Postprandial Glucodynamic Response to Insulin Glargine/Lixisenatide Fixed Ratio Combination in Japanese Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Primary Objective: To assess the postprandial glucodynamic response to 2 doses of insulin glargine/lixisenatide fixed-ratio combination compared to placebo in Japanese patients with type 2 diabetes mellitus (T2DM). Secondary Objectives: To assess the pharmacokinetics (PK) of lixisenatide following administration of 2 different doses of insulin glargine/lixisenatide fixed-ratio combination in Japanese patients with T2DM. To assess the postprandial glucodynamic response to insulin glargine/lixisenatide fixed-ratio combination compared to insulin glargine alone in Japanese patients with T2DM. To assess the safety and tolerability of insulin glargine/lixisenatide fixed-ratio combination in Japanese patients with T2DM.

Detailed Description
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The total study duration per patient will be approximately 6 to 13 weeks that will consist of a 2-28 days of screening period, a 3-day treatment period, a 7-14 days of washout period, and 1-day end of study visit.

Official Title
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A Randomized, Open Label, Placebo-controlled, 4-sequence, 4-period, 4-treatment Crossover Study to Investigate the Postprandial Glucodynamic Response to Single Dose of Insulin Glargine/Lixisenatide Fixed Ratio Combination in Japanese Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin glargine/ lixisenatide fixed-ratio combination HOE901/AVE0010
* Drug: Insulin glargine HOE901
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Japanese male or female patients with T2DM diagnosed for at least 1 year prior to the time of screening as established in the medical history. Patients aged 20 to 75 years at screening. Body mass index ≤35 kg/m^2 at screening. Glycohemoglobin ≥7.0% and ≤10.0% at screening. Fasting C-peptide ≥0.6 ng/mL at screening. Exclusion criteria: Diabetes other than T2DM. History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening. History of hypoglycemia unawareness. Hemoglobinopathy or hemolytic anemia. History of myocardial infarction, stroke, or heart failure, history or presence of clinically significant diabetic retinopathy, history or presence of macular edema likely to require laser treatment within the study period. History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease. Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including, but not limited to gastroparesis and gastroesophageal reflux disease requiring medical treatment. Personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (e.g., multiple endocrine neoplasia syndromes). If female, pregnancy or breast-feeding. 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
Maximum Age: 75 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin glargine/ lixisenatide dose 1 Test 1<br>Test 1 will be administered thru subcutaneous (SC) injection into one peri-umbilical site of the abdomen 1 hour prior to breakfast under fasted condition | Drug: Insulin glargine/ lixisenatide fixed-ratio combination HOE901/AVE0010<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>|
| Experimental: Insulin glargine/ lixisenatide dose 2 Test 2<br>Test 2 will be administered thru SC injection into one peri-umbilical site of the abdomen 1 hour prior to breakfast under fasted condition | Drug: Insulin glargine/ lixisenatide fixed-ratio combination HOE901/AVE0010<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>|
| Placebo Comparator: Placebo - Reference 1<br>Reference 1 will be administered thru SC injection into one peri-umbilical site of the abdomen 1 hour prior to breakfast under fasted condition | Drug: Placebo<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>|
| Other: Insulin glargine (Lantus) - Reference 2<br>Reference 2 will be administered thru SC injection into one peri-umbilical site of the abdomen 1 hour pior to breakfast under fasted condition | Drug: Insulin glargine HOE901<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>* Other names: Lantus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of plasma glucose concentrations |  | 1 day (D1) in each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of serum insulin concentrations |  | 1 day (D1) in each treatment period | 
| Measurement of serum C-peptide concentrations |  | 1 day (D1) in each treatment period | 
| Measurement of plasma glucagon concentrations |  | 1 day (D1) in each treatment period | 
| Measurement of plasma lixisenatide concentrations |  | 1 day (D1) in each treatment period | 
| Number of patients with hypoglycemic events |  | Up to 2 weeks after each treatment | 
| Number of patients with adverse events |  | Up to 2 weeks after each treatment | 
| Measurement of anti-lixisenatide antibodies |  | 2 days (prior to first dosing and end of study visit) | 
| Measurement of anti-insulin antibodies |  | 2 days (prior to first dosing and end of study visit) |