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Safety and Efficacy Study of Insulin Lispro Versus Insulin Aspart in Participants With Type 2 Diabetes on Insulin Pump Therapy

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01474538
Collaborator
(none)
122
Enrollment
12
Locations
2
Arms
14.1
Duration (Months)
10.2
Patients Per Site
0.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will provide information on the use of insulin lispro and insulin aspart in insulin pumps in participants with type 2 diabetes.

Condition or Disease Intervention/Treatment Phase
  • Drug: Insulin Lispro
  • Drug: Insulin Aspart
 Phase 3

Detailed Description

This study will provide clinical information on the use of insulin lispro in continuous subcutaneous insulin infusion (CSII) in participants with type 2 diabetes. This study is designed to allow comparison of the 2 rapid-acting insulin analogs, with regard to their efficacy and safety, when used as a pump insulin therapy in this participant population. Each participant will be randomized to 1 of the 2 sequence groups in a 1:1 ratio and randomization will be stratified according to screening A1C (less than or equal to 8.0% or greater than 8.0%) and thiazolidinedione (TZD) use (yes or no). The study design includes the following periods: Screening/Randomization, Treatment Period 1 (16 weeks), and Treatment Period 2 (16 weeks).

Study Design

Study Type:
Interventional
Actual Enrollment :
122 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Crossover Trial Comparing the Safety and Efficacy of Insulin Lispro With the Safety and Efficacy of Insulin Aspart in Subjects With Type 2 Diabetes on CSII Therapy
Study Start Date :
Dec 1, 2011
Actual Primary Completion Date :
Feb 1, 2013
Actual Study Completion Date :
Feb 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Insulin Lispro, then Insulin Aspart

Insulin lispro [100 units/milliliter (U/mL)] administered by continuous subcutaneous insulin infusion (CSII) pump for 16 weeks in Treatment Period 1, followed by insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 2.

Drug: Insulin Lispro
Insulin lispro (100 U/mL) administered by CSII pump
Other Names:
  • Humalog
  • LY275585

    		•
    Active Comparator: Insulin Aspart, then Insulin Lispro

    Insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 1, followed by insulin lispro (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 2.

    Drug: Insulin Aspart
    Insulin aspart (100 U/mL) administered by CSII pump
    Other Names:
  • Novolog

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Glycosylated Hemoglobin A1C (HbA1c) at Endpoint [After 16 weeks of each treatment (Periods1 and 2)]

      Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over the last 8-12 weeks. Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline HbA1c (>8% or ≤8%) and participants.

    Secondary Outcome Measures

    1. Total Daily Insulin Dose [Week 16 of each treatment (Periods 1 and 2)]

      Total daily insulin dose was the average of the last 3 days total insulin dose immediately prior to the Week 16 (endpoint) visit of each treatment period. Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline Hemoglobin A1c (HbA1c) (>8% or ≤8%) and participants.

    2. Rate of Hypoglycemic Events Per 30 Days [Baseline through 16 weeks of each treatment (Periods 1 and 2)]

      A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose concentration of ≤70 milligrams/deciliter [mg/dL (3.9 millimoles/liter (mmol/L)]. Least Squares (LS) means were adjusted for treatment, period, sequence, baseline hypoglycemic event rate, thiazolidinedione use (Yes/No) and baseline Hemoglobin A1c (HbA1c) (>8% or ≤8%).

    3. Change From Baseline in Weight [Baseline, Week 16 of treatment Periods 1 and 2]

      Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline Hemoglobin A1c (HbA1c) (>8% or ≤8%), baseline weight and participants.

