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Microvascular Coronary Artery DiseasePhase 1NCT03462017

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

A Phase 1 study testing SAR247799, Sildenafil and Acetylcholine in people with Microvascular Coronary Artery Disease, run by Sanofi at 2 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
Microvascular Coronary Artery Disease
What is being tested?
SAR247799, Sildenafil and Acetylcholine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
54 participants
Where
2 sitesGermany
Study dates
7 Mar 2018to 22 Dec 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

2 sites in 1 country.

Germany2 sites

  • Investigational Site Number 2760002

    Mainz, 55116

  • Investigational Site Number 2760001

    Neuss, 41460

Other trials in Germany

About this study

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

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.
Read the detailed description

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

Being tested
SAR247799, Placebo, Sildenafil, Acetylcholine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SAR247799Drug

    Pharmaceutical form:Capsule Route of administration: Oral

  • PlaceboDrug

    Pharmaceutical form:Capsule Route of administration: Oral

  • SildenafilDrug

    Pharmaceutical form:Encapsulated tablet Route of administration: Oral

  • AcetylcholineDrug

    Pharmaceutical form:Solution Route of administration: Transdermal

Study groups in NCT03462017
Study groupRoleWhat they receive
SAR247799ExperimentalSAR247799 repeated doses once daily in the morning under fasted condition for 28 days according to a sequential dose design
Receives: Drug: SAR247799; Drug: Acetylcholine
PlaceboPlacebo comparatorIdentical matching placebo for SAR247799 and for sildenafil once daily in the morning under fasted condition for 28 days
Receives: Drug: Placebo; Drug: Acetylcholine
SildenafilActive comparatorSildenafil once daily in the morning under fasted condition for 28 days
Receives: Drug: Sildenafil; Drug: Acetylcholine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Flow Mediated Dilation (FMD)

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

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

Secondary outcomes (6)

  1. Microvascular reactivity

    Change from baseline in peak flow induced by acetylcholine iontophoresis measured using Laser Doppler perfusion monitoring

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

  2. Number of adverse events

    Number of participants with adverse events

    Measured: Up to Day 42

  3. Assessment of pharmacokinetic (PK) parameter: Cmax

    Cmax: Maximum plasma concentration observed

    Measured: Days 1, 2, 3, 7, and 14

  4. Assessment of PK parameter: Ctrough

    Ctrough: Plasma concentration observed just before treatment administration during repeated dosing

    Measured: Days 1, 2, 3, 7, and 14

  5. Assessment of PK parameter: tmax

    tmax: Time to reach Cmax

    Measured: Days 1, 2, 3, 7, and 14

  6. Assessment of PK parameter: AUC0-24

    AUC0-24: Area under the plasma concentration versus time curve over the dosing interval (24h)

    Measured: Days 1, 2, 3, 7, and 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2018
  2. Study start7 Mar 2018
  3. Primary completion22 Dec 2018
  4. Study completion22 Dec 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Sequential
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03462017
Sponsor's protocol ID
PDY15286
Other IDs
2017-002592-26, U1111-1197-8124, 2017
Status last verified
Apr 2022
First submitted
6 Mar 2018
Last updated
25 Apr 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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://vivli.org

Publications

  • 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.

    PubMed 33125753

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SAR247799, Sildenafil and Acetylcholine in people with Microvascular Coronary Artery Disease, run by Sanofi at 2 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Flow Mediated Dilation (FMD) (time frame: Baseline to Days 14, 21, 28, 35, and 42). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03462017, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2022.

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