The Impact of LY2189265 Versus Insulin Glargine in Combination With Insulin Lispro for the Treatment to Target of Type 2 Diabetes Mellitus (AWARD-4: Assessment of Weekly AdministRation of LY2189265 in Diabetes - 4)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 884
- Locations
- 1
- Primary Endpoint
- Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c)
Study Overview
Brief Summary
The purpose of this study is to assess the efficacy and safety of LY2189265 in comparison to Insulin Glargine, both in combination with Insulin Lispro (plus or minus Metformin), in participants with Type 2 Diabetes treated with 1 or 2 injections of insulin.
Detailed Description
The term rescue therapy in this trial was defined as therapy for participants who met criteria for persistent severe hyperglycemia and therapy for participants who required new intervention for any other reason. The latter included participants who discontinued study drug due to adverse events, participant decision, or any other reason. For efficacy analyses, participants who received rescue medication were included in the analysis population, but only measurements obtained prior to taking rescue therapy were included in the efficacy analysis. For safety analyses, with the exception of hypoglycemia, all measurements including those obtained after taking rescue therapy were included in the analysis.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Type 2 diabetes
- •Currently using insulin for at least 3 months with a conventional insulin regimen with or without oral medications
- •Glycosylated hemoglobin (HbA1c) greater than or equal to 7% and less than or equal to 11%
- •Willing to inject subcutaneous medication
- •Willing to monitor blood glucose levels and adjust insulin dose
- •Willing to maintain a study diary
- •Body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m^2)
- •Stable weight for 3 months prior to screening
- •Females of child bearing potential must test negative for pregnancy at screening and be willing to use a reliable method of birth control during the study and for 1 month following the last dose of study drug
Exclusion Criteria
- •Type 1 Diabetes
- •Previous therapy with glucagon-like peptide 1 (GLP-1) agonists within 3 months prior to screening
- •1 or more episodes of ketoacidosis within 6 months prior to screening
- •Have been treated with prescription or over the counter medication to promote weight loss within 3 months prior to screening
- •Estimated glomerular filtration rate (eGFR) less than or equal to 30 milliliters per minute per 1.73 square meters (mL/min/1.73 m^2) at screening
- •Taking steroids for greater than 14 days except for topical, eye, nasal, or inhaled
- •History of heart failure, New York Heart Classification III or IV within 2 months prior to screening
- •Gastrointestinal (GI) problems such as diabetic gastroparesis or bariatric surgery (stomach stapling) or chronically taking medications that directly affect GI motility
- •Acute or chronic hepatitis or pancreatitis
- •Self or family history of 2A or type 2B multiple endocrine neoplasia or medullary C-Cell hyperplasia
- •Serum calcitonin greater than or equal to 20 picograms per milliliter (pcg/mL) at screening
- •Organ transplant except cornea
- •Significant active autoimmune disease such as Lupus or Rheumatoid Arthritis
- •History of or active malignancy except skin or in situ cervical or prostate cancer within the last 5 years
- •Known drug or alcohol abuse
- •Have enrolled in another clinical trial within the last 30 days
- •Have previously signed an informed consent or participated in a LY2189265 study
Arms & Interventions
1.5 mg LY2189265
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Intervention: LY2189265 (Drug)
1.5 mg LY2189265
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Intervention: Insulin Lispro (Drug)
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Intervention: LY2189265 (Drug)
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Intervention: Insulin Lispro (Drug)
Insulin Glargine
Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks
Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Intervention: Insulin Glargine (Drug)
Insulin Glargine
Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks
Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Intervention: Insulin Lispro (Drug)
Outcomes
Primary Outcomes
Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c)
Time Frame: Baseline, 26 weeks
Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, baseline metformin, and baseline HbA1c.
Secondary Outcomes
- Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose(Baseline and 52 weeks and 4 weeks after last dose)
- Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI)(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in the EQ-5D(Baseline, 26 weeks, and 52 weeks)
- Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose(Baseline and 52 weeks and 4 weeks after last dose)
- Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c)(Baseline, 52 weeks)
- Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52(26 weeks and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in the Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% Without Nocturnal or Severe Hypoglycemia(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate(Baseline, 26 weeks, and 52 weeks)
- Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks(Baseline through 52 weeks)
- Number of Participants With Treatment Emergent LY2189265 Antibodies up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose(Baseline through 4 weeks after last dose)
- Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose(Baseline through 26 weeks, 52 weeks, and 4 weeks after last dose)
- Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose(Baseline through 52 weeks)
- Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose(Baseline through 26 weeks and 52 weeks)
- Rate of Self-reported Hypoglycemic Events up to 52 Weeks(Baseline through 52 weeks)
- Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in Fasting Serum Glucose(Baseline, 26 weeks, and 52 weeks)
- Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine)(Baseline and 26 weeks and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in Body Weight(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL)(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP)(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in the Low Blood Sugar Survey (LBSS)(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes(Baseline, 26 weeks, and 52 weeks)
- Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose(Baseline and 52 weeks and 4 weeks after last dose)
- Change From Baseline to 26 and 52 Weeks in Serum Calcitonin(Baseline, 26 weeks, and 52 weeks)
- Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose(Baseline and 52 weeks and 4 weeks after last dose)
- Change From Baseline to 26 and 52 Weeks in Blood Pressure(Baseline, 26 weeks, and 52 weeks)
- Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose(Baseline and 52 weeks and 4 weeks after last dose)
- Change From Baseline to 26 and 52 Weeks in Pulse Rate(Baseline, 26 weeks, and 52 weeks)