A Study of LY2605541 in Participants With Type 1 Diabetes Mellitus (IMAGINE 7)

Lilly

Status and phase: Completed; Phase 3

Conditions: Type 1 Diabetes Mellitus

Treatments: Drug: Insulin Lispro; Drug: LY2605541

Study type: Interventional

Funder types: Industry

Identifiers

NCT01792284

14184

I2R-MC-BIAX (Other Identifier)

Details and patient eligibility

About

The primary purpose of participation in this study is to compare the safety and efficacy of different dosing schedules of LY2605541 and how different dosing schedules of LY2605541 affect Hemoglobin A1c (HbA1c). Participants will be treated for up to 36 weeks with LY2605541 (one 12-week Lead-in period and two 12-week Randomization periods) and will participate in a total of 42 weeks of total study enrollment, including a 2-week Screening period and a 4-week Follow-up period.

Full description

This study involved a comparison of LY2605541 regimens, each administered with bolus insulin lispro. Eligible participants were switched to a fixed evening LY2605541dosing regimen at the beginning of the 12-week lead-in period. LY2605541 was administered SQ once-daily using a prefilled insulin device. The LY2605541dose was adjusted using a dosing algorithm adapted from Bartley and Bolli (Bartley et al. 2008, Bolli et al. 2009) based on the participant's blood glucose (BG) values and documented hypoglycemia during the previous week. Participants not already receiving insulin lispro for prandial dosing were switched to insulin lispro at the beginning of the 12-week lead-in period. Adjustments to insulin lispro doses were based on the insulin dosing algorithms adapted from Riddle and Bergenstal (Riddle et al. 2003, Bergenstal et al. 2008). At the time of randomization, participants were randomized to begin either the fixed evening dosing regimen or the variable time dosing regimen. Each participant was crossed over to the alternate regimen after 12 weeks. The insulin device (prefilled pen) remained the same throughout the study.

Enrollment: 212 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Type 1 diabetes mellitus for at least 1 year
• Have an HbA1c value <9.0%
• Have a body mass index (BMI) ≤35.0 kilogram per square meter (kg/m^2)
• Currently using basal/ bolus insulin
• Women of childbearing potential are not breastfeeding and must use methods to prevent pregnancy

Exclusion criteria

• Have excessive insulin resistance
• Are taking medications other than insulin for diabetes
• High triglycerides
• 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
• Have cardiac disease with functional status that is New York Heart Association (NYHA) Class III or IV (per NYHA Cardiac Disease Classification)
• Have impaired renal function
• Have impaired liver function
• 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 HbA1c measurement
• Have cancer, recent cancer, or risk of cancer
• Have a known hypersensitivity or allergy to any of the study insulins or their excipients
• Have chronic systemic glucocorticoid users
• Have clinically significant diabetic autonomic neuropathy
• Have irregular sleep/wake cycle
• Have been treated with a drug within the last 30 days that has not received regulatory approval at the time of study entry
• Prior study participation
• Are using or have used niacin preparations as a lipid-lowering medication and/or bile acid sequestrants within 90 days prior to screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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212 participants in 2 patient groups

LY2605541 Fixed Time Dosing

Experimental group

Description:

Participant-specific dose of LY2605541 administered subcutaneously (SQ) at approximately the same time every evening for 12 weeks in the Lead-in Period and in Randomization Period 1 or Randomization Period 2. Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal). Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on self-monitored blood glucose (SMBG). Target glucose values were as follows: Preprandial and bedtime BG between 71 and 130 milligrams/deciliter (mg/dL) Insulin adjustment and glucose correction between 71 and 100 mg/dL.

Treatment:

Drug: LY2605541

Drug: Insulin Lispro

LY2605541 Variable Time Dosing

Experimental group

Description:

Participant-specific dose of LY2605541 administered SQ on a variable time schedule (8- and 40-hour dosing intervals) for 12 weeks in Randomization Period 1 or Randomization Period 2. Dosing schedules were to remain approximately the same throughout the 12 weeks. Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal). Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on SMBG. Target glucose values were as follows: Preprandial and bedtime BG between 71 and 130 mg/dL Insulin adjustment and glucose correction between 71 and 100 mg/dL.

Treatment:

Drug: LY2605541

Drug: Insulin Lispro