period + Baseline Insulin Total Dose.
Method Crossover Model
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.506
Comments P-value for Basal Insulin Dose computed using Crossover model: Variable = Treatment + Sequence + Period + Baseline Insulin Basal Dose.
Method Crossover Model
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.790
Comments P-value for Bolus Insulin Dose computed using Crossover model: Variable = Treatment + Sequence + Period + Baseline Insulin Bolus Dose.
Method Crossover Model
Comments [Not Specified]
7.Other Pre-specified Outcome
Title Percentage of Participants Having a Hyperglycemic Episode
Hide Description A hyperglycemic episode was defined as an event with (1) a measured blood glucose concentration >250 milligrams per deciliter (mg/dL) (13.9 millimoles per liter [mmol/L]) and ≥3 hours after eating, or (2) a measured blood glucose concentration >300 mg/dL (16.7 mmol/L) and <3 hours after eating
Time Frame Days 1-6 for each reservoir cycle throughout each 12-week treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug. Participants included in hyperglycemia analyses are only those for whom data existed regarding hyperglycemia.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 124 124
Measure Type: Number
Unit of Measure: percentage of participants
97.6 98.4
8.Other Pre-specified Outcome
Title Hyperglycemic Episode Rate Per 30 Days
Hide Description Hyperglycemia was defined as an episode with (1) a measured blood glucose concentration >250 milligrams per deciliter [mg/dL] (13.9 millimoles per liter [mmol/L]) and ≥3 hours after eating, or (2) a measured blood glucose concentration >300 mg/dL (16.7 mmol/L) and <3 hours after eating. Rate is presented as the number of hyperglycemic episodes adjusted for 30 days.
Time Frame Days 1-6 for each reservoir cycle throughout each 12-week treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug. Participants included in hyperglycemia analyses are only those for whom data existed regarding hyperglycemia.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 124 124
Mean (Standard Deviation)
Unit of Measure: hyperglycemic episodes per 30 days
15.47  (9.25) 14.23  (10.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.059
Comments [Not Specified]
Method negative binomial test
Comments P-value computed using a negative binomial test including factors for treatment, period and sequence.
9.Other Pre-specified Outcome
Title Percentage of Participants With Pump Complications
Hide Description Overall pump complications are defined as any combination of the following, reported by the participant: tubing clogged, tubing kinked, tubing disconnect, tubing pulled out, blood in tubing, too much heat, too much cold, empty reservoir, low battery, occlusion alarm, no delivery alarm, skin abscess at site, excessive redness at site, swelling (not nodule) at site, bleeding at site, bruising at site, reservoir change (infusion set change reason only), and other. When either a reservoir change or an infusion set change was reported, participants were questioned whether the change occurred early (prior to 6 days). If he/she responded 'yes', then the reported change was recorded as a premature change.
Time Frame Days 1-6 for each reservoir cycle throughout each 12-week treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who completed at least one post-randomization visit. Participants included in pump complication analyses are only those for whom data existed regarding pump complications.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 127 127
Measure Type: Number
Unit of Measure: percentage of participants
Pump Complication: Premature Reservoir Change 42.5 44.1
Pump Complication: Premature Infusion Set Change 74.8 70.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments P-value for overall pump complications associated with a premature reservoir change computed using Gart's Test. Participants represented in both treatment groups and with non-missing incidence value in each treatment period are used.
Method Gart's Test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.472
Comments P-value for overall pump complications associated with a premature infusion set change computed using Gart's Test. Participants represented in both treatment groups and with non-missing incidence value in each treatment period are used.
Method Gart's Test
Comments [Not Specified]
10.Other Pre-specified Outcome
Title Pump Complications Rate Per 30 Days
Hide Description Overall pump complications are defined as any combination of the following reported by the participant: tubing clogged, tubing kinked, tubing disconnect, tubing pulled out, blood in tubing, too much heat, too much cold, empty reservoir, low battery, occlusion alarm, no delivery alarm, skin abscess at site, excessive redness at site, swelling (not nodule) at site, bleeding at site, bruising at site, reservoir change (infusion set change reason only), and other. When either a reservoir change or an infusion set change was reported, participants were questioned whether the change occurred early (prior to 6 days). If he/she responded 'yes', then the reported change was recorded as a premature change.
Time Frame Days 1-6 for each reservoir cycle throughout each 12-week treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who completed at least one post-randomization visit. Participants included in pump complication analyses are only those for whom data existed regarding pump complications.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 127 127
Mean (Standard Deviation)
Unit of Measure: pump complications per 30 days
Pump Complication: Premature Reservoir Change 0.42  (0.93) 0.45  (1.03)
Pump Complication: Premature Infusion Set Change 1.01  (1.41) 1.10  (1.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.383
Comments P-value for Premature Reservoir Change computed using negative binomial test including factors for treatment, period and sequence.
Method negative binomial test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.499
Comments P-value for Premature Infusion Set Change computed using negative binomial test including factors for treatment, period and sequence.
Method negative binomial test
Comments [Not Specified]
11.Other Pre-specified Outcome
Title Percentage of Participants Having a Hypoglycemic Episode
Hide Description

