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    Clinical Trial Results:
    A Prospective, Randomized, Double-Blind Comparison of LY900014 to Humalog with an Open-Label Postprandial LY900014 Treatment Group in Children and Adolescents with Type 1 Diabetes PRONTO-PEDS

    Summary
    EudraCT number
    		 2018-002371-18
    Trial protocol
    		 DK   CZ   DE   FR   GB   AT   ES   PL   IT  
    Global end of trial date
    02 Jul 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Jan 2022
    First version publication date
    11 Jan 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    I8B-MC-ITSB
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03740919
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 16698
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    02 Jul 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Jul 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    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).
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 Apr 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 138
    Country: Number of subjects enrolled
    Czechia: 60
    Country: Number of subjects enrolled
    Japan: 12
    Country: Number of subjects enrolled
    Ukraine: 138
    Country: Number of subjects enrolled
    United Kingdom: 10
    Country: Number of subjects enrolled
    Spain: 52
    Country: Number of subjects enrolled
    Russian Federation: 62
    Country: Number of subjects enrolled
    Austria: 1
    Country: Number of subjects enrolled
    China: 23
    Country: Number of subjects enrolled
    Brazil: 57
    Country: Number of subjects enrolled
    Poland: 34
    Country: Number of subjects enrolled
    Denmark: 1
    Country: Number of subjects enrolled
    Italy: 39
    Country: Number of subjects enrolled
    Mexico: 60
    Country: Number of subjects enrolled
    Israel: 43
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Germany: 17
    Worldwide total number of subjects
    751
    EEA total number of subjects
    208
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    265
    Adolescents (12-17 years)
    486
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    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
    Screening 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.

    Period 1
    Period 1 title
    Lead-in Period
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Insulin Lispro (Humalog) Lead-in
    Arm description
    		 Participants were switched to open-label insulin lispro (Humalog) administered subcutaneously (SC), using a unit for unit conversion or the dose could have been determined based on investigator's clinical judgement.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Insulin Lispro
    Investigational medicinal product code
    LY275585
    Other name
    Humalog
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Insulin lispro (Humalog) administered SC using unit for unit conversion or dose may be determined based on investigator's clinical judgement.

    Number of subjects in period 1
    		Insulin Lispro (Humalog) Lead-in
    Started
    751
    Received at Least One Dose of Study Drug
    751
    Completed
    716
    Not completed
    35
         Consent withdrawn by subject
    10
         Physician decision
    2
         Study Task Too Burdensome
    1
         Withdrew Consent Due to Required Procedures
    1
         Due to Coronavirus Disease 2019 (COVID-19)
    18
         Lab Results Did Not Match Inclusion Criteria
    1
         Lost to follow-up
    1
         Protocol deviation
    1
    Period 2
    Period 2 title
    Treatment Period
    Is this the baseline period?
    		 Yes [1]
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Insulin Lispro (Humalog)
    Arm description
    		 Participants received insulin lispro (Humalog) 100 units per milliliter (U/mL) 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.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Insulin Lispro
    Investigational medicinal product code
    LY275585
    Other name
    Humalog
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    100 U/mL administered SC 0 to 2 minutes before each meal.

    Arm title
    		 LY900014
    Arm description
    		 Participants received 100 U/mL LY900014 administered SC 0 to 2 minutes before start of the meal.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LY900014
    Investigational medicinal product code
    Other name
    Ultra-Rapid Lispro
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    100 U/mL LY900014 administered SC 0 to 2 minutes before start of the meal.

    Arm title
    		 LY900014 Postmeal
    Arm description
    		 Participants received 100 U/mL LY900014 administered SC up to 20 minutes after the start of the meal.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LY900014
    Investigational medicinal product code
    Other name
    Ultra-Rapid Lispro
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    100 U/mL LY900014 administered SC up to 20 minutes after the start of the meal.

