A Study in Adults With Type 2 Diabetes

Study Overview
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Brief Summary
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The main purpose of this study is to compare the effectiveness and safety of LY2963016 versus Lantus in controlling blood sugar levels in combination with two or more oral diabetes medications.

Official Title
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A Prospective, Randomized, Double-Blind Comparison of a Long-Acting Basal Insulin Analog LY2963016 to Lantus in Adult Patients With Type 2 Diabetes Mellitus: The ELEMENT 2 Study

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: LY2963016
* Drug: Lantus
* Drug: OAMs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have Type 2 Diabetes Mellitus based on the disease diagnostic criteria World Health Organization (WHO) classification Have been taking at least 2 types of oral diabetes medications for at least 12 weeks prior to entering the study Have a Hemoglobin A1c value greater than or equal to 7.0 percent and less than or equal to 11.0 percent if insulin naive If previously on Lantus, then Hemoglobin A1c must be less than or equal to 11.0 percent Have a body mass index of less than or equal to 45 kilogram per meter squared (kg/m^2) Exclusion Criteria: Have significant liver, cardiac or gastrointestinal disease Have active cancer or have had cancer within the past 5 years (with the exception of basal cell carcinoma or carcinoma in situ) Have an excessive resistance to insulin or hypersensitivity to Lantus Have had more than one episode of severe low blood sugar (defined as needing someone else to help because you had very low blood sugar) within the 6 months before entering the study Have taken any other insulin other than Lantus within the past 30 days Taking any other diabetes medicines that are not allowed in the study or not approved to be taken with insulin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2963016 + OAMs<br>LY2963016 titrated based on blood glucose readings, administered subcutaneously, once daily in combination with at least 2 oral antihyperglycemic medications (OAMs) [alpha glucosidase inhibitors (AGI), dipeptidyl peptidases intravenous (DPP-IV), meglitinide (MEG), metformin (MET), sulfonylurea (SU), and thiazolidinedione (TZD)] administered per standard of care for 24 weeks | Drug: LY2963016<br>* Administered subcutaneously<br>Drug: OAMs<br>* Administered orally<br>|
| Active Comparator: Lantus + OAMs<br>Lantus titrated based on blood glucose readings, administered subcutaneously, once daily in combination with at least 2 OAMs (AGI, DPP-IV, MEG, MET, SU, and TZD) administered per standard of care for 24 weeks | Drug: Lantus<br>* Administered subcutaneously<br>Drug: OAMs<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline up to 24 Weeks in Hemoglobin A1c (HbA1c) | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection and treatment. | Baseline, Endpoint (up to 24 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Insulin Antibody Levels | Blood samples are collected from participants and percentage of insulin antibody binding measured. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline of response and treatment. | Baseline and 4 weeks and 12 weeks and Endpoint (24 weeks and up to 24 weeks) | 
| Change From Baseline in Hemoglobin A1c (HbA1c) | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection and treatment. | Baseline and 4 weeks and 8 weeks and 12 weeks and 16 weeks and 20 weeks and 24 weeks | 
| 7-Point Self-Monitored Blood Glucose (SMBG) Profiles | Seven-point SMBG are completed at the following timepoints: Morning (AM) Pre-Meal, Morning (AM) Post-Prandial (PP), Midday (MD) Pre-Meal, Midday PP, Evening (EV) Pre-Meal, Bed Time and 0300 hours. PP glucose is measured 2 hours (hrs) after the start of the meal. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment. | Baseline and Endpoint [up to 24 weeks (wk)] | 
| Glycemic Variability of Fasting Blood Glucose | Glycemic variability is measured by the intra-participant standard deviation (SD) value of fasting blood glucose as measured by the actual morning pre-meal blood glucose value from the 7-point self-monitoring blood glucose [SMBG] profiles. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment. | Baseline and Endpoint (up to 24 weeks) | 
