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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03350191
Recruitment Status : Completed
First Posted : November 22, 2017
Last Update Posted : October 11, 2018
Sponsor:
Collaborator:
Antaros Medical AB
Information provided by (Responsible Party):
Sanofi

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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus 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) Phase 1

Detailed Description:
Study duration is approximately 7 weeks with a 20 days treatment period.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A PET/CT Study to Assess the Receptor Occupancy by SAR425899 After Repeat Dosing Using Radiolabelled Tracers for the Glucagon and GLP-1 Receptor in Overweight to Obese T2DM Patients
Actual Study Start Date : December 20, 2017
Actual Primary Completion Date : June 7, 2018
Actual Study Completion Date : June 7, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Glucagon

Arm Intervention/treatment
Experimental: SAR425899 high dose
Repeated once daily subcutaneous (SC) doses of SAR425899 administered over 20 days
Drug: SAR425899

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


Experimental: SAR425899 low dose
Repeated once daily SC doses of SAR425899 administered over 20 days
Drug: SAR425899

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





Primary Outcome Measures :
  1. Glucagon receptor occupancy [ Time Frame: Day 1 and Day 20 ]
    Change of glucagon receptor tracer binding in the liver with SAR425899 between Day 1 and Day 20


Secondary Outcome Measures :
  1. GLP-1 receptor occupancy [ Time Frame: Day 1 and Day 17 ]
    Change of GLP-1 receptor tracer binding in the pancreas with SAR425899 between Day 1 and Day 17

  2. Adverse events [ Time Frame: Up to 27 days ]
    Number of adverse events in patients under treatment with SAR425899

  3. Pharmacokinetics [ Time Frame: Day 20 ]
    Assessment of SAR425899 maximum plasma concentration (Cmax)

  4. Change in fasting plasma glucose (FPG) [ Time Frame: Day 1 to Day 20 ]
    Absolute change in FPG from baseline to Day 20

  5. Change in ketone bodies [ Time Frame: Day 1 to Day 20 ]
    Absolute change in ketone bodies from baseline to Day 20

  6. Change lipid biomarkers [ Time Frame: Day 1 to Day 20 ]
    Absolute change cholesterol from baseline to Day 20

  7. Change in volume of distribution (Vt) in the liver [ Time Frame: Day 1 and Day 20 ]
    Change of glucagon receptor tracer Vt in the liver with SAR425899 between Day 1 and Day 20

  8. Change in Vt in the pancreas [ Time Frame: Day 1 and Day 17 ]
    Change of GLP-1 receptor tracer Vt in the pancreas with SAR425899 between Day 1 and Day 17

  9. Average standard uptake values (SUVs) of PET tracers in the liver and pancreas [ Time Frame: Day 1, Day 17 and Day 20 ]
    Average SUVs for glucagon and GLP-1 tracer in liver and pancreas

  10. Pharmacokinetics [ Time Frame: Day 20 ]
    Assessment of SAR425899 time to reach Cmax ( tmax)

  11. Pharmacokinetics [ Time Frame: Day 20 ]
    Assessment of SAR425899 area under the concentration versus time curve (AUC)

  12. Pharmacokinetics [ Time Frame: Day 20 ]
    Assessment of SAR425899 terminal elimination half-life ( t1/2)

  13. Pharmacokinetics [ Time Frame: Day 20 ]
    Assessment of SAR425899 total body clearance from the plasma (CL)

  14. Change lipid biomarkers [ Time Frame: Day 1 to Day 20 ]
    Absolute change in free fatty acids from baseline to Day 20

  15. Change lipid biomarkers [ Time Frame: Day 1 to Day 20 ]
    Absolute change in triglycerides from baseline to Day 20



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03350191


Locations
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Sweden
Investigational Site Number 7520001
Uppsala, Sweden, 75237
Sponsors and Collaborators
Sanofi
Antaros Medical AB
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03350191    
Other Study ID Numbers: PDY15264
2017-001789-23
First Posted: November 22, 2017    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Overweight
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Body Weight
Signs and Symptoms
Exenatide
Glucagon
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Incretins
Hypoglycemic Agents
Anti-Obesity Agents