Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination (LixiLan) to Lixisenatide on Top of Oral Anti-diabetic Drugs (OADs) With Type 2 Diabetes in Japan

Study Overview
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Brief Summary
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Primary Objective: To compare LixiLan to lixisenatide in glycated hemoglobin (HbA1c) change from baseline to Week 26 in patients with type 2 diabetes mellitus. Secondary Objective: To compare the overall efficacy and safety of LixiLan to lixisenatide (with or without OADs) over a 52 week treatment period in patients with type 2 diabetes mellitus.

Detailed Description
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Approximately 55 weeks: an up-to 2-week screening period, a 26-week randomized open-label treatment period, a 26-week safety extension treatment period and a 3-day post-treatment safety follow up period.

Official Title
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A Randomized, Active-controlled, Open Label, 2-treatment Arm, and Multicenter Study Comparing the Efficacy and Safety of Insulin Glargine/Lixisenatide Combination to Lixisenatide on Top of OADs in Japanese Patients With Type 2 DM With an Extension Period

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin glargine/Lixisenatide (HOE901/AVE0010)
* Drug: Lixisenatide (AVE0010)
* Drug: Oral anti-diabetic drugs


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Patient with type 2 diabetes mellitus (T2DM) diagnosed for at least 1 year before the screening visit, receiving 1 or 2 OADs that can be biguanide, thiazolidinedione, alpha-glucosidase-inhibitor, sodium glucose co-transporter 2 inhibitor; sulfonylurea, rapid-acting insulin secretagogue, or dipeptidyl-peptidase-4 inhibitor. Signed written informed consent. Exclusion criteria: At the screening visit: age <20 years. At the screening visit: HbA1c <7.5% or >10%. At the screening visit: fasting plasma glucose (FPG) >250 mg/dL (13.8 mmol/L). Pregnancy or lactation, women of childbearing potential with no effective contraceptive method. Use of oral or injectable glucose-lowering agents other than those stated in the inclusion criteria during the 3 months before the screening visit. Previous treatment with insulin (except for short-term treatment due to intercurrent illness including gestational diabetes at the discretion of the trial physician). Laboratory findings at the screening visit, including: Amylase and/or lipase >3 times the upper limit of the normal laboratory range (ULN), Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 ULN, Calcitonin ≥20 pg/mL (5.9 pmol/L), Positive serum pregnancy test. Contraindication to use of lixisenatide according to the local labeling. History of hypersensitivity to any glucagon-like peptide-1 receptor agonist (GLP-1RA) or to metacresol. Contraindication to use of insulin glargine according to the local labeling. History of hypersensitivity to insulin glargine or to any of the excipients. Patient who has a severe renal function impairment with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2 or end-stage renal disease for patient not treated with metformin. Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (eg, multiple endocrine neoplasia syndromes). History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy, stomach/gastric surgery. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 20 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: LixiLan<br>LixiLan (insulin glargine/lixisenatide fixed ratio combination) is injected subcutaneously (under the skin) once daily. Dose is individually adjusted. Background therapy with OADs (except dipeptidyl-peptidase-4 inhibitor) should be continued during the treatment period. | Drug: Insulin glargine/Lixisenatide (HOE901/AVE0010)<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>* Other names: LixiLan;Drug: Oral anti-diabetic drugs<br>* Pharmaceutical form: tablet Route of administration: Oral<br>|
| Active Comparator: lixisenatide<br>Lixisenatide (AVE0010) is injected subcutaneously (under the skin) once daily. It will be initiated with Dose 1 for 1 week and then continue with Dose 2 for 1 week followed by the maintenance dose of Dose 3 up to the end of treatment period. Background therapy with OADs (except dipeptidyl-peptidase-4 inhibitor) should be continued during the treatment period. | Drug: Lixisenatide (AVE0010)<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>Drug: Oral anti-diabetic drugs<br>* Pharmaceutical form: tablet Route of administration: Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HbA1c |  | Baseline, 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients reaching HbA1c <7% or ≤6.5% |  | 26 weeks | 
| Change from baseline in fasting plasma glucose |  | Baseline, 26 weeks | 
| Change in from baseline in 7 point self-monitored plasma profiles |  | Baseline, 26 weeks | 
| Percentage of patients reaching HbA1c <7% with no body weight gain |  | 26 weeks | 
| Change from baseline in body weight |  | Baseline, 26 weeks | 
| Percentage of patients requiring a rescue therapy |  | 26 weeks | 
| Change in daily dose of insulin glargine for the combination group |  | Day 1, 26 weeks | 
| Number of hypoglycemic events |  | 26 weeks, 52 weeks | 
| Number of adverse events |  | 26 weeks, 52 weeks | 
| Measurement of anti-lixisenatide antibodies from baseline |  | Baseline, 26 weeks, 52 weeks | 
| Measurement of anti-insulin antibodies from baseline |  | Baseline, 26 weeks, 52 weeks |