The objectives are to evaluate the safety and efficacy of TRC4186 and to define the recommended dose level for further pivotal studies.
ID
Source
Brief title
Condition
- Heart failures
- Diabetic complications
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy parameters are the *Physical dimension of Minnesota Living
with Heart Failure Questionnaire (MLHFQ)* and the *Oxygen uptake efficiency
slope*.
Secondary outcome
Secondary parameters are NT-proBNP levels, peak VO2, NYHA classification,
change in diuretic dosage, Impedance cadiography (ICG) parameters, conventional
and tissue Doppler echocardiography, VAS scale *Oxygen Cost Diagram*.
Background summary
Patients of CHF with diabetes are a high risk population with compromised
prognosis due to increased accumulation of AGEs (Advanced Glycosylation
Endproducts) which cause macro-and micro-vascular complications. The
Investigational Medicinal Product (IMP) TRC4186 retards the progression of and
reverses diabetic macro-and micro-vascular complications by reducing AGEs
burden in various target tissue. Thus improving the endothelial and myocardial
function in animal models of diabetes. Its safety has been ascertained in
pre-clinical and clinical studies. Therefore, TRC4186 could offer a potentially
effective therapy for the complications of diabetes.
Study objective
The objectives are to evaluate the safety and efficacy of TRC4186 and to define
the recommended dose level for further pivotal studies.
Study design
This is a randomised, double-blind, multinational, multi-centre,
placebo-controlled, parallel-group study.
Intervention
During a period of 14 months patients have to attend the study site for 9-13
ambulant visits. Then blood samples, in total 240 ml, for safety assessments
will be collected. Other measurements like ECG, ICG or spiroergometry are
non-invasive.
Study burden and risks
Based on preclinical studies patients with symptoms of congestive heart failure
(CHF) on antihypertensive medication may experience a fall in blood pressure.
Additionally, observed effects of the proposed study drug may be similar to
events associated with the use of Losartan (hypotensive pharmaceutical).
As this is a clinical research trial and despite the careful control and the
exclusion of any risk factors throughout the study, it cannot be excluded that
unforeseen effects occur from treatment with TRC4186.
Since this a first study in patients with CHF and impaired glucose tolerance
participants may benefit from study treatment and are otherwise, e.g. placebo
group, under close supervision by the investigational site, and appropriate
measures can be initiated early.
Village Bhat, Dist Gandhinagar
382428 Gujarat
IN
Village Bhat, Dist Gandhinagar
382428 Gujarat
IN
Listed location countries
Age
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-006237-27-NL |
| CCMO | NL28020.042.09 |