PTH-Lowering Efficacy of Extended-Release Calcifediol Is Not Affected By Underlying Diabetes in Stage 3 or 4 CKD

Presentation Number: SUN 341
Date of Presentation: April 2nd, 2017

Stuart M Sprague*1, Stephen Strugnell2, Douglass Laidlaw2, Martin Petkovich3 and Charles W Bishop2
1NorthShore University Health System-University of Chicago, Pritzker School of Medicine, Evanston, IL, 2OPKO Renal, Miami, FL, 3Queens University, Kingston, ON


Many chronic kidney disease (CKD) patients have underlying diabetes. It is unclear whether diabetes affects responses to therapy for secondary hyperparathyroidism (SHPT) associated with vitamin D insufficiency (VDI). To address this issue, intact parathyroid hormone (iPTH) responses to extended-release calcifediol (ERC) were compared in diabetic and non-diabetic CKD patients.

ERC (trade name Rayaldee®) efficacy and safety was studied in two identical, randomized, double-blind, placebo-controlled phase 3 trials in subjects with iPTH >85 pg/mL, stage 3 or 4 CKD, and low serum 25-hydroxyvitamin D (25D) (10-29 ng/mL). The trials randomized a total of 429 subjects from 77 US sites, stratified by stage, 2:1 to receive oral ERC or placebo for 26 weeks. ERC dosing started at 30 mcg/day and increased to 60 mcg/day after 12 weeks if plasma iPTH remained above 70 pg/mL.

Data were analyzed from diabetic (n=154) or non-diabetic (n=202) subjects who completed treatment. Mean age was 66 and 65 years, respectively, and mean baseline serum 25D was 20 ng/mL for both groups. Mean eGFR was 31 and 32 mL/min/1.73mm2, respectively. Diabetic subjects treated with ERC had mean plasma iPTH reduced by 22.6%, from 133 pg/mL at baseline to 103 pg/mL in the efficacy assessment period (EAP, mean of treatment weeks 20, 22, 24 and 26). Non-diabetic subjects treated with ERC had mean iPTH reduced by 22.4%, from 152 to 118 pg/mL. Mean iPTH in the corresponding placebo groups increased by 6 and 8 pg/mL. iPTH reductions ≥ 10% were observed in 74% and 72% of ERC-treated diabetic and non-diabetic subjects, vs 31% and 24% of the corresponding placebo groups (p<0.0001 vs placebo for both). Mean serum 25D levels increased to 69 and 66 ng/mL in diabetic and non-diabetic subjects, respectively, vs. no changes in the placebo groups. Mean serum 1,25-dihydroxyvitamin D (1,25D) increased by 14 and 12 pg/mL vs. increases of 2 and 1 pg/ml in the respective placebo groups. Serum calcium in the EAP increased with ERC by 0.1 and 0.2 mg/dL relative to placebo in diabetic (p=ns) and non-diabetic (p<0.05) subjects, respectively. Serum phosphorus was unchanged relative to placebo for diabetic subjects and increased by 0.1 mg/dL relative to placebo for nondiabetic subjects (p < 0.05).

In conclusion, ERC increased mean serum 25D and 1,25D and reduced mean plasma iPTH comparably in diabetic and non-diabetic subjects, with similar effects on serum calcium and phosphorus. Underlying diabetes did not impact the efficacy of ERC as a treatment for SHPT in patients with stage 3 or 4 CKD and VDI.


Disclosure: SMS: Consultant, OPKO Pharm, Coinvestigator, Opko. SS: Employee, OPKO Renal, Employee, OPKO Renal. DL: Vice President, OPKO Renal, Vice President, OPKO Renal. MP: Consultant, OPKO Renal. CWB: Chief Executive Officer, OPKO Renal, Chief Executive Officer, OPKO Renal.