Safety and efficacy of TRC4186 in the treatment of stable heart failure associated with HbA1c >= 6.5 % or type 2 diabetes receiving oral hypoglycaemic therapy (with or without additional insulin) as an add-on to conventional treatment for heart failure

Phase 2

• Conditions: diabetes; heart failure; 10019280; 10012653

• Registration Number: NL-OMON33519
• Lead Sponsor: Torrent Pharmaceuticals Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 15

Inclusion Criteria

1. Male and female subjects aged >= 45 years. Female and male subjects must be of non-childbearing potential 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 stable chronic heart failure for 3 months (NYHA class II - III) according to the criteria given in Appendix I and on stable medication for at least 6 weeks.
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 6.5% -10.0% at screening)
4. Subjects with NT-proBNP (N-terminal fragment of the a brain natriuretic peptide (BNP)) >= 600 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.

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 the symptom limiting treadmill/bicycle exercise
5. Evidence of myocardial ischemia in ECG during CPET
6. Presence of a left ventricular (LV) aneurysm
7. History of symptomatic or sustained ventricular fibrillation or ventricular tachycardia unless treated with a
defibrillator
8. Second-degree or third-degree heart block (unless treated with a pacemaker), LBBB and patients receiving
CRT
9. Left ventricular assist device (or an activated minute ventilation pacemaker)
10. Gross obesity (body mass index (BMI) > 40 kg/m2)
11. Pulmonary function (FEV1) less than 60 % of predicted or requiring long-term corticosteroids
12. Type I diabetes
13. Severe joint disease or peripheral arterial disease sufficient to impede exercise testing
14. History of systemic and other vascular inflammatory disease
15. Uncontrolled hypertension (systolic blood pressure >= 160 mmHg under antihypertensive treatment)
16. Screening liver enzyme test (AST or ALT) exceeding 3 times the upper limit of normal range or hepatic
impairment of Child-Pugh class C
17. Serum creatinine > 1.6 mg /dl or glomerular filtration rate (eGFR) < 40 ml/min
18. Hemoglobin < 10.5 mg%.
19. Gastrointestinal disorder that could interfere with study drug absorption
20. Medical history of Chronic hepatitis B, C
21. Medical history of HIV seropositivity
22. Pregnancy or nursing females
23. 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
24. Prior history of radiation and chemotherapy for malignancies
25. Known hypersensitivity to any ingredient of the study medication
26. Current participation (including prior 30 days) in any other therapeutic clinical trial
27. Unwilling or unable to comply with protocol

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary efficacy parameters are the *Physical dimension of Minnesota Living<br /><br>with Heart Failure Questionnaire (MLHFQ)* and the *Oxygen uptake efficiency<br /><br>slope*. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary parameters are NT-proBNP levels, peak VO2, NYHA classification,<br /><br>change in diuretic dosage, Impedance cadiography (ICG) parameters, conventional<br /><br>and tissue Doppler echocardiography, VAS scale *Oxygen Cost Diagram*. </p><br>