Evaluation of the reduction in heart rate, of the quantity of drug in the plasma and of the safety after different ascending oral doses of the active substance or a placebo in heart failure patients with a reduction of left ventricular ejection fraction (i.e. thequantity of blood the heart is able to eject in the body at each heart beat).
- Conditions
- Patients with chronic heart failure and left ventricular systolicdysfunctionMedDRA version: 17.0Level: LLTClassification code 10007648Term: Cardiovascular disease, unspecifiedSystem Organ Class: 100000004849Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2013-003000-39-SK
- Lead Sponsor
- Institut de Recherches Internationales Servier
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 200
- Documented sinus rhythm and mean HR = 75 bpm measured on two consecutive resting 12-leads ECGs recordings one minute registration - performed at least 5 minutes apart (supine position for at least 10 minutes rest). If one of the two HR measurements is 73 or 74 bpm at the inclusion visit, the patient can be included provided that the mean of both HR measurements at the visit is = 75 bpm,
- LVEF = 35% as measured and documented within the previous 6 months (in stable clinical condition). For patient without known diagnosis of LVEF = 35%, a LVEF will be scheduled before inclusion visit,
- Compliant to study treatment during run-in period (70-130%),
- Symptomatic CHF of New York Heart Association (NYHA) class II, III or IV for at least 3 months prior to selection,
- In stable clinical condition with regards to CHF symptoms for at least 4 weeks prior to selection,
- With optimal and unchanged CHF medications or dosages, for at least 4 weeks prior to selection.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80
- LVEF of 35% or higher on a recently performed measurement (less than 6 months),
- Serum haemoglobin < 110 g/L,
- ALT or AST > 3 times the upper limit of normal values,
- Significant change in cardiovascular condition, since the informed consent signature, change in heart failure background therapy or dosage, or use of intravenous inotropic therapies,
- Recent (less than 3 months) myocardial infarction or coronary revascularization,
- Scheduled coronary revascularization,
- Severe aortic or mitral stenosis, or severe aortic regurgitation, or severe primary mitral regurgitation,
- Scheduled surgery for valvular heart disease,
- Cardiac Resynchronisation Therapy (CRT),
- Pacemaker carrier,
- Documented permanent atrial fibrillation or other cardiac arrhythmia that interfere with the sinus node function, or recent hospitalization for atrial fibrillation or other cardiac arrhythmia that interfere with the sinus node function within the last 3 months.
- Positive blood and / or urinary pregnancy test
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the pharmacodynamics in relation to resting heart rate (HR) of two different schemes of starting doses and two step titration doses of S 38844 versus placebo in patients with moderate to severe chronic heart failure and left ventricular systolic dysfunction treated with optimal background therapy.;Secondary Objective: - To assess the pharmacokinetics of S 38844 and its main metabolites and the pharmacokinetic/pharmacodynamic (PK/PD) relationship with respect to resting heart rate (HR) for each tested dose of S 38844.<br>- To evaluate the global and cardiac safety of two different schemes of starting doses and two step titration doses of S 38844 versus placebo.;Primary end point(s): HR change from baseline to end of each treatment period is the main endpoint to assess the pharmacodynamics effect of S 38844 (mean HR measured at trough from two 12-lead ECGs).;Timepoint(s) of evaluation of this end point: All along the study
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Safety endpoints: <br>- occurence of adverse events<br>- 24-hour Holter ECG parameters,<br>- Physical examination including weight, systolic and diastolic blood pressure change,<br>- HR on 12-lead ECG,<br>- Laboratory test parameters (haematology and biochemistry parameters).<br>Pharmacokinetic endpoints: <br>- Plasma pharmacokinetics parameters of the parent drug S 38844 and of its main metabolites,<br>- Pharmacokinetic/pharmacodynamic (PK/PD) relationship with respect to resting heart rate (HR) for each tested dose of S38844.;Timepoint(s) of evaluation of this end point: All along the study