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A Study in Participants With Type 1 Diabetes Mellitus (IMAGINE 1)

Primary Purpose

Diabetes Mellitus, Type 1

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Glargine

LY2605541

Insulin Lispro

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Have had diabetes mellitus for at least 1 year
Have an hemoglobin A1c (HbA1c) value less than 12% according to the central laboratory at screening
Have a body mass index (BMI) 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 the following:
- Insulin detemir, insulin glargine, or human insulin isophane suspension (NPH) insulin in combination with premeal insulin,
- Self-mixed or premixed insulin regimens with any basal and bolus insulin combination administered at least twice daily, or
- Continuous SC insulin infusion therapy
This inclusion criterion applies to female participants:
- Are not breastfeeding
- Test negative for pregnancy at screening and randomization based on serum pregnancy tests
- Do not intend to become pregnant during the study
- Have practiced a reliable method of birth control (for example, use of oral contraceptives or levonorgestrel, diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms with contraceptive foam, intrauterine devices, partner with vasectomy, or abstinence) for at least 6 weeks prior to screening
- Agree to continue to use a reliable method of birth control during the study, as determined by the investigator (and for 2 weeks following the last dose of study drug)
Capable of and willing and desirous to do the following: adhere to a multiple daily injection regimen, inject insulin with a prefilled pen and perform Self-Monitored Blood Glucose (SMBG) and record keeping as required by this protocol, as determined by the investigator. Caregiver may be responsible for all of the above.

Exclusion Criteria:

Are using twice-daily insulin glargine having been inadequately controlled on once-daily dosed glargine prior to screening
Have excessive insulin resistance defined as having received a total daily dose of insulin greater than 1.5 units per kilogram (units/kg) at the time of randomization
Receiving any oral or injectable medication (other than metformin for treatment of polycystic ovarian disease) intended for the treatment of diabetes mellitus other than insulins in the 90 days prior to screening
Lipid-lowering medications:
- Are using niacin preparations as a 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 greater than or equal to 90 days prior to screening
- If a participant has not been on a stable dose of lipid-lowering medication for greater than or equal to 90 days prior to screening, the site should wait to screen the participant. If the results of the screening laboratory tests require a change to the participant's current lipid-lowering medication or initiation of lipid-lowering medication, it is acceptable to change the lipid-lowering medication for the participant and to have the participant return greater than or equal to 90 days later to complete some of the screening procedures again
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 as determined by the investigator) within 6 months prior to entry into the study
Have had 2 or more emergency room visits or hospitalizations due to poor glucose control (hyperglycemia or diabetic ketoacidosis) in the past 6 months
Cardiovascular: have cardiac disease with functional status that is New York Heart Association Class III or IV (per New York Heart Association Cardiac Disease Classification)
Renal: Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine greater than 2.5 mg/dL
Hepatic: 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 greater than or equal to 2 times the upper limit of normal (ULN) as defined by the central laboratory,
- Alanine aminotransferase (ALT)/(serum glutamic pyruvic transaminase (SGPT) greater than 2.5 times ULN as defined by the central laboratory, or
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) greater than 2.5 times ULN as defined by the central laboratory.
Malignancy: 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 an increased risk for developing cancer or a recurrence of cancer in the opinion of the investigator
Allergy: Have known hypersensitivity or allergy to any of the study insulins or their excipients
Hematologic: Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the HbA1c measurement
Glucocorticoid therapy: Receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical , intraocular, intranasal, and inhaled preparations) or have received such therapy within 8 weeks immediately before screening with the exception of replacement therapy for adrenal insufficiency
Diagnosed clinically significant diabetic autonomic neuropathy, in the opinion of the investigator
Have any other condition (including known drug or alcohol abuse or psychiatric disorder including eating disorder) that precludes the participant from following and completing the protocol

Sites / Locations

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

LY2605541 + Insulin Lispro

Glargine + Insulin Lispro

Arm Description

LY2605541 titrated based on blood glucose readings, administered by subcutaneous (SC) injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.

Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.

Outcomes

Primary Outcome Measures

Hemoglobin A1c (HbA1c) at 26 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 (baseline low-density lipoprotein cholesterol [LDL-C] [<100 milligrams per deciliter (mg/dL) and ≥100 mg/dL] and country), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.

Secondary Outcome Measures

Hemoglobin A1c (HbA1c)

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 (baseline LDL-C [<100 mg/dL and ≥100 mg/dL] and country), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects.

