IMAGINE 3: A Study in Participants With Type I Diabetes Mellitus

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01454284
• Collaborator: (none)
• Enrollment: 1,114
• Locations: 119
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 9.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is:

• To compare blood sugar control on LY2605541 with insulin glargine after 52 weeks of treatment.

• To compare the rate of nocturnal low blood sugar episodes on LY2605541 with insulin glargine during 52 weeks of treatment.

• To compare the number of participants on LY2605541 reaching blood sugar targets without low blood sugar episodes at night to those taking insulin glargine after 52 weeks of treatment.

• To compare the rate of low blood sugar episodes on LY2605541 with insulin glargine during 52 weeks of treatment

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Glargine; Drug: LY2605541; Drug: Insulin Lispro	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Impact of LY2605541 Versus Insulin Glargine for Patients With Type 1 Diabetes Mellitus Treated With Preprandial Insulin Lispro: a Double-Blind, Randomized, 52-week Study
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2605541 + Insulin Lispro LY2605541 titrated based on blood glucose readings, administered subcutaneously (SC) once daily at bedtime for 52 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered SC at meal times for 52 weeks.	Drug: LY2605541; Drug: Insulin Lispro; Other Names: LY275585 Humalog
Active Comparator: Glargine + Insulin Lispro Glargine dose titrated based on blood glucose readings, administered SC once daily at bedtime for 52 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered SC at meal times for 52 weeks.	Drug: Glargine; Drug: Insulin Lispro; Other Names: LY275585 Humalog

Outcome Measures

Primary Outcome Measures

1. Hemoglobin A1c (HbA1c) [52 weeks]

   HbA1c is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. Least squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, stratification factors (country, baseline low density lipoprotein cholesterol [LDL-C] [<100 milligrams/deciliter (mg/dL) (2.6 millimoles/liter [mmol/L]) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.

Secondary Outcome Measures

1. Hemoglobin A1c (HbA1c) [26 weeks]

   HbA1c is a test that measures a participant's average blood glucose level over the past 2 to 3 months. LS means were calculated using MMRM adjusting for treatment, stratification factors (country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.

2. Change From Baseline to 52 Weeks in HbA1c [Baseline, 52 weeks]

   HbA1c is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. LS means were calculated using MMRM adjusting for treatment, stratification factors (country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.

3. Total Hypoglycemia Events [Baseline through 26 weeks, Baseline through 52 weeks]

   Hypoglycemic episodes are defined as events which are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 mmol/L). Group mean rates of total hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline total hypoglycemia rate, with log [exposure in days/30] as an offset variable). Group mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.

4. Percentage of Participants With Total Hypoglycemic Events [Baseline through 26 weeks, Baseline through 52 weeks]

   Hypoglycemic episodes are defined as events that are associated with the reported signs and symptoms of hypoglycemia and/or documented BG concentrations of ≤70 mg/dL (3.9 mmol/L). The percentage of participants was calculated by dividing the number of participants with hypoglycemic episodes by the total number of participants analyzed, multiplied by 100.

5. Percentage of Participants With HbA1c Equal to or Less Than 6.5% and Less Than 7.0% [up to 26 weeks, up to 52 weeks]

   The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.

6. Percentage of Participants With HbA1c Less Than 7.0% and Without Nocturnal Hypoglycemia [up to 26 weeks, up to 52 weeks]

   Hypoglycemic episodes are defined as events associated with reported signs and symptoms of hypoglycemia and/or a documented blood glucose concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. The percentage of participants was calculated by dividing the number of participants with HbA1c <7.0% without nocturnal hypoglycemia by the total number of participants analyzed, multiplied by 100.

7. Nocturnal Hypoglycemia Rates [Baseline through 26 weeks, Baseline through 52 weeks]

   Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or a documented BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. Group mean rates of nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline nocturnal hypoglycemia rate, with log [exposure in days/30] as an offset variable). Group mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.

8. Percentage of Participants With Nocturnal Hypoglycemic Events [Baseline through 26 weeks, Baseline through 52 weeks]

   Hypoglycemic episodes are defined as events associated with the reported signs and symptoms of hypoglycemia and/or a BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. The percentage of participants was calculated by dividing the number of participants with nocturnal hypoglycemic episodes by the total number of participants analyzed, multiplied by 100.

9. Change in Body Weight [Baseline, 26 weeks, 52 weeks]

   LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline body weight as fixed effects and participant as the random effect.

10. 9 Point Self-monitored Blood Glucose (SMBG) [26 weeks and 52 weeks]

    9-point SMBG profiles were obtained over 2 days within the week prior to Weeks 0, 4, 12, 26, 39, and 52. SMBG measurements were taken at 9 time points: pre-morning meal, 2 hours post-morning meal, pre-midday meal, 2 hours post-midday meal, pre-evening meal, 2 hours post-evening meal, bedtime, at approximately 0300 hours, and the subsequent morning prior to the morning meal. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline BG values as the fixed effects and participant as the random effect.

11. Fasting Serum Glucose (by Laboratory Measurement) [26 weeks and 52 weeks]

    Fasting serum glucose (FSG) is measured in blood before the morning meal. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.

12. Fasting Blood Glucose (by Participant Self Monitored Blood Glucose Readings) [26 weeks and 52 weeks]

    Fasting blood glucose (FBG) was measured by SMBG pre-morning meal. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline FBG as the fixed effects and participant as the random effect.

13. Intra-participant Variability of Fasting Blood Glucose (FBG) [26 weeks and 52 weeks]

    FBG was measured by SMBG. Between-day glucose variability is measured by the standard deviation (SD) of FBG. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline SD of FBG as the fixed effects and participant as the random effect.

14. 0300 Hours Blood Glucose (BG) to Fasting BG Excursion [26 weeks and 52 weeks]

    Results of a 0300-hour to pre-morning meal (FBG) excursion are presented (only excursions within a single SMBG profile are included). LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline excursion as the fixed effects and participant as the random effect.

