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CLASSIFY: Comparison of Insulin Mix25 Versus Mix50

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01773473
Collaborator
(none)
403
Enrollment
27
Locations
2
Arms
19
Duration (Months)
14.9
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy and safety of insulin Lispro Mix25 (LM25) compared to insulin Lispro Mix50 (LM50) as an insulin starter in participants with Type 2 diabetes mellitus (T2DM).

Condition or Disease Intervention/Treatment Phase
  • Drug: Insulin Lispro Mix25
  • Drug: Insulin Lispro Mix50
 Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
403 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Comparison Between Low Mixed Insulin and Mid Mixed Insulin AS Starter Insulin For Patients With TYpe 2 Diabetes Mellitus (CLASSIFY Study)
Study Start Date :
Jan 1, 2013
Actual Primary Completion Date :
Aug 1, 2014
Actual Study Completion Date :
Aug 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Insulin Lispro Mix25

Insulin Lispro Mix25 administered subcutaneously (SC) using prefilled pen twice daily for 26 weeks.

Drug: Insulin Lispro Mix25
Administered SC
Other Names:
  • LY275585-75

    		•
    Experimental: Insulin Lispro Mix50

    Insulin Lispro Mix50 administered SC using prefilled pen twice daily for 26 weeks.

    Drug: Insulin Lispro Mix50
    Administered SC
    Other Names:
  • LY275585-50

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 [Baseline, Week 26]

      HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. Least Squares (LS) means were calculated by Mixed Models Repeated Measurements (MMRM) analysis using change from baseline in HbA1c at all post baseline measurement as dependent variables, treatment, blood glucose (BG) excursion, country, visit and treatment-by-visit interaction as fixed effects, baseline HbA1c value as a covariate and participants as a random effect.

    Secondary Outcome Measures

    1. Percentage of Participants Achieving HbA1c of <7.0% or ≤6.5% Baseline Through Week 26 [Baseline through Week 26]

      HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. The percentage of participants with HbA1c <7.0% or HbA1c ≤6.5% is calculated as the number of participants with an HbA1c level of the cut-off value (<7.0% or ≤6.5%) divided by the number of participants treated, then multiplied by 100.

    2. Change From Baseline in Fasting Blood Glucose (FBG) at Week 26 [Baseline, Week 26]

      LS means were calculated by MMRM analysis using change from baseline in FBG variables at all post baseline measurement as dependent variables, treatment, country, BG excursion, visit and treatment-by-visit interaction as fixed effects, baseline self-monitoring blood glucose (SMBG) variable value as a covariate and participants as a random effect.

    3. Change From Baseline in Body Weight at Week 26 [Baseline, Week 26]

      LS means were calculated by MMRM analysis using change from baseline in weight variables at all post baseline measurement as dependent variables, treatment, country, BG excursion, visit and treatment-by-visit interaction as fixed effects, baseline SMBG variable value as a covariate and participants as a random effect.

    4. Number of Hypoglycemic Events Baseline Through Week 26 (Incidence) [Baseline through Week 26]

      A hypoglycemic event is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has a BG concentration of ≤ 70milligrams/deciliter [mg/dL (3.9 mmol/L)], even if it was not associated with signs, symptoms, or treatment consistent with current guidelines [American Diabetes Association (ADA) 2005].

    5. Insulin Dose at Week 26 [Week 26]

      Insulin dose is the total daily dose including basal and prandial doses.

    6. Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 26 [Baseline, Week 26]

      LS means were calculated by MMRM analysis using change from baseline in 1.5-AG variables at all post baseline measurement as dependent variables, treatment, country, BG excursion, visit and treatment-by-visit interaction as fixed effects, baseline SMBG variable value as a covariate and participants as a random effect.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Have a diagnosis of Type 2 Diabetes Mellitus (T2DM) for at least 6 months

    • Have been taking sulfonylureas, biguanide, thiazolidinedione, alpha-glucosidase inhibitor, glinide, or dipeptidyl peptidase IV inhibitor, or any combination of these

    • Have a qualifying hemoglobin A1c (HbA1C) value ≥7.0% and ≤11.0% at screening

    • Have a body mass index (BMI) ≥18.5 and <35.0 kilogram per square meter (kg/m²)

    • Have given written informed consent to participate in the study in accordance with local regulations and the ethical review board (ERB) governing the study site

    Exclusion Criteria:

