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Comparison of the Efficacy and Safety of Two Insulin Intensification Strategies

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01175824
Collaborator
(none)
478
Enrollment
18
Locations
2
Arms
19.1
Duration (Months)
26.6
Patients Per Site
1.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is a comparison of twice-daily insulin lispro low mixture versus once-daily basal insulin glargine and once-daily prandial insulin lispro, in participants with Type 2 Diabetes.

Condition or Disease Intervention/Treatment Phase
  • Drug: Insulin Lispro Low Mixture (LM)
  • Drug: Insulin Glargine
  • Drug: Prandial Insulin Lispro
 Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
478 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Comparison of Twice-Daily Insulin Lispro Low Mixture Versus Once-Daily Basal Insulin Glargine and Once-Daily Prandial Insulin Lispro as Insulin Intensification Strategies in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Basal Insulin Glargine and Metformin and/or Pioglitazone
Study Start Date :
Apr 1, 2011
Actual Primary Completion Date :
Nov 1, 2012
Actual Study Completion Date :
Nov 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: Insulin lispro low mixture (LM)

Two daily injections (breakfast and dinner) of insulin lispro mix 75/25

Drug: Insulin Lispro Low Mixture (LM)
Participant-dependent dose, administered subcutaneously for 24 weeks
Other Names:
  • Humalog Mix75/25 (75% insulin lispro protamine suspension and 25% insulin lispro injection)

    		•
    Active Comparator: Insulin glargine+insulin lispro

    Once-daily (bedtime) basal insulin glargine and once-daily (before the main meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro

    Drug: Insulin Glargine
    Participant-dependent dose, administered subcutaneously for 24 weeks

    Drug: Prandial Insulin Lispro
    Participant-dependent dose, administered subcutaneously for 24 weeks
    Other Names:
  • Humalog
  • LY275585

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in HbA1c From Baseline to 24 Weeks Endpoint (Per Protocol Population) [Baseline, 24 weeks]

      The change from baseline to 24 weeks in the percentage of glycosylated hemoglobin A1c (HbA1c) in plasma. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline HbA1c concentration as a covariate, treatment, country, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.

    2. Change in HbA1c From Baseline to 24 Weeks Endpoint (Intention-to-Treat Population) [Baseline, 24 weeks]

      The change from baseline to 24 weeks in the percentage of glycosylated hemoglobin A1c (HbA1c) in plasma. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline HbA1c concentration as a covariate, treatment, country, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.

    Secondary Outcome Measures

    1. Change in the HbA1c Concentration From Baseline to 12 Weeks Endpoint [Baseline, 12 weeks]

      The change from baseline to 12 weeks in the percentage of glycosylated hemoglobin A1c (HbA1c) in plasma. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline HbA1c concentration as a covariate, treatment, country, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.

    2. Number of Participants Who Achieve a Target HbA1c Concentration of Less Than 7% or Less Than or Equal to 6.5% at 24 Weeks [24 weeks]

    3. Change in the Fasting Plasma Glucose Concentration From Baseline to 12 Weeks and 24 Weeks [Baseline, 12 weeks, and 24 weeks]

      The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline fasting plasma glucose value as a covariate, treatment, country, baseline HbA1c stratification level, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.

    4. 7-point Self-Monitored Blood Glucose (SMBG) Profiles at 12 Weeks and 24 Weeks [12 weeks, 24 weeks]

      7-point Self-monitored Blood Glucose (SMBG) Profiles are measures of blood glucose taken 7 times a day at the morning pre-meal, morning 2-hours post-meal, midday pre-meal, midday 2-hours post-meal, evening pre-meal, evening 2-hours post-meal, and 0300 hour [3 am]. Each participant took measures on 3 non-consecutive days and the average was calculated for each of the 7 time points. The mean of the 7-point averages was calculated for all the participants at baseline, Weeks 12 and 24. The least squares (LS) mean was estimated from mixed-effects model with repeated measures that included the baseline value of the variable as a covariate, treatment, country, baseline glycosylated hemoglobin A1c (HbA1c)stratification level, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.

    5. Glycemic Variability From the 7-point Self-Monitored Blood Glucose (SMBG) Profiles at 12 Weeks and 24 Weeks [12 weeks, 24 weeks]

      The 7-point SMBG profile was calculated as the average blood glucose concentration across the 7 pre-specified time points in a day that was then averaged over 3 non-consecutive days in the 2 weeks prior to the 12 week visit and 24 week visit. Glycemic variability was calculated as the standard deviation of the 7-point SMBG profiles. Standard deviation was first calculated for each day and then averaged over 3 non-consecutive days for each visit. The least squares (LS) mean was estimated from mixed-effects model with repeated measures that included the baseline value of the variable as a covariate, treatment, country, baseline glycosylated hemoglobin A1c (HbA1c)stratification level, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.

    6. Daily Insulin Dose: Total, Basal, and Prandial at 12 Weeks and 24 Weeks [12 weeks, 24 weeks]

    7. Change in Weight From Baseline to 12 Weeks and 24 Weeks [Baseline, 12 weeks, 24 weeks]

      The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline weight as a covariate, treatment, country, baseline glycosylated hemoglobin A1c (HbA1c) stratification level, week of visit, and the treatment-by-week interaction as fixed effects, and participant and error as random effects.

    8. The Number of Participants With a Hypoglycemic Episodes (Incidence) [Baseline through 24 weeks]

      A hypoglycemic episode was defined as an event associated with 1) reported signs and symptoms of hypoglycemia, and/or 2) a documented blood glucose (BG) concentration of <= 70 milligrams per deciliter [mg/dL, 3.9 millimoles per liter (mmol/L)].

