Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus GLP-1 Receptor Agonist in Patients With Type 2 Diabetes
- Conditions
- Type 2 Diabetes MellitusMedDRA version: 19.0 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2014-004850-32-ES
- Lead Sponsor
- sanofi-aventis recherche & développement
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 770
-Patients with type 2 diabetes mellitus diagnosed at least 1 year prior to screening visit.
-Patients who have been treated with one of the following glucagon-like peptide 1 (GLP-1) receptor agonists for at least 4 months prior to screening visit (V1), and with stable dose for at least 3 months prior to screening visit (V1):
-Liraglutide (Victoza®) 1.8 mg QD or 1.2 mg QD, if the 1.8 mg QD dose is not well tolerated according to the Investigator's judgment or
-Exenatide (Byetta®) 10 ?g BID or of 5 ?g BID, if 10 ?g BID dose is not well tolerated according to the Investigator's judgment in combination with metformin (daily dose ?1500 mg/day or maximum tolerated dose [MTD]), with or without pioglitazone, both at stable dose for at least 3 months prior to screening.
or
Patients who have been treated with stable dose of one of the following GLP-1 receptor agonists for at least 6 months prior to screening visit (V1):
-Exenatide extended-release (Bydureon®) 2 mg once weekly (QW), if well tolerated according to Investigator?s judgment,
-Albiglutide (Tanzeum®, Eperzan®) 50 mg QW or 30 mg QW, if 50 mg QW is not well tolerated according to Investigator?s judgment,
-Dulaglutide (Trulicity®) 1.5 mg QW or 0.75 mg QW, if 1.5 mg QW is not well tolerated according to Investigator?s judgment in combination with metformin (daily dose ?1500 mg/day or MTD), with or without pioglitazone, both at stable dose for at least 3 months prior to screening;
-Signed written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 616
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 154
-At screening visit, age <18.
-Screening HbA1c <7% and >9%.
-Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.
-Any use of oral antidiabetic drugs within 3 months prior to the screening visit other than those described in the inclusion criteria.
-Previous treatment with insulin in the year prior to screening visit (note: short-term treatment with insulin [?10 days] due to intercurrent illness including gestational diabetes is allowed at the discretion of the study physician).
-Laboratory findings at the time of screening, including:
-Fasting plasma glucose (FPG) >250 mg/dL (13.9 mmol/L),
-Amylase and/or lipase >3 times the upper limit of the normal laboratory range (ULN),
-Alanine transaminase or aspartate transaminase >3 ULN,
-Calcitonin ?20 pg/mL (5.9 pmol/L),
-Positive pregnancy test.
-Patient who has renal function impairment with estimated glomerular filtration rate <30 mL/min (using the Modification of Diet in Renal Disease formula) or end-stage renal disease.
-Contraindication to use of insulin glargine, or lixisenatide or GLP-1 receptor agonist (Victoza®, Byetta®, Bydureon®, Tanzeum®/Eperzan® or Trulicity®) according to local labeling.
-Any contraindication to metformin or pioglitazone use, according to local labeling.
-History of hypersensitivity to insulin glargine, or to any of the excipients.
-History of allergic reaction to any GLP-1 receptor agonist or to meta-cresol.
-Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (eg, multiple endocrine neoplasia type 2 syndromes).
-History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy was already performed), chronic pancreatitis, pancreatitis during a previous treatment with incretin therapies, pancreatectomy, stomach/gastric surgery.
-Body mass index ?20 or >40 kg/m^2.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination (FRC) versus GLP-1 receptor agonist (GLP-1 RA) in hemoglobin A1c (HbA1c) change.;Secondary Objective: To compare the overall efficacy and safety of the insulin glargine/lixisenatide fixed ratio combination (FRC) to GLP-1 receptor agonist (GLP-1 RA) on top of metformin (with or without pioglitazone) in patients with type 2 diabètes.;Primary end point(s): Change from baseline in HbA1c;Timepoint(s) of evaluation of this end point: Baseline to 26 weeks
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): 1- Percentage of participants reaching HbA1c targets<br> 2- Change from baseline in FPG<br> 3- Change from baseline in 7-point self-monitored plasma glucose<br> (SMPG) profiles<br> 4- Change from baseline in 2-hour postprandial glucose (PPG)<br> during standardized meal test<br> 5- Change from baseline in blood glucose excursion during<br> standardized meal test<br> 6- Change from baseline in body weight<br> 7- Percentage of participants with symptomatic hypoglycemia<br> 8- Number of adverse events<br> ;<br> Timepoint(s) of evaluation of this end point: 1- 26 weeks<br> 2-3-4-5-6 Baseline to 26 weeks<br> 7-8 26 weeks<br>