15. Triglycerides, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol [26 weeks and 52 weeks]

    Concentrations of cholesterol, HDL-C, and LDL-C, and triglycerides are presented. LS means were calculated using MMRM adjusting for stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L), except for the LDL-C outcome variable], prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment, treatment-by-visit interaction, and baseline value of corresponding lipid outcome variable as the fixed effects and participant as a random effect.

16. Percentage of Participants With Change in Anti-LY2605541 Antibodies [26 weeks, 52 weeks]

    The percentage of participants with anti-LY2605541 treatment-emergent antibody response (TEAR) is summarized. TEAR is defined as change from baseline to post-baseline in the anti-LY2605541 antibody level either from undetectable to detectable, or from detectable to the value with at least 130% relative increase from baseline.

17. Basal, Meal Time, and Total Insulin Dose Per Body Weight [26 weeks and 52 weeks]

    Basal insulin dose, meal-time insulin dose (short-acting bolus dose), and total insulin dose were calculated based on the dose during the last 7 days prior to the post-treatment visit or last 3 days prior to the randomization visit. LS means were calculated using a constrained Longitudinal Data Analysis (cLDA) model adjusting for indicator variables of each treatment group at each postbaseline visit and stratification variables (baseline HbA1c [≤8.5% and> 8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], and baseline prior basal insulin therapy [insulin glargine/detemir/ other]) as fixed effects.

18. Insulin Treatment Satisfaction Questionnaire [up to 52 weeks]

    Insulin Treatment Satisfaction Questionnaire (ITSQ) is a validated measure containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Convenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data are transformed to a scale of 0-100, where higher scores indicate better treatment satisfaction. LS means were calculated using an ANCOVA model adjusting for treatment, baseline HbA1c (≤8.5% and >8.5%), country, and baseline prior basal insulin therapy (insulin glargine/detemir/other) as fixed effects and baseline ITSQ scores as a covariate.

19. European Quality of Life -5 Dimension (EQ-5D-3L) [up to 52 weeks]

    The EQ-5D-3L is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a three-level scale of 1-3 (no problem, some problems, and extreme problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United States population-based algorithm. Scores range from -0.11 to 1.0, where a score of 1.0 indicates perfect health. LS means were calculated using an ANCOVA adjusting for treatment, baseline HbA1c (≤8.5% and >8.5%), country, baseline prior basal insulin therapy (insulin glargine/detemir/other), and baseline EQ-5D-3L score as covariates.

20. Adult Low Blood Sugar Survey [26 weeks and 52 weeks]

    Low Blood Sugar Survey (LBSS) (also referenced as Hypoglycemia Fear Survey - II [HFS-II]) is a questionnaire that measures 1) behaviors to avoid hypoglycemia and its negative consequences (15 items) and 2) worries about hypoglycemia and its negative consequences (18 items). Responses are made on a 5-point Likert-type scale where 0 = Never and 4 = Always. Total score is the sum of all items (range 0-132). Higher total scores reflect greater fear of hypoglycemia. LS means were calculated using MMRM adjusting for treatment, baseline HbA1c (≤8.5% and >8.5%), country, baseline prior basal insulin therapy (insulin glargine/detemir/other), visit, treatment-by-visit interaction, and baseline LBSS score as the fixed effects and participant as the random effect.

21. Rapid Assessment of Physical Activity (RAPA) [52 weeks]

    The RAPA questionnaire assesses the level and intensity of physical activity of adult participants. It contains 2 subscales: RAPA 1 (Aerobic) and RAPA 2 (Strength and Flexibility). RAPA 1 contains 7 questions regarding the participant's amount and intensity of physical activity, allowing each participant's aerobic activity level to be categorized as sedentary, underactive, light activity, regular underactive, or active. RAPA 2 contains 2 questions regarding participants' physical activities that increase strength and improve flexibility. Each participant's strength and flexibility activity level is then categorized as neither strength nor flexibility activity, either strength or flexibility activity (not both), both strength and flexibility activity. The percentage of participants in each RAPA 1/2 category is presented and was calculated by dividing the number of participants in each RAPA 1/2 category by the total number of participants analyzed, multiplied by 100.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Type 1 diabetes for at least 1 year

• HbA1c value less than 12 percent according to the central laboratory at screening

• Body mass index of less than or equal to 35.0 kilograms per square meter (kg/m^2)

• Have been treated for at least 90 days prior to screening with

• insulin detemir, insulin glargine, or Neutral Protamine Hagedorn (NPH) in combination with pre-meal insulin, or

• self-mixed or pre-mixed insulin regimens with any basal and bolus insulin combination administered at least twice daily, or

• continuous SC insulin infusion therapy

• Women who are not breast feeding and test negative for pregnancy before receiving treatment and agree to use reliable birth control until 2 weeks after last treatment with study drug

• Are capable and willing to adhere to multiple daily injections, inject with a vial and syringe and prefilled pen and perform self-monitored blood glucose (SMBG) readings and record keeping

Exclusion Criteria:

• Are using twice daily insulin glargine having been inadequately controlled on single daily dose of glargine prior to screening

• Excessive insulin resistance defined as having received a total daily dose of insulin greater than 1.5 units per kilogram (U/kg) at the time of randomization

• Receiving any oral or injectable medication (other than insulins or metformin for treatment of polycystic ovarian disease) intended for the treatment of diabetes mellitus in the 90 days prior to screening

• Lipid lowering medications:

• are using niacin preparations as lipid lowering medication and/or bile acid sequestrants within 90 days prior to screening; or,

• are using lipid lowering medication at a dose that has not been stable for 90 days or more prior to screening

• Have fasting hypertriglyceridemia (defined as greater than 4.5 millimoles per liter [mmol/L], greater than 400 milligrams per deciliter [mg/dL]) at screening, as determined by the central laboratory.

