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

NCT03462017 | Completed Phase 1

• 3 other identifiers: PDY152862017-002592-26U1111-1197-8124
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

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.

Conditions

Microvascular Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• Change in Flow Mediated Dilation (FMD)

  Absolute change from baseline in the % FMD index of the brachial artery

  Baseline to Days 14, 21, 28, 35, and 42

Secondary Outcomes (6)

• Microvascular reactivity

  Baseline to Days 14, 21, 28, 35, and 42

• Number of adverse events

  Up to Day 42

• Assessment of pharmacokinetic (PK) parameter: Cmax

  Days 1, 2, 3, 7, and 14

• Assessment of PK parameter: Ctrough

  Days 1, 2, 3, 7, and 14

• Assessment of PK parameter: tmax

  Days 1, 2, 3, 7, and 14

Study Arms (3)

SAR247799

EXPERIMENTAL

SAR247799 repeated doses once daily in the morning under fasted condition for 28 days according to a sequential dose design

Drug: SAR247799; Drug: Acetylcholine

Placebo

PLACEBO COMPARATOR

Identical matching placebo for SAR247799 and for sildenafil once daily in the morning under fasted condition for 28 days

Drug: Placebo; Drug: Acetylcholine

Sildenafil

ACTIVE COMPARATOR

Sildenafil once daily in the morning under fasted condition for 28 days

Drug: Sildenafil; Drug: Acetylcholine

Interventions

SAR247799 DRUG

Pharmaceutical form:Capsule Route of administration: Oral

SAR247799

Placebo DRUG

Pharmaceutical form:Capsule Route of administration: Oral

Placebo

Sildenafil DRUG

Pharmaceutical form:Encapsulated tablet Route of administration: Oral

Sildenafil

Acetylcholine DRUG

Pharmaceutical form:Solution Route of administration: Transdermal

Placebo; SAR247799; Sildenafil

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female stable Type 2 diabetes mellitus (T2DM) patients.
• Body Mass Index between 18 and 35 kg/m\^2.
• Stable T2DM patients, but otherwise healthy as assessed by a clinical and laboratory assessments and detailed medical history.
• Diagnosis of T2DM for at least 6 months at the time of the screening visit.
• Glycosylated hemoglobin (HbA1c) \< 8.5%.
• estimated glomerular filtration rate ˃60 mL/min/1.73 m\^2.
• Flow-mediated dilatation (FMD) ≤7% at screening.
• No clinically significant abnormality detected in cardiac echography, as assessed by certified Cardiologist, performed at screening.

You may not qualify if:

• Any history or presence of clinically relevant or symptomatic gastrointestinal, hepatic, metabolic (except stable T2DM and controlled dyslipidemia), hematological, osteomuscular, articular, psychiatric, systemic, gynecologic (if female), or infectious disease, or ongoing cancer (including basal cell skin carcinoma), or signs of acute illness which as judged by the Investigator, may affect the patient's participation in or the outcome of this study.
• Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure ≥30 mmHg within 3 minutes when changing from 10 min supine to standing position, at screening.
• History of symptomatic bradycardia, fainting, collapse, syncope, or vasovagal reactions in the last 6 months.
• Presence or history of drug hypersensitivity and/or allergy to any ingredients of the investigational product and/or non-investigational product diagnosed and treated by a physician.
• Any subject who cannot be treated with sildenafil because of conditions mentioned in the contra-indication, warning and precautions sections of sildenafil product information notably subjects with anatomical deformity of the penis.
• Loss of vision due to non-arteritic, neuro-optic, anterior ischemia assessed in ophtalmologic examination at screening.
• If female, pregnancy (defined as positive β-human chorionic gonadotropin blood and urine test), breast-feeding.
• Generally any medication which has a potential to interfere with the safety, pharmacokinetics of SAR247799 and sildenafil, or with study measurements is not allowed, and in particular:
• Nitrates, all calcium channel blockers, phosphodiesterase type 5 inhibitors (except investigational medicinal product \[IMP\]), guanylate cyclase stimulators use or anticipated during the study;
• Beta-blockers;
• Glucagon-like peptide-1 agonists;
• Insulins (all types);
• Anticoagulants, antithrombotics except aspirin;
• Any drugs which decrease heart rate;
• Antiarrhythmics;

Sponsors & Collaborators

• Sanofi: lead

Study Sites (2)

Investigational Site Number 2760002

Mainz, 55116, Germany

Location

Investigational Site Number 2760001

Neuss, 41460, Germany

Location

Related Publications (1)

• Bergougnan L, Andersen G, Plum-Morschel L, Evaristi MF, Poirier B, Tardat A, Ermer M, Herbrand T, Arrubla J, Coester HV, Sansone R, Heiss C, Vitse O, Hurbin F, Boiron R, Benain X, Radzik D, Janiak P, Muslin AJ, Hovsepian L, Kirkesseli S, Deutsch P, Parkar AA. Endothelial-protective effects of a G-protein-biased sphingosine-1 phosphate receptor-1 agonist, SAR247799, in type-2 diabetes rats and a randomized placebo-controlled patient trial. Br J Clin Pharmacol. 2021 May;87(5):2303-2320. doi: 10.1111/bcp.14632. Epub 2020 Nov 26.

  PMID: 33125753 DERIVED

MeSH Terms

Interventions

Sildenafil Citrate; Acetylcholine

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Biogenic Amines; Amines

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2018
• First Posted: March 12, 2018
• Study Start: March 7, 2018
• Primary Completion: December 22, 2018
• Study Completion: December 22, 2018
• Last Updated: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (2)