An Open-Label Extension Study of Parathyroid Hormone Rhpth(1-84) in Adults with Hypoparathyroidism |
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| Institution: | 1. From the 1st Department of Medicine, Semmelweis University Medical School, Budapest, Hungary;;2. 1st Department of Medicine, University of Pécs, School of Medicine, Pécs, Hungary;;3. Clinical Development, NPS Pharmaceuticals, Inc, Bedminster, New Jersey, United States;;4. 1st Department of Internal Medicine, University of Szeged and Albert Szent-Györgyi Medical and Pharmaceutical Center, Szeged, Hungary.;1. From the Cooper University Hospital, Camden, New Jersey. |
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| 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 rhPTH1-84]; n = 8 rhPTH1-84]-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.Conclusion: 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.Abbreviations:AE = adverse eventBMD = bone mineral densityBSAP = bone-specific alkaline phosphataseBTM = bone turnover markerCa × P product = calcium × phosphate productCTX = cross-linked C-telopeptide of type 1 collagenOCN = osteocalcin25(OH)D = 25-hydroxyvitamin DP1NP = aminoterminal propeptide of type 1 collagenPTH = parathyroid hormonerhPTH(1-84) = recombinant human parathyroid hormoneTEAE = treatment-emergent adverse eventULN = upper limit of normal |
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