A Study of LY2605541 in Participants With Type 2 Diabetes Mellitus (IMAGINE 5)

Lilly

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Insulin glargine; Drug: LY2605541

Study type: Interventional

Funder types: Industry

Identifiers

NCT01582451

I2R-MC-BIDJ (Other Identifier)

14703

Details and patient eligibility

About

The purpose of this study is to compare LY2605541 and insulin glargine using the following measures after participants have been treated for 26 weeks:

• Change in participants' overall blood sugar control
• The rate of night time low blood sugar episodes
• The number of participants that reach blood sugar targets without low blood sugar episodes at night
• The rate of low blood sugar episodes reported over a 24-hour period

Enrollment: 466 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have had type 2 diabetes mellitus for at least 1 year
• Have been receiving basal insulin (neutral protamine Hagedorn [NPH], detemir, or glargine) and a stable dose of 0 to 3 oral antihyperglycemic medications (OAMs) used as specified in the local prescribing information for at least 90 days prior to screening. At least 1 of the OAMs must be dosed at, or above, half the maximum daily dose allowed by local regulations or at the maximally tolerated dose
• Have a hemoglobin A1c (HbA1c) less than or equal to 9.0% at screening
• Have a body mass index (BMI) less than or equal to 45.0 kilograms per square meter (kg/m^2)
• Women of childbearing potential who are not breastfeeding, have a negative pregnancy test at screening and randomization, do not plan to become pregnant during the study, and have practiced reliable birth control for at least 6 weeks prior to screening and will continue to do so during the study and until 2 weeks after the last dose of study drug

Exclusion criteria

• Have routinely used insulin glargine twice daily in the 90 days prior to the study or have used routine, mealtime insulin therapy (outside of pregnancy) anytime in the past 6 months, except for short-term treatment up to a maximum of 4 continuous weeks

• Have used rosiglitazone, pramlintide, glucagon-like peptide 1 (GLP-1) receptor agonist concurrently or within 90 days prior to screening

• For participants on OAMs: have any restrictions for cardiac, renal, and hepatic diseases in the local product regulations

• Are taking, or have taken within the 90 days preceding screening, prescription or over-the-counter medications to promote weight loss

• Have had any episodes of severe hypoglycemia within 6 months prior to screening

• Have had 1 or more episodes of diabetic ketoacidosis or hyperosmolar state/coma in the 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 or equal to 2 milligrams per deciliter (mg/dL) (177 micromoles per liter [µmol/L])

• 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

• Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the measurement of HbA1c

• Have active or untreated cancer, have been in remission from clinically significant cancer(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 in the opinion of the investigator

• Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intranasal, intraocular, and inhaled preparations) or have received such therapy within the 8 weeks immediately preceding screening

• Have fasting triglycerides greater than 400 mg/dL (4.5 millimoles per liter [mmol/L]) at screening

• Have an irregular sleep/wake cycle (for example, participants who sleep during the day and work during the night) in the investigator's opinion

• Lipid-lowering medication: Are using or have used any of the following:

  • niacin preparations as a lipid-lowering medication and/or bile acid sequestrants within 90 days prior to screening or
  • lipid-lowering medication at a dose that has not been stable for at least 90 days prior to screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

466 participants in 2 patient groups

LY2605541

Experimental group

Description:

Administered by subcutaneous (SQ) injection once daily at bedtime. Initial dose based on dose of prestudy basal insulin and adjusted based on fasting blood glucose (FBG). LY2605541 will be given alone or in combination with up to 3 pre-study oral antihyperglycemic medications (OAMs) whose use is not excluded in combination with insulin. Treatment may last up to 52 weeks.

Treatment:

Drug: LY2605541

Insulin glargine

Active Comparator group

Description:

Administered by SQ injection once daily at bedtime. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG. Insulin glargine will be used alone or in combination with up to 3 pre-study OAMs whose use is not excluded in combination with insulin. Treatment may last up to 52 weeks.

Treatment:

Drug: Insulin glargine