Extended-release calcifediol identifies a therapeutic vitamin D range in chronic kidney disease stages 3 and 4.

Background: Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD) driven by dysregulated vitamin D metabolism. The serum 25-hydroxyvitamin D (25D) levels required for targeted intact parathyroid hormone (iPTH) reductions are poorly defined, and conventional sufficiency thresholds of 20 or 30 ng/ml are inadequate. Exposure-response (E-R) modeling was used to define a 25D range associated with a 30% iPTH reduction during treatment with extended-release calcifediol (ERC). Methods: E-R relationships between 25D and iPTH were evaluated using pooled data from randomized clinical trials of ERC in participants with SHPT, CKD stage 3-4, and vitamin D insufficiency (VDI). Mixed-effects models characterized percent change in iPTH as a function of concurrent 25D. Mechanistic analyses evaluated associations between 25D, its key metabolites, and iPTH. Associations between achieved 25D and markers of mineral metabolism were assessed. Results: E-R modeling demonstrated a nonlinear relationship between 25D and iPTH reduction with a population-average of 84 ng/ml associated with 30% iPTH reduction (ER Conclusions: Elevation of 25D to 84 ng/ml (range: 66.9-102.6 ng/ml) during ERC treatment was associated with a 30% iPTH reduction in participants with SHPT, CKD stage 3-4, and VDI. This range was unassociated with adverse changes in mineral metabolism.