Abstract Body: Introduction
SAL0108 by Shenzhen Salubris Pharmaceuticals Co., Ltd is a novel SPC containing 240mg of allisartan isoproxil (AI) and 1.5 mg of sustained-release (SR) indapamide. AI is a novel angiotensin receptor blocke available in China for over ten years and has the same active compound EXP3174 with losartan, while indapamide SR is a long-standing thiazide-type diuretic.
Hypothesis
We assessed the hypothesis that SAL0108 is more effective than AI monotherapy.
Methods
Patients with uncontrolled HTN after AI monotherapy for a minimum duration of 4 weeks were enrolled and randomized 2:1 to receive SAL0108 or continue AI treatment for a 12-week duration (double-blinded phase). Subsequently, all participants receive SAL0108 treatment until week 52 (extended period). The primary endpoint was the change in mean seated systolic blood pressure (msSBP) from baseline to week 12, assessed utilizing a treatment policy estimand within the full analysis set.
Results
A total of 366 patients were enrolled, with 243 randomized to SAL0108 cohort and 123 to AI cohort. The mean age was 58.7 years, with 50.3% of patients being female. Baseline characteristics were comparable between the two cohorts. After 12 weeks of treatment, the mean change in msSBP from baseline was -15.48±17.96 mmHg in SAL0108 cohort, and -10.19±17.93 mmHg in AI cohort. SAL0108 demonstrated a significantly greater reduction in msSBP compared to AI, showing a mean difference of -5.29 mmHg (95% CI: -9.24 to -1.33; P=0.009). The achievement of msSBP/diastolic blood pressure of < 130/80 mmHg at week 12 was observed in 15.3% and 6.3% of patients in SAL0108 and AI cohorts, respectively (proportion difference 8.9%; P=0.016). Throughout the double-blinded phase, adverse events were observed in 56.8% of patients in SAL0108 cohort (most commonly being hyperuricemia, hyperlipidemia and COVID-19 infection) and 45.5% in AI cohort. Serious adverse events (SAEs) occurred in 1.7% and 4.1% of patients receiving SAL0108 and AI, respectively, and were deemed unrelated to the study drugs. Hypokalemia was infrequent, noted in 4.1% of SAL0108 recipients and 1.6% of AI recipients. During extended period, SAEs were observed in 3.9% of patients and were unrelated to SAL0108. No deaths related to the study drugs were reported.
Conclusions
In conclusion, SAL0108 exhibits better efficacy in reducing blood pressure compared to AI monotherapy. The results also highlight the favorable safety profile of SAL0108 for long-term HTN management.