Efficacy and Safety of Soliqua Versus Lantus in Ethnically/Racially Diverse Patients With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Antidiabetic Agents

Study Overview
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Brief Summary
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Primary Objective: To demonstrate the superiority of Soliqua 100/33 versus Lantus in the hemoglobin A1c (HbA1c) change within the overall population. To demonstrate the benefit of Soliqua 100/33 versus Lantus in the HbA1c within each ethnic/racial subgroup evaluated (ie, Hispanics of any race, non-Hispanic black/African Americans and non-Hispanic Asians). Secondary Objective: To assess the effects of Soliqua 100/33 versus Lantus on the secondary efficacy parameters within each ethnic/racial subgroup evaluated. To assess the change in daily insulin glargine dose within each ethnic/racial subgroup. To evaluate the safety and tolerability (e.g., gastrointestinal tolerability) of Soliqua 100/33 versus Lantus within each ethnic/racial subgroup.

Detailed Description
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The study duration was approximately 29 weeks including 2 weeks screening period, 26 weeks open label treatment period, and a 3 days follow-up period.

Official Title
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A 26-week Randomized, Open-label, Active-controlled, 2-treatment Arm, Parallel Group Multi-center Study, Comparing the Efficacy and Safety of Soliqua™100/33 Versus Lantus® in Ethnically/Racially Diverse Patients With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Antidiabetic Agents

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin glargine/Lixisenatide
* Drug: Insulin glargine (HOE901)
* Drug: Background therapy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Participants with type 2 diabetes mellitus (T2DM) diagnosed at least 1 year prior to the screening visit (signing of informed consent). Uncontrolled diabetes as demonstrated by a screening centrally measured hemoglobin A1c (HbA1c) between 7.5% and 10% (inclusive). Participants who were Hispanics of any race, non-Hispanic black/African Americans or non-Hispanic Asians. Note: Decision for ethnic/racial inclusion was made based on the participant's self-identification. Mixed-race participants must select 1 of the above-mentioned categories. If such selection could not be made, the candidate would be ineligible to participate in the study. Participants who had been treated with any basal insulin (ie, glargine - U100 or U300, detemir, degludec, intermediate-acting [human Neutral Protamine Hagedorn (NPH]) for at least 6 months prior to Visit 1. The basal insulin regimen (ie, type of insulin and time/frequency of the injection) had been stable for at least 3 months prior to Visit 1. The basal insulin dose had been stable (defined as up to ±20% [1/5 of the dose] variability) for at least 2 months prior to Visit 1 within the following dose ranges: 15 to 50 units/day if HbA1c at Visit 1 is less than or equal to (<=)8.5%, and 15 to 40 units/day if HbA1c at Visit 1 is greater than (>)8.5%. Participants receiving 1 or 2 of the following OAD drugs: metformin, pioglitazone/rosiglitazone, an sodium-glucose transport protein 2 (SGLT-2) inhibitor or a sulfonylurea (SU), at stable doses for at least 12 weeks prior to Visit 1. Exclusion criteria: Age <18 years of age at Visit 1. A body mass index (BMI) <=20 or >40 kg/m^2 at Visit 1. Fasting plasma glucose (FPG) >200 mg/dL (by central lab measurement) at Visit 1 (1-time repeat measurement before Visit 2 is permitted). Type 1 DM or any diabetes other than T2DM. Any use of OAD drugs other than those described in the inclusion criteria (e.g., but not limited to, glucagon like peptide-1 receptor agonist (GLP-1 RA), dipeptidyl peptidase 4 (DPP4) inhibitors) within 12 weeks prior Visit 1. Use of any other type of insulin except for basal insulin (e.g., prandial or premixed insulin, insulin pump) within 6 months prior to Visit 1. Note: History of short-term treatment (i.e, <=10 days) with other insulin types due to intercurrent illness was permitted at the discretion of the Investigator. Known history of discontinuation of treatment with a GLP-1 RA due to safety/tolerability reasons. Use of systemic glucocorticoids for a total duration of >7 days within 12 weeks prior to Visit 1. Initiation/change in type or dose of a weight loss drug within 12 weeks prior to Visit 1. The above information is not intended to contain all considerations relevant to a participants'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: Soliqua 100/33<br>Soliqua 100/33 (Insulin glargine/lixisenatide) once daily in the morning within 1 hour before breakfast, on top of oral anti-diabetic drug (OAD) therapy for 26 weeks. | Drug: Insulin glargine/Lixisenatide<br>* Insulin glargine (100 units per milliliter [U/mL]) and lixisenatide (33 micrograms per milliliter [mcg/mL]) self administered by a subcutaneous injection using a prefilled pen. Dose was individually titrated to achieve target fasting self-monitoring of plasma glucose (SMPG) of 80 to 100 milligrams per deciliter (mg/dL) (4.4 to 5.6 millimoles per liter [mmol/L]) while avoiding hypoglycemia.<br>* Other names: HOE901/AVE0010;Drug: Background therapy<br>* Oral Anti diabetics Drugs (OADs) administered orally according to the locally approved label.<br>|
| Active Comparator: Lantus<br>Lantus (Insulin glargine) once daily at any time of the day but at about the same time every day on top of OAD therapy for 26 weeks. | Drug: Insulin glargine (HOE901)<br>* Insulin glargine 100 U/mL self-administered by a subcutaneous injection using a prefilled pen. Dose was individually titrated to achieve target fasting SMPG of 80 to 100 mg/dL (4.4 to 5.6 mmol/L) while avoiding hypoglycemia.<br>* Other names: HOE901;Drug: Background therapy<br>* Oral Anti diabetics Drugs (OADs) administered orally according to the locally approved label.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26 | Change in HbA1c was calculated by subtracting baseline value from Week 26 value. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving HbA1c Target of <7% at Week 26 | Participants who had no available assessment for HbA1c at Week 26 were considered as non-responders. | Week 26 | 
| Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Standardized Mixed Meal at Week 26 | The 2-hour PPG test measured blood glucose 2 hours after eating a standardized breakfast meal. | Baseline, Week 26 | 
| Change From Baseline in 2-Hour Blood Glucose Excursion During Standardized Meal Test at Week 26 |  | Baseline, Week 26 | 
| Change From Baseline in Daily Insulin Glargine Dose at Week 26 | Change in daily dose was calculated by subtracting baseline value from Week 26 value. | Baseline, Week 26 | 
| Change From Baseline in Body Weight at Week 26 | Change in body weight was calculated by subtracting baseline value from Week 26 value. | Baseline, Week 26 | 
| Percentage of Participants With Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Hypoglycemia) During the On-Treatment Period | Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Documented hypoglycemia with plasma glucose cut-off of <=70 mg/dL (3.9 mmol/L) was any hypoglycemia documented by a measured plasma glucose <=70 mg/dL (3.9 mmol/L) and excluding plasma glucose <54 mg/dL regardless of symptoms. Documented hypoglycemia with plasma glucose cut-off of <54 mg/dL (3.0 mmol/L) was any hypoglycemia documented by a measured plasma glucose <54 mg/dL (3.0 mmol/L) regardless of symptoms. | Baseline to Week 26 |