• Have had more than 1 episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia) within 6 months prior to screening

• Have had 2 or more emergency room visits or hospitalizations due to poor glucose control within 6 months prior to screening

• Have cardiac disease with functional status that is New York Heart Association Class III or IV

• Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine greater than 2.5 mg/dL

• Have obvious clinical signs or symptoms of liver disease (excluding non-alcoholic fatty liver disease [NAFLD]), acute or chronic hepatitis, non-alcoholic steatohepatitis (NASH), or elevated liver enzyme measurements as indicated below:

• total bilirubin 2 times or more than the upper limit of normal (ULN) as defined by the central laboratory, or

• alanine aminotransferase (ALT)/(serum glutamic pyruvic transaminase (SGPT) more than 2.5 times ULN as defined by the central laboratory, or

• aspartate aminotransferase (AST)/(serum glutamic oxaloacetic transaminase (SGOT) more than 2.5 times ULN as defined by the central laboratory

• Have active or untreated malignancy, have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years, or are at increased risk for developing cancer or a recurrence of cancer

• Diagnosed clinically significant diabetic autonomic neuropathy

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.	Concord	California	United States	94520
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.	Fresno	California	United States	93720
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.	La Mesa	California	United States	91942
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.	Lancaster	California	United States	93534
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.	Tustin	California	United States	92780
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.	Aurora	Colorado	United States	80045
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.	Longmont	Colorado	United States	80501
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.	Bradenton	Florida	United States	34208
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.	Hollywood	Florida	United States	33021
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.	Jacksonville	Florida	United States	32258
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.	New Port Richey	Florida	United States	34652
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.	West Palm Beach	Florida	United States	33401
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.	Roswell	Georgia	United States	30076
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.	Honolulu	Hawaii	United States	96814
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.	Idaho Falls	Idaho	United States	83404
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.	Springfield	Illinois	United States	62704
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.	Des Moines	Iowa	United States	50314
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.	Topeka	Kansas	United States	66606
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Wichita	Kansas	United States	67226
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lexington	Kentucky	United States	40503
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Metairie	Louisiana	United States	70006
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Baltimore	Maryland	United States	21204
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Eagan	Minnesota	United States	55123
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Minneapolis	Minnesota	United States	55416
25	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chesterfield	Missouri	United States	63017
26	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Springfield	Missouri	United States	65807
27	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Billings	Montana	United States	59101
28	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.	Omaha	Nebraska	United States	68114
29	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.	Las Vegas	Nevada	United States	89148
30	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.	Nashua	New Hampshire	United States	03063
31	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.	Albany	New York	United States	12208
32	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.	Durham	North Carolina	United States	27713
33	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.	Morehead City	North Carolina	United States	28557
34	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.	Mentor	Ohio	United States	44060
35	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.	Eugene	Oregon	United States	97401
36	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.	Portland	Oregon	United States	97210
37	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.	Greer	South Carolina	United States	29651
38	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.	Myrtle Beach	South Carolina	United States	29572
39	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
40	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
41	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.	Dallas	Texas	United States	75231
42	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.	Houston	Texas	United States	77095
43	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.	Round Rock	Texas	United States	78681
44	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.	Ogden	Utah	United States	84403
45	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.	Federal Way	Washington	United States	98003
46	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.	Spokane	Washington	United States	99202
47	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.	Tacoma	Washington	United States	98405
48	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.	Merewether	New South Wales	Australia	2291
49	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.	Keswick	South Australia	Australia	5035
50	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.	Box Hill	Victoria	Australia	3128
51	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.	Parkville	Victoria	Australia	3050
52	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.	Brussels		Belgium	1070
53	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.	Edegem		Belgium	2650
54	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.	Huy		Belgium	4500
55	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.	Sint-Niklaas		Belgium	9100
56	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.	Fortaleza		Brazil	60430-350
57	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	91350250
58	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
59	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.	Edmonton	Alberta	Canada	T5J 3N4
60	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.	Red Deer	Alberta	Canada	T4N 6V7
61	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.	Winnipeg	Manitoba	Canada	R3E 3P4
62	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.	Halifax	Nova Scotia	Canada	B3H 2Y9
63	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.	Oakville	Ontario	Canada	L6H 3P1
64	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.	Laval	Quebec	Canada	H7T 2P5
65	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.	Montreal	Quebec	Canada	H2W 1T8
66	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.	Osijek		Croatia	31000
67	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.	Kobenhavn		Denmark	2400
68	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.	La Rochelle		France	17019
69	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.	Le Creuzot		France	71200
70	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.	Paris		France	75022
71	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.	Rouen		France	76031
72	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.	Athens		Greece	10552
73	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.	Chalkida		Greece	341 00
74	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.	Thessaloniki		Greece	56429
75	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.	Dublin		Ireland
76	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.	Haifa		Israel	31096
77	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.	Jerusalem		Israel	91120
78	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.	Petah Tikva		Israel	49100
79	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.	Petah Tiqva		Israel	49451
80	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.	Tel Hashomer		Israel	52621
81	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.	Jonava		Lithuania	LT-55201
82	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.	Kaunas		Lithuania	LT-51270
83	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.	Dordrecht		Netherlands	3317 NM
84	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.	Groningen		Netherlands	9728 NT
85	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.	Christchurch		New Zealand	8001
86	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.	Wellington		New Zealand	6021
87	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.	Gdansk		Poland	80-546
88	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.	Katowice		Poland	40-057
89	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.	Krakow		Poland	31-261
90	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.	Lubin		Poland	59-300
91	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.	Lublin		Poland	20-538
92	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.	Szczecin		Poland	70-506
93	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.	Warsaw		Poland	02-507
94	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.	Sturovo		Slovakia	943 01
95	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.	Houghton		South Africa	2198
96	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.	Pretoria		South Africa	0002
97	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.	Somerset West		South Africa	7130
98	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.	Alcala De Henares		Spain	28805
99	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.	Alcira		Spain	46600
100	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.	Barcelona		Spain	08036
101	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	29006
102	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.	Sevilla		Spain	41014
103	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.	Seville		Spain	41003
104	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.	Valencia		Spain	46014
105	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.	Alingsås		Sweden	44183
106	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.	Helsingborg		Sweden	25187
107	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.	Huddinge		Sweden	14186
108	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.	Karlstad		Sweden	SE-651 85
109	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.	Bristol	Avon	United Kingdom	BS10 5NB
110	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.	Portsmouth	Hampshire	United Kingdom	P06 3LY
111	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.	Blackburn	Lancashire	United Kingdom	BB2 3HH
112	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.	Leicester	Leicestershire	United Kingdom	LE5 4PW
113	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.	Inverness	Scotland	United Kingdom	IV2 3JH
114	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.	Ipswich	Suffolk	United Kingdom	IP4 5PD
115	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.	Guildford	Surrey	United Kingdom	GU2 7XX
116	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.	Swansea	Wales	United Kingdom	SA6 6NL
117	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.	Glasgow		United Kingdom	G21 3UW
118	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.	Northampton		United Kingdom	NN1 5BD
119	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.	Oxford		United Kingdom	OX3 7LJ

