A Real World Trial to Determine Efficacy and Health Outcomes of Toujeo Compared to Standard of Care Basal Insulin in Patients Already Using Basal Insulin

Study Overview
=================
Brief Summary
-----------------
Primary Objective: To demonstrate noninferiority of Toujeo versus standard of care basal insulin therapy as measured by glycated hemoglobin (HbA1c) change Secondary Objectives: To demonstrate superiority of Toujeo versus standard of care basal insulin if non-inferiority criterion is met, measured by HbA1c change. To compare Toujeo to other standard of care basal insulin in terms of patient persistence with assigned basal insulin therapy with or without intensification. Risk of hypoglycemia including documented, symptomatic hypoglycemia (≤70 mg/dL) or severe (according to ADA Working Group). Change in fasting plasma glucose (FPG). Change in body weight. Differences in patient reported outcomes measured by Diabetes Treatment Satisfaction Questionnaire Status and Change versions (DTSQs and DTSQc). Change in hypoglycemic control subscale (HCS). Healthcare resource utilization including hospitalizations and emergency department or other health care provider visits and healthcare costs.

Detailed Description
-----------------
The total study duration will be up to 55 weeks, consisting of a 1 week screening period at the site, a 26 week treatment period, and a 26 week extension period.

Official Title
-----------------
A Twenty-six Week, Randomized, Open-label, 2-arm Parallel Group Real World Pragmatic Trial to Assess the Clinical and Health Outcomes Benefit of Transition to Toujeo Compared to Standard of Care Insulin in Basal Insulin Treated Patients With Uncontrolled Type 2 Diabetes Mellitus, With Six-Month Extension

Conditions
-----------------
Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: insulin glargine (U300)
* Drug: insulin glargine (U100)
* Drug: NPH insulin
* Drug: insulin detemir
* Drug: insulin degludec


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria : Patients with type 2 diabetes insufficiently controlled (HbA1c >7%) with current (≥6 months) standard of care basal insulin therapy (including insulin glargine U100, Levemir, NPH, or Tresiba) with or without oral agents (metformin, sulfonylurea, thiazolidinedione, DPP-4 inhibitor, SGLT-2 inhibitor, glinides, α glucosidase inhibitors) and with or without use of a GLP-1 receptor agonist. Fasting plasma glucose (FPG) >130 mg/dL (7.2 mmol/L). Adult patients who have signed Informed Consent Form (ICF) and privacy form(s). Exclusion criteria: HbA1c ≤7%, no upper bound. Age <18 years. Type 1 diabetes mellitus. Any clinically significant abnormality identified on physical examination, laboratory tests, or vital signs at the time of screening, or any major systemic disease resulting in short life expectancy that in the opinion of the Investigator would restrict or limit the patient's successful participation for the duration of the study. Use of any product containing short or rapid acting insulin since the time of diagnosis with type 2 diabetes mellitus other than temporary use during a pregnancy or hospitalization. Use of any product containing short or rapid acting insulin occurring within 3 months prior to the time of screening. Use of oral hypoglycemic agents other than those noted in the inclusion criteria, GLP-1 receptor agonists not approved for use with insulin, or any investigational agent (drug, biologic, device) within 3 months prior to the time of screening. All contraindications to standard of care insulin therapy or warnings/precautions of use as displayed in the respective National Product labeling for these products. Hypersensitivity to insulin glargine or Toujeo excipients. Pregnancy or lactation. Women of childbearing potential with no effective contraceptive method. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Toujeo<br>Toujeo will be administered once daily in addition to non-insulin antidiabetic agents | Drug: insulin glargine (U300)<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>* Other names: HOE901; Toujeo;|
| Active Comparator: Standard of care commercially available basal insulin<br>Lantus, Humulin Neutral Protamine Hagedorn (NPH), Levemir, and Tresiba or other basal insulin, including biosimilar insulin will be administered once or twice daily according to label in addition to non-insulin antidiabetic agents | Drug: insulin glargine (U100)<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>* Other names: HOE901; Lantus;Drug: NPH insulin<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>* Other names: Humulin NPH;Drug: insulin detemir<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>* Other names: Levemir;Drug: insulin degludec<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>* Other names: Tresiba;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (percentage %) |  | Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who remain on assigned basal insulin therapy before intensification (persistent with assigned therapy) |  | At Month 6 and Month 12 | 
| Proportion of patients who remain on assigned basal insulin therapy whether intensification occurred or not |  | At Month 6 and Month 12 | 
| Proportion of patients who achieve target HbA1c (<6.5%, <7%, <7.5%, <8.0%) |  | At Month 6 and Month 12 | 
| Proportion of patients with HbA1c target (thresholds listed above) (attainment of metabolic benefit) without documented (blood glucose (BG) ≤70 mg/dl [3.9 mmol/L]) symptomatic or severe |  | At Month 6 and Month 12 | 
| Proportion of patients with HbA1c target (thresholds listed above) (attainment of metabolic benefit) without documented (BG <54 mg/dL, [3.0 mmol/L]) symptomatic or severe hypoglycemia |  | At Month 6 and Month 12 | 
| Change in HbA1c (percentage %) |  | Baseline, Month 12 | 
| Percentage of patients whose HbA1c decreased at least 0.5% |  | At Month 6 and Month 12 | 
| Percentage of patients whose HbA1c decreased at least 0.5% |  | At Month 6 and maintained at Month 12 | 
| Percentage of patients requiring intensification |  | At Month 6 and Month 12 | 
| Time to intensification |  | At Month 6 and Month 12 | 
| Change in fasting plasma glucose |  | From baseline to Month 6 and Month 12 |