A Documented Hypoglycemic Episode is defined as an event which is associated with a documented blood glucose (BG) concentration of <= 70 mg/dL (3.9 mmol/L).

All Reported Hypoglycemic Episodes are defined as an event which is associated with

  1. reported signs and symptoms of hypoglycemia, and/or
  2. a documented blood glucose (BG) concentration of <= 70 mg/dL (3.9 mmol/L)
Time Frame All days for each reservoir cycle throughout each 12-week treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug. Participants included in hypoglycemia analyses are only those for whom data existed regarding hypoglycemia.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 127 127
Measure Type: Number
Unit of Measure: percentage of participants
Documented Hypoglycemic Episodes 91.3 93.7
All Reported Hypoglycemic Episodes 99.2 99.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments The p-value is for the Documented Hypoglycemic Episodes category treatment arm comparison. The p-value for the All Reported Hypoglycemic Episodes category could not be generated using Gart's Test.
Method Gart's Test
Comments Participants represented in both treatment groups, and with non-missing incidence value in each treatment period, were used for p-value calculation.
12.Other Pre-specified Outcome
Title Hypoglycemic Episode Rate Per 30 Days
Hide Description

All Reported Hypoglycemic Episodes are defined as an event which is associated with

  1. reported signs and symptoms of hypoglycemia, and/or
  2. a documented blood glucose (BG) concentration of <= 70 mg/dL (3.9 mmol/L)
Time Frame All days for each reservoir cycle throughout each 12-week treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug. Participants included in hypoglycemia analyses are only those for whom data existed regarding hypoglycemia.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 127 127
Mean (Standard Deviation)
Unit of Measure: hypoglycemic episodes per 30 days
16.94  (10.69) 18.90  (11.58)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Negative Binomial Test
Comments P-value computed using a negative binomial test including factors for treatment, period and sequence.
13.Other Pre-specified Outcome
Title Change From Baseline to 12 Week Endpoint for Each Treatment in Weight
Hide Description [Not Specified]
Time Frame Baseline, endpoint for each 12-week treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had both baseline and post-baseline weight measurements for the respective treatment period.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 126 123
Mean (Standard Deviation)
Unit of Measure: kilograms (kg)
-0.04  (2.25) 0.56  (2.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Crossover Model
Comments P-value computed using crossover model. Response = treatment + sequence + period + baseline body weight
14.Other Pre-specified Outcome
Title Change From Baseline to 12 Weeks Endpoint for Each Treatment in Blood Pressure
Hide Description [Not Specified]
Time Frame Baseline, endpoint for each 12-week treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had both baseline and post-baseline blood pressure measurements for the respective treatment period.
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description:
Insulin Lispro 6D administered by infusion pump for 12 week treatment period
Insulin Aspart 6D administered by infusion pump for 12 week treatment period
Overall Number of Participants Analyzed 126 121
Mean (Standard Deviation)
Unit of Measure: millimeters of mercury (mmHg)
Systolic Blood Pressure (SBP) -2.25  (14.71) -1.36  (12.12)
Diastolic Blood Pressure (DBP) -1.61  (10.36) -1.57  (9.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.147
Comments P-value for the Systolic Blood Pressure (SBP) computed using crossover model. Response = treatment + sequence + period + baseline systolic blood pressure.
Method Crossover Model
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Insulin Lispro 6D, Insulin Aspart 6D
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.894
Comments P-value for Diastolic Blood Pressure (DBP) computed using crossover model. Response = treatment + sequence + period + baseline diastolic blood pressure.
Method Crossover Model
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Insulin Lispro 6D Insulin Aspart 6D
Hide Arm/Group Description Insulin Lispro 6D administered by infusion pump for 12 week treatment period Insulin Aspart 6D administered by infusion pump for 12 week treatment period
All-Cause Mortality