Change From Baseline in Hemoglobin A1c (HbA1c)

Percentage of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% or Less Than or Equal to 6.5% Using Last Observation Carried Forward (LOCF)

HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, then multiplying by 100.

Proportion of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% Without Nocturnal Hypoglycemia

Hypoglycemic episodes are defined as an event that is associated with reported signs and symptoms of hypoglycemia and/or a documented blood glucose concentration of ≤70 mg/dL (3.9 millimoles per liter [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, then multiplying by 100.

Total Hypoglycemia Rates (Adjusted by 30 Days)

Hypoglycemic episodes are defined as events that 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.

Percentage of Participants With Total Hypoglycemia Events

Hypoglycemic events are defined as events that are associated with 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, then multiplying by 100.

Nocturnal Hypoglycemia Rates (Adjusted by 30 Days)

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.

Percentage of Participants With Nocturnal Hypoglycemic Events

Hypoglycemic episodes are defined as an event that is associated with 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, then multiplying by 100.

Fasting Serum Glucose (FSG) by Laboratory Measurement

LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects, and participants as the random effect.

Fasting Blood Glucose (FBG) Intra-participant Variability

FBG was measured by self-monitored blood glucose (SMBG). Between-day glucose variability is measured by the standard deviation of FBG. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects, and participants as the random effect.

0300-hour Blood Glucose (BG) to Fasting Blood (FBG) Glucose Excursion

Results of a 0300-hour to pre-morning meal (FBG) excursion are presented (only SMBG profiles with both 0300 hours and the next day pre-morning measurements are included for the calculation of such excursion). LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects and participants as the random effect.

9 Point Self-monitored Blood Glucose (SMBG)

9-point SMBG profiles were obtained over 2 days within the week prior to Weeks 0, 4, 12, 26, 39, 52, 65, and 78. 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 pre-morning meal the next day. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects and participants as the random effect.

Change From Baseline in Body Weight

Basal, Bolus, and Total Insulin Dose

Basal insulin dose, short-acting bolus insulin dose (each meal and overall), 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 MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects and participants as the random effect.

Lipid Profile

Concentrations of cholesterol, high-density lipoprotein cholesterol (HDL-C), LDL-C, and triglycerides are summarized. LS means were calculated using MMRM, adjusting for stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, LDL-C [<100 mg/dL and ≥100 mg/dL] except for the LDL-C outcome variable), visit, treatment, treatment-by-visit interaction, and baseline value of corresponding lipid outcome variable.

Percentage of Participants With Change in Anti-LY2605541 Antibodies

The percentage of participants with a treatment-emergent anti-LY2605541 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.

Insulin Treatment Satisfaction Questionnaire (ITSQ)

ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data presented are the transformed overall score on a scale of 0-100, where higher scores indicate better treatment satisfaction. LS means were calculated using an analysis of covariance (ANCOVA) model with treatment and stratification (baseline HbA1c [≤8.5% or >8.5%] and country) as fixed effects and baseline value of the dependent variable as a covariate.

Low Blood Sugar Survey (LBSS)

LBSS (also referenced as Hypoglycemia Fear Survey - II [HFS-II]) is a 33-item 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 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, stratification factors (baseline HbA1c [≤8.5% and >8.5%] and country), visit, treatment-by-visit interaction , and corresponding baseline dependent variable as the fixed effects and participants as the random effect.

European Quality of Life-5 Dimension (EQ-5D)

The EQ-5D 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 3-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 ANCOVA, adjusting for treatment and stratification factors (baseline HbA1c [≤8.5% or >8.5%] and country) as fixed effects and baseline EQ-5D score as a covariate.

Rapid Assessment of Physical Activity (RAPA)

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 activities, 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 (flex) activity, either strength or flex (not both), both strength and flex 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, then multiplying by 100.

Full Information

NCT ID

NCT01481779

First Posted

November 28, 2011

Last Updated

March 16, 2018

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT01481779

Brief Title

A Study in Participants With Type 1 Diabetes Mellitus

Acronym

IMAGINE 1

Official Title

The Impact of LY2605541 Versus Insulin Glargine for Patients With Type 1 Diabetes Mellitus Treated With Preprandial Insulin Lispro: An Open-Label, Randomized, 78-Week Study - The IMAGINE 1 Study

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Completed

Study Start Date

January 2012 (undefined)

Primary Completion Date

May 2013 (Actual)

Study Completion Date

June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is: To compare the blood sugar control of LY2605541 with insulin glargine after 78 weeks of treatment. To compare the rate of night-time low blood sugar episodes on LY2605541 with insulin glargine during 78 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 78 weeks of treatment. To compare the rate of hypoglycemia episodes on LY2605541 with insulin glargine during 78 weeks of treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 1

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

455 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LY2605541 + Insulin Lispro

Arm Type

Experimental

Arm Description

Arm Title

Glargine + Insulin Lispro

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Glargine

Intervention Description

Administered by SC injection via a pen device.

