Patients with hypoparathyroidism lack sufficient parathyroid hormone (PTH) and exhibit reduced bone turnover, abnormally increased bone mineral density (BMD), and abnormal bone microarchitecture. Current treatment regimens fail to address underlying PTH deficiency. In the REPLACE phase III trial, treatment with rhPTH(184) restored mineral homeostasis, increased bone turnover markers (BTMs), and decreased BMD in patients with hypoparathyroidism.
REPEAT was a 24-week, open-label, flexible-dose extension study at three sites in Hungary. Patients received 50 μg/day (escalated to 75 and then 100 μg/day, if needed) rhPTH(184). Serum BTMs analyzed were bone-specific alkaline phosphatase (BSAP), cross-linked C-telopeptide of type 1 collagen (CTX), aminoterminal propeptide of type 1 collagen (P1NP), and osteocalcin (OCN). BMD was determined by dual-energy X-ray absorptiometry (DXA).
At the initiation of REPEAT, enrolled patients (n=16, previously treated with rhPTH(184) in the REPLACE study; n=8, rhPTH(184)-naive) had mean BSAP, CTX, and P1NP levels within normal limits, but OCN levels (3.82±1.89 μg/l) were lower than normal. At week 24, mean BSAP, CTX, P1NP, and OCN levels increased by 21.2±14.0 μg/l (229%), 651.7±390.8 ng/l (398%), 213.4±118.5 μg/l (728%), and 27.6±24.2 μg/l (748%), respectively. Compared with patients who received rhPTH(184) in REPLACE, rhPTH(184)-naive patients had greater increases in BTMs, with the exception of OCN, for which both groups had similar changes from baseline. Changes in mean absolute DXA values for BMD direct measurements ranged from 0.0349±0.0786 to −0.0138±0.0658 g/cm2 for the seven locations evaluated. Trends toward decreased BMD measurements were greater among rhPTH(184)-naive patients. Z-scores showed minimal differences from baseline among all patients, but a trend toward decreased Z-scores was observed among treatment-naive patients, with the exception of the distal one-third radius. rhPTH(184) was generally well tolerated.
Treatment with rhPTH(184) was associated with increases in BTMs for all patients, even when retreated with rhPTH, and decreases in most BMD measurements and Z-scores for rhPTH(184)-naive patients.
17 May 2014 - 20 May 2014