Session: SUN 234-256-Bone & Calcium Metabolism: Clinical Trials & Case Series
Poster Board SUN-246
C09-002 was an acute open-label, phase I dosing study. Patients received 2 rhPTH(1-84) injections (50 or 100 μg per day), separated by >=7 day washout. REPLACE was a double-blind, phase III trial; patients received (2:1 randomization) daily injections of rhPTH(1-84) at 50 μg/day (escalated to 75 and then to 100 μg/day, if needed) or placebo for 24 weeks. Serum and urine samples were collected at various pre-defined timepoints throughout the study for analyses.
Both studies demonstrated substantial effects of rhPTH(1-84) on serum and urinary PO4 levels. In the phase I study, rhPTH(1-84) injections (50-µg, n=6; 100-µg, n=7) acutely decreased mean serum PO4 levels by a maximum of 1.5 mg/dL within 5 hours. rhPTH(1-84) also increased total 24-hour urinary PO4 excretion by 51% (50-µg) and 60% (100-µg). In REPLACE, a marked decrease in serum PO4 in the rhPTH(1-84) group followed initiation of study drug and was maintained throughout the treatment period, with serum PO4 declining from baseline of 4.53±0.7 to 4.08±0.7mg/dL at Week 24; serum PO4 did not change from baseline in the placebo group. The rhPTH(1-84) group showed a significantly greater decrease over placebo in serum PO4 values at all timepoints (P<=0.003); at Week 24, the mean change from baseline (least squares±SE) was −0.47±0.07 mg/dL for rhPTH(1-84) vs −0.06±0.10 mg/dL for placebo (P<0.001). In both groups, 24-hour urine PO4 excretion was reduced from baseline at Week 24; these results were not statistically significant (P=0.07).
Changes in serum PO4 and urine PO4 excretion towards normal after single and chronic rhPTH(1-84) administration suggest that replacement therapy with rhPTH(1-84) provides better control of PO4 homeostasis in addition to the improved control of serum and urinary calcium.
Disclosure: BLC: Advisory Group Member, NPS. DMS: Advisory Group Member, NPS, Investigator, NPS. MM: Advisory Group Member, NPS. TJV: Advisory Group Member, NPS. HL: Employee, NPS. JPB: Advisory Group Member, NPS, Principal Investigator, NPS.
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