Heart failure with Preserved Ejection Fraction MedDRA version: 12.1 Level: LLT Classification code 10069211 Term: Diastolic heart failure
Conditions
Interventions
Product Name: Ranolazine injection
Pharmaceutical Form: Concentrate for solution for injection
INN or Proposed INN: Ranolazine
CAS Number: 95635-55-5
Concentration unit: mg/ml milligram(s)/millilitre
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males or females aged = 40 years 2. Clinical symptoms of heart failure (NYHA class II-III) at time of screening (e.g., dyspnea, paroxysmal nocturnal dyspnea, orthopnea, bilateral lower extremity edema) 3. Left ventricular ejection fraction (LVEF) = 45% at screening 4. With: a. E/E' > 15 measured by Tissue Doppler echocardiography at screening OR b. NT-pro-BNP > 220pg/mL at screening AND c. Average resting LVEDP = 18 mm Hg (refer to continued eligibility criteria), d. Average resting time constant of relaxation (tau) = 50 ms at time of cardiac catheterization (refer to continued eligibility criteria) 5. For female patients only: be postmenopausal (no menses for last 24 months) or sterilized, or if of child-bearing potential, is not breastfeeding, has a negative pregnancy test at time of study, has no intention of becoming pregnant during the course of the study, and is using one or more of the following contraceptive measures: a. Stable regimen of hormonal contraception b. Intrauterine device c. Condoms with spermicide d. Diaphragm with spermicide e. Abstinence 6. Signed informed consent 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Acute cardiac decompensation requiring mechanical ventilation 2. Hypotension with blood pressure 100 beats per minute 11. Need for treatment with Class I or III antiarrhythmic medications 12. Implantable pacemaker, cardioverter-defibrillator, or left ventricular assist device 13. Clinically significant chronic hepatic impairment (Child-Pugh Class B [moderate] or Class C [severe]) 14. Severe renal insufficiency defined as creatinine clearance < 30 mL/min as calculated by Cockroft-Gault formula or Modified Diet in renal Disease (MDRD) equation. 15. History of congenital or a family history of long QT syndrome, or known acquired QT interval prolongation. 16. Inability to exercise due to other co-morbidities that may affect performance of cardiopulmonary exercise test, CPET (e.g., osteoarthritis, peripheral vascular disease) 17. Current treatment with potent and moderate CYP3A inhibitors 18. Current treatment with potent CYP3A inducers (e.g., rifampin/rifampicin, St. John’s Wort, carbamazepin/carbamazepine) 19. Prior treatment with ranolazine 20. Participation in another trial of an investigational drug or device within 30 days prior to screening 21. Other conditions that in the opinion of the investigator may increase the risk to the patient (e.g. pts with weight = 60 kg), prevent compliance with study protocol or compromise the quality of the clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine if ranolazine, compared to placebo, will be more effective in improving diastolic function in patients with HFpEF.;Secondary Objective: To collect further information about the safety and tolerability of ranolazine in this patient population through Day 28 safety follow-up.;Primary end point(s): The study will include the following exploratory endpoints; 1. Change from baseline to 30 minutes from initiation of study drug bolus No. 1 (T = 30 min) in cardiac catheterization hemodynamic parameters at both resting and paced conditions: a. time-constant of relaxation (tau) b. left ventricular end-diastolic pressure (LVEDP) c. dP/dtmin (minimal rate of LV pressure change) 2. Change from baseline to Day 14 in: a. mitral E wave velocity/mitral annular velocity (E/E') ratio assessed by Tissue Doppler (TD) echocardiography b. VO2 max assessed by cardiopulmonary exercise test (CPET) c. N-terminal pro-brain B-type natriuretic peptide (NT-pro-BNP) | — |
Countries
Germany
Outcome results
None listed