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: NCT01454284
• Other Study ID Numbers: 12147; I2R-MC-BIAO; 2011-001253-82
• First Posted: Oct 18, 2011
• Last Update Posted: Apr 17, 2018
• Last Verified: Mar 1, 2018

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin Lispro

Study Results

Participant Flow

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Includes participants randomized to receive LY2605541 plus Insulin Lispro. Participant-specific dose of LY2605541 was administered subcutaneously (SC) once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Includes participants randomized to receive Insulin Glargine plus Insulin Lispro. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Period Title: Overall Study
STARTED	664	450
Received at Least 1 Dose of Study Drug	663	449
COMPLETED	548	377
NOT COMPLETED	116	73

Baseline Characteristics

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro	Total
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Total of all reporting groups
Overall Participants	664	450	1114
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.58 (13.50)	42.28 (13.16)	41.86 (13.36)
Sex: Female, Male (Count of Participants)
Female	267 40.2%	169 37.6%	436 39.1%
Male	397 59.8%	281 62.4%	678 60.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	23 3.5%	18 4%	41 3.7%
Not Hispanic or Latino	477 71.8%	315 70%	792 71.1%
Unknown or Not Reported	164 24.7%	117 26%	281 25.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.3%	2 0.4%	4 0.4%
Asian	6 0.9%	2 0.4%	8 0.7%
Native Hawaiian or Other Pacific Islander	1 0.2%	0 0%	1 0.1%
Black or African American	15 2.3%	14 3.1%	29 2.6%
White	625 94.1%	426 94.7%	1051 94.3%
More than one race	15 2.3%	6 1.3%	21 1.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	343 51.7%	229 50.9%	572 51.3%
Slovakia	5 0.8%	5 1.1%	10 0.9%
Greece	15 2.3%	8 1.8%	23 2.1%
Spain	44 6.6%	30 6.7%	74 6.6%
Ireland	2 0.3%	3 0.7%	5 0.4%
Lithuania	2 0.3%	5 1.1%	7 0.6%
Israel	13 2%	9 2%	22 2%
United Kingdom	38 5.7%	25 5.6%	63 5.7%
France	12 1.8%	7 1.6%	19 1.7%
Canada	33 5%	19 4.2%	52 4.7%
Belgium	20 3%	16 3.6%	36 3.2%
Brazil	19 2.9%	11 2.4%	30 2.7%
Poland	51 7.7%	33 7.3%	84 7.5%
Croatia	5 0.8%	5 1.1%	10 0.9%
Denmark	0 0%	1 0.2%	1 0.1%
Australia	22 3.3%	17 3.8%	39 3.5%
South Africa	16 2.4%	8 1.8%	24 2.2%
Netherlands	2 0.3%	1 0.2%	3 0.3%
New Zealand	9 1.4%	5 1.1%	14 1.3%
Sweden	13 2%	13 2.9%	26 2.3%

Outcome Measures

1. Primary Outcome

Title	Hemoglobin A1c (HbA1c)
Description	HbA1c is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. Least squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, stratification factors (country, baseline low density lipoprotein cholesterol [LDL-C] [<100 milligrams/deciliter (mg/dL) (2.6 millimoles/liter [mmol/L]) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	648	444
Least Squares Mean (Standard Error) [percentage of HbA1c]	7.38 (0.03)	7.61 (0.04)

2. Secondary Outcome

Title	Hemoglobin A1c (HbA1c)
Description	HbA1c is a test that measures a participant's average blood glucose level over the past 2 to 3 months. LS means were calculated using MMRM adjusting for treatment, stratification factors (country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	648	444
Least Squares Mean (Standard Error) [percentage of HbA1c]	7.09 (0.03)	7.42 (0.03)

3. Secondary Outcome

Title	Change From Baseline to 52 Weeks in HbA1c
Description	HbA1c is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. LS means were calculated using MMRM adjusting for treatment, stratification factors (country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.
Time Frame	Baseline, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	648	444
Least Squares Mean (Standard Error) [percentage of HbA1c]	-0.46 (0.03)	-0.24 (0.04)

4. Secondary Outcome

Title	Total Hypoglycemia Events
Description	Hypoglycemic episodes are defined as events which are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 mmol/L). Group mean rates of total hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline total hypoglycemia rate, with log [exposure in days/30] as an offset variable). Group mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.
Time Frame	Baseline through 26 weeks, Baseline through 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	662	449
Weeks 0-26	16.83 (0.36)	14.66 (0.36)
Weeks 0-52	15.34 (0.32)	13.88 (0.35)

5. Secondary Outcome

Title	Percentage of Participants With Total Hypoglycemic Events
Description	Hypoglycemic episodes are defined as events that are associated with the reported signs and symptoms of hypoglycemia and/or documented BG concentrations of ≤70 mg/dL (3.9 mmol/L). The percentage of participants was calculated by dividing the number of participants with hypoglycemic episodes by the total number of participants analyzed, multiplied by 100.
Time Frame	Baseline through 26 weeks, Baseline through 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	662	449
Weeks 0-26	99.1 14.9%	99.3 22.1%
Weeks 0-52	99.2 14.9%	99.3 22.1%

6. Secondary Outcome

Title	Percentage of Participants With HbA1c Equal to or Less Than 6.5% and Less Than 7.0%
Description	The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.
Time Frame	up to 26 weeks, up to 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data. Missing endpoints were imputed with the last observation carried forward (LOCF) method, using only post-baseline data.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	648	444
HbA1c ≤6.5%, Week 26	29.6 4.5%	17.8 4%
HbA1c ≤6.5%, Week 52	20.8 3.1%	15.1 3.4%
HbA1c <7.0%, Week 26	45.1 6.8%	34.5 7.7%
HbA1c <7.0%, Week 52	35.3 5.3%	26.1 5.8%

