heart failure associated with impaired glucose tolerance or type 2 diabetes mellitus MedDRA version: 9.1 Level: LLT Classification code 10019279 Term: Heart failure
Conditions
Interventions
Product Name: TRC4186
Product Code: TRC4186
Pharmaceutical Form: Film-coated tablet
CAS Number: 357625-50-4
Current Sponsor code: TRC4186
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
Torrent Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects aged = 45 years. Female and male subjects must be of non-childbearing or non-fertile potential, i.e. surgically sterile (bilateral oophorectomy, hysterectomy, bilateral tubal ligation, vasectomy) or post-menopausal for at least one year. Male subjects of fertile potential, must use an effective method of birth control 2. Subjects with chronic heart failure stable for last 6 weeks (NYHA class II – III) according to the criteria given in Appendix I (see section 15.1) and on stable medication for heart failure for at least 2 weeks prior to screening, with no change in drug or dose in that period. 3. Subjects with established type 2 diabetes mellitus (i.e. receiving oral therapy with or without insulin) or an impaired glucose tolerance (HbA1c should be =6.0% at screening) 4. Subjects with NT-proBNP (N-terminal fragment of the a brain natriuretic peptide (BNP)) = 400 pg/mL (subjects with atrial fibrillation NT-proBNP = 1200 pg/mL) 5. Subjects receiving a loop, thiazide or thiazide like diuretic (Metolazone, Chlorthalidon, Indapamide and Xipamide) for treating heart failure (HF) 6. Subjects able to undergo cardiopulmonary exercise testing 7. Subjects able to communicate well with the investigator and to comply with the requirements of the entire study 8. Subjects willing to give written informed consent (prior to any study-related procedures being performed) and able to adhere to the study restrictions and assessments schedule. 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. CHF caused by myocarditis, cor pulmonale, congenital heart disease, constrictive pericarditis, or hypertrophic or restrictive cardiomyopathy. 2. Significant important hemodynamic disease in the investigators opinion, e.g. mitral regurgitation and/or planned for surgery. 3. Acute coronary syndrome or coronary revascularization within 3 months 4. Angina as symptom limiting treadmill/bicycle exercise. 5. Evidence of myocardial ischemia which in the investigator’s opinion requires investigation by angiography with a view to coronary revascularization 6. Presence of a left ventricular (LV) aneurysm. 7. History of ventricular fibrillation or symptomatic sustained ventricular tachycardia without clear reversible precipitating cause (eg:- Severe hypokalemia [Serum potassium 40 kg/m2). 12. Pulmonary function (FEV1) less than 60 % of predicted or requiring long-term corticosteroids. 13. Type I diabetes. 14. Severe joint disease or peripheral arterial disease sufficient to impede exercise testing. 15. History of systemic and other vascular inflammatory disease. 16. Uncontrolled hypertension (systolic blood pressure = 160 mmHg under antihypertensive treatment). 17. Screening liver enzyme test (AST or ALT) exceeding 3 times the upper limit of normal range or hepatic impairment of Child-Pugh class C 18. Glomerular filtration rate (eGFR) 10 % 21. Gastrointestinal disorder that could interfere with study drug absorption 22. Medical history of chronic hepatitis B, C 23. Medical history of HIV seropositivity 24. Pregnancy or nursing females 25. Any cancer disease, except non-invasive skin cancer (e. g. actinic keratosis or basal cell carcinoma), or any other condition that may preclude full participation in the study or that limit survival 26. Prior history of radiation and chemotherapy for malignancies 27. Known hypersensitivity to any ingredient of the study medication 28. Current participation (including prior 30 days) in any other therapeutic clinical trial 29. Unwilling or unable to comply with protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate safety and efficacy of TRC4186 in the treatment of stable heart failure associated with HbA1c = 6% or type 2 diabetes receiving oral hypoglycaemic therapy (with or without additional insulin) as an add-on to conventional treatment for heart failure (Proof of Concept);Secondary Objective: To define the recommended dose level for further pivotal studies ;Primary end point(s): Efficacy •Physical dimension of Minnesota Living with Heart Failure Questionnaire (MLHFQ), a change of 5 points is regarded as clinically relevant •Oxygen uptake efficiency slope (OUES), a change of 10% is regarded as clinically relevant Safety •Morbidity/hospitalization for cardiac reasons •Mortality •Glomerular filtration rate (eGFR) | — |
Countries
Netherlands, United Kingdom
Outcome results
None listed