    • Have a diagnosis of type 1 diabetes

    • Have had more than 1 episode of severe hypoglycemia within the 6 months before screening

    • Have any of the following cardiovascular conditions within 3 months prior to screening: acute myocardial infarction, New York Heart Association (NYHA) class III or class IV heart failure, or cerebrovascular accident (stroke)

    • Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase levels ≥3.0 times the upper limit of the reference range at screening, as determined by the central laboratory

    • Have an estimated creatinine clearance (CrCl), Cockcroft-Gault formula <30 milliliter per minute (mL/min), as determined by the central laboratory at screening

    • Have evidence of a significant, active, uncontrolled endocrine or autoimmune abnormality, as judged by the investigator

    • Have an active or untreated malignancy or have been in remission from a clinically significant malignancy for <5 years

    • Have any other condition (such as, known drug or alcohol abuse or a psychiatric disorder) that may prevent the participants from following and completing the protocol

    • Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Beijing China 100029
    2 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Changsha China 410013
    3 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Chengdu China 610041
    4 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Chongqing China 404000
    5 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Nanjing China 210028
    6 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Shanghai China 200092
    7 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Wulumuqi China 830000
    8 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Zhengzhou China 450052
    9 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Ibaraki Japan 302-0118
    10 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Kagoshima Japan 895-0052
    11 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Kanagawa Japan 242-0004
    12 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Miyagi Japan 985-0835
    13 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Nagano Japan 399-0006
    14 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Okayama Japan 700-0013
    15 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Osaka Japan 530-0001
    16 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Saitama Japan 350-1305
    17 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Tochigi Japan 329-0433
    18 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Tokyo Japan 206-0633
    19 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Yamaguchi Japan 751-0815
    20 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Daejeon Korea, Republic of 302-799
    21 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Incheon Korea, Republic of 403-720
    22 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Jeju Special Self-Governing Pr Korea, Republic of 690-767
    23 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Seoul Korea, Republic of 137-701
    24 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Suwon Korea, Republic of 442-723
    25 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Ankara Turkey 06500
    26 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Antalya Turkey 07070
    27 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Gaziantep Turkey 27070

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01773473
    Other Study ID Numbers:
    • 14675
    • F3Z-CR-IOQI
    First Posted:
    Jan 23, 2013
    Last Update Posted:
    May 21, 2015
    Last Verified:
    May 1, 2015
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Insulin
    Insulin, Globin Zinc
    Insulin Lispro

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail This study consisted of a 26-week treatment period (12-week, weekly-intensive, dose-adjustment period and 14-week maintenance period).
    Arm/Group Title Insulin Lispro Mix25 Insulin Lispro Mix50
    Arm/Group Description Insulin Lispro Mix25 administered subcutaneously (SC) using prefilled pen twice daily for 26 weeks. Insulin Lispro Mix50 administered SC using prefilled pen twice daily for 26 weeks.
    Period Title: Overall Study
    STARTED 207 196
    Received at Least 1 Dose of Study Drug 207 196
    COMPLETED 191 177
    NOT COMPLETED 16 19

    Baseline Characteristics

    Arm/Group Title Insulin Lispro Mix25 Insulin Lispro Mix50 Total
    Arm/Group Description Insulin Lispro Mix25 administered SC using prefilled pen twice daily for 26 weeks. Insulin Lispro Mix50 administered SC using prefilled pen twice daily for 26 weeks. Total of all reporting groups
    Overall Participants 207 196 403
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55.74
    (10.026)
    57.34
    (9.664)
    56.52
    (9.871)
    Sex: Female, Male (Count of Participants)
    Female
    76
    36.7%
    77
    39.3%
    153
    38%
    Male
    131
    63.3%
    119
    60.7%
    250
    62%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    192
    92.8%
    182
    92.9%
    374
    92.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    White
    15
    7.2%
    14
    7.1%
    29
    7.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    Turkey
    15
    7.2%
    14
    7.1%
    29
    7.2%
    Japan
    88
    42.5%
    84
    42.9%
    172
    42.7%
    China
    80
    38.6%
    76
    38.8%
    156
    38.7%
    Korea, Republic of
    24
    11.6%
    22
    11.2%
    46
    11.4%
    Duration of Type-2 Diabetes Mellitus (T2DM) (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    9.74
    (6.169)
    9.15
    (6.336)
    9.45
    (6.250)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26
    Description HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. Least Squares (LS) means were calculated by Mixed Models Repeated Measurements (MMRM) analysis using change from baseline in HbA1c at all post baseline measurement as dependent variables, treatment, blood glucose (BG) excursion, country, visit and treatment-by-visit interaction as fixed effects, baseline HbA1c value as a covariate and participants as a random effect.
    Time Frame Baseline, Week 26