    9. Insulin Treatment Satisfaction Questionnaire (ITSQ) Score at 24 Weeks [24 weeks]

      ITSQ: validated instrument containing 22 items which are measured on a 7-point scale: 1 (no bother at all) to 7 (a tremendous bother) used to assess insulin treatment satisfaction. Items are divided into 5 domains: Inconvenience of Regimen (5 items: domain score range 5 to 35), Lifestyle Flexibility (3 items: domain score range 3 to 21), Glycemic Control (3 items: domain score range 3 to 21), Hypoglycemic Control (5 items: domain score range 5 to 35), Insulin Delivery Device (6 items: domain score range 6 to 42) lower scores reflect better outcome. ITSQ Total Overall Score ranged from 22 to 154. Raw domain scores transformed on 0-100 scale, where transformed domain score = 100×[(7-raw domain score)/6]. Higher scores indicate better treatment satisfaction. Least squares (LS) mean estimated from analysis of covariance (ANCOVA) model that included baseline score as covariate and treatment, glycosylated hemoglobin A1c (HbA1c) stratum, and country as fixed effects.

    10. Perceptions About Medications-Diabetes 21 (PAM-D21) Questionnaire Score at 24 Weeks [24 weeks]

      PAM-D21 is a validated questionnaire consisting of 21 items to assess a participant's perceptions about their diabetes treatment regimens and perceived emotional and physical side-effects. The PAM-D21 consists of 4 subscales: Convenience/Flexibility (items 1 to 3); Perceived Effectiveness (items 4 to 6); Emotional Effects (items 7 to 11); and Physical Effects (items 12 to 21). Item scores range from 1 (none of the time) to 4 (all of the time). Subscale scores were linearly transformed to a 0-100, with higher score corresponds to better perceptions about diabetes medications. The least squares (LS) mean was estimated from an analysis of covariance (ANCOVA) model that included baseline score as a covariate and treatment, glycosylated hemoglobin A1c (HbA1c) stratum, and country as fixed effects.

    11. The Rate of Hypoglycemic Episodes [Baseline through 24 weeks]

      The hypoglycemia rate per 30 days was calculated as the number of episodes reported for the interval between visits and during the study divided by the number of days in the given interval and multiplied by 30.

    12. The Number of Participants With Severe Hypoglycemic Episodes [Baseline through 24 weeks]

      The number of participants who had a severe hypoglycemic episode anytime during the study. Severe hypoglycemia was defined as any event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Present with type 2 diabetes mellitus

    • Have been taking metformin and/or pioglitazone

    • Have received treatment with basal insulin glargine, injected once a day, for greater than or equal to 90 days

    • Have glycosylated hemoglobin A1c (HbA1c) concentration between greater than or equal to 7.5% and less than or equal to 10.5

    • Have a fasting plasma glucose concentration of less than or equal to 6.7 millimoles per liter [mmol/L, less than or equal to 121 milligrams per deciliter (mg/dL)], or greater than 6.7 mmol/L (greater than 121 mg/dL) if the investigator considers that further titration of basal insulin glargine is not possible for safety reasons

    • Not pregnant or breastfeeding

    Exclusion Criteria:

    • Have Type 1 Diabetes

    • Their stable dose of pioglitazone is greater than the maximum dose approved for use in combination with insulin in their country

    • Have a body mass index (BMI) greater than 45 kilograms per square meter (kg/m2).

    • Have a history of scheduled mealtime (prandial) insulin use within 12 weeks of the screening visit and the total duration of the prandial insulin treatment was greater than 2 weeks

    • Have had more than one episode of severe hypoglycaemia within 24 weeks prior to entry into the study

    • Have cardiac disease with a functional status that is Class III or IV

    • Have a history of renal or liver disease

    • Have had a blood transfusion or have a blood disorder

    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. Mar Del Plata Argentina B7600FZN
    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. Ramos Mejia Argentina B1704ETD
    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. Porto Alegre Brazil 90035-170
    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. São Paulo Brazil 01244-030
    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. Changzhou China 213003
    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. Harbin China 150086
    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. Alexandria Egypt
    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. Cairo Egypt 11562
    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. Jaipur India 302018
    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. Vishakhapatnam India 530002
    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. Daegu Korea, Republic of 700-712
    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. Goyang-Si Korea, Republic of 410-719
    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. Kyunggi-Do Korea, Republic of 425-020
    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. Seoul Korea, Republic of 134-090
    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. Málaga Spain 29010
    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. San Boi De Llobregat Spain 08830
    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. Antalya Turkey 07070
    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. Istanbul Turkey 34865

    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:
    NCT01175824
    Other Study ID Numbers:
    • 13493
    • F3Z-CR-IOQE
    First Posted:
    Aug 5, 2010
    Last Update Posted:
    Feb 24, 2014
    Last Verified:
    Jan 1, 2014
    Keywords provided by Eli Lilly and Company
    Metabolic Diseases
    Diabetes Mellitus, Type 2
    Glargine
    Diabetes Mellitus
    Insulin LISPRO
    Insulin
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Insulin
    Insulin, Globin Zinc
    Insulin Glargine
    Insulin Lispro
    Protamines

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Period Title: Overall Study
    STARTED 236 242
    Received at Least 1 Dose of Study Drug 236 240
    COMPLETED 220 220
    NOT COMPLETED 16 22