Insulin Lispro 6D Insulin Aspart 6D
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Insulin Lispro 6D Insulin Aspart 6D
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/127 (2.36%)      7/127 (5.51%)    
Metabolism and nutrition disorders     
Diabetic ketoacidosis  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Hypoglycaemia  1 [1]  2/127 (1.57%)  2 7/127 (5.51%)  8
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
[1]
These events were severe hypoglycemic events.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Insulin Lispro 6D Insulin Aspart 6D
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   34/127 (26.77%)      31/127 (24.41%)    
Blood and lymphatic system disorders     
Haemorrhagic anaemia  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Iron deficiency anaemia  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain upper  1  0/127 (0.00%)  0 1/127 (0.79%)  1
Diarrhoea  1  0/127 (0.00%)  0 1/127 (0.79%)  1
Dyspepsia  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Toothache  1  1/127 (0.79%)  1 2/127 (1.57%)  2
General disorders     
Device occlusion  1  1/127 (0.79%)  2 1/127 (0.79%)  2
Pyrexia  1  1/127 (0.79%)  1 1/127 (0.79%)  1
Immune system disorders     
Hypersensitivity  1  2/127 (1.57%)  2 0/127 (0.00%)  0
Seasonal allergy  1  0/127 (0.00%)  0 1/127 (0.79%)  1
Infections and infestations     
Acute tonsillitis  1  0/127 (0.00%)  0 1/127 (0.79%)  2
Bronchitis  1  0/127 (0.00%)  0 3/127 (2.36%)  3
Cystitis  1  0/127 (0.00%)  0 1/127 (0.79%)  1
Ear infection  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Gastroenteritis  1  3/127 (2.36%)  3 2/127 (1.57%)  2
Herpes zoster  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Influenza  1  3/127 (2.36%)  3 3/127 (2.36%)  3
Nasopharyngitis  1  10/127 (7.87%)  10 6/127 (4.72%)  6
Pharyngitis  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Rash pustular  1  1/127 (0.79%)  1 1/127 (0.79%)  1
Rhinitis  1  0/127 (0.00%)  0 1/127 (0.79%)  1
Sinusitis  1  0/127 (0.00%)  0 1/127 (0.79%)  1
Tracheobronchitis  1  0/127 (0.00%)  0 1/127 (0.79%)  1
Urinary tract infection  1  1/127 (0.79%)  1 2/127 (1.57%)  2
Uterine infection  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Injury, poisoning and procedural complications     
Foot fracture  1  1/127 (0.79%)  1 1/127 (0.79%)  1
Joint dislocation  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Open wound  1  1/127 (0.79%)  1 1/127 (0.79%)  1
Metabolism and nutrition disorders     
Iron deficiency  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/127 (0.79%)  1 1/127 (0.79%)  1
Tenosynovitis  1  0/127 (0.00%)  0 1/127 (0.79%)  1
Nervous system disorders     
Carpal tunnel syndrome  1  1/127 (0.79%)  1 1/127 (0.79%)  1
Migraine  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Paraesthesia  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Renal and urinary disorders     
Microalbuminuria  1  0/127 (0.00%)  0 1/127 (0.79%)  1
Reproductive system and breast disorders     
Menorrhagia  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Asthma  1  0/127 (0.00%)  0 2/127 (1.57%)  2
Cough  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Oropharyngeal pain  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Sleep apnoea syndrome  1  0/127 (0.00%)  0 1/127 (0.79%)  1
Skin and subcutaneous tissue disorders     
Lipohypertrophy  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Skin fissures  1  1/127 (0.79%)  1 1/127 (0.79%)  1
Subcutaneous nodule  1  0/127 (0.00%)  0 2/127 (1.57%)  2
Surgical and medical procedures     
Atherectomy  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Cataract operation  1  0/127 (0.00%)  0 1/127 (0.79%)  1
Injection  1  1/127 (0.79%)  1 0/127 (0.00%)  0
Vascular disorders     
Hypertension  1  0/127 (0.00%)  0 1/127 (0.79%)  1
Phlebitis  1  0/127 (0.00%)  0 1/127 (0.79%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Input to primary endpoint measurements (SMBG) contained approximately 40% missing data. Several analyses to account for missing data were conducted and results from these additional analyses were consistent with results from the original analysis.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01134107     History of Changes
Other Study ID Numbers: 12175
F3Z-MC-IOPW ( Other Identifier: Eli Lilly and Company )
First Submitted: May 27, 2010
First Posted: May 31, 2010
Results First Submitted: September 27, 2012
Results First Posted: October 26, 2012
Last Update Posted: April 11, 2013