Intervention Type

Drug

Intervention Name(s)

LY2605541

Intervention Description

Administered by SC injection with a pen device.

Intervention Type

Drug

Intervention Name(s)

Insulin Lispro

Other Intervention Name(s)

LY275585, Humalog

Intervention Description

Administered by SC injection with a pen device.

Primary Outcome Measure Information:

Title

Hemoglobin A1c (HbA1c) at 26 Weeks

Description

Time Frame

26 weeks

Secondary Outcome Measure Information:

Title

Hemoglobin A1c (HbA1c)

Description

Time Frame

52 weeks and 78 weeks

Title

Change From Baseline in Hemoglobin A1c (HbA1c)

Description

Time Frame

Baseline, 26 weeks, 52 weeks, 78 weeks

Title

Percentage of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% or Less Than or Equal to 6.5% Using Last Observation Carried Forward (LOCF)

Description

Time Frame

26 weeks and 52 weeks and 78 weeks

Title

Proportion of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% Without Nocturnal Hypoglycemia

Description

Time Frame

26 weeks and 52 weeks and 78 weeks

Title

Total Hypoglycemia Rates (Adjusted by 30 Days)

Description

Time Frame

Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks

Title

Percentage of Participants With Total Hypoglycemia Events

Description

Time Frame

Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks

Title

Nocturnal Hypoglycemia Rates (Adjusted by 30 Days)

Description

Time Frame

Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks

Title

Percentage of Participants With Nocturnal Hypoglycemic Events

Description

Time Frame

Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks

Title

Fasting Serum Glucose (FSG) by Laboratory Measurement

Description

Time Frame

26 weeks and 52 weeks and 78 weeks

Title

Fasting Blood Glucose (FBG) Intra-participant Variability

Description

Time Frame

26 weeks and 52 weeks and 78 weeks

Title

0300-hour Blood Glucose (BG) to Fasting Blood (FBG) Glucose Excursion

Description

Time Frame

26 weeks and 52 weeks and 78 weeks

Title

9 Point Self-monitored Blood Glucose (SMBG)

Description

Time Frame

26 weeks and 52 weeks and 78 weeks

Title

Change From Baseline in Body Weight

Description

Time Frame

Baseline and 26 weeks and 52 weeks and 78 weeks

Title

Basal, Bolus, and Total Insulin Dose

Description

Time Frame

26 weeks and 52 weeks and 78 weeks

Title

Lipid Profile

Description

Time Frame

26 weeks and 52 weeks and 78 weeks

Title

Percentage of Participants With Change in Anti-LY2605541 Antibodies

Description

Time Frame

Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks

Title

Insulin Treatment Satisfaction Questionnaire (ITSQ)

Description

Time Frame

26 weeks

Title

Low Blood Sugar Survey (LBSS)

Description

Time Frame

26 weeks and 52 weeks and 78 weeks

Title

European Quality of Life-5 Dimension (EQ-5D)

Description

Time Frame

26 weeks

Title

Rapid Assessment of Physical Activity (RAPA)