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and analyzed according to the assigned treatment regardless of study drug dose the participant received and had baseline and Week 26 HbA1c measurements.
    Arm/Group Title Insulin Lispro Mix25 Insulin Lispro Mix50
    Arm/Group Description Insulin Lispro Mix25 administered SC using prefilled pen twice daily for 26 weeks. Insulin Lispro Mix50 administered SC using prefilled pen twice daily for 26 weeks.
    Measure Participants 192 179
    Least Squares Mean (95% Confidence Interval) [percentage of glycosylated hemoglobin]
    -1.52
    -1.69
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Mix25, Insulin Lispro Mix50
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Analyses were based on a pre-defined non-inferiority margin of 0.4%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.17
    Confidence Interval (2-Sided) 95%
    -0.01 to 0.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Participants Achieving HbA1c of <7.0% or ≤6.5% Baseline Through Week 26
    Description HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. The percentage of participants with HbA1c <7.0% or HbA1c ≤6.5% is calculated as the number of participants with an HbA1c level of the cut-off value (<7.0% or ≤6.5%) divided by the number of participants treated, then multiplied by 100.
    Time Frame Baseline through Week 26

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and analyzed according to the assigned treatment regardless of study drug dose the participant received and had baseline and at least 1 post-baseline HbA1c measurement.
    Arm/Group Title Insulin Lispro Mix25 Insulin Lispro Mix50
    Arm/Group Description Insulin Lispro Mix25 administered SC using prefilled pen twice daily for 26 weeks. Insulin Lispro Mix50 administered SC using prefilled pen twice daily for 26 weeks.
    Measure Participants 207 196
    <7.0%
    45.9
    22.2%
    59.7
    30.5%
    ≤6.5%
    26.1
    12.6%
    42.3
    21.6%
    3. Secondary Outcome
    Title Change From Baseline in Fasting Blood Glucose (FBG) at Week 26
    Description LS means were calculated by MMRM analysis using change from baseline in FBG variables at all post baseline measurement as dependent variables, treatment, country, BG excursion, visit and treatment-by-visit interaction as fixed effects, baseline self-monitoring blood glucose (SMBG) variable value as a covariate and participants as a random effect.
    Time Frame Baseline, Week 26

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and analyzed according to the assigned treatment regardless of study drug dose the participant received and had baseline and Week 26 FBG measurement.
    Arm/Group Title Insulin Lispro Mix25 Insulin Lispro Mix50
    Arm/Group Description Insulin Lispro Mix25 administered SC using prefilled pen twice daily for 26 weeks. Insulin Lispro Mix50 administered SC using prefilled pen twice daily for 26 weeks.
    Measure Participants 207 196
    Least Squares Mean (95% Confidence Interval) [millimoles per liter (mmol/L)]
    -2.37
    -1.99
    4. Secondary Outcome
    Title Change From Baseline in Body Weight at Week 26
    Description LS means were calculated by MMRM analysis using change from baseline in weight variables at all post baseline measurement as dependent variables, treatment, country, BG excursion, visit and treatment-by-visit interaction as fixed effects, baseline SMBG variable value as a covariate and participants as a random effect.
    Time Frame Baseline, Week 26

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had baseline and Week 26 body weight measurements.
    Arm/Group Title Insulin Lispro Mix25 Insulin Lispro Mix50
    Arm/Group Description Insulin Lispro Mix25 administered SC using prefilled pen twice daily for 26 weeks. Insulin Lispro Mix50 administered SC using prefilled pen twice daily for 26 weeks.
    Measure Participants 207 196
    Least Squares Mean (95% Confidence Interval) [kilogram (kg)]
    2.31
    2.32
    5. Secondary Outcome
    Title Number of Hypoglycemic Events Baseline Through Week 26 (Incidence)
    Description A hypoglycemic event is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has a BG concentration of ≤ 70milligrams/deciliter [mg/dL (3.9 mmol/L)], even if it was not associated with signs, symptoms, or treatment consistent with current guidelines [American Diabetes Association (ADA) 2005].
    Time Frame Baseline through Week 26

