A Study of LY2963016 Compared to Lantus® in Adult Chinese Participants With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of this study is to compare long-acting basal insulin analog LY2963016 to Lantus® in insulin naïve adult Chinese participants with Type 2 Diabetes Mellitus (T2DM) on 2 or more oral antihyperglycemic medications (OAMs). Participants will continue their OAMs throughout the study.

Official Title
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A Prospective, Randomized, Open-Label Comparison of a Long-Acting Basal Insulin Analog LY2963016 to Lantus® in Adult Chinese Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have T2DM based on the disease diagnostic criteria World Health Organization (WHO) classification. Have been receiving 2 or more OAMs at stable doses for the 12 weeks prior to screening. Have a HbA1c ≥7.0% and ≤11.0%. Body mass index (BMI) ≤35 kilograms per meter squared. Exclusion Criteria: Have used insulin therapy (outside of pregnancy) anytime in the past 1 year, except for short-term treatment of acute conditions, and up to a maximum of 4 continuous weeks. Have used any glucagon like peptide (GLP-1) receptor agonists within the previous 90 days. Are currently taking traditional medicine (herbal medicine or patent medicine) with known/specified content of anti-hyperglycemic effects within 3 months before screening. Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study. Have had ≥2 emergency room visits or hospitalizations due to poor glucose control. Have known hypersensitivity or allergy to Lantus® or its excipients. Are receiving chronic systemic glucocorticoid therapy at pharmacological doses or have received such therapy within 4 weeks immediately preceding screening. Have obvious signs or symptoms, or laboratory evidence, of liver disease. Have one of the following concomitant diseases: significant cardiac or gastrointestinal disease. Have a history of renal transplantation, are currently receiving renal dialysis or have a serum creatinine greater than 2.0 milligrams per deciliter. 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. Participants with active cancer or personal history of cancer within the previous 5 years. Are pregnant or intend to become pregnant during the course of the study. Are women who are breastfeeding.

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<br>Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the fasting blood glucose (FBG) ≤100 milligram per deciliter (mg/dL) (5.6 millimoles per litre [mmol/L]) while avoiding hypoglycemia. Participants were allowed to continue oral antihyperglycemic medication (OAM). | Drug: LY2963016<br>* Administered SC<br>|
| Active Comparator: Lantus®<br>Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. | Drug: Lantus®<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 to Lantus®) | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least square (LS) mean was calculated by mixed-effects model for repeated measures (MMRM) with baseline, insulin secretagogues at study entry, treatment, visit and treatment*visit in the model. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (Lantus® to LY2963016) | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, treatment, visit and treatment*visit in the model. | Baseline, Week 24 | 
| Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | Seven-point SMBG are completed at the following timepoints: Before Morning Meal, 2 Hours After Morning Meal, Before Mid-Day Meal, 2 Hours After Mid-Day Meal, Before Evening Meal, 2 Hours After Evening Meal and Bed Time. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model. | Baseline, Week 24 | 
| Percentage of Participants With HbA1c <7% at Week 24 | The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. | Week 24 | 
| Percentage of Participants With HbA1c ≤6.5% at Week 24 | The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. | Week 24 | 
| Change From Baseline in 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 and daily pre-meal blood glucose value from the 7-point self-monitoring blood glucose [SMBG] profiles. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model. | Baseline, Week 24 | 
| Basal Insulin Dose Units Per Day | Units of basal insulin dose taken per day (U/day). LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model. | At Week 24 | 
| Change From Baseline in Basal Insulin Dose Units Per Day | Units of basal insulin dose taken per day (U/day). LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model. | Baseline, Week 24 | 
| Change From Baseline in Body Weight | Change from baseline in body weight was evaluated. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model. | Baseline, Week 24 | 
| 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. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model. | At Week 24 | 
| Number of Participants With Detectable Anti-Glargine Antibodies | Number of participants with detectable anti-glargine antibodies were reported. | Baseline through 24 weeks | 
| Rate of Total Symptomatic and Nocturnal Hypoglycemia Events (Adjusted by 1 Year) | Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 mmol/L). The overall yearly rates (events/participant/year) of those hypoglycemic events, calculated as, for each participant, the number of episodes times 365.25 and then divided by the participants treatment duration, will be summarized, and analyzed by a negative-binomial regression model with treatment as fixed effects and log of (participant's treatment duration/365.25) as an offset variable. A nocturnal hypoglycemic event is defined as any total hypoglycemia event that occurred between bedtime and waking. | Baseline through 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin glargine