title: AN OPEN-LABEL EXTENSION STUDY OF PARATHYROID HORMONE RHPTH(1-84) IN ADULTS WITH HYPOPARATHYROIDISM.
abstract: OBJECTIVE
  Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and bone abnormalities. Adults with hypoparathyroidism treated with recombinant human PTH, rhPTH(1-84), in the 24-week, phase III REPLACE study maintained serum calcium despite reductions in oral calcium and active vitamin D. This study assessed the long-term efficacy and safety of rhPTH(1-84) for hypoparathyroidism.
  
  
  METHODS
  This was a 24-week, open-label, flexible-dose extension study of REPLACE (REPEAT) conducted in 3 outpatient centers in Hungary. Patients who previously completed or enrolled in REPLACE received 50 μg/day rhPTH(1-84), escalated to 75 and then to 100 μg/day, if needed, to reduce active vitamin D and oral calcium. The primary endpoint was ≥50% reduction in oral calcium (or ≤500 mg/day) and active vitamin D (or calcitriol ≤0.25 μg/day or alfacalcidol ≤0.50 μg/day) with normocalcemia.
  
  
  RESULTS
  Twenty-four patients (n = 16 previously treated with rhPTH[1-84]; n = 8 rhPTH[1-84]-naïve) were enrolled and completed the study. At Week 24, 75% of patients (95% confidence interval [CI], 53.3-90.2%) achieved the study endpoint; 58% eliminated oral calcium and active vitamin D. Urinary calcium, serum phosphate, and calcium × phosphate (Ca × P) product decreased by Week 24. Mean serum bone turnover markers increased with rhPTH(1-84). Treatment-emergent adverse events (TEAEs) were reported by 92% of patients. No serious adverse events (AEs) occurred.
  
  
  CONCLUSIONS
  This study used a simplified treatment algorithm intended to better mimic typical clinical practice and demonstrated the extended efficacy and safety of rhPTH(1-84) in patients with hypoparathyroidism and confirmed the REPLACE findings. Sustained rhPTH(1-84) efficacy up to 48 weeks was observed despite treatment interruption between studies.
authors.forename: Peter
authors.initials: P
authors.lastname: Lakatos
authors.forename: Laszlo
authors.initials: L
authors.lastname: Bajnok
authors.forename: Hjalmar
authors.initials: H
authors.lastname: Lagast
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Valkusz
mesh_terms: D000328:Adult; D000368:Aged; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000097:blood / Q000652:urine; D005260:Female; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D007011:Hypoparathyroidism / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000652:urine; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C470125:PTH protein, human; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D002118:Calcium