Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 2 Diabetes Mellitus on Basal Plus Mealtime Insulin

Study Overview
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Brief Summary
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Primary Objective: To compare the efficacy of insulin glargine new formulation and Lantus in terms of change in HbA1c from baseline to endpoint (scheduled month 6) in adult participants with type 2 diabetes mellitus Secondary Objectives: To compare the efficacy of insulin glargine new formulation and Lantus in terms of occurrence of nocturnal Hypoglycemia

Detailed Description
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The maximum study duration was up to approximately 58 weeks per participant, consisting of: up to 2 week screening period 6-month comparative efficacy and safety treatment period 6-month comparative safety extension period 4-week safety follow-up period in a subset of participants a 3-month administration substudy period starting after completion of the 6-month study period for participants willing to in a subset of participants randomized to HOE901-U300

Official Title
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6-Month, Multicenter, Randomized, Open-label, Parallel-group Study Comparing the Efficacy and Safety of a New Formulation of Insulin Glargine and Lantus® Both Plus Mealtime Insulin in Patients With Type 2 Diabetes Mellitus With a 6-month Safety Extension Period

Conditions
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Type 2 Diabetes Mellitus

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


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Participants with type 2 diabetes mellitus Substudy inclusion criteria: Completion of the 6-month study period in main study (Visit 10) Randomized and treated with insulin glargine new formulation during the 6-month treatment period (Baseline - month 6) Exclusion criteria: Age less than (<) 18 years HbA1c <7.0% or greater than (>) 10% at screening Diabetes other than type 2 diabetes mellitus Less than 1 year on basal plus mealtime insulin and self-monitoring of blood glucose Any contraindication to use of insulin glargine as defined in the national product label Participants using human regular insulin as mealtime insulin in the last 3 months before screening visit Use of an insulin pump in the last 6 months before screening visit Initiation of new glucose-lowering agents and/or weight loss drugs in the last 3 months before screening visit History or presence of significant diabetic retinopathy or macular edema likely to require laser or injectable drugs or surgical treatment during the study period Pregnant or breast-feeding women or women who intend to become pregnant during the study period Substudy exclusion criteria: Participant not willing to use the adaptable injection intervals on at least two days per week 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> | Drug: HOE901-U300 (new formulation of insulin glargine)<br>* HOE901-U300 (new insulin glargine 300 units per milliliter [U/mL]) subcutaneous (SC) injection once daily (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]). After 6 months participants were proposed to participate to the administration substudy and to receive either HOE901-U300 once daily at intervals of 24 +/- 3 hours (adaptable dosing intervals) or to continue once daily injections of HOE901-U300 every 24 hours (fixed dosing intervals) up to Month 9.<br>|
| Active Comparator: Lantus<br> | Drug: Lantus (insulin glargine)<br>* Lantus (HOE901-U100, insulin glargine 100 U/mL) SC injection once daily (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).<br>* Other names: Lantus;|

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 At Least One Severe and/or Confirmed Nocturnal Hypoglycemia From Start of Week 9 to Month 6 Endpoint | Nocturnal hypoglycemia was hypoglycemia that occurred between 00:00 and 05:59 hours (clock time), regardless the participant was awake or woke up because of the event. Severe hypoglycemia was an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Confirmed hypoglycemia was an event associated with plasma glucose less than or equal to (<=) 3.9 millimoles per liter (mmol/L) (70 milligram per deciliter [mg/dL]). | Week 9 Up to Month 6 | 
| Change in Average Preinjection Self-Monitored Plasma Glucose (SMPG) From Baseline to 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 Preinjection 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 | 
| Percentage of Participants With HbA1c <7% at Month 6 Endpoint |  | Month 6 | 
| Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint |  | Baseline, Month 6 | 
| Percentage of Participants With FPG <5.6 mmol/L (<100 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 Basal Insulin Dose From Baseline to Month 6 Endpoint |  | Baseline, Month 6 | 
| Change in 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 up 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 |