Session: SUN 234-256-Bone & Calcium Metabolism: Clinical Trials & Case Series
Poster Board SUN-234
All patients enrolled were prescribed calcium and active vitamin D supplements (calcitriol or 1 alpha calcifediol). In the phase I study, patients received 2 subcutaneous injections of rhPTH(1-84) (50 and 100 μg), separated by a >=7-day washout period. In the REPLACE study, patients received (2:1 randomized) daily subcutaneous injections of rhPTH(1-84) 50 μg or placebo and vitamin D3(400 IU/day) for 24 weeks. Dose escalation to 75 µg and then to 100 µg was permitted if needed until active vitamin D could be eliminated and calcium reduced to <=500 mg/day.
In the phase I study, serum 1,25(OH)2D increased, after 8–16 hours, to a maximum baseline-adjusted level (mean±SD) of 27.2±18.3 and 19.6±11.0 pg/mL with the 50-µg (n=6) and 100-µg (n=7) doses of rhPTH(1-84), respectively. 24-hour urine calcium excretion decreased by 13% and 23% with the 50- and 100-µg doses, respectively. Serum calcium levels showed maximum mean increases of approximately 0.7–0.9 mg/dL 12 hours after rhPTH(1-84) administration and remained above baseline levels after 24 hours with either dose.
In REPLACE, 36/84 (43%) patients treated with rhPTH(1-84) became independent of active vitamin D and reduced daily calcium to <=500 mg/day vs 2/37 (5%) patients in the placebo group by Week 24 (P<0.001). Active vitamin D doses were decreased by 79% in the rhPTH(1-84) group (n=90) and 30% in the placebo group (n=44) at Week 24 (P<0.001). Despite reductions in active vitamin D use by rhPTH(1-84)-treated patients, 1,25(OH)2D levels did not change (mean change from baseline at Week 24: +0.4 and 0 pg/mL for rhPTH(1-84) and placebo groups, respectively). In contrast, 25(OH)D showed a greater mean decrease at Week 24 in the rhPTH(1-84) (−11.2 ng/mL) vs the placebo (−1.4 ng/mL) group. At Week 24, mean urine calcium decreased by −74±190 mg/24 hours in the rhPTH(1-84) group and −84±169 mg/24 hours in the placebo group (P=0.06). In the placebo arm, reductions in urine calcium were mirrored by decreased total serum calcium levels. In contrast, total serum calcium remained above or near baseline levels in the rhPTH(1-84)-treated patients. Serum calcium levels were significantly higher in the rhPTH(1-84) vs placebo group at Weeks 1–16 (P<0.05), but not at Week 24.
Results indicate that rhPTH(1-84) treatment maintains serum 1,25(OH)2D in the normal range despite a significant reduction in active vitamin D requirements, while maintaining serum calcium at or near baseline, and reducing 24-hour urinary calcium in patients deficient in endogenous PTH secretion.
Disclosure: DMS: Investigator, NPS, Advisory Group Member, NPS. MM: Advisory Group Member, NPS. BLC: Advisory Group Member, NPS. TJV: Advisory Group Member, NPS. HL: Employee, NPS. JPB: Advisory Group Member, NPS, Principal Investigator, NPS.
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