    4. Percentage of Participants With Hypoglycemic Events [Baseline through 16 weeks of each treatment (Periods 1 and 2)]

      A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose concentration of ≤ 70 milligrams/deciliter [mg/dL (3.9 millimoles/liter (mmol/L)]. The percentage of participants is the total number of participants experiencing hypoglycemic events divided by number of participants in the treatment arm multiplied by 100.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Have type 2 diabetes (per World Health Organization [WHO] Classification of Diabetes)

    • Have been treated with CSII therapy using a rapid-acting analog for the previous 6 months

    • Have a screening A1C less than or equal to 9.0% (no lower limit for A1C)

    • Have a body mass index (BMI) less than 45 kilograms/square meter (kg/m²) at screening

    • Have a history of stable body weight (not varying by greater than 10% for at least 3 months prior to screening)

    • For participants on oral anti-diabetes medications (OAMs): must have been on a stable dose of OAMs, labeled for use with insulin, for at least 3 months prior to study entry

    Exclusion Criteria:

    • Have severe insulin resistance [require greater than 2 units/kilogram/day (U/kg/day) of insulin]

    • Are taking or have taken within the last 3 months, antihyperglycemic medication not approved for use with insulin, injectable non-insulin antihyperglycemic medications, or have a contraindication to current antihyperglycemic medication

    • Have a serum creatinine greater than or equal to 2 milligrams/deciliter (mg/dL) if not on metformin; known metabolic or lactic acidosis; any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis; and/or a radiologic contrast study within 48 hours prior to study entry

    • Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical, intraocular, intraarticular, and inhaled preparations) or have received such therapy within 2 weeks immediately before screening

    • Have had more than 1 episode of hypoglycemia (defined as requiring assistance of a third party due to disabling hypoglycemia) within 6 months prior to entry into the 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. Little Rock Arkansas United States 72205
    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. Jacksonville Florida United States 32216
    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. West Palm Beach Florida United States 33401
    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. Atlanta Georgia United States 30309
    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. Idaho Falls Idaho United States 83404
    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. Des Moines Iowa United States 50314
    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. Topeka Kansas United States 66606
    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. Metairie Louisiana United States 70006
    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. Asheville North Carolina United States 28803
    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. Chattanooga Tennessee United States 37411
    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. Austin Texas United States 78731
    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. Salt Lake City Utah United States 84102

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-877-615-4559 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:
    NCT01474538
    Other Study ID Numbers:
    • 14207
    • F3Z-MC-IOQH
    First Posted:
    Nov 18, 2011
    Last Update Posted:
    Mar 20, 2014
    Last Verified:
    Feb 1, 2014
    Keywords provided by Eli Lilly and Company
    diabetes
    type 2 diabetes
    insulin pump
    continuous subcutaneous insulin infusion
    CSII
    A1C
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Insulin
    Insulin, Globin Zinc
    Insulin Aspart
    Insulin Lispro

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Insulin Lispro / Insulin Aspart Insulin Aspart / Insulin Lispro
    Arm/Group Description Insulin lispro [100 units/milliliter (U/mL)] administered by continuous subcutaneous insulin infusion (CSII) pump for 16 weeks in Treatment Period 1, followed by insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 2. Insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 1, followed by insulin lispro (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 2.
    Period Title: Treatment Period 1
    STARTED 60 62
    Received at Least 1 Dose of Study Drug 60 62
    COMPLETED 57 58
    NOT COMPLETED 3 4
    Period Title: Treatment Period 1
    STARTED 57 58
    Received at Least 1 Dose of Study Drug 57 58
    COMPLETED 51 56
    NOT COMPLETED 6 2

