A Study in Participants With Type I Diabetes Mellitus (IMAGINE 3)

Lilly

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 1

Treatments: Drug: LY2605541; Drug: Glargine; Drug: Insulin Lispro

Study type: Interventional

Funder types: Industry

Identifiers

NCT01454284

2011-001253-82 (EudraCT Number)

I2R-MC-BIAO (Other Identifier)

12147

Details and patient eligibility

About

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

Enrollment: 1,114 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,114 participants in 2 patient groups

LY2605541 + Insulin Lispro

Experimental group

Description:

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.

Treatment:

Drug: Insulin Lispro

Drug: LY2605541

Glargine + Insulin Lispro

Active Comparator group

Description:

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.

Treatment:

Drug: Insulin Lispro

Drug: Glargine