The Impact of LY2189265 Versus Metformin on Glycemic Control in Early Type 2 Diabetes Mellitus (AWARD-3: Assessment of Weekly AdministRation of LY2189265 in Diabetes-3)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 807
- 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 determine if LY2189265 is safe and effective in reducing glycosylated hemoglobin (HbA1c) as compared to metformin in participants with Type 2 Diabetes.
Detailed Description
The term rescue therapy in this trial was defined primarily as additional nontrial antidiabetic medication for the management of severe, persistent hyperglycemia or alternative antidiabetic medication following study drug discontinuation. 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 outcomes, 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Have type 2 diabetes for greater than or equal to 3 months and less than or equal to 5 years based on the disease diagnostic criteria (refer to the World Health Organization's [WHO] Classification of Diabetes).
- •Are treatment-naïve, not optimally controlled with diet and exercise alone, or are taking 1 oral antihyperglycemic medication (OAM) as monotherapy (excluding thiazolidinediones). For those on 1 OAM, the dose must be less than or equal to 50% the maximum authorized per local label.
- •Are able and willing to tolerate a minimum dose of 1500 milligrams per day (mg/day) or up to 2000 mg/day of metformin.
- •Have glycosylated hemoglobin (HbA1c) greater than or equal to 6.5% to less than or equal to 9.5%.
- •Females of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopausal) must: a) test negative for pregnancy at screening based on a serum pregnancy test, and b) agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug; or c) not be breastfeeding.
- •Have a stable weight (plus or minus 5%) greater than or equal to 3 months prior to screening.
- •Have a body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m^2), inclusive.
- •Are well-motivated, capable, and willing to: a) perform self-monitored blood glucose (SMBG) testing; b) learn how to self-inject treatment (LY2189265 or placebo) and c) maintain a study diary.
Exclusion Criteria
- •Have type 1 diabetes mellitus.
- •Are being or have been treated with any of the following medications: a) chronically treated with insulin for the treatment of diabetes in the past; however, a short-term use of insulin more than 3 months prior to screening is allowable, b) glucagon-like peptide 1 (GLP-1) analogs within 3 months prior to this screening, c) drugs to cause weight loss within 3 months prior to screening, d) thiazolidinediones (TZDs) within 3 months prior to screening, e) chronically treated (greater than or equal to 14 days) with an oral glucocorticoid or have received this type of therapy within 4 weeks prior to screening, or f) illegal drugs.
- •Have had 1 or more cases of uncontrolled diabetes that required hospitalization in the 6 months prior to screening.
- •Have stomach problems, have chronically taken medication to increase movement in the digestive tract or slow down the emptying of the digestive tract, or have had gastric bypass (bariatric) surgery.
- •Have had problems with the heart or brain in the past 2 months prior to screening, such as a heart attack, chest pain, heart failure, heart bypass operation, angioplasty or stent insertion, a heart rhythm problem, or a stroke.
- •Have a serum creatinine result which shows a greater than or equal to 1.5 milligrams per deciliter (mg/dL) for men or greater than or equal to 1.4 mg/dL for women.
- •Have a problem with the liver or pancreas.
- •Have a creatinine clearance result which shows less than 60 milliliters per minute (mL/min), evidence of a significant active, uncontrolled endocrine (hormone), or active autoimmune abnormality.
- •Have a serum calcitonin test which shows greater than or equal to 20 picograms per milliliter (pcg/mL) at the time of screening.
- •Have a family history of medullary C-cell hyperplasia or endocrine neoplasia type 2A or type 2B.
- •Have cancer (except for skin cancer) or have been in remission from cancer for less than 5 years.
- •Have had an organ transplant except for corneal transplant.
- •Have received treatment within the last 30 days with a drug which has not been regulatory approved.
- •Have participated in a medical, surgical, or pharmaceutical study where these types of procedures were performed within 30 days prior to screening.
- •Have any condition that is a contraindication to or would interfere with medications provided for this study to treat diabetes.