    Baseline Characteristics

    Arm/Group Title Insulin Lispro / Insulin Aspart Insulin Aspart / Insulin Lispro Total
    Arm/Group Description Insulin lispro [100 units/milliliter (U/mL)] administered by continuous subcutaneous insulin infusion (CSII) pump for 16 weeks in Treatment Period 1, followed by insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 2. Insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 1, followed by insulin lispro (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 2. Total of all reporting groups
    Overall Participants 60 62 122
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.73
    (10.41)
    60.40
    (9.72)
    59.58
    (10.06)
    Sex: Female, Male (Count of Participants)
    Female
    33
    55%
    32
    51.6%
    65
    53.3%
    Male
    27
    45%
    30
    48.4%
    57
    46.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    1.7%
    0
    0%
    1
    0.8%
    Asian
    0
    0%
    2
    3.2%
    2
    1.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    5
    8.3%
    5
    8.1%
    10
    8.2%
    White
    53
    88.3%
    54
    87.1%
    107
    87.7%
    More than one race
    1
    1.7%
    1
    1.6%
    2
    1.6%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (participants) [Number]
    Hispanic or Latino
    2
    3.3%
    1
    1.6%
    3
    2.5%
    Not Hispanic or Latino
    58
    96.7%
    61
    98.4%
    119
    97.5%
    Region of Enrollment (participants) [Number]
    United States
    60
    100%
    62
    100%
    122
    100%

    Outcome Measures

    1. Primary Outcome
    Title Glycosylated Hemoglobin A1C (HbA1c) at Endpoint
    Description Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over the last 8-12 weeks. Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline HbA1c (>8% or ≤8%) and participants.
    Time Frame After 16 weeks of each treatment (Periods1 and 2)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had HbA1c measured at Week 16 of treatment Period 1 or 2. Participants were analyzed based on the treatment they received.
    Arm/Group Title Insulin Lispro Insulin Aspart
    Arm/Group Description Insulin lispro [100 units/milliliter (U/mL)] administered by continuous subcutaneous insulin infusion (CSII) pump for 16 weeks in Treatment Period 1 or Treatment Period 2. Insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 1 or Treatment Period 2.
    Measure Participants 112 111
    Least Squares Mean (Standard Error) [percentage of glycosylated hemoglobin]
    7.50
    (0.12)
    7.40
    (0.12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro, Insulin Aspart
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments If the upper limit of the 95% confidence interval (CI) was below 0.4%, lispro was declared non-inferior to aspart.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS Mean difference
    Estimated Value 0.10
    Confidence Interval (2-Sided) 95%
    -0.002 to 0.210
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Total Daily Insulin Dose
    Description Total daily insulin dose was the average of the last 3 days total insulin dose immediately prior to the Week 16 (endpoint) visit of each treatment period. Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline Hemoglobin A1c (HbA1c) (>8% or ≤8%) and participants.
    Time Frame Week 16 of each treatment (Periods 1 and 2)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had total daily insulin dose recorded during Treatment Period (TP) 1 or 2. If endpoint data was missing for a specific TP, last observation carried forward (LOCF) method was implemented for that respective TP. Participants were analyzed based on the treatment they received.
    Arm/Group Title Insulin Lispro Insulin Aspart
    Arm/Group Description Insulin lispro [100 units/milliliter (U/mL)] administered by continuous subcutaneous insulin infusion (CSII) pump for 16 weeks in Treatment Period 1 or Treatment Period 2. Insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 1 or Treatment Period 2.
    Measure Participants 116 117
    Least Squares Mean (Standard Error) [units of insulin]
    80.41
    (4.78)
    80.69
    (4.77)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro, Insulin Aspart
    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 -0.28
    Confidence Interval (2-Sided) 95%
    -2.92 to 2.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Rate of Hypoglycemic Events Per 30 Days
    Description A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose concentration of ≤70 milligrams/deciliter [mg/dL (3.9 millimoles/liter (mmol/L)]. Least Squares (LS) means were adjusted for treatment, period, sequence, baseline hypoglycemic event rate, thiazolidinedione use (Yes/No) and baseline Hemoglobin A1c (HbA1c) (>8% or ≤8%).
    Time Frame Baseline through 16 weeks of each treatment (Periods 1 and 2)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug. Participants were analyzed based on the treatment they received.
    Arm/Group Title Insulin Lispro Insulin Aspart
    Arm/Group Description Insulin lispro [100 units/milliliter (U/mL)] administered by continuous subcutaneous insulin infusion (CSII) pump for 16 weeks in Treatment Period 1 or Treatment Period 2. Insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 1 or Treatment Period 2.
    Measure Participants 118 119
    Least Squares Mean (Standard Error) [hypoglycemic events per 30 days]
    2.24
    (0.28)
    2.38
    (0.29)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro, Insulin Aspart
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.522
    Comments
    Method Negative binomial
    Comments
    Method of Estimation Estimation Parameter LS Mean Ratio
    Estimated Value 0.94
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline in Weight
    Description Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline Hemoglobin A1c (HbA1c) (>8% or ≤8%), baseline weight and participants.
    Time Frame Baseline, Week 16 of treatment Periods 1 and 2