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug.
    Arm/Group Title Insulin Lispro Mix25 Insulin Lispro Mix50
    Arm/Group Description Insulin Lispro Mix25 administered SC using prefilled pen twice daily for 26 weeks. Insulin Lispro Mix50 administered SC using prefilled pen twice daily for 26 weeks.
    Measure Participants 207 196
    All Hypoglycemic Events
    568
    583
    Severe Hypoglycemic Events
    0
    1
    6. Secondary Outcome
    Title Insulin Dose at Week 26
    Description Insulin dose is the total daily dose including basal and prandial doses.
    Time Frame Week 26

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and analyzed according to the assigned treatment regardless of study drug dose the participant received and had Week 26 insulin dose measurement.
    Arm/Group Title Insulin Lispro Mix25 Insulin Lispro Mix50
    Arm/Group Description Insulin Lispro Mix25 administered SC using prefilled pen twice daily for 26 weeks. Insulin Lispro Mix50 administered SC using prefilled pen twice daily for 26 weeks.
    Measure Participants 207 196
    Mean (Standard Deviation) [units of insulin per day (IU/day)]
    40.02
    (17.771)
    39.32
    (17.991)
    7. Secondary Outcome
    Title Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 26
    Description LS means were calculated by MMRM analysis using change from baseline in 1.5-AG variables at all post baseline measurement as dependent variables, treatment, country, BG excursion, visit and treatment-by-visit interaction as fixed effects, baseline SMBG variable value as a covariate and participants as a random effect.
    Time Frame Baseline, Week 26

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and analyzed according to the assigned treatment regardless of study drug dose the participant received and had baseline and Week 26 1,5-AG measurements.
    Arm/Group Title Insulin Lispro Mix25 Insulin Lispro Mix50
    Arm/Group Description Insulin Lispro Mix25 administered SC using prefilled pen twice daily for 26 weeks. Insulin Lispro Mix50 administered SC using prefilled pen twice daily for 26 weeks.
    Measure Participants 207 196
    Least Squares Mean (95% Confidence Interval) [micrograms/milliliter (µg/mL)]
    4.24
    5.62