    Baseline Characteristics

    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro Total
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks. Total of all reporting groups
    Overall Participants 236 240 476
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    57.4
    (9.93)
    57.7
    (9.12)
    57.5
    (9.52)
    Sex: Female, Male (Count of Participants)
    Female
    120
    50.8%
    142
    59.2%
    262
    55%
    Male
    116
    49.2%
    98
    40.8%
    214
    45%
    Race/Ethnicity, Customized (participants) [Number]
    American Indian or Alaska Native
    15
    6.4%
    17
    7.1%
    32
    6.7%
    Asian
    80
    33.9%
    80
    33.3%
    160
    33.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    5
    2.1%
    1
    0.4%
    6
    1.3%
    White
    133
    56.4%
    136
    56.7%
    269
    56.5%
    More than one race
    3
    1.3%
    6
    2.5%
    9
    1.9%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    Argentina
    40
    16.9%
    39
    16.3%
    79
    16.6%
    Brazil
    20
    8.5%
    23
    9.6%
    43
    9%
    China
    15
    6.4%
    13
    5.4%
    28
    5.9%
    Egypt
    5
    2.1%
    7
    2.9%
    12
    2.5%
    India
    40
    16.9%
    41
    17.1%
    81
    17%
    Korea, Republic of
    25
    10.6%
    26
    10.8%
    51
    10.7%
    Mexico
    20
    8.5%
    20
    8.3%
    40
    8.4%
    Romania
    38
    16.1%
    38
    15.8%
    76
    16%
    Russian Federation
    2
    0.8%
    3
    1.3%
    5
    1.1%
    Spain
    23
    9.7%
    23
    9.6%
    46
    9.7%
    Turkey
    8
    3.4%
    7
    2.9%
    15
    3.2%