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had weight measured at baseline and Week 16 of Treatment Period 1 or 2. Participants were analyzed based on the treatment they received.
    Arm/Group Title Insulin Lispro Insulin Aspart
    Arm/Group Description Insulin lispro [100 units/milliliter (U/mL)] administered by continuous subcutaneous insulin infusion (CSII) pump for 16 weeks in Treatment Period 1 or Treatment Period 2. Insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 1 or Treatment Period 2.
    Measure Participants 116 117
    Least Squares Mean (Standard Error) [kilograms (kg)]
    0.31
    (0.53)
    0.89
    (0.52)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro, Insulin Aspart
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.216
    Comments
    Method Grizzle Model
    Comments
    Method of Estimation Estimation Parameter LS Mean difference
    Estimated Value -0.58
    Confidence Interval () %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Percentage of Participants With Hypoglycemic Events
    Description A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose concentration of ≤ 70 milligrams/deciliter [mg/dL (3.9 millimoles/liter (mmol/L)]. The percentage of participants is the total number of participants experiencing hypoglycemic events divided by number of participants in the treatment arm multiplied by 100.
    Time Frame Baseline through 16 weeks of each treatment (Periods 1 and 2)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug. Participants were analyzed based on the treatment they received.
    Arm/Group Title Insulin Lispro Insulin Aspart
    Arm/Group Description Insulin lispro [100 units/milliliter (U/mL)] administered by continuous subcutaneous insulin infusion (CSII) pump for 16 weeks in Treatment Period 1 or Treatment Period 2. Insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 1 or Treatment Period 2.
    Measure Participants 118 119
    Number [percentage of participants]
    71.2
    118.7%
    74.8
    120.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin Lispro, Insulin Aspart
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.471
    Comments
    Method Prescott test
    Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Insulin Lispro Insulin Aspart
    Arm/Group Description Insulin lispro [100 units/milliliter (U/mL)] administered by continuous subcutaneous insulin infusion (CSII) pump for 16 weeks in Treatment Period 1 or Treatment Period 2. Insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 1 or Treatment Period 2.
    All Cause Mortality
    Insulin Lispro Insulin Aspart
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Insulin Lispro Insulin Aspart
