Phase 4 Study to Evaluate Treatment Optimization With Once-daily Insulin Glargine 300 U/mL

Study Overview
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Brief Summary
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Primary Objective: To evaluate the efficacy of switching treatment from twice-daily basal insulin to once-daily insulin glargine (U300) as part of basal bolus regime in terms of glycated hemoglobin improvement (reduction by at least 0.3%), in uncontrolled type 1 diabetes mellitus patients. Secondary Objectives: To evaluate other efficacy parameters in terms of glycemic control as well as safety including hypoglycemia events, weight changes, and adverse events. To evaluate the effect of insulin glargine (U300) on diabetes treatment satisfaction and fear of hypoglycemia as well as patient's satisfaction regarding the number of daily injections.

Detailed Description
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The estimated average study duration is 29 weeks, including run-in period of 4 weeks; treatment period of 24 weeks, and follow-up period of 1 week.

Official Title
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A 28-week, Prospective, Single-arm, Phase 4 Study to Evaluate Treatment Optimization With Once-daily Insulin Glargine 300 U/mL in Combination With Prandial Rapid-acting Insulin Analogue in Patients With Type 1 Diabetes Previously Uncontrolled on Twice-daily Basal Insulin as Part of Basal-bolus Therapy

Conditions
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Type I Diabetes Mellitus

Intervention / Treatment
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* Drug: INSULIN GLARGINE (U300)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Male or Female. Age ≥ 18 years. With Type 1 diabetes mellitus. Being treated twice-daily with any basal insulin in combination with prandial rapid-acting insulin analogue for at least one year. Have an glycated hemoglobin (HbA1c) measurement of 7.5% - 10.0% at study entry. Patients who have signed an Informed Consent Form. Exclusion criteria: Type 2 diabetes mellitus. Known hypoglycemia unawareness Repeated episodes of severe hypoglycemia or diabetes ketoacidosis within the last 12 months. End-stage renal failure or being on hemodialysis. Any clinically significant abnormality identified on physical examination, laboratory tests, or vital signs at the time of screening or baseline, 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. Known hypersensitivity / intolerance to insulin glargine or any of its excipients. Patients treated with glucagon like peptide agonists. Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 90 days prior to the time of screening. Pregnant or lactating women. Women of childbearing potential with no effective contraceptive method. Participation in another clinical trial. 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
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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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin glargine (U300)<br>Self-administered subcutaneously once daily in the morning, at the same time.The initial dose for patients switching from insulin glargine is 80% of the total daily dose of basal insulin agent that was discontinued. Thereafter, insulin glargine (U300) will follow a titration algorithm for dose adjustment. | Drug: INSULIN GLARGINE (U300)<br>* Pharmaceutical form: Solution for Injection Route of administration: Subcutaneous injection<br>* Other names: Toujeo, HOE901;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in HbA1c | Mean change in glycated hemoglobin (HbA1c) from baseline to Week 24 (%) | From baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in HbA1c | Mean HbA1c change from baseline to Week 12 | From baseline to Week 12 | 
| Mean change in fasting plasma glucose (FPG) | Mean change in FPG from baseline to Week 12 and Week 24 | From baseline to Week 12 and Week 24 | 
| Mean change in fasting SMBG | Mean change in fasting self-monitored blood glucose (SMBG) from baseline to Week 12 and Week 24 | From baseline to Week 12 and Week 24 | 
| Mean change in 8-point SMBG | Mean change in 8-point SMBG from baseline to Week 12 and Week 24 | From baseline to Week 12 and Week 24 | 
| Proportion of patients achieving HbA1c target of <7.0% | Proportion of patients achieving HbA1c target of <7.0% at Week 12 and Week 24 | At Weeks 12 and 24 | 
| Proportion of patients achieving HbA1c target of <7.0% without hypoglycemia event | Proportion of patients achieving HbA1c target of <7.0% without hypoglycemia event during the last 4 weeks of treatment | At Weeks 12 and 24 | 
| Proportion of patients achieving HbA1c improvement of at least 0.3% without nocturnal hypoglycemia | Proportion of patients achieving HbA1c improvement from baseline to week 24 of at least 0.3% without nocturnal hypoglycemia (documented <70 mg/dL) and/or severe hypoglycemia (between 00.00 and 05:59 am SMBG) during the last 4 weeks of treatment | From baseline to Week 24 | 
| Proportion of patients with any improvement in HbA1c | Proportion of patients with any improvement in HbA1c from baseline to week 24 and decrease in occurrence of nocturnal hypoglycemia (nocturnal defined as time between 00.00 and 05:59 am) evaluated from baseline to Week 24 | From baseline to Week 24 | 
| Proportion of patients with no deterioration in HbA1c | Proportion of patients with no deterioration in HbA1c from baseline to week 24 and decrease in occurrence of nocturnal hypoglycemia | From baseline to Week 24 | 
| Proportion of patients with no deterioration in HbA1c | Proportion of patients with no deterioration in HbA1c from baseline to week 24 and no increase in occurrence of nocturnal hypoglycemia | From baseline to Week 24 | 
| Adverse events (AEs) | Number of adverse events and serious adverse events | Up to 28 weeks | 
| Mean change in body weight | Mean change in body weight from baseline to Weeks 12 and 24 | From baseline to Week 12 and Week 24 | 
| Mean change in daily insulin doses | Insulin glargine (U300) dose: Mean change in daily insulin doses (basal, prandial, total) from baseline to Week 24 | From baseline to Week 24 | 
| Number of patients experiencing hypoglycemia |  | Up to 28 weeks | 
| Proportion of patients experiencing hypoglycemia |  | Up to 28 weeks | 
| Number of hypoglycemic events per patient-year |  | Up to 28 weeks |