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Insulin Lispro Mix25 Insulin Lispro Mix50
    Arm/Group Description Insulin Lispro Mix25 administered SC using prefilled pen twice daily for 26 weeks. Insulin Lispro Mix50 administered SC using prefilled pen twice daily for 26 weeks.
    All Cause Mortality
    Insulin Lispro Mix25 Insulin Lispro Mix50
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Insulin Lispro Mix25 Insulin Lispro Mix50
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/207 (3.9%) 7/196 (3.6%)
    Cardiac disorders
    Acute myocardial infarction 0/207 (0%) 0 1/196 (0.5%) 1
    Cardiac failure 0/207 (0%) 0 1/196 (0.5%) 1
    Coronary artery disease 1/207 (0.5%) 1 1/196 (0.5%) 1
    Tachycardia 1/207 (0.5%) 1 0/196 (0%) 0
    Ear and labyrinth disorders
    Vertigo 0/207 (0%) 0 1/196 (0.5%) 1
    Immune system disorders
    Anaphylactic reaction 0/207 (0%) 0 1/196 (0.5%) 1
    Infections and infestations
    Bacteraemia 1/207 (0.5%) 1 0/196 (0%) 0
    Injury, poisoning and procedural complications
    Lumbar vertebral fracture 1/207 (0.5%) 1 0/196 (0%) 0
    Stab wound 0/207 (0%) 0 1/196 (0.5%) 1
    Musculoskeletal and connective tissue disorders
    Spinal osteoarthritis 1/207 (0.5%) 1 0/196 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 1/207 (0.5%) 1 0/196 (0%) 0
    Lymphoma 1/207 (0.5%) 1 0/196 (0%) 0
    Nervous system disorders
    Brain stem infarction 1/207 (0.5%) 1 0/196 (0%) 0
    Cerebellar infarction 1/207 (0.5%) 1 0/196 (0%) 0
    Renal and urinary disorders
    Nephrolithiasis 0/207 (0%) 0 1/196 (0.5%) 1
    Other (Not Including Serious) Adverse Events
    Insulin Lispro Mix25 Insulin Lispro Mix50
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 87/207 (42%) 84/196 (42.9%)
    Cardiac disorders
    Angina pectoris 1/207 (0.5%) 1 0/196 (0%) 0
    Congestive cardiomyopathy 0/207 (0%) 0 1/196 (0.5%) 1
    Palpitations 1/207 (0.5%) 1 0/196 (0%) 0
    Ear and labyrinth disorders
    Tinnitus 1/207 (0.5%) 1 0/196 (0%) 0
    Vertigo 2/207 (1%) 2 0/196 (0%) 0
    Eye disorders
    Arteriosclerotic retinopathy 1/207 (0.5%) 1 0/196 (0%) 0
    Cataract 1/207 (0.5%) 1 1/196 (0.5%) 1
    Diabetic retinopathy 0/207 (0%) 0 1/196 (0.5%) 1
    Dry eye 0/207 (0%) 0 1/196 (0.5%) 1
    Glaucoma 1/207 (0.5%) 1 0/196 (0%) 0
    Keratitis 0/207 (0%) 0 1/196 (0.5%) 1
    Ocular hyperaemia 1/207 (0.5%) 1 0/196 (0%) 0
    Punctate keratitis 1/207 (0.5%) 1 0/196 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort 1/207 (0.5%) 1 2/196 (1%) 2
    Abdominal pain 0/207 (0%) 0 1/196 (0.5%) 2
    Abdominal pain upper 1/207 (0.5%) 1 1/196 (0.5%) 1
    Constipation 2/207 (1%) 2 3/196 (1.5%) 6
    Dental caries 0/207 (0%) 0 4/196 (2%) 4
    Diarrhoea 1/207 (0.5%) 1 7/196 (3.6%) 8
    Dyspepsia 0/207 (0%) 0 3/196 (1.5%) 3
    Faecaloma 1/207 (0.5%) 1 0/196 (0%) 0
    Gastritis 1/207 (0.5%) 1 0/196 (0%) 0
    Gastritis atrophic 0/207 (0%) 0 1/196 (0.5%) 1
    Gastrooesophageal reflux disease 1/207 (0.5%) 1 1/196 (0.5%) 1
    Gingival pain 1/207 (0.5%) 1 1/196 (0.5%) 1
    Large intestine polyp 1/207 (0.5%) 1 2/196 (1%) 2
    Melaena 0/207 (0%) 0 1/196 (0.5%) 1
    Mouth ulceration 0/207 (0%) 0 1/196 (0.5%) 1
    Nausea 2/207 (1%) 2 2/196 (1%) 3
    Oesophageal discomfort 1/207 (0.5%) 1 0/196 (0%) 0
    Oesophagitis 0/207 (0%) 0 1/196 (0.5%) 1
