HFpEF is associated with high morbidity and mortality and the prevalence is on the rise globally. Diabetics are at increased risk of developing HFpEF.~There is no evidence based therapy to improve the disease condition and its associated functional incapacity. Some of the recently concluded trials, PARAGON-HF, EMPERIAL-PRESERVED, failed to demonstrate benefit and it is regarded as an area with high unmet need.~Phase 2 results have demonstrated that in diabetic patients with heart failure having LVEF >30% and receiving guideline-indicated therapy with RAS inhibitors and β-blockers, TRC4186 has the potential to improve worsening of heart failure, functional status, cardiac diastolic function and has no adverse effect on cardiac mortality.~Therefore, TRC041266, the decanoic acid co-crystal of TRC4186 is an innovative product for the management of heart failure with LVEF≥40% in diabetic patients which is expected to modify the underlying disease at multiple levels and confer benefit as add-on to standard of care.~The current phase 3 study has been planned based on the results of the phase 2 trial which demonstrated that the TRC4186 2000 mg/day (in two divided doses; BD) administered orally for 48 weeks resulted in significant improvement in QoL measured by PD-MLHFQ, diastolic dysfunction measured by E/e' and reduction in HF hospitalization.~The dose level to be used in the present study is based on the assessment of safety, efficacy and PK data obtained from phase 1 and 2 studies. In the phase 2 study, a dose response was observed with a trend towards improvement at 500 mg/day dose of TRC4186, and clinically and statistically significant improvement was seen at 2000 mg/day (1000 mg BD). There was plateauing of the response beyond the dose of 2000 mg/day. Hence, the choice of optimal dose of TRC4186 being considered is lower than 2000 mg/day and in between 500 and 2000 mg/day, i.e., 1500 mg/day (750 mg BD). The total daily dose of TRC041266 which would be equivalent to 1500 mg/day of TRC4186, is TRC041266 3000 mg/day, to be administered in two divided doses,i.e., 1500 mg BD.
This study will be conducted as a randomized, multi-centre, double-blind, parallel-group, placebo-controlled study in patients receiving SoC therapy. Eligible participants will be randomized in a ratio of 1:1 to receive either test product, TRC041266 1500 mg or matching placebo twice daily for 48 weeks