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/118 (12.7%) 14/119 (11.8%)
    Cardiac disorders
    Atrial fibrillation 1/118 (0.8%) 1 1/119 (0.8%) 1
    Cardiac failure congestive 1/118 (0.8%) 1 1/119 (0.8%) 1
    Coronary artery disease 3/118 (2.5%) 3 1/119 (0.8%) 1
    Myocardial infarction 1/118 (0.8%) 1 1/119 (0.8%) 1
    Stress cardiomyopathy 0/118 (0%) 0 1/119 (0.8%) 1
    Gastrointestinal disorders
    Abdominal pain 1/118 (0.8%) 1 0/119 (0%) 0
    Lower gastrointestinal haemorrhage 1/118 (0.8%) 1 0/119 (0%) 0
    General disorders
    Chest pain 0/118 (0%) 0 1/119 (0.8%) 1
    Non-cardiac chest pain 1/118 (0.8%) 1 0/119 (0%) 0
    Infections and infestations
    Infusion site abscess 1/118 (0.8%) 1 0/119 (0%) 0
    Pneumonia 0/118 (0%) 0 1/119 (0.8%) 1
    Injury, poisoning and procedural complications
    Laceration 0/118 (0%) 0 1/119 (0.8%) 1
    Subdural haematoma 1/118 (0.8%) 1 0/119 (0%) 0
    Upper limb fracture 1/118 (0.8%) 1 1/119 (0.8%) 1
    Investigations
    International normalised ratio decreased 1/118 (0.8%) 1 1/119 (0.8%) 1
    Metabolism and nutrition disorders
    Diabetic ketoacidosis 0/118 (0%) 0 1/119 (0.8%) 1
    Hypoglycaemia 0/118 (0%) 0 1/119 (0.8%) 1
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion 1/118 (0.8%) 1 0/119 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 1/118 (0.8%) 1 1/119 (0.8%) 1
    Nervous system disorders
    Convulsion 1/118 (0.8%) 1 0/119 (0%) 0
    Hypoaesthesia 1/118 (0.8%) 1 1/119 (0.8%) 1
    Syncope 0/118 (0%) 0 1/119 (0.8%) 1
    Transient ischaemic attack 0/118 (0%) 0 1/119 (0.8%) 1
    Reproductive system and breast disorders
    Epididymitis 0/55 (0%) 0 1/55 (1.8%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 1/118 (0.8%) 1 0/119 (0%) 0
    Pulmonary embolism 1/118 (0.8%) 1 0/119 (0%) 0
    Respiratory failure 1/118 (0.8%) 1 0/119 (0%) 0
    Vascular disorders
    Deep vein thrombosis 1/118 (0.8%) 1 1/119 (0.8%) 1
    Peripheral arterial occlusive disease 1/118 (0.8%) 1 0/119 (0%) 0
    Other (Not Including Serious) Adverse Events
    Insulin Lispro Insulin Aspart
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 59/118 (50%) 62/119 (52.1%)
    Blood and lymphatic system disorders
    Leukocytosis 1/118 (0.8%) 1 1/119 (0.8%) 1
    Cardiac disorders
    Acute coronary syndrome 0/118 (0%) 0 1/119 (0.8%) 1
    Atrial fibrillation 1/118 (0.8%) 1 1/119 (0.8%) 1
    Atrioventricular block first degree 1/118 (0.8%) 1 1/119 (0.8%) 1
    Cardiac failure congestive 1/118 (0.8%) 1 1/119 (0.8%) 1
    Cardiac flutter 1/118 (0.8%) 1 0/119 (0%) 0
    Cardiomyopathy 1/118 (0.8%) 1 1/119 (0.8%) 1
    Ear and labyrinth disorders
    Eustachian tube dysfunction 1/118 (0.8%) 1 1/119 (0.8%) 1