Description

Time Frame

26 weeks and 78 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Have had diabetes mellitus for at least 1 year Have an hemoglobin A1c (HbA1c) value less than 12% according to the central laboratory at screening Have a body mass index (BMI) 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 the following: Insulin detemir, insulin glargine, or human insulin isophane suspension (NPH) insulin in combination with premeal insulin, Self-mixed or premixed insulin regimens with any basal and bolus insulin combination administered at least twice daily, or Continuous SC insulin infusion therapy This inclusion criterion applies to female participants: Are not breastfeeding Test negative for pregnancy at screening and randomization based on serum pregnancy tests Do not intend to become pregnant during the study Have practiced a reliable method of birth control (for example, use of oral contraceptives or levonorgestrel, diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms with contraceptive foam, intrauterine devices, partner with vasectomy, or abstinence) for at least 6 weeks prior to screening Agree to continue to use a reliable method of birth control during the study, as determined by the investigator (and for 2 weeks following the last dose of study drug) Capable of and willing and desirous to do the following: adhere to a multiple daily injection regimen, inject insulin with a prefilled pen and perform Self-Monitored Blood Glucose (SMBG) and record keeping as required by this protocol, as determined by the investigator. Caregiver may be responsible for all of the above. Exclusion Criteria: Are using twice-daily insulin glargine having been inadequately controlled on once-daily dosed glargine prior to screening Have excessive insulin resistance defined as having received a total daily dose of insulin greater than 1.5 units per kilogram (units/kg) at the time of randomization Receiving any oral or injectable medication (other than metformin for treatment of polycystic ovarian disease) intended for the treatment of diabetes mellitus other than insulins in the 90 days prior to screening Lipid-lowering medications: Are using niacin preparations as a 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 greater than or equal to 90 days prior to screening If a participant has not been on a stable dose of lipid-lowering medication for greater than or equal to 90 days prior to screening, the site should wait to screen the participant. If the results of the screening laboratory tests require a change to the participant's current lipid-lowering medication or initiation of lipid-lowering medication, it is acceptable to change the lipid-lowering medication for the participant and to have the participant return greater than or equal to 90 days later to complete some of the screening procedures again 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 as determined by the investigator) within 6 months prior to entry into the study Have had 2 or more emergency room visits or hospitalizations due to poor glucose control (hyperglycemia or diabetic ketoacidosis) in the past 6 months Cardiovascular: have cardiac disease with functional status that is New York Heart Association Class III or IV (per New York Heart Association Cardiac Disease Classification) Renal: Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine greater than 2.5 mg/dL Hepatic: 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 greater than or equal to 2 times the upper limit of normal (ULN) as defined by the central laboratory, Alanine aminotransferase (ALT)/(serum glutamic pyruvic transaminase (SGPT) greater than 2.5 times ULN as defined by the central laboratory, or Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) greater than 2.5 times ULN as defined by the central laboratory. Malignancy: 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 an increased risk for developing cancer or a recurrence of cancer in the opinion of the investigator Allergy: Have known hypersensitivity or allergy to any of the study insulins or their excipients Hematologic: Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the HbA1c measurement Glucocorticoid therapy: Receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical , intraocular, intranasal, and inhaled preparations) or have received such therapy within 8 weeks immediately before screening with the exception of replacement therapy for adrenal insufficiency Diagnosed clinically significant diabetic autonomic neuropathy, in the opinion of the investigator Have any other condition (including known drug or alcohol abuse or psychiatric disorder including eating disorder) that precludes the participant from following and completing the protocol

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

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.