    Outcome Measures

    1. Primary Outcome
    Title Change in HbA1c From Baseline to 24 Weeks Endpoint (Per Protocol Population)
    Description The change from baseline to 24 weeks in the percentage of glycosylated hemoglobin A1c (HbA1c) in plasma. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline HbA1c concentration as a covariate, treatment, country, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.
    Time Frame Baseline, 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Per protocol population: randomized participants with the exception of participants who did not complete Week 24 visit, received study drug different from their randomized study treatment, violated any of the inclusion, exclusion, or discontinuation criteria, or were significantly noncompliant.
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 220 216
    Least Squares Mean (95% Confidence Interval) [percentage of HbA1c]
    -1.30
    -1.09
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Low Mixture, Insulin Glargine+Insulin Lispro
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Non-inferiority will be concluded if the upper limit of the 95% confidence interval (CI) of the difference in the LS mean between the two treatment arms (twice-daily insulin lispro Low Mixture minus the comparator arm) at 24 weeks is <0.4%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value -0.21
    Confidence Interval (2-Sided) 95%
    -0.38 to -0.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change in the HbA1c Concentration From Baseline to 12 Weeks Endpoint
    Description The change from baseline to 12 weeks in the percentage of glycosylated hemoglobin A1c (HbA1c) in plasma. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline HbA1c concentration as a covariate, treatment, country, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.
    Time Frame Baseline, 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Intention-to-treat population (ITT): randomized participants who received at least 1 dose of study drug and had HbA1c data at the 12 weeks. Participants were analyzed per their assigned treatment arm regardless of the treatment they actually received.
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 222 226
    Least Squares Mean (95% Confidence Interval) [percentage of HbA1c]
    -1.12
    -1.01
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Low Mixture, Insulin Glargine+Insulin Lispro
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1858
    Comments
    Method Mixed Models Analysis
    Comments
    3. Secondary Outcome
    Title Number of Participants Who Achieve a Target HbA1c Concentration of Less Than 7% or Less Than or Equal to 6.5% at 24 Weeks
    Description
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Intention-to-treat population (ITT): randomized participants who received at least 1 dose of study drug and had HbA1c data at 24 weeks. Participants were analyzed per their assigned treatment arm regardless of the treatment they actually received.
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 220 220
    HbA1c <7%
    76
    32.2%
    66
    27.5%
    HbA1c <=6.5%
    36
    15.3%
    31
    12.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Low Mixture, Insulin Glargine+Insulin Lispro
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3588
    Comments HbA1c concentration <7%
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Low Mixture, Insulin Glargine+Insulin Lispro
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5958
    Comments HbA1c <=6.5%
    Method Fisher Exact
    Comments
    4. Secondary Outcome
    Title Change in the Fasting Plasma Glucose Concentration From Baseline to 12 Weeks and 24 Weeks
    Description The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline fasting plasma glucose value as a covariate, treatment, country, baseline HbA1c stratification level, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.
    Time Frame Baseline, 12 weeks, and 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Intention-to-treat population (ITT): randomized participants who received at least 1 dose of study drug and had fasting plasma glucose concentration data at the specified time points. Participants were analyzed per their assigned treatment arm regardless of the treatment they actually received.
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 222 222
    Change at 12 Weeks (n= 222, 222)
    1.04
    0.64
    Change at 24 Weeks (n=219, 217)
    0.89
    0.75
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Low Mixture, Insulin Glargine+Insulin Lispro
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0827
    Comments p-value is for the Week 12 comparison
    Method Mixed Models Analysis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Low Mixture, Insulin Glargine+Insulin Lispro
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5353
    Comments p-value is for the Week 24 comparison
    Method Mixed Models Analysis
    Comments
    5. Secondary Outcome
    Title 7-point Self-Monitored Blood Glucose (SMBG) Profiles at 12 Weeks and 24 Weeks
    Description 7-point Self-monitored Blood Glucose (SMBG) Profiles are measures of blood glucose taken 7 times a day at the morning pre-meal, morning 2-hours post-meal, midday pre-meal, midday 2-hours post-meal, evening pre-meal, evening 2-hours post-meal, and 0300 hour [3 am]. Each participant took measures on 3 non-consecutive days and the average was calculated for each of the 7 time points. The mean of the 7-point averages was calculated for all the participants at baseline, Weeks 12 and 24. The least squares (LS) mean was estimated from mixed-effects model with repeated measures that included the baseline value of the variable as a covariate, treatment, country, baseline glycosylated hemoglobin A1c (HbA1c)stratification level, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.