    Tinnitus 1/118 (0.8%) 1 0/119 (0%) 0
    Vertigo 1/118 (0.8%) 1 0/119 (0%) 0
    Endocrine disorders
    Hypothyroidism 1/118 (0.8%) 1 2/119 (1.7%) 2
    Eye disorders
    Conjunctivitis 0/118 (0%) 0 1/119 (0.8%) 1
    Iritis 1/118 (0.8%) 1 0/119 (0%) 0
    Lacrimation increased 1/118 (0.8%) 1 0/119 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort 1/118 (0.8%) 1 0/119 (0%) 0
    Abdominal distension 0/118 (0%) 0 1/119 (0.8%) 1
    Diarrhoea 1/118 (0.8%) 1 1/119 (0.8%) 1
    Gastrooesophageal reflux disease 0/118 (0%) 0 2/119 (1.7%) 2
    Nausea 5/118 (4.2%) 5 2/119 (1.7%) 2
    Pancreatitis 0/118 (0%) 0 1/119 (0.8%) 1
    Parotid gland inflammation 1/118 (0.8%) 1 0/119 (0%) 0
    Rectal haemorrhage 1/118 (0.8%) 1 0/119 (0%) 0
    Tongue ulceration 1/118 (0.8%) 1 1/119 (0.8%) 1
    Tooth impacted 0/118 (0%) 0 1/119 (0.8%) 1
    Vomiting 1/118 (0.8%) 1 0/119 (0%) 0
    General disorders
    Chest discomfort 1/118 (0.8%) 1 0/119 (0%) 0
    Chest pain 1/118 (0.8%) 1 0/119 (0%) 0
    Facial pain 0/118 (0%) 0 1/119 (0.8%) 1
    Fatigue 4/118 (3.4%) 4 4/119 (3.4%) 4
    Injection site haematoma 1/118 (0.8%) 1 0/119 (0%) 0
    Injection site nodule 2/118 (1.7%) 2 2/119 (1.7%) 2
    Non-cardiac chest pain 1/118 (0.8%) 1 1/119 (0.8%) 1
    Oedema 1/118 (0.8%) 1 1/119 (0.8%) 1
    Oedema peripheral 0/118 (0%) 0 2/119 (1.7%) 2
    Pyrexia 1/118 (0.8%) 1 0/119 (0%) 0
    Immune system disorders
    Multiple allergies 1/118 (0.8%) 1 1/119 (0.8%) 1
    Seasonal allergy 1/118 (0.8%) 1 0/119 (0%) 0
    Infections and infestations
    Bacteraemia 1/118 (0.8%) 1 0/119 (0%) 0
    Bronchitis 1/118 (0.8%) 1 0/119 (0%) 0
    Ear infection 1/118 (0.8%) 1 1/119 (0.8%) 2
    Fungal infection 1/118 (0.8%) 1 0/119 (0%) 0
    Gastroenteritis viral 3/118 (2.5%) 3 0/119 (0%) 0
    Herpes zoster 1/118 (0.8%) 1 0/119 (0%) 0
    Influenza 2/118 (1.7%) 2 2/119 (1.7%) 2
    Infusion site infection 1/118 (0.8%) 1 0/119 (0%) 0
    Labyrinthitis 1/118 (0.8%) 1 1/119 (0.8%) 1
    Lower respiratory tract infection 0/118 (0%) 0 1/119 (0.8%) 1
    Nasopharyngitis 5/118 (4.2%) 5 5/119 (4.2%) 6
    Onychomycosis 1/118 (0.8%) 1 1/119 (0.8%) 1
    Osteomyelitis 1/118 (0.8%) 1 0/119 (0%) 0
    Pharyngitis streptococcal 0/118 (0%) 0 1/119 (0.8%) 1
    Post procedural infection 1/118 (0.8%) 1 1/119 (0.8%) 1
    Sepsis 0/118 (0%) 0 1/119 (0.8%) 1
    Sinusitis 3/118 (2.5%) 3 4/119 (3.4%) 4
    Staphylococcal bacteraemia 1/118 (0.8%) 1 0/119 (0%) 0
    Staphylococcal infection 0/118 (0%) 0 1/119 (0.8%) 1
    Subcutaneous abscess 0/118 (0%) 0 1/119 (0.8%) 1
    Tooth abscess 1/118 (0.8%) 1 1/119 (0.8%) 1
    Tooth infection 1/118 (0.8%) 1 0/119 (0%) 0