7. Secondary Outcome

Title	Percentage of Participants With HbA1c Less Than 7.0% and Without Nocturnal Hypoglycemia
Description	Hypoglycemic episodes are defined as events associated with reported signs and symptoms of hypoglycemia and/or a documented blood glucose concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. The percentage of participants was calculated by dividing the number of participants with HbA1c <7.0% without nocturnal hypoglycemia by the total number of participants analyzed, multiplied by 100.
Time Frame	up to 26 weeks, up to 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable data. Missing endpoints were imputed with the LOCF method, using only post-baseline data.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	648	444
Week 26	7.1 1.1%	1.8 0.4%
Week 52	4.3 0.6%	1.1 0.2%

8. Secondary Outcome

Title	Nocturnal Hypoglycemia Rates
Description	Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or a documented BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. Group mean rates of nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline nocturnal hypoglycemia rate, with log [exposure in days/30] as an offset variable). Group mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.
Time Frame	Baseline through 26 weeks, Baseline through 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	662	449
Weeks 0-26	1.37 (0.07)	2.70 (0.12)
Weeks 0-52	1.31 (0.06)	2.46 (0.10)

9. Secondary Outcome

Title	Percentage of Participants With Nocturnal Hypoglycemic Events
Description	Hypoglycemic episodes are defined as events associated with the reported signs and symptoms of hypoglycemia and/or a BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. The percentage of participants was calculated by dividing the number of participants with nocturnal hypoglycemic episodes by the total number of participants analyzed, multiplied by 100.
Time Frame	Baseline through 26 weeks, Baseline through 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	662	449
Weeks 0-26	81.7 12.3%	94.7 21%
Weeks 0-52	87.5 13.2%	96.2 21.4%

10. Secondary Outcome

Title	Change in Body Weight
Description	LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline body weight as fixed effects and participant as the random effect.
Time Frame	Baseline, 26 weeks, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable body weight data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	648	439
Week 26	-0.55 (0.14)	0.78 (0.16)
Week 52	-0.61 (0.17)	1.21 (0.20)

11. Secondary Outcome

Title	9 Point Self-monitored Blood Glucose (SMBG)
Description	9-point SMBG profiles were obtained over 2 days within the week prior to Weeks 0, 4, 12, 26, 39, and 52. SMBG measurements were taken at 9 time points: pre-morning meal, 2 hours post-morning meal, pre-midday meal, 2 hours post-midday meal, pre-evening meal, 2 hours post-evening meal, bedtime, at approximately 0300 hours, and the subsequent morning prior to the morning meal. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline BG values as the fixed effects and participant as the random effect.
Time Frame	26 weeks and 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable SMBG data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	615	416
Pre-morning meal, Week 26	153.85 (2.67)	148.91 (3.17)
Pre-morning meal, Week 52	156.18 (2.75)	155.25 (3.30)
2 hour post-morning meal, Week 26	164.59 (3.44)	178.47 (4.07)
2 hour post-morning meal, Week 52	171.94 (3.43)	183.35 (4.10)
Pre-midday meal, Week 26	136.70 (2.70)	152.87 (3.22)
Pre-midday meal, Week 52	145.22 (2.87)	158.50 (3.42)
2 hour post-midday meal, Week 26	150.66 (3.32)	164.47 (3.94)
2 hour post-midday meal, Week 52	156.92 (3.73)	172.61 (4.42)
Pre-evening meal, Week 26	155.38 (3.13)	176.50 (3.73)
Pre-evening meal, Week 52	153.30 (3.21)	170.83 (3.79)
2 hour post-evening meal, Week 26	160.50 (3.85)	181.18 (4.54)
2 hour post-evening meal, Week 52	169.61 (4.19)	184.19 (4.99)
Bedtime, Week 26	163.90 (3.24)	180.97 (3.84)
Bedtime, Week 52	168.04 (3.58)	187.09 (4.30)
0300 Hours, Week 26	169.64 (3.69)	163.09 (4.39)
0300 Hours, Week 52	168.72 (3.94)	174.11 (4.72)
Pre-morning meal next day, Week 26	150.04 (2.76)	145.77 (3.23)
Pre-morning meal next day, Week 52	151.22 (2.70)	149.56 (3.20)

12. Secondary Outcome

Title	Fasting Serum Glucose (by Laboratory Measurement)
Description	Fasting serum glucose (FSG) is measured in blood before the morning meal. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.
Time Frame	26 weeks and 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable FSG data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	646	443
Week 26	139.76 (2.75)	155.23 (3.25)
Week 52	142.02 (2.95)	171.67 (3.48)

13. Secondary Outcome

Title	Fasting Blood Glucose (by Participant Self Monitored Blood Glucose Readings)
Description	Fasting blood glucose (FBG) was measured by SMBG pre-morning meal. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline FBG as the fixed effects and participant as the random effect.
Time Frame	26 weeks and 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable FBG data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	643	441
Week 26	154.84 (1.96)	151.46 (2.31)
Week 52	159.85 (2.02)	153.09 (2.39)

14. Secondary Outcome

Title	Intra-participant Variability of Fasting Blood Glucose (FBG)
Description	FBG was measured by SMBG. Between-day glucose variability is measured by the standard deviation (SD) of FBG. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline SD of FBG as the fixed effects and participant as the random effect.
Time Frame	26 weeks and 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable FBG data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	639	437
Week 26	51.70 (1.22)	64.73 (1.44)
Week 52	53.97 (1.24)	63.11 (1.46)

15. Secondary Outcome

Title	0300 Hours Blood Glucose (BG) to Fasting BG Excursion
Description	Results of a 0300-hour to pre-morning meal (FBG) excursion are presented (only excursions within a single SMBG profile are included). LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], baseline prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment-by-visit interaction, and baseline excursion as the fixed effects and participant as the random effect.
Time Frame	26 weeks and 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable SMBG data at baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	498	332
Week 26	-25.49 (3.96)	-16.44 (4.72)
Week 52	-23.36 (4.10)	-29.01 (4.87)