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: The 4-week Lead-in period allowed all enrolled participants to switch to Humalog to determine baseline hypoglycemia rates. Not all participants in the Lead-in period chose to continue into the treatment period and treatment period is considered the baseline period.
    Number of subjects in period 2 [2]
    		Insulin Lispro (Humalog) LY900014 LY900014 Postmeal
    Started
    298
    280
    138
    Received at Least One Dose of Study Drug
    298
    280
    138
    Completed
    288
    266
    135
    Not completed
    10
    14
    3
         Terminated by Sponsor
    1
    -
    -
         Consent withdrawn by subject
    7
    6
    2
         Adverse event, non-fatal
    -
    2
    -
         Not Completing Diary
    -
    1
    -
         Insulin Painful to Participant
    -
    1
    -
         Due to COVID-19 Pandemic
    -
    3
    1
         Issue with Insulin Pump
    1
    -
    -
         Protocol deviation
    1
    -
    -
         Failure of Inclusion Criteria
    -
    1
    -
    Notes
    [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Not all participants in the Lead-in period chose to continue into the treatment period and treatment period is considered the baseline period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Insulin Lispro (Humalog)
    Reporting group description
    		 Participants received insulin lispro (Humalog) 100 units per milliliter (U/mL) 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.

    Reporting group title
    LY900014
    Reporting group description
    		 Participants received 100 U/mL LY900014 administered SC 0 to 2 minutes before start of the meal.

    Reporting group title
    LY900014 Postmeal
    Reporting group description
    		 Participants received 100 U/mL LY900014 administered SC up to 20 minutes after the start of the meal.

    Reporting group values
    		 Insulin Lispro (Humalog) LY900014 LY900014 Postmeal Total
    Number of subjects
    		 298 280 138 716
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 12.4 ± 3.2 12.1 ± 3.4 12.3 ± 3.8 -
    Gender categorical
    Units: Subjects
        Female
    		 140 144 65 349
        Male
    		 158 136 73 367
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 6 6 0 12
        Asian
    		 20 13 7 40
        Native Hawaiian or Other Pacific Islander
    		 2 0 0 2
        Black or African American
    		 7 3 1 11
        White
    		 256 256 126 638
        More than one race
    		 4 0 1 5
        Unknown or Not Reported
    		 3 2 3 8
    Region of Enrollment
    Units: Subjects
        United States
    		 51 55 25 131
        Czechia
    		 26 23 11 60
        Japan
    		 7 3 2 12
        Ukraine
    		 57 53 27 137
        United Kingdom
    		 3 5 2 10
        Spain
    		 21 19 8 48
        Russia
    		 23 21 12 56
        Austria
    		 1 0 0 1
        China
    		 11 7 4 22
        Brazil
    		 22 20 13 55
        Poland
    		 14 13 6 33
        Denmark
    		 0 1 0 1
        Italy
    		 15 15 6 36
        Mexico
    		 25 22 11 58
        Israel
    		 15 15 5 35
        France
    		 1 1 2 4
        Germany
    		 6 7 4 17
    HbA1c at Baseline
    Units: percent HbA1c
        arithmetic mean (standard deviation)
    		 7.81 ± 0.91 7.81 ± 0.87 7.77 ± 0.85 -

    End points

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    End points reporting groups
    Reporting group title
    Insulin Lispro (Humalog) Lead-in
    Reporting group description
    		 Participants were switched to open-label insulin lispro (Humalog) administered subcutaneously (SC), using a unit for unit conversion or the dose could have been determined based on investigator's clinical judgement.
    Reporting group title
    Insulin Lispro (Humalog)
    Reporting group description
    		 Participants received insulin lispro (Humalog) 100 units per milliliter (U/mL) 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.

    Reporting group title
    LY900014
    Reporting group description
    		 Participants received 100 U/mL LY900014 administered SC 0 to 2 minutes before start of the meal.

    Reporting group title
    LY900014 Postmeal
    Reporting group description
    		 Participants received 100 U/mL LY900014 administered SC up to 20 minutes after the start of the meal.

