Abstract: TH-PO515

PTH Suppression with Extended-Release Calcifediol (ERC) Is Directly Proportional to Severity of Secondary Hyperparathyroidism (SHPT)

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 305 CKD: Clinical Trials and Tubulointerstitial Disorders

Authors

  • Sprague, Stuart M., NorthShore University HealthSystem University of Chicago Pritzker School of Medicine, Chicago, Illinois, United States
  • Strugnell, Stephen A., OPKO Health, Miami, Florida, United States
  • Ashfaq, Akhtar, OPKO Health, Miami, Florida, United States
  • Petkovich, Martin P., Queen's University, Kingston, Ontario, Canada
  • Bishop, Charles W., Opko Health, Miami, Florida, United States
Background

Oversuppression of parathyroid hormone (PTH) is a significant concern in patients with stage 3-4 CKD treated with calcitriol or its 1α-hydroxylated analogs since iatrogenic induction of a low PTH concentration is an independent strong risk factor for adynamic bone disease, fractures and cardiovascular death. Randomized controlled trials have shown that ERC gradually but effectively reduces PTH without oversuppression. These data have been further examined post-hoc to determine the impact of baseline PTH levels on end-of-treatment (EOT) levels.

Methods

Two identical, randomized, double-blind, placebo-controlled trials were conducted in 429 adult subjects with stage 3-4 CKD, SHPT (>85 pg/mL) and vitamin D insufficiency. Subjects were randomized 2:1 to receive ERC (30 or 60 mcg/day) or placebo (PL) for 26 weeks. Per-protocol data for plasma intact (i) PTH, serum calcium (Ca) and phosphorus (P), serum total 1,25-dihydroxyvitamin D (1,25D), and serum total 25-hydroxyvitamin D (25D) were pooled and analyzed by baseline plasma iPTH tertile. Mean baseline iPTH in each tertile was 98, 130 and 203 pg/mL for ERC and 102, 133, and 201 for PL.

Results

The table shows the mean changes from baseline to EOT in iPTH, Ca, P, 1,25D and 25D with ERC (n=78 in each tertile) and PL (n=40-41 in each tertile). Significant differences from the corresponding placebo groups are as marked.

ERC and PL had similar, minor effects on mean serum Ca and P. ERC increased serum 25D and 1,25D significantly and to comparable levels irrespective of baseline iPTH tertile. However, decreases in mean iPTH with ERC differed between tertiles and were directly proportional to baseline levels, with EOT suppression increasing from 19 to 26% of baseline from T1 to T3. Oversuppression was not observed.

Conclusion

ERC produced mean absolute iPTH reductions that were proportional to baseline iPTH levels, consistent with a mechanism of action involving physiological regulation of iPTH modulated by SHPT severity.

 Plasma iPTH
(pg/mL)
Serum Ca
(mg/dL)
Serum P
(mg/dL)
1,25D
(pg/mL)
25D
(ng/mL)
 ERCPLERCPLERCPLERCPLERCPL
T1-18b40.20.10.20.111b148b-2
T2-28b20.1a0.00.3a0.113b246b-1
T3-50b150.3b0.10.20.112b247b-1

aP<0.05 bP<0.001

Funding

  • Commercial Support