Supplemental Material for: Paricalcitol Capsule for Secondary Hyperparathyroidism in Stage 3/4 Chronic Kidney Disease: A Randomised Multicentre, Double-blind, Placebo-controlled Phase 3 Clinical Trial

In this multicenter, randomised, double-blind, placebo-controlled phase 3 trial (ClinicalTrials.gov, NCT04994080), patients (aged ≥18 years) with stage 3 and 4 CKD and SHPT were enrolled if the mean of two consecutive intact parathyroid hormone (iPTH) measurements was ≥150 pg/mL, the serum calcium level was between 8.0 and 10.0 mg/dL (1.99 and 2.50 mmol/L), and serum phosphorus level was ≤5.2 mg/dL (1.68 mmol/L). Eligible patients were randomised (2:1) to receive HR081702 or placebo orally once a day for 24 weeks.

Dose adjustments were primarily based on iPTH levels and were guided by serum calcium and phosphorous levels. The primary endpoint was the proportion of patients to achieve at least two consecutive iPTH reductions of ≥30% from baseline within 24 weeks of treatment.</p><p dir="ltr">Results: A total of 90 patients were randomised to the HR081702 group (n=60) or the placebo group (n=30). After 24 weeks treatment, 91.7% of patients (55/60) in the HR081702 group achieved the primary endpoint, compared with 16.7% of patients (5/30) in the placebo group (difference, 75.0% [95% CI, 59.9 to 90.1]; P<0.0001).

Furthermore, at least four consecutive reductions of ≥30% in iPTH levels from baseline were observed in 68.3% of HR081702-treated patients, compared with 6.7% of placebo-treated patients. Treatment-related adverse events (TRAEs) were reported in 50.0% of patients receiving HR081702 and 26.7% of patients in the placebo group; all TRAEs were mild or moderate in severity. Hyperphosphatemia was the most common TRAE (20.0% in the HR081702 group and 6.7% in the placebo group).</p><p dir="ltr">Conclusion: Paricalcitol capsule (HR081702) is a safe and effective treatment option for stages 3 and 4 CKD patients with SHPT, significantly reducing iPTH levels.</p>