    Time Frame 12 weeks, 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Intention-to-treat population (ITT): randomized participants who received at least 1 dose of study drug and had SMBG data at the specified time points. Participants were analyzed per their assigned treatment arm regardless of the treatment they actually received.
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 229 235
    pre-morning meal (Week 12) (n=223, 222)
    6.87
    6.20
    2 hour post-morning meal (Week 12) (n=220, 221)
    8.82
    9.01
    pre-midday meal (Week 12) (n=220, 221)
    6.96
    7.44
    2 hours post-midday meal (Week 12) (n=220, 221)
    9.46
    9.14
    pre-evening meal (Week 12) (n=221, 221)
    7.98
    8.25
    2 hours post-evening meal (Week 12) (n=217, 220)
    9.15
    9.10
    3 am - during the night (Week 12)(n=197, 201)
    8.21
    8.52
    pre-morning meal (Week 24) (n=217, 216)
    6.60
    6.26
    2 hours post-morning meal (Week 24) (n=216, 215)
    8.52
    8.86
    pre-midday meal (Week 24) (n=215, 216)
    6.82
    7.44
    2 hours post-midday meal (Week 24) (n=216, 216)
    9.08
    8.99
    pre-evening meal (Week 24) (n=216, 216)
    7.70
    7.95
    2 hours post-evening meal (Week 24) (n=212, 216)
    9.11
    8.95
    3 am - during the night (Week 24)(n=198, 195)
    8.05
    8.26
    6. Secondary Outcome
    Title Glycemic Variability From the 7-point Self-Monitored Blood Glucose (SMBG) Profiles at 12 Weeks and 24 Weeks
    Description The 7-point SMBG profile was calculated as the average blood glucose concentration across the 7 pre-specified time points in a day that was then averaged over 3 non-consecutive days in the 2 weeks prior to the 12 week visit and 24 week visit. Glycemic variability was calculated as the standard deviation of the 7-point SMBG profiles. Standard deviation was first calculated for each day and then averaged over 3 non-consecutive days for each visit. The least squares (LS) mean was estimated from mixed-effects model with repeated measures that included the baseline value of the variable as a covariate, treatment, country, baseline glycosylated hemoglobin A1c (HbA1c)stratification level, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.
    Time Frame 12 weeks, 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Intention-to-treat population (ITT): randomized participants who received at least 1 dose of study drug and had SMBG glycemic variability data at the specified time points. Participants were analyzed per their assigned treatment arm regardless of the treatment they actually received.
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 220 221
    SMBG glycemic variability, 12 weeks (n=220, 221)
    2.12
    2.13
    SMBG glycemic variability, 24 weeks (n=216, 216)
    2.03
    1.99
    7. Secondary Outcome
    Title Daily Insulin Dose: Total, Basal, and Prandial at 12 Weeks and 24 Weeks
    Description
    Time Frame 12 weeks, 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Intention-to-treat population (ITT): randomized participants who received at least 1 dose of study drug and had dosing data at the specified time points. Participants were analyzed per their assigned treatment arm regardless of the treatment they actually received.
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 236 240
    Total Insulin Dose at 12 Weeks (n=224, 224)
    51.2
    (23.60)
    49.2
    (20.89)
    Total Insulin Dose at 24 Weeks LOCF (n=236, 240)
    53.1
    (24.60)
    50.8
    (21.96)
    Basal Insulin Dose at 12 Weeks (n=224, 224)
    38.4
    (17.70)
    37.1
    (18.34)
    Basal Insulin Dose at 24 Weeks LOCF (n=236, 240)
    39.8
    (18.45)
    37.4
    (18.76)
    Prandial Insulin Dose at 12 Weeks (n=224, 224)
    12.8
    (5.90)
    12.1
    (5.10)
    Prandial Insulin Dose at 24 Weeks LOCF(n=236, 240)
    13.3
    (6.15)
    13.5
    (6.46)
    8. Secondary Outcome
    Title Change in Weight From Baseline to 12 Weeks and 24 Weeks
    Description The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline weight as a covariate, treatment, country, baseline glycosylated hemoglobin A1c (HbA1c) stratification level, week of visit, and the treatment-by-week interaction as fixed effects, and participant and error as random effects.
    Time Frame Baseline, 12 weeks, 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety population: randomized participants who took at least 1 dose of study drug and had evaluable body weight data at the specified time points.
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 224 225
    Change at 12 weeks (n=224, 225)
    0.54
    0.34
    Change at 24 weeks (n=219, 217)
    1.13
    0.50
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Low Mixture, Insulin Glargine+Insulin Lispro
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2833
    Comments p-value is for the comparison at Week 12.
    Method Mixed Models Analysis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Low Mixture, Insulin Glargine+Insulin Lispro
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0176
    Comments p-value is for the comparison at Week 24.
    Method Mixed Models Analysis
    Comments
    9. Secondary Outcome
    Title The Number of Participants With a Hypoglycemic Episodes (Incidence)
    Description A hypoglycemic episode was defined as an event associated with 1) reported signs and symptoms of hypoglycemia, and/or 2) a documented blood glucose (BG) concentration of <= 70 milligrams per deciliter [mg/dL, 3.9 millimoles per liter (mmol/L)].
