Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 2 Diabetes on Non-insulin Antidiabetic Therapy

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 in terms of change of HbA1c from baseline to endpoint (scheduled at Month 6, Week 26) in participants with type 2 diabetes mellitus Secondary Objectives: To compare a new formulation of insulin glargine and Lantus in terms of: - occurrence of nocturnal hypoglycemia

Detailed Description
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The maximum study duration was up to approximately 54 weeks per participant, consisting of: Up to 2 week screening period; it can be exceptionally extended of up to one additional week 6-month comparative efficacy and safety treatment period 6-month comparative safety extension period 2-day post-treatment safety follow-up period

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® in Insulin-Naïve Patients With Type 2 Diabetes Mellitus Not Adequately Controlled With Non-Insulin Antihyperglycemic Drugs 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 : Adult participants with type 2 diabetes mellitus inadequately controlled with non-insulin antihyperglycemic drug(s); Signed written informed consent. Exclusion criteria: HbA1c less than (<) 7.0% (< 53 millimole per mole [mmol/mol]) or greater than (>) 11% (> 97 mmol/mol) History of type 2 diabetes mellitus for less than 1 year before screening Less than 6 months before screening with non-insulin antihyperglycemic treatment Change in dose of non-insulin antihyperglycemic treatment in the last 3 month before screening Initiation of new glucose-lowering medications and/or weight loss drug in the last 3 months before screening visit and/or initiation of Glucagon-like peptide-1 (GLP-1) receptor agonist in the last 6 months before screening visit Participants receiving only non-insulin antihyperglycemic drugs not approved for combination with insulin according to local labeling/local treatment guidelines and/or sulfonylurea or glinide (Note: non-insulin antihyperglycemic drugs not approved for combination with insulin, sulfonylurea and glinide are to be discontinued at baseline) Current or previous insulin use except for a maximum of 8 consecutive days (for example, acute illness, surgery) during the last year prior to screening Unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to require treatment (for 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> | 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 non-insulin antihyperglycemic drug(s). Dose titration seeking fasting plasma glucose 4.4-5.6 millimole per liter (mmol/L) (80 - 100 milligram per deciliter [mg/dL]).<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 non-insulin antihyperglycemic drug(s). 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 | Only HbA1c measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. | 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 | 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]). Only nocturnal hypoglycemia occurring before initiation of rescue therapy were considered in the analysis. Week 9 and Month 6 value correspond to the observed value at Week 9 and Month 6 visit respectively. | Week 9 Up to Month 6 | 
| Change in 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. Except for baseline value average of preinjection SMPG was assessed by the mean of at least 3 SMPG calculated over the 7 days preceding the assessment visit. Only preinjection SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. | Baseline, Month 6 | 
| Variability of Preinjection SMPG at 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. Only preinjection SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. | Month 6 | 
| Percentage of Participants With HbA1c <7% at Month 6 | Only HbA1c measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit. | Month 6 | 
| Change in Fasting Plasma Glucose (FPG) From Baseline to Month 6 Endpoint | Only FPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. | Baseline, Month 6 | 
| Percentage of Participants With FPG <5.6 mmol/L (100 mg/dL) at Month 6 | Only FPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit. | Month 6 | 
| Change in 8-Point SMPG Profiles Per Time Point From Baseline to Month 6 | 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. Only 8-point SMPG profiles measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit. | Baseline, Month 6 | 
| Change in 24-hour Average 8-point SMPG Profile From Baseline to Month 6 Endpoint | Change in 24-hour average of 8-point SMPG profile. 8-point SMPG was assessed at: 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. Only 24-hour average 8-point SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. | Baseline, Month 6 | 
| Change in Variability of 24 Hour Average 8-point SMPG Profiles From Baseline to Month 6 Endpoint | Variability is assessed by the mean of coefficient of variation calculated as 100 multiplied by (standard deviation/mean) over at least 5 measurements of the 8-point profiles. Only variability of 24-hour 8-point SMPG measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. | Baseline, Month 6 | 
| Change in Daily Basal Insulin Dose From Baseline to Month 6 | Only insulin dose measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 value corresponds to the observed value at Month 6 visit. | 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. Only DTSQ total score measurements performed before initiation of rescue therapy were considered in the analysis. Month 6 Endpoint is either the observed value at Month 6 visit or value retrieved according to time windows. | 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 12 months |