16. Secondary Outcome

Title	Triglycerides, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol
Description	Concentrations of cholesterol, HDL-C, and LDL-C, and triglycerides are presented. LS means were calculated using MMRM adjusting for stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L), except for the LDL-C outcome variable], prior basal insulin therapy [insulin glargine/detemir/other]), visit, treatment, treatment-by-visit interaction, and baseline value of corresponding lipid outcome variable as the fixed effects and participant as a random effect.
Time Frame	26 weeks and 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable lipid data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	650	446
Cholesterol, Week 26	185.51 (1.09)	179.30 (1.29)
Cholesterol, Week 52	184.66 (1.13)	178.13 (1.34)
HDL-C, Week 26	58.44 (0.39)	61.52 (0.46)
HDL-C, Week 52	58.13 (0.39)	59.52 (0.46)
LDL-C, Week 26	106.25 (0.90)	100.90 (1.07)
LDL-C, Week 52	105.80 (0.96)	101.20 (1.14)
Triglycerides, Week 26	105.26 (2.30)	85.11 (2.73)
Triglycerides, Week 52	104.84 (2.17)	88.12 (2.57)

17. Secondary Outcome

Title	Percentage of Participants With Change in Anti-LY2605541 Antibodies
Description	The percentage of participants with anti-LY2605541 treatment-emergent antibody response (TEAR) is summarized. TEAR is defined as change from baseline to post-baseline in the anti-LY2605541 antibody level either from undetectable to detectable, or from detectable to the value with at least 130% relative increase from baseline.
Time Frame	26 weeks, 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable anti-LY2605541 antibody data at baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	556	399
Week 26	30.2 4.5%	14.0 3.1%
Week 52	32.8 4.9%	10.2 2.3%

18. Secondary Outcome

Title	Basal, Meal Time, and Total Insulin Dose Per Body Weight
Description	Basal insulin dose, meal-time insulin dose (short-acting bolus dose), and total insulin dose were calculated based on the dose during the last 7 days prior to the post-treatment visit or last 3 days prior to the randomization visit. LS means were calculated using a constrained Longitudinal Data Analysis (cLDA) model adjusting for indicator variables of each treatment group at each postbaseline visit and stratification variables (baseline HbA1c [≤8.5% and> 8.5%], country, baseline LDL-C [<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)], and baseline prior basal insulin therapy [insulin glargine/detemir/ other]) as fixed effects.
Time Frame	26 weeks and 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable insulin dose data.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	551	392
Basal insulin, Week 26	0.46 (0.01)	0.35 (0.01)
Basal insulin, Week 52	0.47 (0.01)	0.35 (0.01)
Meal time insulin, Week 26	0.32 (0.01)	0.44 (0.01)
Meal time insulin, Week 52	0.33 (0.01)	0.43 (0.01)
Total insulin, Week 26	0.75 (0.01)	0.77 (0.01)
Total insulin, Week 52	0.78 (0.01)	0.77 (0.02)

19. Secondary Outcome

Title	Insulin Treatment Satisfaction Questionnaire
Description	Insulin Treatment Satisfaction Questionnaire (ITSQ) is a validated measure containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Convenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data are transformed to a scale of 0-100, where higher scores indicate better treatment satisfaction. LS means were calculated using an ANCOVA model adjusting for treatment, baseline HbA1c (≤8.5% and >8.5%), country, and baseline prior basal insulin therapy (insulin glargine/detemir/other) as fixed effects and baseline ITSQ scores as a covariate.
Time Frame	up to 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable ITSQ data at both baseline and post-baseline. Missing endpoints were imputed with the LOCF method.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	561	406
Least Squares Mean (Standard Error) [units on a scale]	73.60 (0.57)	72.92 (0.67)

20. Secondary Outcome

Title	European Quality of Life -5 Dimension (EQ-5D-3L)
Description	The EQ-5D-3L is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a three-level scale of 1-3 (no problem, some problems, and extreme problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United States population-based algorithm. Scores range from -0.11 to 1.0, where a score of 1.0 indicates perfect health. LS means were calculated using an ANCOVA adjusting for treatment, baseline HbA1c (≤8.5% and >8.5%), country, baseline prior basal insulin therapy (insulin glargine/detemir/other), and baseline EQ-5D-3L score as covariates.
Time Frame	up to 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable EQ-5D-3L data at both baseline and post-baseline. Missing endpoints were imputed with the LOCF method.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	566	406
Least Squares Mean (Standard Error) [units on a scale]	0.91 (0.00)	0.92 (0.01)

21. Secondary Outcome

Title	Adult Low Blood Sugar Survey
Description	Low Blood Sugar Survey (LBSS) (also referenced as Hypoglycemia Fear Survey - II [HFS-II]) is a questionnaire that measures 1) behaviors to avoid hypoglycemia and its negative consequences (15 items) and 2) worries about hypoglycemia and its negative consequences (18 items). Responses are made on a 5-point Likert-type scale where 0 = Never and 4 = Always. Total score is the sum of all items (range 0-132). Higher total scores reflect greater fear of hypoglycemia. LS means were calculated using MMRM adjusting for treatment, baseline HbA1c (≤8.5% and >8.5%), country, baseline prior basal insulin therapy (insulin glargine/detemir/other), visit, treatment-by-visit interaction, and baseline LBSS score as the fixed effects and participant as the random effect.
Time Frame	26 weeks and 52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable LBSS data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	657	447
Week 26	29.48 (0.55)	29.12 (0.65)
Week 52	30.43 (0.59)	29.27 (0.70)

22. Secondary Outcome

Title	Rapid Assessment of Physical Activity (RAPA)
Description	The RAPA questionnaire assesses the level and intensity of physical activity of adult participants. It contains 2 subscales: RAPA 1 (Aerobic) and RAPA 2 (Strength and Flexibility). RAPA 1 contains 7 questions regarding the participant's amount and intensity of physical activity, allowing each participant's aerobic activity level to be categorized as sedentary, underactive, light activity, regular underactive, or active. RAPA 2 contains 2 questions regarding participants' physical activities that increase strength and improve flexibility. Each participant's strength and flexibility activity level is then categorized as neither strength nor flexibility activity, either strength or flexibility activity (not both), both strength and flexibility activity. The percentage of participants in each RAPA 1/2 category is presented and was calculated by dividing the number of participants in each RAPA 1/2 category by the total number of participants analyzed, multiplied by 100.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable RAPA data.

