Type 2 Diabetes Mellitus
Conditions
Brief summary
Primary Objectives: The co-primary objective of this study is: * To demonstrate the superiority of iGlarLixi (fixed ratio combination of insulin glargine and lixisenatide) versus lixisenatide on glycemic control as assessed by glycated hemoglobin A1c (HbA1c) change. * To demonstrate the non-inferiority of iGlarLixi versus insulin glargine on glycemic control as assessed by HbA1c change. Secondary Objectives: * To assess the effects of iGlarLixi in comparison with insulin glargine alone and lixisenatide alone. * To assess the safety in each treatment group.
Detailed description
The maximum study duration per patient will be approximately 31 weeks: an up-to 6-week screening and run-in period (with an up-to 2-week screening phase and a 4-week run-in phase), followed by a 24-week randomized treatment period and a 3-day post-treatment safety follow up period.
Interventions
Pharmaceutical form: solution Route of administration: subcutaneous
Pharmaceutical form: solution Route of administration: subcutaneous
DRUGLixisenatide (AVE0010)
Pharmaceutical form: solution Route of administration: subcutaneous
DRUGMetformin
Pharmaceutical form: tablet Route of administration: oral
DRUGSGLT2 inhibitor
Pharmaceutical form:tablet Route of administration: oral
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Patients with type 2 diabetes mellitus (T2DM) diagnosed for at least 1 year before the screening visit (V1), treated for at least 3 months prior to the screening visit (V1) with metformin alone or metformin and a second oral antidiabetic treatment that can be a sulfonylurea (SU), a glinide, an alpha-glucosidase inhibitor (alpha-GI), a dipeptidyl peptidase-4 (DPP-4) inhibitor or a sodium-glucose co transporter 2 (SGLT-2) inhibitor and who are not adequately controlled with this treatment. * Signed written informed consent.
Exclusion criteria
* Age \< legal age of majority at the screening visit (V1). * Body mass index (BMI) \>40 kg/m² at screening. * Glycated hemoglobin A1c (HbA1c) at screening visit: * \<7.5% or \>11% for patients previously treated with metformin alone; * \<7.0% or \>10% for patients previously treated with metformin and a second oral antidiabetic treatment. * History of hypoglycemia unawareness. * History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening. * Use of oral or injectable glucose-lowering agents other than those stated in the inclusion criteria within 3 months prior to screening. * Previous treatment with insulin (except for short-term treatment due to intercurrent illness at the discretion of the Investigator) within 1 year prior to screening. * History of discontinuation of a previous treatment with glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) due to safety/tolerability reasons or lack of efficacy. * Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to screening. * Use of weight loss drugs within 3 months prior to screening. * Use of any investigational drug other than specified in this protocol within 1 month or 5 half-lives, whichever is longer, prior to screening. * Within 6 months prior to screening: history of myocardial infarction, stroke, or heart failure requiring hospitalization. * Planned coronary, carotid, or peripheral artery revascularization procedures to be performed during the study period. * Known history of drug or alcohol abuse within 6 months prior to screening. * Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic blood pressure \>180 mmHg or diastolic blood pressure \>95 mmHg. * Laboratory findings at screening visit (V1): * Amylase and/or lipase \>3 times the upper limit of normal (ULN) laboratory range. * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 ULN. * Total bilirubin \>1.5 ULN (except in case of Gilbert's syndrome). * Calcitonin ≥20 pg/mL (5.9 pmol/L). * Hemoglobin \<10.5 g/dL and/or neutrophils \<1500/mm3 and/or platelets \<100 000/mm3. * Positive urine pregnancy test in female of childbearing potential. * Patient who has a severe renal function impairment with an estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m2 or end-stage renal disease. * History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy. * Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (eg, multiple endocrine neoplasia syndromes). * Use of SU, glinide, alpha-GI, DPP-4 inhibitor, and SGLT-2 inhibitor after start of run-in (from V2 \[Week -4\]). * HbA1c at V4 (Week -1) : \<7.0% or \>10%. * Fasting plasma glucose \>250 mg/dL (13.9 mmol/L) at V4 (Week-1) (can be repeated once to confirm). * Metformin maximal tolerated dose \<1500 mg/day. * Amylase and/or lipase \>3 ULN at V4 (Week-1). The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c | From Baseline to Week 24 | Change in glycated hemoglobin (HbA1c) from baseline to Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in postprandial plasma glucose (PPG) | From Baseline to Week 24 | Absolute change in 2-hour blood glucose excursion and PPG during meal test from baseline to Week 24 (for all patients in iGlarLixi or insulin glargine group and patients who receive morning injection in the lixisenatide group) |
| Change in self-monitored plasma glucose (SMPG) profile | From Baseline to Week 24 | Absolute change in 7-point SMPG profiles from baseline to Week 24 (each time point and average daily value) |
| Patients with HbA1c <7.0% | At Week 24 | Percentage of patients reaching HbA1c \<7% at Week 24 |
| Patients with HbA1c ≤ 6.5% | At Week 24 | Percentage of patients reaching HbA1c ≤ 6.5% at Week 24 |
| Change in body weight | From Baseline to Week 24 | Absolute change in body weight from baseline to Week 24 |
| Change in fasting plasma glucose (FPG) | From Baseline to Week 24 | Absolute change in FPG from baseline to Week 24 |
| Patients with HbA1c <7.0% with no body weight gain and no documented symptomatic hypoglycemia | At Week 24 | Percentage of patients reaching HbA1c \<7% with no body weight gain at Week 24 and no documented (plasma glucose \[PG\] ≤70 mg/dL \[3.9 mmol/L\]) symptomatic hypoglycemia during the 24 week treatment period |
| Confirmed hypoglycemia | From Baseline to Week 24 | Including severe hypoglycemia and episodes of hypoglycemia documented with PG ≤70 mg/dL (3.9 mmol/L) regardless of symptoms from baseline to Week 24 |
| Adverse events (AEs) | From Baseline to Week 24 | Number of AEs, serious AEs, AEs of Special Interest, and AEs requiring specific monitoring from baseline to Week 24 |
| Immunogenicity (antibody variables) | From Baseline to Week 24 | Anti-lixisenatide antibodies and anti-insulin antibodies (depending on the treatment group) from baseline to Week 24 |
| Patients with HbA1c <7.0% with no body weight gain | At Week 24 | Percentage of patients reaching HbA1c \<7% with no body weight gain at Week 24 |
Countries
China, Malaysia, South Korea, Taiwan
Outcome results
None listed