Abstract

Aim: This study aimed at evaluating the efficacy and safety of a fixed-dose combination (FDC) of Efonidipine and Chlorthalidone in a randomized, Phase III trial setting.

Study Design: Multicentric, randomized, double-blind, parallel, comparative, active-controlled Phase III.

Place and Duration of Study: Six geographically distributed sites across India were involved in this trial.

Methodology: Present study enrolled patients of Indian origin who were diagnosed with Stage I or Stage II hypertension as per JNC VII guideline. A total of 240 hypertensive patients were randomized (1:1) to receive either FDC of Efonidipine 40 mg + Chlorthalidone 12.5 mg tablet (E+C group) or FDC of Cilnidipine 10 mg + Chlorthalidone 12.5 mg tablet (C+C group) once daily for 90 days. The study site staff, investigator and patients were blinded to the treatment allocation. Patients were evaluated for changes in their blood pressure (BP) from baseline to Day 30, 60 and 90. BP was recorded as the mean of 3 consecutive measurements taken in a sitting position. the number of patients achieving target BP as per JNC VIII guideline was also evaluated. The safety and tolerability were assessed based on the incidences of adverse events (AEs) and serious adverse events (SAEs) reported.

Results: The mean (±SD) Systolic BP (SBP) and Diastolic BP (DBP) at baseline was 159.10±11.43/101.19±10.03 mmHg in the E+C group. After 30 days of treatment with the E+C group, the mean (±SD) reduction in SBP/DBP of 25.13±16.23/16.11±10.35 mmHg was observed whereas at Day 60 reduction of 32.51±19.73/17.91±11.06 mmHg was seen from baseline. The primary endpoint focused on evaluating the mean BP reduction from baseline at Day 90. As compared to baseline, BP decreased from 159.10±11.43/101.19±10.03 mmHg to 118.95±15.31/ 81.59±3.78 mmHg with a mean reduction of 40.15/19.60 mmHg at day 90 in the E+C group. The secondary endpoint of target BP <140/90 mmHg attainment as per JNC VIII guideline, was also achieved in 90.99% of the patients given the E+C group regimen. Furthermore, it was observed that 94% of Stage I and 88% of Stage II hypertensive patients achieved the target BP goal. Overall, 2.54% of patients from the E+C group reported adverse events (AEs) which were mild in severity and resolved without any sequelae at the end of the study. No unexpected AEs were reported, and the E+C group regimen was well tolerated.

Conclusion: It was concluded that the FDC of Efonidipine 40 mg and Chlorthalidone 12.5 mg was efficacious in the management of hypertension in both Stage I and Stage II hypertensive patients. It was evident from the study results that clinically meaningful reductions in blood pressure were observed over a period of 90 days. The test drug was safe and well tolerated by the patients after being administered as a single tablet daily.