City

Concord

State/Province

California

ZIP/Postal Code

94520

Country

United States

Facility Name

City

Escondido

State/Province

California

ZIP/Postal Code

92026

Country

United States

Facility Name

City

Fresno

State/Province

California

ZIP/Postal Code

93720

Country

United States

Facility Name

City

Greenbrae

State/Province

California

ZIP/Postal Code

94904

Country

United States

Facility Name

City

Huntington Beach

State/Province

California

ZIP/Postal Code

92648

Country

United States

Facility Name

City

San Mateo

State/Province

California

ZIP/Postal Code

94401

Country

United States

Facility Name

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80010

Country

United States

Facility Name

City

Idaho Falls

State/Province

Idaho

ZIP/Postal Code

83404

Country

United States

Facility Name

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89148

Country

United States

Facility Name

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84102

Country

United States

Facility Name

City

Renton

State/Province

Washington

ZIP/Postal Code

98057

Country

United States

Facility Name

City

Spokane

State/Province

Washington

ZIP/Postal Code

99202

Country

United States

Facility Name

City

Graz

ZIP/Postal Code

8036

Country

Austria

Facility Name

City

Vienna

ZIP/Postal Code

1130

Country

Austria

Facility Name

City

Bar Le Duc

ZIP/Postal Code

55000

Country

France

Facility Name

City

Corbeil-Essonnes

ZIP/Postal Code

91100

Country

France

Facility Name

City

Montpellier

ZIP/Postal Code

34295

Country

France

Facility Name

City

Nantes

ZIP/Postal Code

44093

Country

France

Facility Name

City

Nice

ZIP/Postal Code

06002

Country

France

Facility Name

City

Saint Mande

ZIP/Postal Code

94160

Country

France

Facility Name

City

Toulouse

ZIP/Postal Code

31059

Country

France

Facility Name

City

Venissieux

ZIP/Postal Code

69200

Country

France

Facility Name

City

Berlin

ZIP/Postal Code

10409

Country

Germany

Facility Name

City

Eisenach

ZIP/Postal Code

99817

Country

Germany

Facility Name

City

Falkensee

ZIP/Postal Code

14612

Country

Germany

Facility Name

City

Hamburg

ZIP/Postal Code

22559

Country

Germany

Facility Name

City

Mainz

ZIP/Postal Code

55116

Country

Germany

Facility Name

City

Mayen

ZIP/Postal Code

56727

Country

Germany

Facility Name

City

Münster

ZIP/Postal Code

48153

Country

Germany

Facility Name

City

Neuwied

ZIP/Postal Code

56564

Country

Germany

Facility Name

City

Pohlheim

ZIP/Postal Code

35415

Country

Germany

Facility Name

City

Cagliari

ZIP/Postal Code

09100

Country

Italy

Facility Name

City

Catania

ZIP/Postal Code

95100

Country

Italy

Facility Name

City

Lecce

ZIP/Postal Code

73100

Country

Italy

Facility Name

City

Padova

ZIP/Postal Code

35128

Country

Italy

Facility Name

City

Perugia

ZIP/Postal Code

06100

Country

Italy

Facility Name

City

Ravenna

ZIP/Postal Code

48100

Country

Italy

Facility Name

City

Hokkaido

ZIP/Postal Code

060-0002

Country

Japan

Facility Name

City

Kanagawa

ZIP/Postal Code

235-0045

Country

Japan

Facility Name

City

Kumamoto

ZIP/Postal Code

862-0976

Country

Japan

Facility Name

City

Tokyo

ZIP/Postal Code

162-8666

Country

Japan

Facility Name

City

Guadalajara Jalisco

ZIP/Postal Code

04460

Country

Mexico

Facility Name

City

Guadalajara

ZIP/Postal Code

44150

Country

Mexico

Facility Name

City

Monterrey

ZIP/Postal Code

64460

Country

Mexico

Facility Name

City

Katowice

ZIP/Postal Code

40-057

Country

Poland

Facility Name

City

Lodz

ZIP/Postal Code

93-338

Country

Poland

Facility Name

City

Poznan

ZIP/Postal Code

61-655

Country

Poland

Facility Name

City

Warsaw

ZIP/Postal Code

01-192

Country

Poland

Facility Name

City

Arkhangelsk

ZIP/Postal Code

163045

Country

Russian Federation

Facility Name

City

Moscow

ZIP/Postal Code

119991

Country

Russian Federation

Facility Name

City

Saint Petersburg

ZIP/Postal Code

193257

Country

Russian Federation

12. IPD Sharing Statement

Citations:

PubMed Identifier

29167192

Citation

Sanyal A, Cusi K, Hartman ML, Zhang S, Bastyr EJ 3rd, Bue-Valleskey JM, Chang AM, Haupt A, Jacober SJ, Konrad RJ, Zhang Q, Hoogwerf BJ. Cytokeratin-18 and enhanced liver fibrosis scores in type 1 and type 2 diabetes and effects of two different insulins. J Investig Med. 2018 Mar;66(3):661-668. doi: 10.1136/jim-2017-000609. Epub 2017 Nov 21.

Results Reference

derived

PubMed Identifier

28587667

Citation

Orchard TJ, Cariou B, Connelly MA, Otvos JD, Zhang S, Antalis CJ, Ivanyi T, Hoogwerf BJ. The effects of basal insulin peglispro vs. insulin glargine on lipoprotein particles by NMR and liver fat content by MRI in patients with diabetes. Cardiovasc Diabetol. 2017 Jun 6;16(1):73. doi: 10.1186/s12933-017-0555-1.

Results Reference

derived

PubMed Identifier

28417532

Citation

Cusi K, Sanyal AJ, Zhang S, Hartman ML, Bue-Valleskey JM, Hoogwerf BJ, Haupt A. Non-alcoholic fatty liver disease (NAFLD) prevalence and its metabolic associations in patients with type 1 diabetes and type 2 diabetes. Diabetes Obes Metab. 2017 Nov;19(11):1630-1634. doi: 10.1111/dom.12973. Epub 2017 Jun 22.

Results Reference

derived

Learn more about this trial

A Study in Participants With Type 1 Diabetes Mellitus

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