    Primary: Change from Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26

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    End point title
    		 Change from Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26 [1]
    End point description
    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. Analysis Population Description (APD): All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug, per protocol.
    End point type
    Primary
    End point timeframe
    Baseline, Week 26
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol, only participants who received Humalog and LY900014 administered before meals were included in the analysis.
    End point values
    		 Insulin Lispro (Humalog) LY900014
    Number of subjects analysed
    280
    260
    Units: percentage of HbA1c
        least squares mean (standard error)
    0.09 ± 0.052
    0.06 ± 0.054
    Statistical analysis title
    		 Change from Baseline in HbA1c Efficacy Estimand
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    540
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    P-value
    		 = 0.783
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Squares Mean Difference (LS Mean)
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.17
         upper limit
    		 0.13
    Notes
    [2] - Noninferiority margin [NIM]=0.4% for HbA1c

    Secondary: Change from Baseline in HbA1c (Postprandial) at Week 26

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    End point title
    		 Change from Baseline in HbA1c (Postprandial) at Week 26 [3]
    End point description
    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. APD: All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while of study drug, per protocol.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol, only participants who received Humalog administered before meals and LY900014 Postmeal were included in the analysis.
    End point values
    		 Insulin Lispro (Humalog) LY900014 Postmeal
    Number of subjects analysed
    280
    131
    Units: percentage of HbA1c
        least squares mean (standard error)
    0.09 ± 0.052
    0.07 ± 0.076
    Statistical analysis title
    		 Change from Baseline in HbA1c (Postprandial)
    Comparison groups
    Insulin Lispro (Humalog) v LY900014 Postmeal
    Number of subjects included in analysis
    411
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    P-value
    		 = 0.867
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.17
    Notes
    [4] - NIM of 0.4%

    Secondary: Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose

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    End point title
    		 Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose
    End point description
    Documented post-dose hypoglycemia <54 milligrams per deciliter (mg/dL) and ≤ 70 mg/dL that occurred 1 and 2 hours after prandial dose. APD: 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.
    End point type
    Secondary
    End point timeframe
    Baseline through Week 26
    End point values
    		 Insulin Lispro (Humalog) LY900014 LY900014 Postmeal
    Number of subjects analysed
    298
    280
    138
    Units: percentage of participants
    least squares mean (standard error)
        <54 mg/dL 1 Hour Post-dose
    26.50 ± 2.563
    36.79 ± 2.891
    29.70 ± 3.897
        <54 mg/dL 2 Hour Post-dose
    54.04 ± 2.896
    63.61 ± 2.883
    57.88 ± 4.216
        ≤70 mg/dL 1 Hour Post-dose
    49.67 ± 2.901
    63.92 ± 2.874
    48.51 ± 4.261
        ≤70 mg/dL 2 Hour Post-dose
    77.03 ± 2.449
    82.67 ± 2.267
    70.29 ± 3.912
    Statistical analysis title
    		 Documented Post-dose Hypoglycemic Events 1 hr
    Statistical analysis description
    < 54 mg/dL 1-hour post-dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.008
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.13
         upper limit
    		 2.3
    Statistical analysis title
    		 Documented Post-dose Hypoglycemic Events 1 hr
    Statistical analysis description
    < 54 mg/dL 1-hour post-dose
    Comparison groups
    LY900014 Postmeal v Insulin Lispro (Humalog)
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.487
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.83
    Statistical analysis title
    		 Documented Post-dose Hypoglycemic Events 1 hr
    Statistical analysis description
    < 54 mg/dL 1-hour post-dose
    Comparison groups
    LY900014 v LY900014 Postmeal
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.153
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 1.13
    Statistical analysis title
    		 Documented Post-dose Hypoglycemic Events 2 hr
    Statistical analysis description
    < 54 mg/dL 2-hour post-dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.02
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.06
         upper limit
    		 2.08
    Statistical analysis title
    		 Documented Post-dose Hypoglycemic Events 2 hr
    Statistical analysis description
    < 54 mg/dL 2-hour post-dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014 Postmeal
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.455
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.76
    Statistical analysis title
    		 Documented Post-dose Hypoglycemic Events 2 hr
    Statistical analysis description
    < 54 mg/dL 2-hour post-dose
    Comparison groups
    LY900014 v LY900014 Postmeal
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.259
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 1.19
    Statistical analysis title
    		 Documented Post-dose Hypoglycemic Events 1 hr
    Statistical analysis description
    ≤ 70 mg/dL 1-hour post-dose
    Comparison groups
    LY900014 v Insulin Lispro (Humalog)
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.29
         upper limit
    		 2.51
    Statistical analysis title
    		 Documented Post-dose Hypoglycemic Events 1 hr
    Statistical analysis description
    ≤ 70 mg/dL 1-hour post-dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014 Postmeal
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.822
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 1.43
    Statistical analysis title
    		 Documented Post-dose Hypoglycemic Events 1 hr
    Statistical analysis description
    ≤ 70 mg/dL 1-hour post-dose
    Comparison groups
    LY900014 v LY900014 Postmeal
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.35
         upper limit
    		 0.8
    Statistical analysis title
    		 Documented Post-dose Hypoglycemic Events 2 hr
    Statistical analysis description
    ≤ 70 mg/dL 2-hour post-dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.092
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.94
         upper limit
    		 2.14
    Statistical analysis title
    		 Documented Post-dose Hypoglycemic Events 2 hr
    Statistical analysis description
    ≤ 70 mg/dL 2-hour post-dose
    Comparison groups
    LY900014 Postmeal v Insulin Lispro (Humalog)
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.133
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 1.11
    Statistical analysis title
    		 Documented Post-dose Hypoglycemic Events 2 hr
    Statistical analysis description
    ≤ 70 mg/dL 2-hour post-dose
    Comparison groups
    LY900014 v LY900014 Postmeal
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.31
         upper limit
    		 0.8