    Time Frame Baseline through 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety population: randomized participants who took at least 1 dose of study drug.
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 236 240
    Number [participants]
    144
    61%
    150
    62.5%
    10. Secondary Outcome
    Title Insulin Treatment Satisfaction Questionnaire (ITSQ) Score at 24 Weeks
    Description ITSQ: validated instrument containing 22 items which are measured on a 7-point scale: 1 (no bother at all) to 7 (a tremendous bother) used to assess insulin treatment satisfaction. Items are divided into 5 domains: Inconvenience of Regimen (5 items: domain score range 5 to 35), Lifestyle Flexibility (3 items: domain score range 3 to 21), Glycemic Control (3 items: domain score range 3 to 21), Hypoglycemic Control (5 items: domain score range 5 to 35), Insulin Delivery Device (6 items: domain score range 6 to 42) lower scores reflect better outcome. ITSQ Total Overall Score ranged from 22 to 154. Raw domain scores transformed on 0-100 scale, where transformed domain score = 100×[(7-raw domain score)/6]. Higher scores indicate better treatment satisfaction. Least squares (LS) mean estimated from analysis of covariance (ANCOVA) model that included baseline score as covariate and treatment, glycosylated hemoglobin A1c (HbA1c) stratum, and country as fixed effects.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had ITSQ scores at 24 weeks. Last observation carried forward (LOCF).
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 230 229
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    80.91
    81.84
    11. Secondary Outcome
    Title Perceptions About Medications-Diabetes 21 (PAM-D21) Questionnaire Score at 24 Weeks
    Description PAM-D21 is a validated questionnaire consisting of 21 items to assess a participant's perceptions about their diabetes treatment regimens and perceived emotional and physical side-effects. The PAM-D21 consists of 4 subscales: Convenience/Flexibility (items 1 to 3); Perceived Effectiveness (items 4 to 6); Emotional Effects (items 7 to 11); and Physical Effects (items 12 to 21). Item scores range from 1 (none of the time) to 4 (all of the time). Subscale scores were linearly transformed to a 0-100, with higher score corresponds to better perceptions about diabetes medications. The least squares (LS) mean was estimated from an analysis of covariance (ANCOVA) model that included baseline score as a covariate and treatment, glycosylated hemoglobin A1c (HbA1c) stratum, and country as fixed effects.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Randomized participants who received at least 1 dose of study drug and had PAM-D21 scores at 24 weeks.
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 231 230
    Convenience/Flexibility (n= 231, 230)
    83.90
    84.13
    Perceived Effectiveness (n=231, 230)
    76.78
    78.76
    Emotional Effects (n=231, 230)
    81.84
    81.86
    Physical Effects (n=231, 228)
    87.89
    89.04
    12. Secondary Outcome
    Title The Rate of Hypoglycemic Episodes
    Description The hypoglycemia rate per 30 days was calculated as the number of episodes reported for the interval between visits and during the study divided by the number of days in the given interval and multiplied by 30.
    Time Frame Baseline through 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety population: randomized participants who took at least 1 dose of study drug.
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 236 240
    Mean (Standard Deviation) [hypoglycemic episodes per 30 day period]
    1.07
    (1.181)
    1.36
    (2.172)
    13. Secondary Outcome
    Title The Number of Participants With Severe Hypoglycemic Episodes
    Description The number of participants who had a severe hypoglycemic episode anytime during the study. Severe hypoglycemia was defined as any event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
    Time Frame Baseline through 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety population: randomized participants who took at least 1 dose of study drug.
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 236 240
    Number [participants]
    2
    0.8%
    0
    0%
    14. Primary Outcome
    Title Change in HbA1c From Baseline to 24 Weeks Endpoint (Intention-to-Treat Population)
    Description The change from baseline to 24 weeks in the percentage of glycosylated hemoglobin A1c (HbA1c) in plasma. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline HbA1c concentration as a covariate, treatment, country, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.
    Time Frame Baseline, 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Intention-to-treat population (ITT): randomized participants who received at least 1 dose of study drug and had HbA1c data at 24 weeks. Participants were analyzed per their assigned treatment arm regardless of the treatment they actually received.
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    Measure Participants 220 220
    Least Squares Mean (95% Confidence Interval) [percentage of HbA1c]
    -1.30
    -1.08
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro Low Mixture, Insulin Glargine+Insulin Lispro
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value -0.22
    Confidence Interval (2-Sided) 95%
    -0.39 to -0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Arm/Group Description Two daily injections (breakfast and dinner) of insulin lispro mix 75/25. Participant-dependent doses, administered subcutaneously for 24 weeks. Once-daily injection (bedtime) basal insulin glargine and once-daily injection (before the meal with the highest average 2-hour postprandial blood glucose concentration) prandial insulin lispro. Participant-dependent doses, administered subcutaneously for 24 weeks.
