| Eligibility |
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 ß-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.
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