    Secondary: Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose

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    End point title
    		 Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose
    End point description
    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 variables and number of episodes as dependent variables with log (exposure/365.25 days) as the offset in the model. APD: All randomized participants who received at least 1 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.
    End point type
    Secondary
    End point timeframe
    Baseline through Week 26
    End point values
    		 Insulin Lispro (Humalog) LY900014 LY900014 Postmeal
    Number of subjects analysed
    298
    280
    138
    Units: Events per participant per year
    least squares mean (standard error)
        < 54mg/dL 1 Hour Post-dose
    1.59 ± 0.251
    2.04 ± 0.262
    1.38 ± 0.287
        < 54 mg/dL 2 Hour Post-dose
    4.48 ± 0.454
    5.95 ± 0.510
    6.17 ± 0.816
        ≤70 mg/dL 1 Hour Post-dose
    6.54 ± 1.036
    8.46 ± 0.992
    5.29 ± 1.145
        ≤70 mg/dL 2 Hour Post-dose
    19.0 ± 1.58
    23.7 ± 1.86
    21.1 ± 2.31
    Statistical analysis title
    		 Rate Documented Post-dose Hypoglycemic Events 1 hr
    Statistical analysis description
    < 54 mg/dL 1 hour post-dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.22
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate Documented Post-dose Hypoglycemic Events 1 hr
    Statistical analysis description
    < 54 mg/dL 1-hour post-dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014 Postmeal
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.599
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate Documented Post-dose Hypoglycemic Events 1 hr
    Statistical analysis description
    < 54 mg/dL 1 hour post-dose
    Comparison groups
    LY900014 v LY900014 Postmeal
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.112
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate Documented Post-dose Hypoglycemic Events 2 hr
    Statistical analysis description
    < 54 mg/dL 2 hour post-dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.034
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate Documented Post-dose Hypoglycemic Events 2 hr
    Statistical analysis description
    < 54 mg/dL 2 hour post-dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014 Postmeal
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.055
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate Documented Post-dose Hypoglycemic Events 2 hr
    Statistical analysis description
    < 54 mg/dL 2 hour post-dose
    Comparison groups
    LY900014 v LY900014 Postmeal
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.814
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate Documented Post-dose Hypoglycemic Events 1 hr
    Statistical analysis description
    ≤70 mg/dL 1 hour post-dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.194
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate Documented Post-dose Hypoglycemic Events 1 hr
    Statistical analysis description
    ≤70 mg/dL 1 hour post-dose
    Comparison groups
    LY900014 Postmeal v Insulin Lispro (Humalog)
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.428
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate Documented Post-dose Hypoglycemic Events 1 hr
    Statistical analysis description
    ≤70 mg/dL 1 hour post-dose
    Comparison groups
    LY900014 v LY900014 Postmeal
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.057
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate Documented Post-dose Hypoglycemic Events 2 hr
    Statistical analysis description
    ≤70 mg/dL 2 hour post-dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.056
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate Documented Post-dose Hypoglycemic Events 2 hr
    Statistical analysis description
    ≤70 mg/dL 2 hour post-dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014 Postmeal
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.435
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate Documented Post-dose Hypoglycemic Events 2 hr
    Statistical analysis description
    ≤70 mg/dL 2 hour post-dose
    Comparison groups
    LY900014 Postmeal v LY900014
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.404
    Method
    		 Negative binomial regression
    Confidence interval

    Secondary: Percentage of Participants With Documented Hypoglycemic Events

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    End point title
    		 Percentage of Participants With Documented Hypoglycemic Events
    End point description
    Documented hypoglycemia is defined as <54 mg/dL and ≤70 mg/dL respectively. APD: 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.
    End point type
    Secondary
    End point timeframe
    Baseline through Week 26
    End point values
    		 Insulin Lispro (Humalog) LY900014 LY900014 Postmeal
    Number of subjects analysed
    298
    280
    138
    Units: percentage of participants
    least squares mean (standard error)
        <54 mg/dL
    80.81 ± 2.283
    81.37 ± 2.329
    74.45 ± 3.718
        ≤70 mg/dL
    93.98 ± 1.375
    92.55 ± 1.569
    87.62 ± 2.806
    Statistical analysis title
    		 Percentage Documented Hypoglycemic Events
    Statistical analysis description
    <54 mg/dL
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.864
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 1.57
    Statistical analysis title
    		 Percentage Documented Hypoglycemic Events
    Statistical analysis description
    <54 mg/dL
    Comparison groups
    Insulin Lispro (Humalog) v LY900014 Postmeal
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.132
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 1.12
    Statistical analysis title
    		 Percentage Documented Hypoglycemic Events
    Statistical analysis description
    <54 mg/dL
    Comparison groups
    LY900014 v LY900014 Postmeal
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.104
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 1.09
    Statistical analysis title
    		 Percentage Documented Hypoglycemic Events
    Statistical analysis description
    ≤70 mg/dL
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.489
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 1.52
    Statistical analysis title
    		 Percentage Documented Hypoglycemic Events
    Statistical analysis description
    ≤70 mg/dL
    Comparison groups
    Insulin Lispro (Humalog) v LY900014 Postmeal
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.025
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.23
         upper limit
    		 0.9
    Statistical analysis title
    		 Percentage Documented Hypoglycemic Events
    Statistical analysis description
    ≤70 mg/dL
    Comparison groups
    LY900014 v LY900014 Postmeal
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.099
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.29
         upper limit
    		 1.11

