A Clinical Study to Investigate if SAR425899 Binds to the Liver and Pancreas in Overweight to Obese Type 2 Diabetes Mellitus Patients

NCT ID: NCT03350191

Last Updated: 2022-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-20
• Study Completion Date: 2018-06-07

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

SAR425899 high dose

Repeated once daily subcutaneous (SC) doses of SAR425899 administered over 20 days

Group Type: EXPERIMENTAL

SAR425899

Intervention Type: DRUG

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous

[68Ga] Ga-DO3A-VS-Cys40-Tuna-2 (glucagon receptor tracer)

Intervention Type: DRUG

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous

[68Ga] Ga-DO3A-VS-Cys40-Exendin-4 (GLP-1 receptor tracer)

Intervention Type: DRUG

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous

SAR425899 low dose

Repeated once daily SC doses of SAR425899 administered over 20 days

Group Type: EXPERIMENTAL

SAR425899

Intervention Type: DRUG

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous

[68Ga] Ga-DO3A-VS-Cys40-Tuna-2 (glucagon receptor tracer)

Intervention Type: DRUG

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous

[68Ga] Ga-DO3A-VS-Cys40-Exendin-4 (GLP-1 receptor tracer)

Intervention Type: DRUG

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous

Interventions

SAR425899

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous

Intervention Type: DRUG

[68Ga] Ga-DO3A-VS-Cys40-Tuna-2 (glucagon receptor tracer)

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous

Intervention Type: DRUG

[68Ga] Ga-DO3A-VS-Cys40-Exendin-4 (GLP-1 receptor tracer)

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Antaros Medical

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 7520001

Uppsala, , Sweden

Countries

Sweden

References

Eriksson O, Velikyan I, Haack T, Bossart M, Laitinen I, Larsen PJ, Berglund JE, Antoni G, Johansson L, Pierrou S, Tillner J, Wagner M. Glucagonlike Peptide-1 Receptor Imaging in Individuals with Type 2 Diabetes. J Nucl Med. 2022 May;63(5):794-800. doi: 10.2967/jnumed.121.262506. Epub 2021 Sep 9.

Reference Type: DERIVED

PMID: 34503957 (View on PubMed)

Other Identifiers

2017-001789-23

Identifier Type: -

Identifier Source: secondary_id

PDY15264

Identifier Type: -

Identifier Source: org_study_id