    All Cause Mortality
    Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/236 (4.7%) 8/240 (3.3%)
    Cardiac disorders
    Myocardial infarction 1/236 (0.4%) 1 0/240 (0%) 0
    Eye disorders
    Retinal vein occlusion 0/236 (0%) 0 1/240 (0.4%) 1
    Infections and infestations
    Bronchitis 0/236 (0%) 0 1/240 (0.4%) 1
    Epiglottitis 1/236 (0.4%) 2 0/240 (0%) 0
    Laryngitis 0/236 (0%) 0 1/240 (0.4%) 1
    Nasopharyngitis 1/236 (0.4%) 1 0/240 (0%) 0
    Respiratory tract infection 1/236 (0.4%) 1 0/240 (0%) 0
    Injury, poisoning and procedural complications
    Fall 1/236 (0.4%) 1 0/240 (0%) 0
    Overdose 0/236 (0%) 0 1/240 (0.4%) 1
    Pelvic fracture 1/236 (0.4%) 1 0/240 (0%) 0
    Metabolism and nutrition disorders
    Hyperglycaemia 0/236 (0%) 0 1/240 (0.4%) 1
    Hypoglycaemia 3/236 (1.3%) 3 1/240 (0.4%) 1
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion 2/236 (0.8%) 3 0/240 (0%) 0
    Limb discomfort 1/236 (0.4%) 1 0/240 (0%) 0
    Pain in extremity 1/236 (0.4%) 1 0/240 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign neoplasm of adrenal gland 0/236 (0%) 0 1/240 (0.4%) 1
    Gastric cancer 1/236 (0.4%) 1 0/240 (0%) 0
    Nervous system disorders
    Cerebral haemorrhage 0/236 (0%) 0 1/240 (0.4%) 1
    Renal and urinary disorders
    Nephrolithiasis 1/236 (0.4%) 1 0/240 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure 1/236 (0.4%) 1 0/240 (0%) 0
    Surgical and medical procedures
    Toe amputation 0/236 (0%) 0 1/240 (0.4%) 1
    Other (Not Including Serious) Adverse Events
    Insulin Lispro Low Mixture Insulin Glargine+Insulin Lispro
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 109/236 (46.2%) 93/240 (38.8%)
    Blood and lymphatic system disorders
    Anaemia 1/236 (0.4%) 1 2/240 (0.8%) 2
    Cardiac disorders
    Myocardial ischaemia 1/236 (0.4%) 1 0/240 (0%) 0
    Palpitations 2/236 (0.8%) 2 0/240 (0%) 0
    Congenital, familial and genetic disorders
    Birth mark 0/236 (0%) 0 1/240 (0.4%) 1
    Ear and labyrinth disorders
    Vertigo 3/236 (1.3%) 3 1/240 (0.4%) 1
    Eye disorders
    Cataract 1/236 (0.4%) 1 0/240 (0%) 0
    Conjunctival hyperaemia 1/236 (0.4%) 1 0/240 (0%) 0
    Conjunctivitis 0/236 (0%) 0 1/240 (0.4%) 1
    Diabetic retinopathy 1/236 (0.4%) 1 0/240 (0%) 0
    Eye pain 1/236 (0.4%) 1 0/240 (0%) 0
    Vision blurred 0/236 (0%) 0 1/240 (0.4%) 1
    Gastrointestinal disorders
    Abdominal discomfort 1/236 (0.4%) 1 0/240 (0%) 0
    Abdominal distension 0/236 (0%) 0 1/240 (0.4%) 1
    Abdominal pain 3/236 (1.3%) 3 2/240 (0.8%) 2
    Abdominal pain upper 0/236 (0%) 0 4/240 (1.7%) 4
    Apical granuloma 1/236 (0.4%) 1 1/240 (0.4%) 1
    Constipation 2/236 (0.8%) 2 3/240 (1.3%) 3
    Dental caries 0/236 (0%) 0 1/240 (0.4%) 1
    Diarrhoea 6/236 (2.5%) 6 4/240 (1.7%) 6
    Dyspepsia 2/236 (0.8%) 2 3/240 (1.3%) 3
    Enteritis 1/236 (0.4%) 1 0/240 (0%) 0
    Enterocolitis 1/236 (0.4%) 1 0/240 (0%) 0
    Food poisoning 1/236 (0.4%) 1 0/240 (0%) 0
    Gastric ulcer 1/236 (0.4%) 1 0/240 (0%) 0
    Gastritis 0/236 (0%) 0 2/240 (0.8%) 2
    Gastrointestinal disorder 1/236 (0.4%) 1 0/240 (0%) 0
    Inguinal hernia 1/236 (0.4%) 1 0/240 (0%) 0
    Mouth haemorrhage 0/236 (0%) 0 1/240 (0.4%) 1
    Nausea 0/236 (0%) 0 4/240 (1.7%) 4
    Odynophagia 1/236 (0.4%) 1 2/240 (0.8%) 2
    Periodontal disease 1/236 (0.4%) 1 0/240 (0%) 0
    Stomatitis 0/236 (0%) 0 1/240 (0.4%) 1
    Tongue oedema 1/236 (0.4%) 1 0/240 (0%) 0
    Toothache 1/236 (0.4%) 1 0/240 (0%) 0
    Vomiting 4/236 (1.7%) 4 1/240 (0.4%) 1
    General disorders
    Asthenia 3/236 (1.3%) 3 1/240 (0.4%) 1
    Chest discomfort 0/236 (0%) 0 1/240 (0.4%) 1
    Chest pain 1/236 (0.4%) 1 2/240 (0.8%) 2
    Discomfort 1/236 (0.4%) 1 1/240 (0.4%) 1
    Face oedema 1/236 (0.4%) 1 0/240 (0%) 0
    Fatigue 0/236 (0%) 0 2/240 (0.8%) 4
    Influenza like illness 1/236 (0.4%) 1 0/240 (0%) 0
    Injection site haematoma 1/236 (0.4%) 1 0/240 (0%) 0
    Injection site pain 0/236 (0%) 0 2/240 (0.8%) 2
    Oedema 0/236 (0%) 0 1/240 (0.4%) 1
    Oedema peripheral 1/236 (0.4%) 1 2/240 (0.8%) 2
    Pyrexia 3/236 (1.3%) 3 4/240 (1.7%) 4
    Hepatobiliary disorders
    Cholecystitis 1/236 (0.4%) 1 0/240 (0%) 0
    Cholelithiasis 0/236 (0%) 0 1/240 (0.4%) 1
    Hepatic steatosis 2/236 (0.8%) 2 0/240 (0%) 0
    Immune system disorders
    Drug hypersensitivity 0/236 (0%) 0 1/240 (0.4%) 1
    Infections and infestations
    Acute tonsillitis 2/236 (0.8%) 2 1/240 (0.4%) 1
    Bronchitis 3/236 (1.3%) 3 0/240 (0%) 0
    Cystitis 1/236 (0.4%) 1 1/240 (0.4%) 1
    Dengue fever 1/236 (0.4%) 1 0/240 (0%) 0
    Furuncle 0/236 (0%) 0 1/240 (0.4%) 1
    Gastroenteritis 4/236 (1.7%) 4 0/240 (0%) 0
    Gastroenteritis viral 1/236 (0.4%) 1 0/240 (0%) 0
    Gingivitis 1/236 (0.4%) 1 0/240 (0%) 0
    Herpes zoster 0/236 (0%) 0 1/240 (0.4%) 1
    Influenza 3/236 (1.3%) 3 4/240 (1.7%) 4
    Keratitis herpetic 0/236 (0%) 0 1/240 (0.4%) 1
    Laryngitis 1/236 (0.4%) 1 0/240 (0%) 0
    Localised infection 0/236 (0%) 0 1/240 (0.4%) 1
    Nasopharyngitis 20/236 (8.5%) 24 13/240 (5.4%) 13
    Orchitis 0/236 (0%) 0 1/240 (0.4%) 1
    Periodontitis 1/236 (0.4%) 1 1/240 (0.4%) 1
    Pharyngitis 2/236 (0.8%) 2 3/240 (1.3%) 3
    Pulpitis dental 1/236 (0.4%) 1 0/240 (0%) 0
    Pyelonephritis acute 0/236 (0%) 0 1/240 (0.4%) 2
    Respiratory tract infection 2/236 (0.8%) 3 0/240 (0%) 0
    Respiratory tract infection viral 0/236 (0%) 0 2/240 (0.8%) 2
    Rhinitis 1/236 (0.4%) 1 1/240 (0.4%) 1
    Sinusitis 1/236 (0.4%) 1 2/240 (0.8%) 2