    Secondary: Rate of Documented Hypoglycemia Events

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    End point title
    		 Rate of Documented Hypoglycemia Events
    End point description
    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 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. APD: All randomized participants who received at least 1 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.
    End point type
    Secondary
    End point timeframe
    Week 0 through Week 26
    End point values
    		 Insulin Lispro (Humalog) LY900014 LY900014 Postmeal
    Number of subjects analysed
    298
    280
    138
    Units: events per participant per year
    least squares mean (standard error)
        < 54 mg/dL
    16.6 ± 1.23
    16.1 ± 1.20
    17.7 ± 1.99
        ≤70 mg/dL
    78.0 ± 4.23
    75.1 ± 4.44
    76.1 ± 6.10
    Statistical analysis title
    		 Rate of Documented Hypoglycemia Events
    Statistical analysis description
    < 54 mg/dL
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.732
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate of Documented Hypoglycemia Events
    Statistical analysis description
    < 54 mg/dL
    Comparison groups
    Insulin Lispro (Humalog) v LY900014 Postmeal
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.638
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate of Documented Hypoglycemia Events
    Statistical analysis description
    <54 mg/dL
    Comparison groups
    LY900014 Postmeal v LY900014
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.462
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate of Documented Hypoglycemia Events
    Statistical analysis description
    ≤ 70 mg/dL
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.632
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate of Documented Hypoglycemia Events
    Statistical analysis description
    ≤ 70 mg/dL
    Comparison groups
    LY900014 Postmeal v Insulin Lispro (Humalog)
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8
    Method
    		 Negative binomial regression
    Confidence interval
    Statistical analysis title
    		 Rate of Documented Hypoglycemia Events
    Statistical analysis description
    ≤ 70 mg/dL
    Comparison groups
    LY900014 v LY900014 Postmeal
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.889
    Method
    		 Negative binomial regression
    Confidence interval

    Secondary: Rate of Severe Hypoglycemia

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    End point title
    		 Rate of Severe Hypoglycemia
    End point description
    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. 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.
    End point type
    Secondary
    End point timeframe
    Week 0 through Week 26
    End point values
    		 Insulin Lispro (Humalog) LY900014 LY900014 Postmeal
    Number of subjects analysed
    298
    280
    138
    Units: Per participant per 100 years
        number (not applicable)
    2.05
    2.20
    0.00
    No statistical analyses for this end point

    Secondary: Change from Baseline in Insulin Dose at Week 26

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    End point title
    		 Change from Baseline in Insulin Dose at Week 26
    End point description
    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. APD: All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Insulin Lispro (Humalog) LY900014 LY900014 Postmeal
    Number of subjects analysed
    283
    264
    132
    Units: Unit per day
    least squares mean (standard error)
        Total Daily Basal Insulin Dose
    2.3 ± 0.28
    2.9 ± 0.29
    2.7 ± 0.40
        Total Daily Insulin Dose
    5.3 ± 0.66
    5.8 ± 0.69
    5.0 ± 0.96
    Statistical analysis title
    		 Change from Baseline in Insulin Dose
    Statistical analysis description
    Total Daily Basal Insulin
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    547
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.13
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 1.4
    Statistical analysis title
    		 Change from Baseline in Insulin Dose
    Statistical analysis description
    Total Daily Basal Insulin
    Comparison groups
    Insulin Lispro (Humalog) v LY900014 Postmeal
    Number of subjects included in analysis
    415
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.404
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 1.4
    Statistical analysis title
    		 Change from Baseline in Insulin Dose
    Statistical analysis description
    Total Daily Basal Insulin
    Comparison groups
    LY900014 v LY900014 Postmeal
    Number of subjects included in analysis
    396
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.693
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.8
    Statistical analysis title
    		 Change from Baseline in Insulin Dose
    Statistical analysis description
    Total Daily Insulin Dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    547
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.625
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 2.3
    Statistical analysis title
    		 Change from Baseline in Insulin Dose
    Statistical analysis description
    Total Daily Insulin Dose
    Comparison groups
    Insulin Lispro (Humalog) v LY900014 Postmeal
    Number of subjects included in analysis
    415
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.758
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.6
         upper limit
    		 1.9
    Statistical analysis title
    		 Change from Baseline in Insulin Dose
    Statistical analysis description
    Total Daily Insulin Dose
    Comparison groups
    LY900014 v LY900014 Postmeal
    Number of subjects included in analysis
    396
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.485
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.1
         upper limit
    		 1.5