    Periodontal disease 0/207 (0%) 0 1/196 (0.5%) 1
    Stomatitis 0/207 (0%) 0 1/196 (0.5%) 1
    Toothache 1/207 (0.5%) 1 1/196 (0.5%) 1
    General disorders
    Asthenia 0/207 (0%) 0 1/196 (0.5%) 1
    Chest pain 1/207 (0.5%) 1 0/196 (0%) 0
    Feeling abnormal 1/207 (0.5%) 1 0/196 (0%) 0
    Injection site bruising 1/207 (0.5%) 1 0/196 (0%) 0
    Injection site erythema 1/207 (0.5%) 1 0/196 (0%) 0
    Injection site haemorrhage 1/207 (0.5%) 2 0/196 (0%) 0
    Injection site induration 2/207 (1%) 2 0/196 (0%) 0
    Injection site pain 0/207 (0%) 0 1/196 (0.5%) 1
    Injection site pruritus 1/207 (0.5%) 1 0/196 (0%) 0
    Injection site reaction 0/207 (0%) 0 2/196 (1%) 2
    Local swelling 1/207 (0.5%) 1 0/196 (0%) 0
    Hepatobiliary disorders
    Hepatic function abnormal 1/207 (0.5%) 1 0/196 (0%) 0
    Immune system disorders
    Drug hypersensitivity 1/207 (0.5%) 1 0/196 (0%) 0
    Hypersensitivity 0/207 (0%) 0 1/196 (0.5%) 1
    Seasonal allergy 2/207 (1%) 2 0/196 (0%) 0
    Infections and infestations
    Abscess 0/207 (0%) 0 1/196 (0.5%) 1
    Acute sinusitis 0/207 (0%) 0 1/196 (0.5%) 1
    Bronchitis 1/207 (0.5%) 1 1/196 (0.5%) 1
    Cellulitis 0/207 (0%) 0 1/196 (0.5%) 1
    Conjunctivitis 1/207 (0.5%) 1 1/196 (0.5%) 1
    Conjunctivitis bacterial 1/207 (0.5%) 1 0/196 (0%) 0
    Cystitis 1/207 (0.5%) 1 1/196 (0.5%) 1
    Enterocolitis bacterial 1/207 (0.5%) 1 0/196 (0%) 0
    Enterocolitis viral 1/207 (0.5%) 1 0/196 (0%) 0
    Gastroenteritis 2/207 (1%) 2 2/196 (1%) 2
    Gingivitis 0/207 (0%) 0 1/196 (0.5%) 1
    Herpes zoster 3/207 (1.4%) 3 0/196 (0%) 0
    Influenza 2/207 (1%) 2 3/196 (1.5%) 4
    Localised infection 1/207 (0.5%) 1 0/196 (0%) 0
    Nasopharyngitis 28/207 (13.5%) 32 34/196 (17.3%) 42
    Oral herpes 1/207 (0.5%) 1 0/196 (0%) 0
    Periodontitis 0/207 (0%) 0 1/196 (0.5%) 2
    Pharyngitis 1/207 (0.5%) 1 0/196 (0%) 0
    Respiratory tract infection 0/207 (0%) 0 1/196 (0.5%) 1
    Tonsillitis 0/207 (0%) 0 1/196 (0.5%) 1
    Upper respiratory tract infection 4/207 (1.9%) 4 0/196 (0%) 0
    Urinary tract infection 0/207 (0%) 0 2/196 (1%) 2
    Viral myocarditis 0/207 (0%) 0 1/196 (0.5%) 1
    Injury, poisoning and procedural complications
    Avulsion fracture 0/207 (0%) 0 1/196 (0.5%) 1
    Bone contusion 1/207 (0.5%) 1 0/196 (0%) 0
    Contusion 1/207 (0.5%) 1 1/196 (0.5%) 1
    Ligament sprain 2/207 (1%) 4 0/196 (0%) 0
    Wrist fracture 1/207 (0.5%) 1 0/196 (0%) 0
    Investigations
    Aspartate aminotransferase increased 1/207 (0.5%) 1 0/196 (0%) 0
    Endoscopy gastrointestinal 0/207 (0%) 0 1/196 (0.5%) 1
    Weight increased 9/207 (4.3%) 9 12/196 (6.1%) 12
    White blood cell count decreased 0/207 (0%) 0 1/196 (0.5%) 1
    White blood cell count increased 0/207 (0%) 0 1/196 (0.5%) 1
    Metabolism and nutrition disorders
    Dyslipidaemia 0/207 (0%) 0 1/196 (0.5%) 1
    Hyperlipidaemia 1/207 (0.5%) 1 0/196 (0%) 0
    Hypertriglyceridaemia 2/207 (1%) 2 0/196 (0%) 0
    Hypokalaemia 1/207 (0.5%) 1 0/196 (0%) 0
    Lipid metabolism disorder 0/207 (0%) 0 1/196 (0.5%) 1
    Obesity 1/207 (0.5%) 1 1/196 (0.5%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/207 (1.4%) 3 2/196 (1%) 2
    Back pain 3/207 (1.4%) 3 3/196 (1.5%) 3
    Exostosis 1/207 (0.5%) 1 0/196 (0%) 0
    Lumbar spinal stenosis 1/207 (0.5%) 1 0/196 (0%) 0