Arm/Group Title	LY2605541 + Insulin Lispro	Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.	Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
Measure Participants	367	254
RAPA 1, Sedentary	1.1 0.2%	1.2 0.3%
RAPA 1, Underactive	3.8 0.6%	4.8 1.1%
RAPA 1, Light activity	13.7 2.1%	14.5 3.2%
RAPA 1, Regular underactive	24.5 3.7%	28.5 6.3%
RAPA 1, Active	56.9 8.6%	51.0 11.3%
RAPA 2, Neither strength/flexibility	39.0 5.9%	46.9 10.4%
RAPA 2, Either strength/flexibility	28.9 4.4%	26.8 6%
RAPA 2, Both strength/flexibility	32.2 4.8%	26.4 5.9%

Adverse Events

Arm/Group Title	LY2605541 + Insulin Lispro		Insulin Glargine + Insulin Lispro
Arm/Group Description	Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.		Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks. Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
All Cause Mortality
	LY2605541 + Insulin Lispro		Insulin Glargine + Insulin Lispro
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2605541 + Insulin Lispro		Insulin Glargine + Insulin Lispro
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	117/663 (17.6%)		92/449 (20.5%)
Blood and lymphatic system disorders
Autoimmune thrombocytopenia	1/663 (0.2%)	1	0/449 (0%)	0
Lymphadenopathy	1/663 (0.2%)	1	0/449 (0%)	0
Cardiac disorders
Acute myocardial infarction	1/663 (0.2%)	1	2/449 (0.4%)	3
Angina pectoris	0/663 (0%)	0	2/449 (0.4%)	2
Angina unstable	1/663 (0.2%)	1	0/449 (0%)	0
Arteriosclerosis coronary artery	0/663 (0%)	0	1/449 (0.2%)	1
Cardiac failure	0/663 (0%)	0	1/449 (0.2%)	1
Coronary artery disease	1/663 (0.2%)	1	0/449 (0%)	0
Coronary artery occlusion	0/663 (0%)	0	1/449 (0.2%)	1
Myocardial infarction	0/663 (0%)	0	1/449 (0.2%)	1
Gastrointestinal disorders
Colitis microscopic	1/663 (0.2%)	1	0/449 (0%)	0
Constipation	1/663 (0.2%)	1	0/449 (0%)	0
Enteritis	1/663 (0.2%)	1	0/449 (0%)	0
Gastric ulcer	1/663 (0.2%)	1	0/449 (0%)	0
Gastritis	1/663 (0.2%)	1	0/449 (0%)	0
Gastrooesophageal reflux disease	1/663 (0.2%)	1	1/449 (0.2%)	1
Vomiting	0/663 (0%)	0	1/449 (0.2%)	1
General disorders
Pyrexia	0/663 (0%)	0	1/449 (0.2%)	1
Hepatobiliary disorders
Cholelithiasis	1/663 (0.2%)	2	0/449 (0%)	0
Drug-induced liver injury	1/663 (0.2%)	1	1/449 (0.2%)	1
Immune system disorders
Drug hypersensitivity	1/663 (0.2%)	1	0/449 (0%)	0
Food allergy	0/663 (0%)	0	1/449 (0.2%)	1
Infections and infestations
Abscess limb	0/663 (0%)	0	1/449 (0.2%)	1
Abscess oral	0/663 (0%)	0	1/449 (0.2%)	1
Appendicitis	1/663 (0.2%)	1	0/449 (0%)	0
Cellulitis	2/663 (0.3%)	2	1/449 (0.2%)	1
Gastritis viral	1/663 (0.2%)	1	0/449 (0%)	0
Gastroenteritis	0/663 (0%)	0	1/449 (0.2%)	1
Lobar pneumonia	1/663 (0.2%)	1	0/449 (0%)	0
Osteomyelitis	0/663 (0%)	0	1/449 (0.2%)	1
Pneumonia	2/663 (0.3%)	2	0/449 (0%)	0
Pyelonephritis	1/663 (0.2%)	1	0/449 (0%)	0
Sepsis	0/663 (0%)	0	1/449 (0.2%)	1
Viraemia	1/663 (0.2%)	1	0/449 (0%)	0
Injury, poisoning and procedural complications
Accident at home	0/663 (0%)	0	1/449 (0.2%)	1
Eye injury	0/663 (0%)	0	1/449 (0.2%)	1
Fall	0/663 (0%)	0	1/449 (0.2%)	1
Femur fracture	1/663 (0.2%)	1	0/449 (0%)	0
Gun shot wound	0/663 (0%)	0	1/449 (0.2%)	1
Hand fracture	0/663 (0%)	0	1/449 (0.2%)	1
Intentional overdose	0/663 (0%)	0	1/449 (0.2%)	1
Radius fracture	0/663 (0%)	0	1/449 (0.2%)	1
Rib fracture	1/663 (0.2%)	1	0/449 (0%)	0
Road traffic accident	1/663 (0.2%)	1	1/449 (0.2%)	1
Thermal burn	0/663 (0%)	0	1/449 (0.2%)	1
Tibia fracture	0/663 (0%)	0	2/449 (0.4%)	3
Upper limb fracture	1/663 (0.2%)	1	0/449 (0%)	0
Wrist fracture	0/663 (0%)	0	1/449 (0.2%)	1
Investigations
Hepatic enzyme increased	1/663 (0.2%)	2	0/449 (0%)	0
Liver function test abnormal	0/663 (0%)	0	1/449 (0.2%)	2
Weight decreased	1/663 (0.2%)	1	0/449 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/663 (0%)	0	1/449 (0.2%)	1
Diabetic ketoacidosis	3/663 (0.5%)	3	6/449 (1.3%)	7
Hyperglycaemia	1/663 (0.2%)	1	3/449 (0.7%)	4
Hypoglycaemia	71/663 (10.7%)	108	58/449 (12.9%)	95