    Secondary: Percentage of Participants with HbA1c < 7.0% and <7.5%

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    End point title
    		 Percentage of Participants with HbA1c < 7.0% and <7.5%
    End point description
    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. APD: 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 were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    		 Insulin Lispro (Humalog) LY900014 LY900014 Postmeal
    Number of subjects analysed
    298
    280
    138
    Units: percentage of participants
    number (not applicable)
        HbA1c <7%
    20.00
    21.92
    19.08
        HbA1c < 7.5%
    40.00
    37.31
    32.82
    Statistical analysis title
    		 Percentage HbA1c < 7.0%
    Statistical analysis description
    HbA1c < 7%
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.396
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 2
    Statistical analysis title
    		 Percentage HbA1c < 7.0%
    Statistical analysis description
    HbA1c < 7%
    Comparison groups
    Insulin Lispro (Humalog) v LY900014 Postmeal
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.814
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.49
         upper limit
    		 1.75
    Statistical analysis title
    		 Percentage HbA1c < 7.0%
    Statistical analysis description
    HbA1c < 7%
    Comparison groups
    LY900014 Postmeal v LY900014
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.384
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.39
         upper limit
    		 1.43
    Statistical analysis title
    		 Percentage HbA1c < 7.5%
    Statistical analysis description
    HbA1c < 7.5%
    Comparison groups
    Insulin Lispro (Humalog) v LY900014
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 1.27
    Statistical analysis title
    		 Percentage HbA1c < 7.5%
    Statistical analysis description
    HbA1c < 7.5%
    Comparison groups
    Insulin Lispro (Humalog) v LY900014 Postmeal
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.094
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.36
         upper limit
    		 1.08
    Statistical analysis title
    		 Percentage HbA1c < 7.5%
    Statistical analysis description
    HbA1c < 7.5%
    Comparison groups
    LY900014 v LY900014 Postmeal
    Number of subjects included in analysis
    418
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.306
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 1.31

    Secondary: Change from Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26

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    End point title
    		 Change from Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26
    End point description
    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. All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26
    End point values
    		 Insulin Lispro (Humalog) LY900014 LY900014 Postmeal
    Number of subjects analysed
    298
    280
    138
    Units: milligram per dL (mg/dL)
    least squares mean (standard error)
        Morning Premeal-Fasting: n= 265, 247, 122
    1.0 ± 2.78
    -3.4 ± 2.88
    -5.9 ± 4.11
        Morning 1 hour Postmeal: n= 263, 239, 117
    -3.2 ± 2.92
    -17.9 ± 3.06
    -9.8 ± 4.39
        Midday Premeal: n= 265, 247,122
    -3.1 ± 3.06
    2.5 ± 3.17
    -6.0 ± 4.52
        Midday 1 hour Postmeal: n= 262, 237, 120
    0.9 ± 2.99
    -5.2 ± 3.14
    -1.5 ± 4.43
        Evening Premeal: n= 264, 247,122
    1.0 ± 3.18
    4.6 ± 3.29
    0.3 ± 4.69
        Evening 1 hour Postmeal: n= 261, 234, 118
    6.9 ± 3.22
    -6.2 ± 3.39
    -3.9 ± 4.79
        Bedtime: n= 257, 240, 116
    -1.9 ± 3.03
    -2.3 ± 3.14
    -2.7 ± 4.53
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Lead-in to Safety Follow-up (up to 32 Weeks)
    Adverse event reporting additional description
    All randomized participants who receive at least 1 dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Humalog Lead-in
    Reporting group description
    		 Participants were switched to open-label Insulin lispro (Humalog) administered SC, using a unit for unit conversion or the dose may be determined based on investigator's clinical judgement.

    Reporting group title
    LY900014
    Reporting group description
    		 Participants received 100 Units per milliliter (U/mL) LY900014 administered SC 0 to 2 minutes before each meal with either basal insulin glargine given SC once or twice daily or insulin degludec given SC once daily. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.

    Reporting group title
    LY900014 Postmeal
    Reporting group description
    		 Participants received 100 U/mL LY900014 administered SC up to 20 minutes after the start of the meal.

    Reporting group title
    Insulin Lispro (Humalog)
    Reporting group description
    		 Participants received 100 U/mL Insulin lispro (Humalog) administered subcutaneously (SC) 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.

