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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 1,114
- Locations
- 1
- Primary Endpoint
- Hemoglobin A1c (HbA1c)
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- 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
Arms & Interventions
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.
Intervention: LY2605541 (Drug)
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.
Intervention: Insulin Lispro (Drug)
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.
Intervention: Glargine (Drug)
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.
Intervention: Insulin Lispro (Drug)
Outcomes
Primary Outcomes
Hemoglobin A1c (HbA1c)
Time Frame: 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 Outcomes
- Total Hypoglycemia Events(Baseline through 26 weeks, Baseline through 52 weeks)
- Percentage of Participants With Total Hypoglycemic Events(Baseline through 26 weeks, Baseline through 52 weeks)
- 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)
- Fasting Serum Glucose (by Laboratory Measurement)(26 weeks and 52 weeks)
- Fasting Blood Glucose (by Participant Self Monitored Blood Glucose Readings)(26 weeks and 52 weeks)
- Triglycerides, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol(26 weeks and 52 weeks)
- Intra-participant Variability of Fasting Blood Glucose (FBG)(26 weeks and 52 weeks)
- Rapid Assessment of Physical Activity (RAPA)(52 weeks)
- Nocturnal Hypoglycemia Rates(Baseline through 26 weeks, Baseline through 52 weeks)
- Percentage of Participants With Change in Anti-LY2605541 Antibodies(26 weeks, 52 weeks)
- European Quality of Life -5 Dimension (EQ-5D-3L)(up to 52 weeks)
- Hemoglobin A1c (HbA1c)(26 weeks)
- Change From Baseline to 52 Weeks in HbA1c(Baseline, 52 weeks)
- Change in Body Weight(Baseline, 26 weeks, 52 weeks)
- 9 Point Self-monitored Blood Glucose (SMBG)(26 weeks and 52 weeks)
- Basal, Meal Time, and Total Insulin Dose Per Body Weight(26 weeks and 52 weeks)
- Percentage of Participants With HbA1c Less Than 7.0% and Without Nocturnal Hypoglycemia(up to 26 weeks, up to 52 weeks)
- Percentage of Participants With Nocturnal Hypoglycemic Events(Baseline through 26 weeks, Baseline through 52 weeks)
- 0300 Hours Blood Glucose (BG) to Fasting BG Excursion(26 weeks and 52 weeks)
- Adult Low Blood Sugar Survey(26 weeks and 52 weeks)
- Insulin Treatment Satisfaction Questionnaire(up to 52 weeks)