Ketoacidosis	0/663 (0%)	0	1/449 (0.2%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/663 (0%)	0	1/449 (0.2%)	1
Lumbar spinal stenosis	1/663 (0.2%)	1	0/449 (0%)	0
Neuropathic arthropathy	1/663 (0.2%)	2	0/449 (0%)	0
Osteoarthritis	0/663 (0%)	0	1/449 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric	1/663 (0.2%)	1	0/449 (0%)	0
Basal cell carcinoma	1/663 (0.2%)	1	1/449 (0.2%)	2
Benign hydatidiform mole	1/663 (0.2%)	2	0/449 (0%)	0
Bladder papilloma	0/663 (0%)	0	1/449 (0.2%)	1
Cerebellopontine angle tumour	0/663 (0%)	0	1/449 (0.2%)	1
Intraductal proliferative breast lesion	0/663 (0%)	0	1/449 (0.2%)	1
Non-small cell lung cancer metastatic	1/663 (0.2%)	1	0/449 (0%)	0
Oesophageal carcinoma	1/663 (0.2%)	1	0/449 (0%)	0
Squamous cell carcinoma of the tongue	1/663 (0.2%)	1	0/449 (0%)	0
Uterine leiomyoma	0/267 (0%)	0	1/169 (0.6%)	1
Nervous system disorders
Cerebral infarction	1/663 (0.2%)	1	0/449 (0%)	0
Cerebrovascular accident	1/663 (0.2%)	1	0/449 (0%)	0
Convulsion	1/663 (0.2%)	1	0/449 (0%)	0
Encephalopathy	0/663 (0%)	0	1/449 (0.2%)	1
Epilepsy	1/663 (0.2%)	1	0/449 (0%)	0
Headache	0/663 (0%)	0	1/449 (0.2%)	1
Hypoglycaemic seizure	1/663 (0.2%)	1	0/449 (0%)	0
Hypoglycaemic unconsciousness	4/663 (0.6%)	4	1/449 (0.2%)	1
Transient global amnesia	1/663 (0.2%)	1	0/449 (0%)	0
Transient ischaemic attack	0/663 (0%)	0	1/449 (0.2%)	1
Pregnancy, puerperium and perinatal conditions
Hyperemesis gravidarum	0/267 (0%)	0	1/169 (0.6%)	1
Pregnancy	1/267 (0.4%)	1	0/169 (0%)	0
Psychiatric disorders
Acute psychosis	1/663 (0.2%)	1	0/449 (0%)	0
Anxiety	0/663 (0%)	0	1/449 (0.2%)	2
Major depression	0/663 (0%)	0	1/449 (0.2%)	1
Suicide attempt	0/663 (0%)	0	1/449 (0.2%)	1
Renal and urinary disorders
Nephrotic syndrome	0/663 (0%)	0	1/449 (0.2%)	1
Reproductive system and breast disorders
Ovarian cyst	0/267 (0%)	0	1/169 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	0/663 (0%)	0	1/449 (0.2%)	1
Pleural effusion	1/663 (0.2%)	1	0/449 (0%)	0
Respiratory distress	0/663 (0%)	0	1/449 (0.2%)	1
Skin and subcutaneous tissue disorders
Eczema	1/663 (0.2%)	1	0/449 (0%)	0
Lipohypertrophy	2/663 (0.3%)	4	0/449 (0%)	0
Skin ulcer	0/663 (0%)	0	1/449 (0.2%)	3
Urticaria	1/663 (0.2%)	1	0/449 (0%)	0
Vascular disorders
Haemorrhage	1/663 (0.2%)	1	0/449 (0%)	0
Peripheral ischaemia	0/663 (0%)	0	1/449 (0.2%)	1
Other (Not Including Serious) Adverse Events
	LY2605541 + Insulin Lispro		Insulin Glargine + Insulin Lispro
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	502/663 (75.7%)		305/449 (67.9%)
Gastrointestinal disorders
Diarrhoea	14/663 (2.1%)	16	16/449 (3.6%)	17
Nausea	21/663 (3.2%)	27	17/449 (3.8%)	18
Vomiting	20/663 (3%)	20	16/449 (3.6%)	21
General disorders
Injection site hypertrophy	16/663 (2.4%)	20	0/449 (0%)	0
Infections and infestations
Bronchitis	16/663 (2.4%)	17	12/449 (2.7%)	14
Gastroenteritis	12/663 (1.8%)	15	11/449 (2.4%)	14
Gastroenteritis viral	18/663 (2.7%)	18	15/449 (3.3%)	15
Influenza	45/663 (6.8%)	47	22/449 (4.9%)	23
Nasopharyngitis	105/663 (15.8%)	141	70/449 (15.6%)	99
Sinusitis	29/663 (4.4%)	33	14/449 (3.1%)	19
Upper respiratory tract infection	61/663 (9.2%)	76	40/449 (8.9%)	52
Urinary tract infection	24/663 (3.6%)	28	15/449 (3.3%)	18
Viral infection	7/663 (1.1%)	9	12/449 (2.7%)	12
Investigations
Alanine aminotransferase increased	17/663 (2.6%)	17	3/449 (0.7%)	4
Weight increased	15/663 (2.3%)	16	6/449 (1.3%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	14/663 (2.1%)	15	10/449 (2.2%)	12
Nervous system disorders
Headache	24/663 (3.6%)	37	14/449 (3.1%)	21
Respiratory, thoracic and mediastinal disorders
Cough	31/663 (4.7%)	32	14/449 (3.1%)	15
Oropharyngeal pain	14/663 (2.1%)	15	12/449 (2.7%)	12
Skin and subcutaneous tissue disorders
Lipohypertrophy	55/663 (8.3%)	69	1/449 (0.2%)	1
Vascular disorders
Hypertension	11/663 (1.7%)	12	11/449 (2.4%)	11

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.