    Serious adverse events
    		 Humalog Lead-in LY900014 LY900014 Postmeal Insulin Lispro (Humalog)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 751 (0.27%)
    6 / 280 (2.14%)
    2 / 138 (1.45%)
    12 / 298 (4.03%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    reactive gastropathy
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    0 / 280 (0.00%)
    0 / 138 (0.00%)
    1 / 298 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    skin laceration
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    0 / 280 (0.00%)
    0 / 138 (0.00%)
    1 / 298 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    spinal fracture
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    0 / 280 (0.00%)
    0 / 138 (0.00%)
    1 / 298 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    macroglossia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    0 / 280 (0.00%)
    0 / 138 (0.00%)
    1 / 298 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    headache
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    1 / 280 (0.36%)
    0 / 138 (0.00%)
    0 / 298 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hypoglycaemic coma
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    0 / 280 (0.00%)
    0 / 138 (0.00%)
    1 / 298 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    anaphylactic reaction
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    0 / 280 (0.00%)
    0 / 138 (0.00%)
    1 / 298 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    abdominal pain
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    1 / 280 (0.36%)
    0 / 138 (0.00%)
    0 / 298 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastritis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    0 / 280 (0.00%)
    0 / 138 (0.00%)
    1 / 298 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    mental disorder
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 751 (0.13%)
    0 / 280 (0.00%)
    0 / 138 (0.00%)
    0 / 298 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    complicated appendicitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    0 / 280 (0.00%)
    1 / 138 (0.72%)
    0 / 298 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastroenteritis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    0 / 280 (0.00%)
    0 / 138 (0.00%)
    1 / 298 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pilonidal cyst
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    0 / 280 (0.00%)
    0 / 138 (0.00%)
    1 / 298 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    upper respiratory tract infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    1 / 280 (0.36%)
    0 / 138 (0.00%)
    0 / 298 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    diabetic ketoacidosis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    2 / 280 (0.71%)
    1 / 138 (0.72%)
    0 / 298 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hyperglycaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    0 / 751 (0.00%)
    0 / 280 (0.00%)
    0 / 138 (0.00%)
    1 / 298 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hypoglycaemia
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 751 (0.13%)
    3 / 280 (1.07%)
    0 / 138 (0.00%)
    2 / 298 (0.67%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 Humalog Lead-in LY900014 LY900014 Postmeal Insulin Lispro (Humalog)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    39 / 751 (5.19%)
    67 / 280 (23.93%)
    21 / 138 (15.22%)
    60 / 298 (20.13%)
    Nervous system disorders
    headache
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    6 / 751 (0.80%)
    13 / 280 (4.64%)
    5 / 138 (3.62%)
    13 / 298 (4.36%)
         occurrences all number
    6
    22
    5
    21
    General disorders and administration site conditions
    injection site reaction
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 751 (0.13%)
    11 / 280 (3.93%)
    2 / 138 (1.45%)
    0 / 298 (0.00%)
         occurrences all number
    1
    14
    2
    0
    Gastrointestinal disorders
    vomiting
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    1 / 751 (0.13%)
    9 / 280 (3.21%)
    3 / 138 (2.17%)
    9 / 298 (3.02%)
         occurrences all number
    1
    10
    3
    11
    Infections and infestations
    nasopharyngitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    21 / 751 (2.80%)
    28 / 280 (10.00%)
    7 / 138 (5.07%)
    23 / 298 (7.72%)
         occurrences all number
    21
    37
    9
    30
    rhinitis
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    7 / 751 (0.93%)
    6 / 280 (2.14%)
    4 / 138 (2.90%)
    10 / 298 (3.36%)
         occurrences all number
    7
    6
    5
    10
    upper respiratory tract infection
    alternative dictionary used: MedDRA 24.0
         subjects affected / exposed
    3 / 751 (0.40%)
    15 / 280 (5.36%)
    2 / 138 (1.45%)
    16 / 298 (5.37%)
         occurrences all number
    3
    17
    3
    18

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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