- •Have a blood disorder that would interfere with the drawing of blood glucose measurements or lab samples.
- •Have previously participated or signed an informed consent document for this same type of study and study drug.
Arms & Interventions
1.5 mg LY2189265
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: 1 tablet per day, orally, for Week 1; 2 tablets per day, orally, for Week 2; 3 tablets per day, orally, for Week 3; 4 or at least 3 tablets, orally, for Weeks 4 through Week 52
Intervention: LY2189265 (Drug)
1.5 mg LY2189265
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: 1 tablet per day, orally, for Week 1; 2 tablets per day, orally, for Week 2; 3 tablets per day, orally, for Week 3; 4 or at least 3 tablets, orally, for Weeks 4 through Week 52
Intervention: Placebo (oral) (Drug)
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: 1 tablet per day, orally, for Week 1; 2 tablets per day, orally, for Week 2; 3 tablets per day, orally, for Week 3; 4 or at least 3 tablets, orally, for Weeks 4 through Week 52
Intervention: LY2189265 (Drug)
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: 1 tablet per day, orally, for Week 1; 2 tablets per day, orally, for Week 2; 3 tablets per day, orally, for Week 3; 4 or at least 3 tablets, orally, for Weeks 4 through Week 52
Intervention: Placebo (oral) (Drug)
Metformin
Metformin: 500 milligrams per day (mg/day), orally, for Week 1; 1000 mg/day, orally, for Week 2; 1500 mg/day, orally, for Week 3; 2000 or at least 1500 mg/day, orally, for Weeks 4 through Week 52
Placebo: subcutaneously (SC), once weekly for 52 weeks
Intervention: Metformin (Drug)
Metformin
Metformin: 500 milligrams per day (mg/day), orally, for Week 1; 1000 mg/day, orally, for Week 2; 1500 mg/day, orally, for Week 3; 2000 or at least 1500 mg/day, orally, for Weeks 4 through Week 52
Placebo: subcutaneously (SC), once weekly for 52 weeks
Intervention: Placebo (subcutaneous) (Drug)
Outcomes
Primary Outcomes
Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c)
Time Frame: Baseline, 26 weeks
Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group (previous oral antihyperglycemic medication \[OAM\] versus no previous OAM) as fixed effects and baseline HbA1c as a covariate.
Secondary Outcomes
- Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI)(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c)(Baseline, 52 weeks)
- Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose(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) Score(Baseline, 26 weeks, and 52 weeks)
- Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks(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 Homeostasis Model Assessment of Beta-cell Function(Baseline, 26 weeks, and 52 weeks)
- Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Change Version(52 weeks)
- Number of Participants With Treatment Emergent Adverse Events at 26 and 52 Weeks(26 weeks and 52 weeks)
- Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol(Baseline, 26 weeks, and 52 weeks)
- Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C)(Baseline, 26 weeks, and 52 weeks)
- Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C)(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in Serum Calcitonin(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in Pulse Rate(Baseline, 26 weeks, and 52 weeks)
- Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides(Baseline, 26 weeks, and 52 weeks)
- Number of Participants With Treatment Emergent Anti-LY2189265 Antibodies(Baseline through 52 weeks)
- Number of Participants With Adjudicated Pancreatitis at 52 Weeks Plus 30-day Follow up(Baseline through 52 weeks plus 30-day follow up)
- Change From Baseline to 26 and 52 Weeks in Blood Pressure(Baseline, 26 weeks, and 52 weeks)
- Measurement of LY2189265 Drug Concentration for Pharmacokinetics: Area Under the Concentration Curve (AUC)(4 weeks, 13 weeks, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score(Baseline, 26 weeks, and 52 weeks)
- Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status Version(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)
- Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes(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)
- Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up(Baseline through 52 weeks plus 30-day follow up)
- Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks(Baseline through 26 weeks and 52 weeks)
- Rate of Self-reported Hypoglycemic Events at 52 Weeks(Baseline through 52 weeks)