HEXT (Hypo EXTended): Effect of PTH on Skeleton in Hypoparathyroidism

Summary

This is an open-label study of PTH(1-84) treatment that seeks: 1. To determine the actions of PTH(1-84) to provide long term control of serum calcium and urinary calcium excretion with use of standard amounts of calcium and vitamin D supplementation. 2. To determine the extent to which PTH(1-84) improves quality-of-life on long-term basis. 3. To establish the safety of PTH(1-84) when administered for up to 12 years. 4. To attempt to quantify improvements in the typical signs/symptoms of hypoparathyroidism post PTH administration. There will be one visit conducted every six months in the study offices of the principal investigator, Dr. John Bilezikian. In addition to these visits, there will be, for new patients who have not used PTH (1-84) before, a Screening Visit four weeks prior to the baseline visit for the purpose of performing screening labs as well as a Pre-Baseline Local Quest Lab performed to ensure stability prior to Baseline.

Timeline

Start

2009-12

Primary completion

2017-06-26

Completion

2017-06-26

Publications

• Background Rubin MR, Bilezikian JP. Hypoparathyroidism: clinical features, skeletal microstructure and parathyroid hormone replacement. Arq Bras Endocrinol Metabol. 2010 Mar;54(2):220-6. doi: 10.1590/s0004-27302010000200019.
• Background Rubin MR, Sliney J Jr, McMahon DJ, Silverberg SJ, Bilezikian JP. Therapy of hypoparathyroidism with intact parathyroid hormone. Osteoporos Int. 2010 Nov;21(11):1927-34. doi: 10.1007/s00198-009-1149-x. Epub 2010 Jan 22.
• Background Rubin MR, Dempster DW, Kohler T, Stauber M, Zhou H, Shane E, Nickolas T, Stein E, Sliney J Jr, Silverberg SJ, Bilezikian JP, Muller R. Three dimensional cancellous bone structure in hypoparathyroidism. Bone. 2010 Jan;46(1):190-5. doi: 10.1016/j.bone.2009.09.020. Epub 2009 Sep 25.
• Background Rubin MR, Dempster DW, Zhou H, Shane E, Nickolas T, Sliney J Jr, Silverberg SJ, Bilezikian JP. Dynamic and structural properties of the skeleton in hypoparathyroidism. J Bone Miner Res. 2008 Dec;23(12):2018-24. doi: 10.1359/jbmr.080803.
• Background Cusano NE, Rubin MR, Bilezikian JP. PTH(1-84) replacement therapy for the treatment of hypoparathyroidism. Expert Rev Endocrinol Metab. 2015 Jan 1;10(1):5-13. doi: 10.1586/17446651.2015.971755.
• Background Cusano NE, Rubin MR, McMahon DJ, Irani D, Anderson L, Levy E, Bilezikian JP. PTH(1-84) is associated with improved quality of life in hypoparathyroidism through 5 years of therapy. J Clin Endocrinol Metab. 2014 Oct;99(10):3694-9. doi: 10.1210/jc.2014-2267. Epub 2014 Jun 30.
• Background Cusano NE, Rubin MR, Irani D, Sliney J Jr, Bilezikian JP. Use of parathyroid hormone in hypoparathyroidism. J Endocrinol Invest. 2013 Dec;36(11):1121-7. doi: 10.1007/BF03346763.
• Background Cusano NE, Rubin MR, McMahon DJ, Irani D, Tulley A, Sliney J Jr, Bilezikian JP. The effect of PTH(1-84) on quality of life in hypoparathyroidism. J Clin Endocrinol Metab. 2013 Jun;98(6):2356-61. doi: 10.1210/jc.2013-1239. Epub 2013 Apr 17.
• Background Cusano NE, Rubin MR, McMahon DJ, Zhang C, Ives R, Tulley A, Sliney J Jr, Cremers SC, Bilezikian JP. Therapy of hypoparathyroidism with PTH(1-84): a prospective four-year investigation of efficacy and safety. J Clin Endocrinol Metab. 2013 Jan;98(1):137-44. doi: 10.1210/jc.2012-2984. Epub 2012 Nov 15.
• Background Christen P, Ito K, Muller R, Rubin MR, Dempster DW, Bilezikian JP, van Rietbergen B. Patient-specific bone modelling and remodelling simulation of hypoparathyroidism based on human iliac crest biopsies. J Biomech. 2012 Sep 21;45(14):2411-6. doi: 10.1016/j.jbiomech.2012.06.031. Epub 2012 Aug 9.
• Background Cusano NE, Rubin MR, Sliney J Jr, Bilezikian JP. Mini-review: new therapeutic options in hypoparathyroidism. Endocrine. 2012 Jun;41(3):410-4. doi: 10.1007/s12020-012-9618-y. Epub 2012 Feb 7.
• Background Rubin MR, Dempster DW, Sliney J Jr, Zhou H, Nickolas TL, Stein EM, Dworakowski E, Dellabadia M, Ives R, McMahon DJ, Zhang C, Silverberg SJ, Shane E, Cremers S, Bilezikian JP. PTH(1-84) administration reverses abnormal bone-remodeling dynamics and structure in hypoparathyroidism. J Bone Miner Res. 2011 Nov;26(11):2727-36. doi: 10.1002/jbmr.452.
• Background Rubin MR, Manavalan JS, Dempster DW, Shah J, Cremers S, Kousteni S, Zhou H, McMahon DJ, Kode A, Sliney J, Shane E, Silverberg SJ, Bilezikian JP. Parathyroid hormone stimulates circulating osteogenic cells in hypoparathyroidism. J Clin Endocrinol Metab. 2011 Jan;96(1):176-86. doi: 10.1210/jc.2009-2682. Epub 2010 Sep 29.
• Ayodele O, Rejnmark L, Mu F, Lax A, Berman R, Swallow E, Gosmanova EO. Five-Year Estimated Glomerular Filtration Rate in Adults with Chronic Hypoparathyroidism Treated with rhPTH(1-84): A Retrospective Cohort Study. Adv Ther. 2022 Nov;39(11):5013-5024. doi: 10.1007/s12325-022-02292-1. Epub 2022 Aug 26.

Drugs

Indications