MedDRA version: 20.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861
Conditions
Interventions
Trade Name: Suliqua®
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Insulin Glargin
Current Sponsor code: iGlarLixi
Concentration unit: IU/ml international unit(
Sponsors
University Hospital Tuebingen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects meeting all of the following criteria will be considered for admission to the trial: • Must be between 18 and 65 years at the time of signing the informed consent. • BMI 25-45 kg/m² • Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures. • Ability to adhere to the study visit schedule and other protocol requirements. • Patients with type 2 diabetes mellitus diagnosed for at least 1 year before the screening visit (visit 1) treated for at least 3 months prior to visit 1 with only metformin or metformin and a sodium glucose co-transporter 2 inhibitor, and patients who are not adequately controlled with this treatment. • Females of childbearing potential (FCBP) must agree ? to utilize a highly effective forms of contraception (Pearl index =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following criteria will not be included in the trial: • HbA1c at screening visit less than 7.5% or more than 12% for patients previously treated with metformin alone or with metformin and a second oral anti-diabetic treatment.• Women during pregnancy and lactation.• History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal products. This includes iGlarLixi, insulin glargine, and human nasal insulin. • Use of oral glucose-lowering agents other than those stated in the inclusion criteria or any injectable glucoselowering agents during 3 months before screening • History of discontinuation of a previous treatment with a GLP-1 receptor agonist (GLP-1 RA) due to safety/tolerability issue or lack of efficacy. • Patient who has previously participated in any clinical trial with lixisenatide or the insulin glargine +lixisenatide fixed ratio combination or has previously received lixisenatide. • Any contraindication to metformin use, according to local labeling. • Use of weight loss drugs within 3 months prior to screening visit. • Within the last 6 months prior to screening visit: myocardial infarction, unstable angina, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures to be performed during the study period. • History of stroke. • 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. • Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (eg, multiple endocrine neoplasia syndromes). • Uncontrolled or inadequately controlled hypertension (systolic blood pressure above 160 mmHg or diastolic blood pressure above 90 mmHg) at screening visit. • At screening visit, Body Mass Index (BMI) less than or equal to 25 or above 45 kg/m². • At screening visit ALT or AST more than 3 ULN. • At screening visit calcitonin above or equal to 20 pg/mL (5.9 pmol/L). • Exclusion Criteria for randomization at the end of the screening period: o HbA1c less than 7.5% or above 12%. o Amylase and/or lipase more than 3 ULN. o Calcitonin above or equal to 20 pg/mL (5.9pmol/L). • Participation in other clinical trials or observation period of competing trials up to 30 days prior to this study. • Known malformation of the central nervous system• Persons working nightshift• Treatment with drugs with central nervous actions or systemic steroid therapy • Any relevant (according to investigator’s judgment) cardiovascular disease, e.g. myocardial infarction, acute coronary syndrome, unstable angina pectoris,PTCA, heart failure (NYHA II-IV), planned coronary,carotid or peripheral artery revascularisation procedures to be performed during the study period. • Indication of liver disease, as per medical history or defined by serum levels of either Alanine,Aminotransferase (ALT [SGPT]), Aspartate Aminotransferase (AST [SGOT]), or Alkaline Phosphatase above 3 x upper limit of normal (ULN) as determined during screening.• Alcohol abuse, defined as more than 20 gr/day • Impaired renal function, defined as estimated Glomerular Filtration Rate (eGFR) = 60 ml/min (MDRD formula) as determined duri
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Objective: To assess whether treatment with insulin glargine + lixisenatide (iGlarLixi) versus insulin glargine changes regional brain insulin sensitivity and thereby glucose metabolism, eating behaviour, and cognition in patients with type 2 diabetes insufficiently controlled with oral antidiabetic drugs (OAD).;Secondary Objective: o Effect of 12 weeks treatment with iGlarLixi or Glargine on resting state brain activity and on brain response to food pictures and control pictures as assessed by functional magnetic resonance imaging. Food intake and food preference will be monitored during an ad libitum buffet. o Effect of 12 weeks treatment with iGlarLixi or Glargine on cognitive function assessed by established neurocognitive tests (CANTAB[Cambridge Neuropsychological Test Automated Battery]containing Motor Screening Task (MOT),Reaction Time (RTI) Paired Associates Learning (PAL), Spatial Working Memory (SWM), PatternRecognition Memory (PRM), Delayed Matching to Sample (DMS), Rapid Visual InformationProcessing (RVP) tests). o Effect of 12 weeks treatment with iGlarLixi or Glargine on glycemic control (HbA1c change from baseline to week 12). o Effect of 12 weeks treatment with iGlarLixi or Glargine on body weight and body fat distribution ;Primary end point(s): o Effect of 12 weeks treatment with iGlarLixi or Glargine on brain insulin sensitivity assessed by functional magnetic resonance imaging (fMRI) as change in regional cerebral blood flow (rCBF) from before to 30 minutes after nasal insulin spray application.;Timepoint(s) of evaluation of this end point: Visit 2 and visit 7 ( week 0 and 12) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): o Effect of 12 weeks treatment with iGlarLixi or Glargine on resting state brain activity and on brain response to food pictures and control pictures as assessed by functional magnetic resonance imaging. Food intake and food preference will be monitored during an ad libitum buffet. o Effect of 12 weeks treatment with iGlarLixi or Glargine on cognitive function assessed by established neurocognitive tests (HVLT [Hopkins Verbal Learning Test]; TMT-A&B [Trail Making Test-A&B], MMSE ; MOCA + Digit Symbol Substitution Test [SDMT ]; CANTAB [Cambridge Neuropsychological Test Automated Battery] Tests). o Effect of 12 weeks treatment with iGlarLixi or Glargine on glycemic control (HbA1c change from baseline to week 12 ). o Effect of 12 weeks treatment with iGlarLixi or Glargine on body weight and body fat distribution ;Timepoint(s) of evaluation of this end point: Effect of 12 weeks treatment with iGlarLixi or Glargine on resting state brain activity and on brain response to food pictures: Week 0 and Week 12 (Visit 0 and Visit 7) Effect of 12 weeks treatment with iGlarLixi or Glargine on cognitive function assessed by established neurocognitive tests: Week 0 and Week 12 (Visit 0 and Visit 7) Effect of 12 weeks treatment with iGlarLixi or Glargine on glycemic control (HbA1c change from baseline to week 12 ): Week 0 and Week 12 (Visit 0 and Visit 7) Effect of 12 weeks treatment with iGlarLixi or Glargine on body weight and body fat distribution: Week 0 and Week 12 (Visit 0 and Visit 7) | — |
Countries
Germany
Contacts
Public ContactInternal Medicine IV
University Hospital Tuebingen
Outcome results
None listed