Abstract: TH-PO969
Efficacy of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3-4 CKD Is Unaffected by Declining eGFR
Session Information
- Late-Breaking Clinical Trials (Posters)
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials
Authors
- Bishop, Charles W., OPKO Health Inc, Miami, Florida, United States
- Strugnell, Stephen A., OPKO Health Inc, Miami, Florida, United States
- Ashfaq, Akhtar, OPKO Health Inc, Miami, Florida, United States
Background
Serum 25-hydroxyvitamin D (25D) repletion for secondary (SHPT) is often abandoned in favor of vitamin D hormone treatment when intact parathyroid hormone (iPTH) levels progressively increase with advancing chronic kidney disease (CKD) with justification that renal CYP27B1 expression has become inadequate for sufficient 1,25-dihydroxyvitamin D (1,25D) production. This study examined the effect of declining estimated glomerular filtration rate (eGFR) on the ability of extended-release calcifediol (ERC) to increase 1,25D production and, thereby, suppress elevated iPTH secretion.
Methods
Two identical, randomized, double-blind, placebo-controlled trials were conducted in patients with SHPT (iPTH>85 pg/mL), stage 3 or 4 CKD and vitamin D insufficiency (VDI; serum 25D of 10-29 ng/mL). The trials enrolled 429 subjects from 77 US sites, stratified by CKD stage and randomized 2:1 to receive ERC or placebo for 26 weeks. ERC dosing started at 30 µg/day and increased, as needed, to 60 µg/day after 3 months. Changes in serum 25D and 1,25D, and plasma iPTH were monitored at baseline and at weekly, biweekly or monthly intervals during treatment.
Results
Pooled per-protocol data from 234 subjects treated with ERC and 120 with placebo were grouped by baseline eGFR of ≤20, 21-30, 31-40 and >40 mL/min/1.73 m2. Mean serum 25D levels increased with ERC treatment from a baseline of 19.7 ng/mL to at least 62 ng/mL by the end of treatment, and produced nearly identical increases in mean serum 1,25D (43-54%) and decreases in mean plasma iPTH (19-25%) irrespective of eGFR group. Serum 25D and 1,25D remained unchanged with placebo. Changes in mean 1,25D and iPTH with ERC were consistently proportional to increases in mean 25D. Mean iPTH (pg/mL) decreased linearly across all eGFR categories in proportion (R2 = 0.9273) to increases in mean 1,25D (pg/mL) indicating that iPTH suppression depended on the degree to which serum 25D was elevated.
Conclusion
ERC effectively raised serum 25D and 1,25D and reduced elevated plasma iPTH in patients with stage 3 or 4 CKD irrespective of declining eGFR. These findings demonstrate that vitamin D repletion with ERC is an attractive alternative to vitamin D hormone therapy for SHPT in pre-dialysis patients with VDI.
Funding
- Commercial Support –