    Musculoskeletal pain 1/207 (0.5%) 1 0/196 (0%) 0
    Musculoskeletal stiffness 1/207 (0.5%) 1 1/196 (0.5%) 1
    Myalgia 0/207 (0%) 0 1/196 (0.5%) 1
    Osteoarthritis 0/207 (0%) 0 1/196 (0.5%) 1
    Osteoporosis 1/207 (0.5%) 1 0/196 (0%) 0
    Pain in extremity 0/207 (0%) 0 3/196 (1.5%) 3
    Periarthritis 0/207 (0%) 0 1/196 (0.5%) 1
    Tenosynovitis 0/207 (0%) 0 1/196 (0.5%) 1
    Nervous system disorders
    Carotid arteriosclerosis 1/207 (0.5%) 1 0/196 (0%) 0
    Carpal tunnel syndrome 2/207 (1%) 2 0/196 (0%) 0
    Cognitive disorder 0/207 (0%) 0 2/196 (1%) 2
    Dementia alzheimer's type 0/207 (0%) 0 1/196 (0.5%) 1
    Diabetic neuropathy 1/207 (0.5%) 1 0/196 (0%) 0
    Dizziness 1/207 (0.5%) 1 2/196 (1%) 2
    Dizziness postural 1/207 (0.5%) 1 0/196 (0%) 0
    Headache 1/207 (0.5%) 1 4/196 (2%) 16
    Hyperaesthesia 1/207 (0.5%) 1 1/196 (0.5%) 1
    Hypoaesthesia 3/207 (1.4%) 3 0/196 (0%) 0
    Loss of consciousness 0/207 (0%) 0 1/196 (0.5%) 1
    Memory impairment 1/207 (0.5%) 1 0/196 (0%) 0
    Neuralgia 0/207 (0%) 0 1/196 (0.5%) 1
    Neuropathy peripheral 0/207 (0%) 0 1/196 (0.5%) 1
    Parosmia 1/207 (0.5%) 1 0/196 (0%) 0
    Sciatica 1/207 (0.5%) 1 0/196 (0%) 0
    Somnolence 1/207 (0.5%) 1 0/196 (0%) 0
    Psychiatric disorders
    Anxiety disorder 0/207 (0%) 0 1/196 (0.5%) 1
    Depression 0/207 (0%) 0 2/196 (1%) 2
    Insomnia 1/207 (0.5%) 1 2/196 (1%) 2
    Post-traumatic stress disorder 0/207 (0%) 0 1/196 (0.5%) 1
    Renal and urinary disorders
    Calculus ureteric 1/207 (0.5%) 1 0/196 (0%) 0
    Calculus urinary 0/207 (0%) 0 1/196 (0.5%) 1
    Cystitis noninfective 0/207 (0%) 0 1/196 (0.5%) 1
    Haematuria 0/207 (0%) 0 1/196 (0.5%) 1
    Nephrolithiasis 0/207 (0%) 0 1/196 (0.5%) 1
    Neurogenic bladder 1/207 (0.5%) 1 0/196 (0%) 0
    Polyuria 1/207 (0.5%) 1 0/196 (0%) 0
    Proteinuria 0/207 (0%) 0 1/196 (0.5%) 1
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 1/131 (0.8%) 1 0/119 (0%) 0
    Menstruation delayed 1/76 (1.3%) 1 0/77 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Asthma 1/207 (0.5%) 1 0/196 (0%) 0
    Cough 1/207 (0.5%) 1 1/196 (0.5%) 1
    Productive cough 0/207 (0%) 0 1/196 (0.5%) 1
    Rhinorrhoea 1/207 (0.5%) 1 0/196 (0%) 0
    Upper respiratory tract inflammation 2/207 (1%) 2 3/196 (1.5%) 3
    Skin and subcutaneous tissue disorders
    Dermatitis 0/207 (0%) 0 1/196 (0.5%) 1
    Dermatitis contact 1/207 (0.5%) 1 1/196 (0.5%) 1
    Eczema 2/207 (1%) 2 1/196 (0.5%) 1
    Pruritus 1/207 (0.5%) 1 2/196 (1%) 2
    Rash 1/207 (0.5%) 1 1/196 (0.5%) 1
    Skin erosion 0/207 (0%) 0 1/196 (0.5%) 1
    Skin fissures 0/207 (0%) 0 1/196 (0.5%) 1
    Urticaria 2/207 (1%) 2 0/196 (0%) 0
    Surgical and medical procedures
    Incisional drainage 1/207 (0.5%) 1 0/196 (0%) 0
    Large intestinal polypectomy 1/207 (0.5%) 1 0/196 (0%) 0
    Tooth extraction 1/207 (0.5%) 2 2/196 (1%) 2
    Vocal cord nodule removal 0/207 (0%) 0 1/196 (0.5%) 1
    Vascular disorders
    Arteriosclerosis 2/207 (1%) 2 1/196 (0.5%) 1
    Hypertension 3/207 (1.4%) 3 2/196 (1%) 2
    Varicose vein 1/207 (0.5%) 1 0/196 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01773473
    Other Study ID Numbers:
    • 14675
    • F3Z-CR-IOQI
    First Posted:
    Jan 23, 2013
    Last Update Posted:
    May 21, 2015
    Last Verified:
    May 1, 2015