Safety Assessment of Lyxumia (Lixisenatide) and Sulfonylurea as Add-on Treatment to Basal Insulin in Uncontrolled Patients With Type 2 Diabetes Mellitus Who Elect to Fast During Ramadan

Study Overview
=================
Brief Summary
-----------------
Primary Objective: To compare the safety, in terms of percentage of patients with symptomatic documented hypoglycemia during Ramadan fast, of lixisenatide versus sulfonylurea (SU). Secondary Objectives: To assess effect of lixisenatide versus SU on: Changes in glycemic control; Changes in body weight. To assess overall safety of lixisenatide and SU.

Detailed Description
-----------------
The total study duration per patient will have a minimum 12 weeks and maximum 22 weeks (up to 2 weeks screening period + 8-12 weeks pre-Ramadan period + 29-30 days Ramadan + 0 4 weeks post-Ramadan period). This is a phase 3b study in Kingdom of Saudi Arabia and Bangladesh (instead of phase 4 for other countries).

Official Title
-----------------
International, Randomized, Open Label Study to Compare the Safety and Efficacy of Lixisenatide vs. Sulfonylurea on Top of Basal Insulin Treatment in Type 2 Diabetes Mellitus Subjects Who Elect to Fast During Ramadan

Conditions
-----------------
Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: Lixisenatide (AVE0010)
* Drug: Sulfonylurea
* Drug: metformin
* Drug: basal insulin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria : Patients with type 2 diabetes mellitus, diagnosed for at least 1 year at the time of the screening visit, insufficiently controlled with basal insulin + SU (≤50% max allowed dose) ±1 oral antidiabetic (OAD) drug. Patients who express the intention to fast during Ramadan. Signed informed consent. Exclusion criteria: At the time of screening age < legal age of majority. Glycated hemoglobin (HbA1c) at screening visit: <7.5% or >10%. Body mass index (BMI) <20kg/m^2. Treatment with basal insulin for less than 6 months prior to screening. Prior antidiabetic medication (basal insulin and OADs) not at stable dose (eg, same medication, frequency and <20% dose change) in the last 8 weeks prior to screening. Previous treatment with short or rapid acting insulin other than for short term use (≤10 days) in relation to hospitalization or an acute illness in the last 6 months prior to screening. Any discontinuation from a glucagon like peptide-1 receptor agonist (GLP-1 RA) due to safety/tolerability issue or lack of efficacy. Patient not willing to perform self-monitored plasma glucose (SMPG) as required by protocol and to follow the instructions provided. Type 1, gestational or secondary diabetes. History of diabetic ketoacidosis. History of hypoglycemia unawareness. Any medical contraindication for sustained and safe fasting. Pregnant or breast-feeding women. Women of childbearing potential (WOCB) not protected by highly effective contraceptive method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy. Known hypersensitivity/intolerance to lixisenatide (Lyxumia) or any of its excipients. All contraindications of the comparator and protocol mandated background therapies or warning/precaution of use (when appropriate) as displayed in the respective National Product Labeling. 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
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lyxumia<br>Patients will receive Lyxumia once daily as investigational medicinal product (IMP) on top of patient's previous basal insulin with/without metformin. Non-IMPs will be administrated as per Investigator's indications according to local labeling, guidelines, and clinical judgment. | Drug: Lixisenatide (AVE0010)<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>* Other names: Lyxumia;Drug: metformin<br>* Pharmaceutical form: tablet Route of administration: oral<br>Drug: basal insulin<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>|
| Active Comparator: Sulfonylurea<br>Patients will continue the treatment with previous Sulfonylurea as IMP on top of patient's previous basal insulin with/without metformin. The IMP and non-IMPs will be administrated as per Investigator's indications according to local labeling, guidelines, and clinical judgment. | Drug: Sulfonylurea<br>* Pharmaceutical form: tablet Route of administration: oral<br>Drug: metformin<br>* Pharmaceutical form: tablet Route of administration: oral<br>Drug: basal insulin<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with at least 1 documented symptomatic hypoglycemia event (plasma glucose ≤70 mg/dL; 3.9 mmol/L) |  | Approximately 30 days (from start to end of Ramadan holy month) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in HbA1c |  | Baseline, 0-4 weeks pre- and 0-4 weeks post-Ramadan | 
| Mean change in body weight |  | Baseline, 0-4 weeks pre- and 0-4 weeks post-Ramadan | 
| Percentage of patients with 2-hour post prandial glucose (2hPPG) <180 mg/dL (10 mmol/L) |  | Last 14 days of Ramadan month | 
| Percentage of patients with HbA1C <7% |  | At 0-4 weeks pre- and 0-4 weeks post-Ramadan | 
| Percentage of patients with fasting plasma glucose (FPG) <130 mg/dL (7.22 mmol/L) |  | At pre-Ramadan visit | 
| Percentage of patients with HbA1c <7%, no weight gain and no documented symptomatic hypoglycemia (plasma glucose ≤70 mg/dL; 3.9 mmol/L) |  | At 0-4 weeks pre- and 0-4 weeks post-Ramadan |