Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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Primary Objective: To compare the efficacy of a new formulation of insulin glargine and Lantus (overall, regardless the injection time) in terms of change of HbA1c from baseline to endpoint (scheduled Month 6) in participants with type 1 diabetes mellitus Secondary Objective: To compare HOE901-U300 and Lantus when given in the morning or in the evening in terms of: Change of HbA1c from baseline to endpoint (scheduled Month 6) Change from baseline to endpoint (Month 6) in fasting plasma glucose (FPG), plasma glucose prior to injection of study drug, plasma glucose at 03:00 hours, mean plasma glucose (8-point profiles), glucose variability, treatment satisfaction and health related quality of life in participants with Type 1 Diabetes Mellitus (T1DM) Reaching target HbA1c values and controlled plasma glucose (all and reaching target without hypoglycemia) Frequency of occurrence and diurnal distribution of hypoglycemia by category of hypoglycemia (symptomatic, asymptomatic, nocturnal, severe, probable and relative) Safety and tolerability of HOE901-U300 including development of anti-insulin antibody (AIAs) during the 12-month study period

Detailed Description
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The maximum study duration was up to approximately 54 weeks per participants: Up to 2-week screening period 6-month open-label comparative efficacy and safety treatment period 6-month open-label comparative safety extension period 48-hour post-treatment safety follow-up period

Official Title
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A 6-Month, Multicenter, Randomized, Open-label, Parallel-group Study Comparing the Efficacy and Safety of a New Formulation of Insulin Glargine and Lantus® Injected in the Morning or Evening in Patients With Type 1 Diabetes Mellitus With a 6-month Safety Extension Period

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: HOE901-U300 (Insulin glargine new formulation)
* Drug: Lantus (Insulin glargine)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Adult participants with type 1 diabetes mellitus Exclusion criteria: HbA1c less than (<) 7.0% (53 mmol/mol) or greater than (>) 10% (86 mmol/mol) at screening Less than 1 year on any basal plus mealtime insulin and self-monitoring of blood glucose before screening visit Participants not on stable insulin dose (+/-20 percent total basal insulin dose) in the last 30 days prior to screening visit Participants using pre-mix insulins, human regular insulin as mealtime insulin and/or any glucose-lowering drugs other than basal insulin and mealtime analogue insulin in the last 3 months before screening visit Use of an insulin pump in the last 6 months before screening visit and no plan to switch to insulin pump in the next 12 months Not willing to inject insulin glargine as assigned by the randomization process once daily in the morning or evening; Severe hypoglycemia resulting in coma/seizures, and/or hospitalization for diabetic ketoacidosis in the last 6 months before screening visit Unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to require treatment (example laser, surgical treatment or injectable drugs) during the study period The above information is not intended to contain all considerations relevant to a participant'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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HOE901-U300<br>HOE901-U300 (new insulin glargine 300 units per milliliter [U/mL]) subcutaneous (SC) injection once daily in morning or evening for 12 months on top of mealtime insulin analogue. Dose titration seeking fasting plasma glucose 4.4-5.6 millimole per liter (mmol/L) (80 - 100 milligram per deciliter [mg/dL]). | Drug: HOE901-U300 (Insulin glargine new formulation)<br> <br> |
| Active Comparator: Lantus<br>Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily in morning or evening for 12 months on top of mealtime insulin analogue. Dose titration seeking fasting plasma glucose 4.4-5.6 mmol/L (80 - 100 mg/dL). | Drug: Lantus (Insulin glargine)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change In HbA1c From Baseline to Month 6 Endpoint |  | Baseline, Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HbA1c <7% at Month 6 Endpoint |  | Month 6 | 
| Percentage of Participants With HbA1c Less Than or Equal to 6.5% at Month 6 Endpoint |  | Month 6 | 
| Change In Average Pre-Injection Self-Monitored Plasma Glucose (SMPG) From Baseline Month 6 Endpoint | Pre-injection SMPG was measured within 30 minutes prior to the injection of the study drug. Average was assessed by the mean of at least 3 SMPG calculated over the 7 days preceding the assessment visit. | Baseline, Month 6 | 
| Change in Variability of Pre-injection SMPG From Baseline to Month 6 Endpoint | Pre-injection SMPG was measured within 30 minutes prior to the injection of the study drug. Variability was assessed by the mean of coefficient of variation calculated as 100 multiplied by (standard deviation/mean) over at least 3 SMPG measured during the 7 days preceding the assessment visit. | Baseline, Month 6 | 
| Change in Fasting Plasma Glucose From Baseline to Month 6 Endpoint |  | Baseline, Month 6 | 
| Percentage of Participants With Fasting Plasma Glucose (FPG) <5.6 mmol/L (100 mg/dL) At Month 6 |  | Month 6 | 
| Percentage of Participants With FPG <7.2 mmol/L (130 mg/dL) at Month 6 Endpoint |  | Month 6 | 
| Change in 8--Point SMPG Profiles Per Time Point From Baseline to Month 6 Endpoint | Change in each time-point of 8-point SMPG profile: 03:00 hours (clock time) at night; before and 2 hours after breakfast; before and 2 hours after lunch; before and 2 hours after dinner; and at bedtime. | Baseline, Month 6 | 
| Change in Daily Average Total Insulin Dose From Baseline to Month 6 Endpoint |  | Baseline, Month 6 | 
| Change in Total Treatment Satisfaction Score Using The Diabetes Treatment Satisfaction Questionnaire (DTSQs) From Baseline to Month 6 Endpoint | DTSQ is a validated measure to assess how satisfied participants with diabetes are with their treatment and how they perceive hyper- and hypoglycemia. It consists of 8 questions which are answered on a Likert scale from 0 to 6. DTSQ treatment satisfaction score is the sum of question 1 and 4-8 scores and ranges between 0 and 36, where higher scores indicate more treatment satisfaction. | Baseline, Month 6 | 
| Percentage of Participants With Hypoglycemia (All and Nocturnal) Events From Baseline to Month 12 | Hypoglycemia events were Severe hypoglycemia (an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions); Documented symptomatic hypoglycemia (typical symptoms of hypoglycemia with plasma glucose level of <=3.9 mmol/L [70 mg/dL]); Asymptomatic hypoglycemia (no typical symptoms of hypoglycemia but plasma glucose level <=3.9 mmol/L); Probable symptomatic hypoglycemia (an event during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination, but was presumably caused by a plasma glucose level <=3.9 mmol/L, symptoms treated with oral carbohydrate without a test of plasma glucose); Relative hypoglycemia (an event during which the person with diabetes reported any of the typical symptoms of hypoglycemia, and interpreted the symptoms as indicative of hypoglycemia, but plasma glucose level >3.9 mmol/L); Severe and/or confirmed a hypoglycemia (plasma glucose <=3.9 mmol/L). | Up to Month 12 |