Intermittent doxercalciferol (1alpha-hydroxyvitamin D(2)) therapy for secondary hyperparathyroidism

Area of Science:

• Nephrology
• Endocrinology
• Pharmacology

Background:

• Secondary hyperparathyroidism is common in hemodialysis patients.
• Elevated calcium and phosphorus often require vitamin D withdrawal.
• Doxercalciferol (1alpha-hydroxyvitamin D(2)) offers a potential alternative for managing secondary hyperparathyroidism.

Purpose of the Study:

• To evaluate the efficacy and safety of oral doxercalciferol (1alphaD(2)) in hemodialysis patients with moderate to severe secondary hyperparathyroidism.
• To assess the effectiveness of a novel dose titration strategy for 1alphaD(2).

Main Methods:

• A modified, double-blinded, controlled trial involving 138 hemodialysis patients.
• Study phases included washout, open-label 1alphaD(2) treatment, and randomized double-blinded treatment with 1alphaD(2) or placebo.
• Doses were titrated to achieve target intact parathyroid hormone (iPTH) levels of 150-300 pg/mL.

Main Results:

• Oral 1alphaD(2) significantly suppressed iPTH levels by 55% at 16 weeks.
• 83% of patients reached target iPTH levels, with 80% experiencing a 70% decrease.
• Serum calcium levels were slightly higher with 1alphaD(2) versus placebo, but phosphorus levels did not differ significantly. Mild hypercalcemia occurred in 3.26% of measurements with 1alphaD(2).

Conclusions:

• Intermittent oral doxercalciferol is an effective therapy for suppressing iPTH in hemodialysis patients.
• The treatment is associated with acceptable mild hypercalcemia and hyperphosphatemia.
• Novel dose titration allows for effective management of secondary hyperparathyroidism in this population.