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Trial record 1 of 1 for:    03462017
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Pharmacodynamic Study to Assess the Effects of Repeated Dosing of SAR247799 on Endothelial Function in Patients With Type 2 Diabetes Mellitus

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ClinicalTrials.gov Identifier: NCT03462017
Recruitment Status : Recruiting
First Posted : March 12, 2018
Last Update Posted : November 30, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Microvascular Coronary Artery Disease Drug: SAR247799 Drug: Placebo Drug: Sildenafil Drug: Acetylcholine Phase 1

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Study to Assess the Pharmacodynamic Effects of Repeated Oral Doses of SAR247799 on Endothelial Function in Male and Female Patients With Type 2 Diabetes Mellitus
Actual Study Start Date : March 7, 2018
Estimated Primary Completion Date : December 21, 2018
Estimated Study Completion Date : December 21, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Sildenafil

Arm Intervention/treatment
Experimental: SAR247799
SAR247799 repeated doses once daily in the morning under fasted condition for 28 days according to a sequential dose design
Drug: SAR247799
Pharmaceutical form:Capsule Route of administration: Oral

Drug: Acetylcholine
Pharmaceutical form:Solution Route of administration: Transdermal

Placebo Comparator: Placebo
Identical matching placebo for SAR247799 and for sildenafil once daily in the morning under fasted condition for 28 days
Drug: Placebo
Pharmaceutical form:Capsule Route of administration: Oral

Drug: Acetylcholine
Pharmaceutical form:Solution Route of administration: Transdermal

Active Comparator: Sildenafil
Sildenafil once daily in the morning under fasted condition for 28 days
Drug: Sildenafil
Pharmaceutical form:Encapsulated tablet Route of administration: Oral

Drug: Acetylcholine
Pharmaceutical form:Solution Route of administration: Transdermal




Primary Outcome Measures :
  1. Change in Flow Mediated Dilation (FMD) [ Time Frame: Baseline to Days 14, 21, 28, 35, and 42 ]
    Absolute change from baseline in the % FMD index of the brachial artery


Secondary Outcome Measures :
  1. Microvascular reactivity [ Time Frame: 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

  2. Number of adverse events [ Time Frame: Up to Day 42 ]
    Number of participants with adverse events

  3. Assessment of pharmacokinetic (PK) parameter: Cmax [ Time Frame: Days 1, 2, 3, 7, and 14 ]
    Cmax: Maximum plasma concentration observed

  4. Assessment of PK parameter: Ctrough [ Time Frame: Days 1, 2, 3, 7, and 14 ]
    Ctrough: Plasma concentration observed just before treatment administration during repeated dosing

  5. Assessment of PK parameter: tmax [ Time Frame: Days 1, 2, 3, 7, and 14 ]
    tmax: Time to reach Cmax

  6. Assessment of PK parameter: AUC0-24 [ Time Frame: Days 1, 2, 3, 7, and 14 ]
    AUC0-24: Area under the plasma concentration versus time curve over the dosing interval (24h)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • 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.
  • Treatment of T2DM with lifestyle interventions or stable oral antidiabetic treatment for at least 3 months prior to inclusion.
  • No clinically significant abnormality detected in cardiac echography, as assessed by certified Cardiologist, performed at screening.

Exclusion criteria:

  • 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;
  • Digoxin;
  • Cholinergic agents eg pilocarpine or cholinesterase inhibitors eg neostigmine, guanidine;
  • Recent (≤3 months) use of systemic immunosuppressive or corticosteroid therapy;
  • Any inactivated vaccination (eg, seasonal influenza) during study treatment, any attenuated vaccination within 2 months before inclusion, and any biologics (antibody or its derivatives) given within 4 months before inclusion;
  • Any consumption of citrus fruits (grapefruit, orange, etc) or their juices within 3 days before inclusion as weak inhibitor of CYP3A4 gut wall metabolism.
  • Any severe dyslipidemia with fasting triglycerides > 450 mg/dL.
  • Any hyperosmolar hyperglycemic episode with severe neurological symptoms (eg, coma, aphasia) in the last 3 months before screening.
  • Weight change of ≥5 kg during the last 2 months prior to screening.
  • History or presence of clinically relevant or symptomatic pulmonary disease, such as asthma, chronic obstructive pulmonary disease, pulmonary embolism, pulmonary fibrosis, pulmonary hypertension which as judged by the Investigator, may affect the patient's participation in or the outcome of this study.
  • Cardiovascular history such as:
  • History or presence of a clinically relevant or symptomatic cardiovascular disease such as acute coronary syndrome (ACS), stroke, transient ischemic accident (TIA), obstructive or congestive heart failure, or structural heart disease (e.g., valvular disease) which as judged by the Investigator, may affect the patient's participation in or the outcome of this study.
  • History of elective percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within the past 6 months.
  • History of clinically relevant or symptomatic cardiac arrhythmia such as sustained ventricular arrhythmia, non-fixed supra-ventricular arrhythmia which as judged by the Investigator, may affect the patient's participation in or the outcome of this study or which occurred within the past 6 months
  • History of clinically relevant or symptomatic cardiac conduction abnormalities (any type of atrioventricular (AV) block, sick sinus syndrome, sinus node disease).
  • Patients with a pacemaker or implantable cardioverter defibrillator.
  • Known history of autoimmune disorders.
  • Any severe viral, systemic, fungal, bacterial or protozoal infection within the past 6 months or chronic severe infection (hepatitis, HIV infection, tuberculosis).
  • Presence of macular edema at fundus examination performed within 6 months before the first study drug administration.

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): NCT03462017


Contacts
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-Us@sanofi.com

Locations
Germany
Investigational Site Number 2760002 Recruiting
Mainz, Germany, 55116
Investigational Site Number 2760001 Recruiting
Neuss, Germany, 41460
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03462017     History of Changes
Other Study ID Numbers: PDY15286
2017-002592-26 ( EudraCT Number )
U1111-1197-8124 ( Other Identifier: UTN )
First Posted: March 12, 2018    Key Record Dates
Last Update Posted: November 30, 2018
Last Verified: November 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/

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:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Sildenafil Citrate
Acetylcholine
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs