Comparison of the Safety and Efficacy of HOE901-U300 With Lantus in Older Patients With Type2 Diabetes Insufficiently Controlled on Their Current Antidiabetic Medications

Study Overview
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Brief Summary
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Primary Objective: To demonstrate the non-inferiority of H0E901-U300 to Lantus, in change of glycated hemoglobin A1c (HbA1c). Secondary Objectives: To demonstrate the superiority of H0E901-U300 in comparison with Lantus in: Percentage of participants with at least one severe and/or confirmed (by plasma glucose ≤70mg/dL [3.9mmol/L]) hypoglycemia event from 22:00 to 08:59 next morning Percentage of participants with at least one nocturnal (from 00:00-05:59) severe and/or confirmed (≤70mg/dL [3.9mmol/L]) hypoglycemia event Percentage of participants with at least one severe and/or confirmed (by plasma glucose ≤70mg/dL [3.9mmol/L]) hypoglycemia event occurring at any time of day HbA1c change

Detailed Description
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The study consisted of a 4-week screening period, a 26-week treatment period comparing HOE901-U300 to Lantus, and a 2-day safety follow-up period.

Official Title
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A Randomized, Open-label, 2-arm Parallel-group, Multicenter, 26-week Study Assessing the Safety and Efficacy of H0E901-U300 Versus Lantus in Older Patients With Type 2 Diabetes Inadequately Controlled on Antidiabetic Regimens Either Including no Insulin, or With Basal Insulin as Their Only Insulin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin Glargine (HOE901 - U300)
* Drug: Insulin Glargine (HOE901 - U100)
* Drug: Background therapy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participants ≥65 years old with type 2 diabetes mellitus, inadequately controlled on antidiabetic regimens either including no insulin, or with basal insulin as their only insulin. Signed informed consent. Exclusion criteria: HbA1c at screening visit: <7.0% or >10.0% for participants taking basal insulin. <7.5% or >11.0% for insulin-naïve participants. History of type 2 diabetes mellitus for less than 1 year before screening. Participants not on stable basal insulin dose (±10% in the last 8 weeks prior to screening visit). Change in dose of antidiabetic treatment or initiation of new glucose-lowering medications in the last 8 weeks prior to screening. Chronic (>10 days continuous use in previous 6 months) use of bolus insulin injections, whether given separately or as part of a combination with basal insulin, e.g. premix insulin; For insulin-naïve individuals: current or previous insulin use except for a maximum of 10 consecutive days (e.g. acute illness, surgery) during the last year prior to screening. Cognitive disorder and dementia assessed clinically and by Mini-Mental State Examination (MMSE) score <24, or any neurologic disorder that would likely affect the participant's ability to follow the study procedure. The participant would be eligible despite an MMSE score <24 if the investigator determined that the low score reflected educational or cultural background and not dementia as long as the participant was otherwise able to meet the study requirements. Participants who had end-stage renal disease (<15 mL/min/1.73m^2, per estimated Glomerular filtration rate (eGFR) measurement by Modification of Diet in Renal Disease (MDRD). The above information was 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: 65 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 (Insulin glargine, 300 U/mL) once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy. | Drug: Insulin Glargine (HOE901 - U300)<br>* Self-administered by subcutaneous (SC) injection in the evening using a pre-filled pen. Dose titration to achieve fasting self-monitored plasma glucose (SMPG) from 90 to 130 mg/dL (5.0 to 7.2 mmol/L).<br>* Other names: Toujeo®;Drug: Background therapy<br>* Non-insulin anti-diabetic drugs with the exception of thiazolidinediones.<br>|
| Active Comparator: Lantus<br>Lantus (Insulin glargine, 100 U/mL) once daily up to Week 26 on top of stable non-insulin antihyperglycemic therapy. | Drug: Insulin Glargine (HOE901 - U100)<br>* Self-administered by SC injection in the evening using a pre-filled pen. Dose titration to achieve fasting SMPG from 90 to 130 mg/dL (5.0 to 7.2 mmol/L).<br>* Other names: Lantus®;Drug: Background therapy<br>* Non-insulin anti-diabetic drugs with the exception of thiazolidinediones.<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 Week 26 | Adjusted least square (LS) means were obtained from analysis of covariance (ANCOVA) after multiple imputation of missing data including post baseline HbA1c data during the 26-week randomized period. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (22:00 to 08:59 Hours Next Morning) During 26-Week Randomized Period | Estimated percentages from multiple imputation approach including data from the 26-week randomized period. 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 ≤3.9 mmol/L (70 mg/dL). | Baseline up to Week 26 | 
| Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Nocturnal Hypoglycemia (00:00 to 05:59 Hours) During 26-Week Randomized Period | Estimated percentages from multiple imputation approach including data from the 26-week randomized period. 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 ≤3.9 mmol/L (70 mg/dL). | Baseline up to Week 26 | 
| Percentage of Participants With At Least One Severe and/ or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia Occurring at Any Time of the Day During 26-Week Randomized Period | Estimated percentages from multiple imputation approach including data from the 26-week randomized period. 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 ≤3.9 mmol/L (70 mg/dL). | Baseline up to Week 26 | 
| Percentage of Participants With HbA1c <7.5% or HbA1c <7% During 26-Week Randomized Period | Participants without any available HbA1c assessment at Week 26 were considered as non-responders in the analyses. | Baseline up to Week 26 | 
| Percentage of Participants With HbA1c <7.5% or <7.0% at Week 26 and No Severe and/or Confirmed (≤3.9 mmol/L [70 mg/dL]) Hypoglycemia During 26-Week Randomized Period | 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 ≤3.9 mmol/L (70 mg/dL). | Baseline up to Week 26 | 
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 | Adjusted LS means from multiple imputation approach including post baseline values during the 26-week randomized period. | Baseline, Week 26 | 
| Change in World Health Organization-5 (WHO-5) Well-Being Questionnaire Percentage Score From Baseline to Week 26 | WHO-5 well-being index evaluates positive psychological well-being during the past 2 weeks and consists of 5 questions, each rated on a 6-point Likert scale from 0 (not present) to 5 (constantly present). Total raw score was transformed into a percentage score ranging from 0 (worst possible quality of life) to 100 (best possible quality of life). | Baseline, Week 26 | 
| Percentage of Participants Requiring Rescue Therapy Over the 26 Weeks of Treatment | Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after Week 14) values were used to determine the requirement of rescue medication. Threshold values at Week 14: FPG >200 mg/dL (11 mmol/L), or HbA1c >8.5%. | Baseline up to Week 26 |