| Change From Baseline in Body Weight | Change from baseline in body weight. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment. | Baseline and 4 weeks (wk) and 8 wk and 12 wk and 16 wk and 20 wk and 24 wk and Endpoint (up to 24 wk) | 
| Adult Low Blood Sugar Survey (ALBSS) | ALBSS contains 33 items, with each item scored on a 5-point response scale: 0 (never) to 4 (almost always). Items are categorized in 2 domains: Behavior (or avoidance) Items 1 to 15 and Worry (or affect) Items 16 to 33. Behavior Total Score range is 0 to 60 and Worry Total Score range is 0 to 72. Higher scores on Behavior items (related to avoidance of hypoglycemia) reflect greater awareness and/or effort of the participant to prevent low blood sugar. Higher scores on Worry items (related to worries about low blood sugar and its consequences) reflect greater participant concern about having low blood sugar. The ALBSS Total Scores (Worry and Behavior item scores combined) range is 0 to 132. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment. | 4 weeks (wk) and 12 wk and Endpoint (up to 24 wk) | 
| Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. Items divided into 5 domains of satisfaction: Inconvenience of Regimen [(IR) 5 items: domain scores range (DSR) 5-35], Lifestyle Flexibility [(LF) 3 items: DSR 3-21], Glycemic Control [(GC) 3 items: DSR 3-21], Hypoglycemic Control [(HC) 5 items: DSR 5-35], Insulin Delivery Device [(IDD) 6 items: DSR 6-42]. All items measured on a 7-point scale: 1 (no bother at all) to 7 (a tremendous bother), with lower scores reflecting better outcomes. ITSQ Total Overall Raw Scores range from 22-154. Both raw domain and overall scores are transformed on a scale of 0-100, where transformed score=100*[(7-mean raw score)/6]. Higher scores indicate better treatment satisfaction. Least Squares (LS) mean are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment. | 4 weeks (wk) and 12 wk and Endpoint (EP) (up to 24 wk) | 
| Insulin Dose Per Body Weight (U/kg) Per Day | Insulin dose in units (U) per body weight in kilograms (kg) per day. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment. | Endpoint (up to 24 weeks) | 
| Insulin Dose (Units) | Units of insulin taken daily. Least Square (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1C, country, sulfonylurea use, time of basal insulin injection and treatment. | Endpoint (up to 24 weeks) | 
| Percentage of Participants With HbA1c <7 % and HbA1c ≤6.5% | Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. | Baseline and 4 weeks and 8 weeks and 12 weeks and 16 weeks and 20 weeks and 24 weeks and Endpoint (up to 24 weeks) | 
| Incidence of Hypoglycemic Events | A hypoglycemic event is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose (BG) concentration of ≤70 milligrams/deciliter (mg/dL) even if it was not associated with signs, symptoms, or treatment consistent with current American Diabetes Association (ADA: 2005) guidelines. Severe hypoglycemia is defined as a hypoglycemic event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions (these episodes may be associated with sufficient neuroglycopenia to induce seizure or coma; also, BG measurements may not be available during such an event). Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking. | Baseline and Endpoint (up to 24 weeks) | 
| Rate Per 30 Days of Hypoglycemic Events | The rate of hypoglycemic events per 30 days between two visits is defined as the total number of events between the visits divided by the actual number of days between the visits, and then multiplied by 30 days. A hypoglycemic event is defined as any time a participant has a blood glucose (BG) level of ≤70 milligrams per deciliter (mg/dL) even if the event was not associated with signs, symptoms, or treatment consistent with current guidelines (American Diabetes Association 2005). Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking. Severe hypoglycemia is defined as a hypoglycemic event requiring assistance of another person to actively administer carbohydrates, glucagons, or other resuscitative actions. Severe Hypoglycemic events may or may not have a reported BG ≤70 mg/dL. These events may be associated with sufficient neuroglycopenia to induce seizure or coma. | Baseline, Endpoint (up to 24 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Type 2 Diabetes