Pharmacodynamic Study to Assess the Effects of Repeated Dosing of SAR247799 on Endothelial Function in Patients With Type 2 Diabetes Mellitus

Phase 1

Completed

• Conditions: Microvascular Coronary Artery Disease
• Interventions: Drug: Placebo; Drug: SAR247799; Drug: Sildenafil; Drug: Acetylcholine

• Registration Number: NCT03462017
• Lead Sponsor: Sanofi

Brief Summary

Primary Objective:

To assess the pharmacodynamic effects of SAR247799 on macrovascular endothelial function of the brachial artery using flow-mediated dilation (FMD) in patients with type 2 diabetes mellitus (T2DM).

Secondary Objective:

* To assess the pharmacodynamic effects of SAR247799 on microvascular endothelial function using laser Doppler perfusion monitoring in patients with T2DM.

* To assess the safety profile of SAR247799 in patients with T2DM.

* To assess the plasma pharmacokinetic profile of SAR247799 in patients with T2DM.

Detailed Description

Study duration per patient is approximately 10 weeks including a 4-week treatment period.

Study Timeline

• Study First Submitted: 2018-03-06
• Study First Submitted QC: 2018-03-06
• Study Start: 2018-03-07
• Study First Posted: 2018-03-12
• Primary Completion: 2018-12-22
• Study Completion: 2018-12-22
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-21
• Last Update Posted: 2022-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Identical matching placebo for SAR247799 and for sildenafil once daily in the morning under fasted condition for 28 days
Placebo	Acetylcholine	Identical matching placebo for SAR247799 and for sildenafil once daily in the morning under fasted condition for 28 days
SAR247799	SAR247799	SAR247799 repeated doses once daily in the morning under fasted condition for 28 days according to a sequential dose design
Sildenafil	Sildenafil	Sildenafil once daily in the morning under fasted condition for 28 days
Sildenafil	Acetylcholine	Sildenafil once daily in the morning under fasted condition for 28 days
SAR247799	Acetylcholine	SAR247799 repeated doses once daily in the morning under fasted condition for 28 days according to a sequential dose design

Primary Outcome Measures

Name	Time	Method
Change in Flow Mediated Dilation (FMD)	Baseline to Days 14, 21, 28, 35, and 42	Absolute change from baseline in the % FMD index of the brachial artery

Secondary Outcome Measures

Name	Time	Method
Microvascular reactivity	Baseline to Days 14, 21, 28, 35, and 42	Change from baseline in peak flow induced by acetylcholine iontophoresis measured using Laser Doppler perfusion monitoring
Assessment of pharmacokinetic (PK) parameter: Cmax	Days 1, 2, 3, 7, and 14	Cmax: Maximum plasma concentration observed
Assessment of PK parameter: Ctrough	Days 1, 2, 3, 7, and 14	Ctrough: Plasma concentration observed just before treatment administration during repeated dosing
Number of adverse events	Up to Day 42	Number of participants with adverse events
Assessment of PK parameter: tmax	Days 1, 2, 3, 7, and 14	tmax: Time to reach Cmax
Assessment of PK parameter: AUC0-24	Days 1, 2, 3, 7, and 14	AUC0-24: Area under the plasma concentration versus time curve over the dosing interval (24h)

Trial Locations

Locations (2)

Investigational Site Number 2760001; 🇩🇪 Neuss, Germany

Investigational Site Number 2760002; 🇩🇪 Mainz, Germany