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

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: 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)

• Registration Number: NCT03350191
• Lead Sponsor: 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.

Detailed Description

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

Study Timeline

• Study First Submitted: 2017-11-16
• Study First Submitted QC: 2017-11-20
• Study First Posted: 2017-11-22
• Study Start: 2017-12-20
• Primary Completion: 2018-06-07
• Study Completion: 2018-06-07
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-21
• Last Update Posted: 2022-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SAR425899 high dose	SAR425899	Repeated once daily subcutaneous (SC) doses of SAR425899 administered over 20 days
SAR425899 low dose	SAR425899	Repeated once daily SC doses of SAR425899 administered over 20 days
SAR425899 low dose	[68Ga] Ga-DO3A-VS-Cys40-Exendin-4 (GLP-1 receptor tracer)	Repeated once daily SC doses of SAR425899 administered over 20 days
SAR425899 high dose	[68Ga] Ga-DO3A-VS-Cys40-Exendin-4 (GLP-1 receptor tracer)	Repeated once daily subcutaneous (SC) doses of SAR425899 administered over 20 days
SAR425899 high dose	[68Ga] Ga-DO3A-VS-Cys40-Tuna-2 (glucagon receptor tracer)	Repeated once daily subcutaneous (SC) doses of SAR425899 administered over 20 days
SAR425899 low dose	[68Ga] Ga-DO3A-VS-Cys40-Tuna-2 (glucagon receptor tracer)	Repeated once daily SC doses of SAR425899 administered over 20 days

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Pharmacokinetics	Day 20	Assessment of SAR425899 total body clearance from the plasma (CL)
Change in ketone bodies	Day 1 to Day 20	Absolute change in ketone bodies from baseline to Day 20
Change lipid biomarkers	Day 1 to Day 20	Absolute change in triglycerides 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
Adverse events	Up to 27 days	Number of adverse events in patients under treatment with SAR425899
Change in fasting plasma glucose (FPG)	Day 1 to Day 20	Absolute change in FPG from baseline to 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

Trial Locations

Locations (1)

Investigational Site Number 7520001; 🇸🇪 Uppsala, Sweden