    Upper respiratory tract infection 2/118 (1.7%) 3 0/119 (0%) 0
    Urinary tract infection 0/118 (0%) 0 3/119 (2.5%) 3
    Viral infection 1/118 (0.8%) 1 1/119 (0.8%) 1
    Injury, poisoning and procedural complications
    Arthropod bite 1/118 (0.8%) 1 0/119 (0%) 0
    Contusion 1/118 (0.8%) 1 0/119 (0%) 0
    Fall 1/118 (0.8%) 1 0/119 (0%) 0
    Fibula fracture 0/118 (0%) 0 2/119 (1.7%) 2
    Ligament sprain 0/118 (0%) 0 2/119 (1.7%) 2
    Meniscus lesion 0/118 (0%) 0 1/119 (0.8%) 1
    Muscle strain 2/118 (1.7%) 2 1/119 (0.8%) 1
    Periorbital haematoma 0/118 (0%) 0 1/119 (0.8%) 1
    Post procedural swelling 1/118 (0.8%) 1 1/119 (0.8%) 1
    Road traffic accident 1/118 (0.8%) 1 0/119 (0%) 0
    Wound 1/118 (0.8%) 1 0/119 (0%) 0
    Investigations
    Angiogram peripheral 1/118 (0.8%) 1 0/119 (0%) 0
    Blood potassium increased 0/118 (0%) 0 1/119 (0.8%) 1
    Blood sodium decreased 1/118 (0.8%) 1 0/119 (0%) 0
    Cardiac murmur 1/118 (0.8%) 1 0/119 (0%) 0
    Catheterisation cardiac 0/118 (0%) 0 1/119 (0.8%) 1
    Glycosylated haemoglobin increased 2/118 (1.7%) 2 2/119 (1.7%) 2
    International normalised ratio decreased 1/118 (0.8%) 1 1/119 (0.8%) 1
    Pulse pressure decreased 1/118 (0.8%) 1 1/119 (0.8%) 1
    Transaminases increased 0/118 (0%) 0 1/119 (0.8%) 1
    Metabolism and nutrition disorders
    Dehydration 0/118 (0%) 0 1/119 (0.8%) 1
    Dyslipidaemia 1/118 (0.8%) 1 0/119 (0%) 0
    Hypercholesterolaemia 1/118 (0.8%) 1 0/119 (0%) 0
    Hyperlipidaemia 2/118 (1.7%) 2 2/119 (1.7%) 2
    Vitamin d deficiency 0/118 (0%) 0 3/119 (2.5%) 3
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/118 (0.8%) 2 0/119 (0%) 0
    Back pain 3/118 (2.5%) 3 4/119 (3.4%) 4
    Bunion 1/118 (0.8%) 1 0/119 (0%) 0
    Exostosis 1/118 (0.8%) 1 1/119 (0.8%) 1
    Fibromyalgia 1/118 (0.8%) 1 0/119 (0%) 0
    Muscle spasms 0/118 (0%) 0 2/119 (1.7%) 2
    Musculoskeletal pain 3/118 (2.5%) 3 3/119 (2.5%) 3
    Osteoarthritis 2/118 (1.7%) 2 1/119 (0.8%) 1
    Pain in extremity 1/118 (0.8%) 1 1/119 (0.8%) 1
    Rotator cuff syndrome 0/118 (0%) 0 1/119 (0.8%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin cancer 0/118 (0%) 0 1/119 (0.8%) 1
    Skin papilloma 1/118 (0.8%) 1 0/119 (0%) 0
    Thyroid cancer 0/118 (0%) 0 1/119 (0.8%) 1
    Nervous system disorders
    Carotid artery occlusion 1/118 (0.8%) 1 1/119 (0.8%) 1
    Diabetic neuropathy 1/118 (0.8%) 1 0/119 (0%) 0
    Dizziness 2/118 (1.7%) 2 1/119 (0.8%) 1
    Essential tremor 0/118 (0%) 0 1/119 (0.8%) 1
    Headache 0/118 (0%) 0 3/119 (2.5%) 3
    Migraine 0/118 (0%) 0 1/119 (0.8%) 1
    Neuropathy peripheral 1/118 (0.8%) 1 1/119 (0.8%) 1
    Paraesthesia 0/118 (0%) 0 1/119 (0.8%) 1
    Psychiatric disorders
