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

NCT03350191 | Completed Phase 1

• 2 other identifiers: PDY152642017-001789-23
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Glucagon receptor occupancy

  Change of glucagon receptor tracer binding in the liver with SAR425899 between Day 1 and Day 20

  Day 1 and Day 20

Secondary Outcomes (15)

• GLP-1 receptor occupancy

  Day 1 and Day 17

• Adverse events

  Up to 27 days

• Pharmacokinetics

  Day 20

• Change in fasting plasma glucose (FPG)

  Day 1 to Day 20

• Change in ketone bodies

  Day 1 to Day 20

Study Arms (2)

SAR425899 high dose

EXPERIMENTAL

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

Drug: SAR425899; Drug: [68Ga] Ga-DO3A-VS-Cys40-Tuna-2 (glucagon receptor tracer); Drug: [68Ga] Ga-DO3A-VS-Cys40-Exendin-4 (GLP-1 receptor tracer)

SAR425899 low dose

EXPERIMENTAL

Repeated once daily SC doses of SAR425899 administered over 20 days

Drug: SAR425899; Drug: [68Ga] Ga-DO3A-VS-Cys40-Tuna-2 (glucagon receptor tracer); Drug: [68Ga] Ga-DO3A-VS-Cys40-Exendin-4 (GLP-1 receptor tracer)

Interventions

SAR425899 DRUG

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

SAR425899 high dose; SAR425899 low dose

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

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

SAR425899 high dose; SAR425899 low dose

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

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

SAR425899 high dose; SAR425899 low dose

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Fasting plasma glucose ≥ 90 mg/dL at screening.
• Glycosylated hemoglobin (HbA1c) ≥6.5% and ≤9 % at screening.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Sanofi: lead
• Antaros Medical: collaborator

Study Sites (1)

Investigational Site Number 7520001

Uppsala, 75237, Sweden

Location

Related Publications (1)

• 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.

  PMID: 34503957 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

SAR425899

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2017
• First Posted: November 22, 2017
• Study Start: December 20, 2017
• Primary Completion: June 7, 2018
• Study Completion: June 7, 2018
• Last Updated: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

SE (1)