Type 2 Diabetes Mellitus
Conditions
Brief summary
Primary Objectives: To assess in overweight to obese T2DM patients: * The glucagon receptor occupancy of SAR425899 at two dose levels in the human liver with positron-emission tomography (PET) imaging using \[68Ga\]Ga-DO3A-VS-Cys40-Tuna-2 as a tracer compound. * The GLP-1 receptor occupancy of SAR425899 at two dose levels in the human pancreas with PET imaging using \[68Ga\]Ga-DO3A-VS-Cys40-Exendin-4 as a tracer compound. * Pharmacodynamic effects on fasting plasma glucose and biomarkers of lipid metabolism. * Pharmacokinetic parameters for SAR425899 after repeated subcutaneous (SC) doses in plasma. * Safety and tolerability of SAR425899.
Detailed description
Study duration is approximately 7 weeks with a 20 days treatment period.
Interventions
DRUGSAR425899
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
DRUG[68Ga] Ga-DO3A-VS-Cys40-Tuna-2 (glucagon receptor tracer)
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
DRUG[68Ga] Ga-DO3A-VS-Cys40-Exendin-4 (GLP-1 receptor tracer)
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous
Sponsors
Antaros Medical
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
: * Male and female patients, between 18 and 75 years of age, inclusive. * Body weight between 60.0 and 120.0 kg, inclusive, body mass index between 28.0 and 38.0 kg/m2, inclusive. * Diagnosis of type 2 diabetes mellitus for at least 1 year at the time of inclusion with stable metformin treatment prior to inclusion, with or without comorbidities related to type 2 diabetes mellitus. * Fasting plasma glucose ≥ 90 mg/dL at screening. * Glycosylated hemoglobin (HbA1c) ≥6.5% and ≤9 % at screening.
Exclusion criteria
* Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female), urologic or infectious disease, hormonal active tumors (e.g. pheochromocytoma or insulinoma), or signs of acute illness that is not related to the metabolic status of the patient. * Presence or history of drug hypersensitivity (including known allergic reactions associated with glucagon like peptide-1 (GLP-1) agonist treatment \[exenatide, liraglutide, lixisenatide\]), or allergic disease diagnosed and treated by a physician. * Any intake of menopausal hormone replacement therapy, systemic corticosteroids, growth hormones, weight-loss drugs, antihyperlipidemic treatment, antihyperglycemic treatment \[e.g., GLP-1 agonists, insulin, thiazolidinediones, dipeptidylpeptidase (DPP-IV) inhibitors, sodium/glucose cotransporter-2 (SGLT-2) inhibitors etc.\]) during the treatment period and within 21 days before first dosing or within 5 times the elimination half-life or pharmacodynamic half-life of the medication (if known), with the exception of metformin, sulphonylureas (SU), standard antihypertensive treatment, statins and acetyl salicylic acid. * Any condition possibly affecting gastric emptying or absorption from gastro-intestinal tract (e.g., gastric surgery, gastrectomy, bariatric surgery, malabsorption syndromes, gastroparesis, abdominal surgery other than appendectomy, hysterectomy, cholecystectomy and herniaplasty). * Surgically treated obesity, bariatric surgery. * Severe dyslipidemia with fasting triglycerides \>450 mg/dL at screening. * Severe hypoglycemia resulting in seizure/unconsciousness/coma or hospitalization for diabetic ketoacidosis in the last 3 months before screening. * Persistent hyperglycemia not adequately controlled by metformin, SUs and/or diet/exercise. * Diagnosed diabetic neuropathy, retinopathy, nephropathy or renal impairment (GFR \<60 mL/min; estimate after Cockcroft-Gault) at screening. * Unstable hypo- or hyperthyroidism (as assessed by TSH) at screening. * History of pancreatitis or pancreatectomy. * Amylase and/or lipase \> 2 upper limit of normal (ULN) at screening. * Personal history or family history of medullary thyroid cancer or a genetic condition that predisposes to medullary thyroid cancer. * Elevated basal calcitonin (≥20 pg/mL / 5.9 pmol/L) at screening. * Known past or present diseases or disorders of any target organ (liver, pancreas, spleen). * Medical positron emitting tomography (PET), single photon emission computer tomography (SPECT), abdominal or thoracic computer tomography (CT) examination during the previous 12 months' time period. * Claustrophobia. 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 |
|---|---|---|
| Glucagon receptor occupancy | Day 1 and Day 20 | Change of glucagon receptor tracer binding in the liver with SAR425899 between Day 1 and Day 20 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Up to 27 days | Number of adverse events in patients under treatment with SAR425899 |
| Pharmacokinetics | Day 20 | Assessment of SAR425899 maximum plasma concentration (Cmax) |
| Change in fasting plasma glucose (FPG) | Day 1 to Day 20 | Absolute change in FPG from baseline to Day 20 |
| Change in ketone bodies | Day 1 to Day 20 | Absolute change in ketone bodies from baseline to Day 20 |
| GLP-1 receptor occupancy | Day 1 and Day 17 | Change of GLP-1 receptor tracer binding in the pancreas with SAR425899 between Day 1 and Day 17 |
| Change in volume of distribution (Vt) in the liver | Day 1 and Day 20 | Change of glucagon receptor tracer Vt in the liver with SAR425899 between Day 1 and Day 20 |
| Change in Vt in the pancreas | Day 1 and Day 17 | Change of GLP-1 receptor tracer Vt in the pancreas with SAR425899 between Day 1 and Day 17 |
| Average standard uptake values (SUVs) of PET tracers in the liver and pancreas | Day 1, Day 17 and Day 20 | Average SUVs for glucagon and GLP-1 tracer in liver and pancreas |
| Change lipid biomarkers | Day 1 to Day 20 | Absolute change cholesterol from baseline to Day 20 |
Countries
Sweden
Outcome results
None listed