    Depression 3/118 (2.5%) 3 3/119 (2.5%) 3
    Insomnia 1/118 (0.8%) 1 1/119 (0.8%) 1
    Renal and urinary disorders
    Dysuria 1/118 (0.8%) 1 1/119 (0.8%) 1
    Incontinence 1/118 (0.8%) 1 1/119 (0.8%) 1
    Nephrolithiasis 0/118 (0%) 0 2/119 (1.7%) 2
    Pollakiuria 0/118 (0%) 0 1/119 (0.8%) 1
    Renal failure 0/118 (0%) 0 1/119 (0.8%) 1
    Urinary incontinence 0/118 (0%) 0 1/119 (0.8%) 1
    Reproductive system and breast disorders
    Cystocele 0/118 (0%) 0 1/119 (0.8%) 1
    Dysmenorrhoea 1/63 (1.6%) 1 1/64 (1.6%) 2
    Prostatitis 1/55 (1.8%) 1 0/55 (0%) 0
    Rectocele 0/118 (0%) 0 1/119 (0.8%) 1
    Uterine prolapse 0/63 (0%) 0 1/64 (1.6%) 1
    Respiratory, thoracic and mediastinal disorders
    Adenoidal hypertrophy 1/118 (0.8%) 1 0/119 (0%) 0
    Asthma 1/118 (0.8%) 1 0/119 (0%) 0
    Chronic obstructive pulmonary disease 1/118 (0.8%) 1 1/119 (0.8%) 1
    Cough 1/118 (0.8%) 1 0/119 (0%) 0
    Dyspnoea 2/118 (1.7%) 2 2/119 (1.7%) 2
    Dyspnoea exertional 1/118 (0.8%) 1 0/119 (0%) 0
    Epistaxis 0/118 (0%) 0 1/119 (0.8%) 1
    Hypoxia 1/118 (0.8%) 1 0/119 (0%) 0
    Oropharyngeal pain 2/118 (1.7%) 2 1/119 (0.8%) 1
    Pneumonitis 1/118 (0.8%) 1 0/119 (0%) 0
    Pulmonary oedema 0/118 (0%) 0 1/119 (0.8%) 1
    Respiratory tract congestion 0/118 (0%) 0 2/119 (1.7%) 2
    Rhinitis allergic 1/118 (0.8%) 1 5/119 (4.2%) 5
    Sinus congestion 1/118 (0.8%) 1 0/119 (0%) 0
    Sneezing 1/118 (0.8%) 1 0/119 (0%) 0
    Throat irritation 1/118 (0.8%) 1 0/119 (0%) 0
    Skin and subcutaneous tissue disorders
    Ecchymosis 1/118 (0.8%) 1 1/119 (0.8%) 1
    Erythema 1/118 (0.8%) 1 0/119 (0%) 0
    Photosensitivity reaction 1/118 (0.8%) 1 1/119 (0.8%) 1
    Surgical and medical procedures
    Arterial repair 0/118 (0%) 0 1/119 (0.8%) 1
    Coronary angioplasty 0/118 (0%) 0 1/119 (0.8%) 1
    Foraminotomy 1/118 (0.8%) 1 0/119 (0%) 0
    Gastric banding 0/118 (0%) 0 1/119 (0.8%) 1
    Mole excision 1/118 (0.8%) 1 0/119 (0%) 0
    Rotator cuff repair 0/118 (0%) 0 1/119 (0.8%) 1
    Spinal fusion surgery 1/118 (0.8%) 1 0/119 (0%) 0
    Spinal laminectomy 1/118 (0.8%) 1 0/119 (0%) 0
    Vascular disorders
    Angiopathy 1/118 (0.8%) 1 1/119 (0.8%) 1
    Deep vein thrombosis 1/118 (0.8%) 1 1/119 (0.8%) 1
    Flushing 1/118 (0.8%) 1 1/119 (0.8%) 1
    Hypertension 2/118 (1.7%) 2 2/119 (1.7%) 2
    Intermittent claudication 1/118 (0.8%) 1 1/119 (0.8%) 1
    Peripheral vascular disorder 2/118 (1.7%) 2 2/119 (1.7%) 2

    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:
    NCT01474538
    Other Study ID Numbers:
    • 14207
    • F3Z-MC-IOQH
    First Posted:
    Nov 18, 2011
    Last Update Posted:
    Mar 20, 2014
    Last Verified:
    Feb 1, 2014