A Study in Adults With Type 1 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness and safety of LY2963016 versus Lantus when taken once daily in combination with insulin lispro before meals three times a day.

Official Title
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A Prospective, Randomized, Open-label Comparison of a Long-Acting Basal Insulin Analog LY2963016 to Lantus in Combination With Mealtime Insulin Lispro in Adult Patients With Type 1 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: LY2963016
* Drug: Lantus
* Drug: Insulin Lispro


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have type 1 diabetes mellitus based on the disease diagnostic criteria [World Health Organization (WHO) Classification] Have duration of diabetes greater than or equal to one year Have Hemoglobin A1c (HbA1c) less than or equal to 11.0% On basal-bolus insulin therapy for at least 1 year [basal insulin must be once daily (QD) injection of human insulin isophane suspension (NPH), Lantus, or detemir and combined with mealtime injections of human regular insulin, or insulin analog lispro, aspart or glulisine] Have a body mass index (BMI) of less than or equal to 35 kilograms/square meter (kg/m²) Exclusion Criteria: 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 had more than one episode of diabetic ketoacidosis or emergency room visits for uncontrolled diabetes leading to hospitalization within the 6 months before entering the study Have known hypersensitivity or allergy to any of the study insulins (insulin glargine or insulin lispro) or to excipients of the study insulins Have significant renal, cardiac, gastrointestinal or liver disease Have active cancer or cancer within the past 5 years

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2963016 + Insulin Lispro<br>LY2963016 titrated based on blood glucose readings, administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro. Insulin lispro titrated based on blood glucose readings, administered subcutaneously, three times a day for 52 weeks. | Drug: LY2963016<br>* Administered subcutaneously<br>Drug: Insulin Lispro<br>* Administered subcutaneously<br>|
| Active Comparator: Lantus + Insulin Lispro<br>Lantus titrated based on blood glucose readings, administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro. Insulin lispro titrated based on blood glucose readings, administered subcutaneously, three times a day for 52 weeks. | Drug: Lantus<br>* Administered subcutaneously<br>Drug: Insulin Lispro<br>* Administered subcutaneously<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 which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline HbA1c, treatment and time of basal insulin injection (daytime, evening/bedtime) and country. | 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 was measured to determine the insulin antibody levels. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country. | Baseline, 6 weeks and 12 weeks and Endpoints (up to 24 weeks and up to 52 weeks) | 
| Change From Baseline in Hemoglobin A1c (HbA1c) | HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline HbA1c, treatment and time of basal insulin injection (daytime, evening/bedtime) and country. | Baseline, 6 weeks and 12 weeks and 24 weeks and 36 weeks and 52 weeks and Endpoint (up to 52 weeks) | 
| 7-Point Self-Monitored Blood Glucose (SMBG) Profiles | 7-point SMBG measurements are completed at the following timepoints: Morning (AM) Pre-Meal, AM Post-Prandial (PP), Midday (MD) Pre-Meal, MD PP, Evening (EV) Pre-Meal, Bed Time and 0300 hours. PP glucose is measured 2 hours (hrs) after the start of the meal. Values for the 7-point SMBG profiles were averaged over the three 7-point SMBG profiles during 2-week period prior to each visit. If only 1 of the 3 days of data was collected, then the value of the 1 day was used. If only 2 of the 3 days of data were collected, then the average of the 2 days was used. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country. | Baseline and Endpoints [up to 24 weeks (wk) and up to 52 weeks] | 
| Glycemic Variability of Fasting Blood Glucose | Glycemic variability is the intra-participant standard deviation (SD) value of fasting blood glucose as measured by the actual morning premeal blood glucose value from the 7-point self-monitoring blood glucose (SMBG) profiles. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country. | Baseline and Endpoints (up to 24 weeks and up 52 weeks) | 
| Change From Baseline in Body Weight | Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country. | Baseline, 6 weeks and 12 weeks and 18 weeks and Endpoints (up to 24 weeks and up to 52 weeks) | 
| 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 (TS) range is 0 to 60 and Worry TS 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. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country. | Baseline and 24 weeks and Endpoint (up to 52 weeks) | 
| 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 measured on a 7-point scale: 1 (no bother at all) to 7 (a tremendous bother), with lower scores reflecting better outcomes. Items divided into 5 domains: Inconvenience of Regimen [(IR) 5 items: scores range 5-35], Lifestyle Flexibility [(LF) 3 items: scores range 3-21], Glycemic Control [(GC) 3 items: scores range 3-21], Hypoglycemic Control [(HC) 5 items: scores range 5-35], Insulin Delivery Device [(IDD) 6 items: scores range 6-42]. ITSQ Total Overall Scores range from 22-154. Data presented are the transformed score on a scale of 0-100, where transformed score=100×[(7-raw score)/6]. Higher scores indicate better treatment satisfaction. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country. | Baseline and 24 weeks and Endpoint (up to 52 weeks) | 
| Insulin Dose Per Body Weight (U/kg) (Total and by Component [Basal and Bolus (Lispro)]) | Total daily insulin dose was adjusted for body weight [units of insulin/kilogram/day (U/kg/day)]. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country. | Endpoints [up to 24 weeks (wk) and up to 52 weeks] | 
| Insulin Dose - Units [Total and by Component [Basal and Bolus (Lispro)]) | Units of insulin taken daily were presented. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country. | Endpoints [up to 24 weeks (wk) and up to 52 weeks] | 
| Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5% | HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. The percentage of participants with Hemoglobin A1c (HbA1c) <7.0% or HbA1c ≤6.5% is calculated as the number of participants with an HbA1c level of the cut-off value (<7.0% or ≤6.5%) divided by the number of participants treated, then multiplied by 100. | Baseline and 6 weeks and 12 weeks and 24 weeks and 36 weeks and 52 weeks and Endpoints (up to 24 weeks and up to 52 weeks) | 
| Incidence of Hypoglycemic Events | Incidence of hypoglycemic events is defined as the number 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 a blood glucose (BG) concentration of ≤ 70 milligrams/deciliter [mg/dL (3.9 millimoles/liter (mmol/L)], even if it was not associated with signs, symptoms, or treatment consistent with current guidelines [American Diabetes Association (ADA) 2005]. 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 through 24 weeks (wk) and 52 weeks | 
| Rate Per 30 Days of Hypoglycemic Events | The rate of hypoglycemic events per 30 days is defined as the total number of events between visits divided by the actual number of days between visits, and then multiplied by 30 days. 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 (3.9 millimoles/liter (mmol/L)], even if it was not associated with signs, symptoms, or treatment consistent with current guidelines (ADA 2005). 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 through 24 weeks (wk) and 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Type 1 Diabetes, Diabetes Mellitus