    Tinea pedis 1/236 (0.4%) 1 0/240 (0%) 0
    Tonsillitis 1/236 (0.4%) 1 0/240 (0%) 0
    Tooth abscess 3/236 (1.3%) 4 1/240 (0.4%) 1
    Tooth infection 1/236 (0.4%) 1 1/240 (0.4%) 1
    Upper respiratory tract infection 2/236 (0.8%) 2 3/240 (1.3%) 3
    Urinary tract infection 3/236 (1.3%) 4 5/240 (2.1%) 7
    Wound infection 0/236 (0%) 0 1/240 (0.4%) 1
    Injury, poisoning and procedural complications
    Arthropod sting 1/236 (0.4%) 1 0/240 (0%) 0
    Burns third degree 0/236 (0%) 0 1/240 (0.4%) 1
    Contusion 1/236 (0.4%) 1 1/240 (0.4%) 1
    Corneal abrasion 0/236 (0%) 0 1/240 (0.4%) 1
    Excoriation 0/236 (0%) 0 1/240 (0.4%) 1
    Injury 0/236 (0%) 0 1/240 (0.4%) 1
    Joint injury 0/236 (0%) 0 2/240 (0.8%) 2
    Laceration 1/236 (0.4%) 1 0/240 (0%) 0
    Ligament sprain 1/236 (0.4%) 1 0/240 (0%) 0
    Limb injury 1/236 (0.4%) 1 0/240 (0%) 0
    Lower limb fracture 0/236 (0%) 0 1/240 (0.4%) 1
    Meniscus lesion 1/236 (0.4%) 1 0/240 (0%) 0
    Muscle strain 0/236 (0%) 0 1/240 (0.4%) 1
    Spinal column injury 0/236 (0%) 0 1/240 (0.4%) 1
    Tooth fracture 1/236 (0.4%) 1 1/240 (0.4%) 1
    Wound secretion 0/236 (0%) 0 1/240 (0.4%) 1
    Wrist fracture 1/236 (0.4%) 1 0/240 (0%) 0
    Investigations
    Alanine aminotransferase increased 1/236 (0.4%) 1 1/240 (0.4%) 1
    Blood creatinine increased 0/236 (0%) 0 1/240 (0.4%) 1
    Blood pressure increased 0/236 (0%) 0 1/240 (0.4%) 1
    Hepatic enzyme increased 1/236 (0.4%) 1 0/240 (0%) 0
    Weight increased 2/236 (0.8%) 2 0/240 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 1/236 (0.4%) 1 0/240 (0%) 0
    Dyslipidaemia 2/236 (0.8%) 2 0/240 (0%) 0
    Hyperlipidaemia 1/236 (0.4%) 1 0/240 (0%) 0
    Hypoalbuminaemia 0/236 (0%) 0 1/240 (0.4%) 1
    Hypocalcaemia 0/236 (0%) 0 1/240 (0.4%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 6/236 (2.5%) 6 5/240 (2.1%) 5
    Back pain 4/236 (1.7%) 4 6/240 (2.5%) 8
    Bursitis 0/236 (0%) 0 1/240 (0.4%) 1
    Gouty arthritis 1/236 (0.4%) 1 0/240 (0%) 0
    Intervertebral disc protrusion 0/236 (0%) 0 2/240 (0.8%) 2
    Joint swelling 0/236 (0%) 0 1/240 (0.4%) 1
    Limb discomfort 0/236 (0%) 0 1/240 (0.4%) 1
    Muscle spasms 0/236 (0%) 0 1/240 (0.4%) 1
    Muscular weakness 1/236 (0.4%) 1 0/240 (0%) 0
    Musculoskeletal pain 0/236 (0%) 0 1/240 (0.4%) 1
    Neck pain 2/236 (0.8%) 2 0/240 (0%) 0
    Osteoarthritis 0/236 (0%) 0 2/240 (0.8%) 2
    Osteoporosis 1/236 (0.4%) 1 0/240 (0%) 0
    Pain in extremity 1/236 (0.4%) 1 6/240 (2.5%) 7
    Periarthritis 1/236 (0.4%) 1 0/240 (0%) 0
    Rheumatic disorder 1/236 (0.4%) 1 0/240 (0%) 0
    Synovial cyst 0/236 (0%) 0 1/240 (0.4%) 1
    Tendonitis 0/236 (0%) 0 1/240 (0.4%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Seborrhoeic keratosis 0/236 (0%) 0 1/240 (0.4%) 1
    Nervous system disorders
    Burning sensation 0/236 (0%) 0 1/240 (0.4%) 1
    Carpal tunnel syndrome 2/236 (0.8%) 3 1/240 (0.4%) 1
    Diabetic neuropathy 0/236 (0%) 0 2/240 (0.8%) 2
    Dizziness 5/236 (2.1%) 6 4/240 (1.7%) 6
    Headache 7/236 (3%) 9 7/240 (2.9%) 7
    Hypoaesthesia 2/236 (0.8%) 2 0/240 (0%) 0
    Paraesthesia 1/236 (0.4%) 1 0/240 (0%) 0
    Radiculopathy 1/236 (0.4%) 1 0/240 (0%) 0
    Sciatica 0/236 (0%) 0 3/240 (1.3%) 3
    Tremor 1/236 (0.4%) 1 1/240 (0.4%) 1
    Psychiatric disorders
    Anxiety 2/236 (0.8%) 2 3/240 (1.3%) 3
    Insomnia 1/236 (0.4%) 1 0/240 (0%) 0
    Sleep disorder 0/236 (0%) 0 1/240 (0.4%) 1
    Renal and urinary disorders
    Dysuria 1/236 (0.4%) 1 0/240 (0%) 0
    Micturition disorder 0/236 (0%) 0 1/240 (0.4%) 1
    Nephrolithiasis 1/236 (0.4%) 1 0/240 (0%) 0
    Renal colic 0/236 (0%) 0 1/240 (0.4%) 1
    Reproductive system and breast disorders
    Vaginal discharge 0/120 (0%) 0 1/142 (0.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm 1/236 (0.4%) 1 0/240 (0%) 0
    Cough 2/236 (0.8%) 3 0/240 (0%) 0
    Epistaxis 0/236 (0%) 0 1/240 (0.4%) 1
    Nasal congestion 1/236 (0.4%) 1 0/240 (0%) 0
    Oropharyngeal pain 0/236 (0%) 0 1/240 (0.4%) 1
    Productive cough 1/236 (0.4%) 2 0/240 (0%) 0
    Respiratory failure 1/236 (0.4%) 1 0/240 (0%) 0
    Rhinalgia 0/236 (0%) 0 1/240 (0.4%) 1
    Rhinitis allergic 1/236 (0.4%) 1 0/240 (0%) 0
    Rhinorrhoea 0/236 (0%) 0 2/240 (0.8%) 2
    Sinus disorder 1/236 (0.4%) 1 0/240 (0%) 0
    Throat irritation 0/236 (0%) 0 1/240 (0.4%) 1
    Skin and subcutaneous tissue disorders
    Dermatitis allergic 1/236 (0.4%) 2 0/240 (0%) 0
    Dermatitis contact 1/236 (0.4%) 1 0/240 (0%) 0
    Eczema 0/236 (0%) 0 1/240 (0.4%) 1
    Hirsutism 0/236 (0%) 0 1/240 (0.4%) 1
    Hyperhidrosis 2/236 (0.8%) 2 2/240 (0.8%) 2
    Pityriasis 0/236 (0%) 0 1/240 (0.4%) 1
    Pruritus 2/236 (0.8%) 2 2/240 (0.8%) 2
    Pruritus generalised 0/236 (0%) 0 1/240 (0.4%) 1
    Rash 0/236 (0%) 0 1/240 (0.4%) 1
    Rash vesicular 1/236 (0.4%) 1 0/240 (0%) 0
    Skin lesion 1/236 (0.4%) 1 1/240 (0.4%) 1
    Urticaria 1/236 (0.4%) 1 1/240 (0.4%) 1
    Surgical and medical procedures
    Carpal tunnel decompression 1/236 (0.4%) 1 0/240 (0%) 0
    Cataract operation 0/236 (0%) 0 1/240 (0.4%) 1
    Meniscus operation 1/236 (0.4%) 1 0/240 (0%) 0
    Shoulder operation 1/236 (0.4%) 1 0/240 (0%) 0
    Tooth extraction 0/236 (0%) 0 2/240 (0.8%) 4
    Vascular disorders
    Haematoma 0/236 (0%) 0 1/240 (0.4%) 1
    Hypertension 1/236 (0.4%) 2 2/240 (0.8%) 2
    Hypertensive crisis 1/236 (0.4%) 1 1/240 (0.4%) 1
    Vein disorder 0/236 (0%) 0 1/240 (0.4%) 1

    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 Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01175824
    Other Study ID Numbers:
    • 13493
    • F3Z-CR-IOQE
    First Posted:
    Aug 5, 2010
    Last Update Posted:
    Feb 24, 2014
    Last Verified:
    Jan 1, 2014