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

NCT01199614 | Completed Phase 3 Results DMC

• 1 other identifier: AAAE0544
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label study of PTH(1-84) treatment that seeks:

1. 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. 2.To determine the extent to which PTH(1-84) improves quality-of-life on long-term basis.
3. 3.To establish the safety of PTH(1-84) when administered for up to 12 years.
4. 4.To attempt to quantify improvements in the typical signs/symptoms of hypoparathyroidism post PTH administration.

Conditions

Hypoparathyroidism

Keywords

Hypoparathyroidism; Hypopara; HPTH; Hypocalcemia; Hypercalciuria; PTH; PTH(1-84)

Outcome Measures

Primary Outcomes (1)

• Change in Dose of Calcium Supplementation

  Serum and urinary calcium levels maintained by change in requirements for calcium supplementation.

  Baseline, up to 4 years

Secondary Outcomes (1)

• Percent Change in BMD by DXA

  Baseline, up to 4 years

Study Arms (1)

open-label PTH(1-84)

EXPERIMENTAL

open-label PTH(1-84) / variable dosing: 25mcg every other day, 25mcg every day, 50mcg every day, 75mcg every day, 100mcg every day

Drug: open-label PTH(1-84)

Interventions

open-label PTH(1-84) DRUG

open label PTH(1-84) at either 25mcg every other day, 25mcg every day, 50mcg daily, 75mcg daily, or 100mcg daily

Also known as: rhPTH1-84, rhPTH(1-84), PTH1-84, PTH(1-84), PTH, parathyroid hormone

open-label PTH(1-84)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have participated in and concluded the CL1-11-040, PAR-C10-007 or PAR-C10-008 Study at any site in the continental United States
• Must have participated in and concluded the Hypopara Study at Columbia University

You may not qualify if:

• For New Participants (20 anticipated):
• Signed and dated informed consent form (ICF) before any study-related procedures are performed.
• Adult males or females 18 to 85 years of age.
• History of hypoparathyroidism for ≥ 18 months, including evidence of hypocalcemia and concomitant serum intact PTH concentrations below the lower limit of normal within 12 months prior to Baseline.
• Requirement for calcitriol ≥0.25 mcg per day per day prior to Baseline.
• Requirement for supplemental oral calcium ≥ 1500 mg per day between supplemental and dietary sources.
• Serum thyroid function tests within normal laboratory limits at screening for all subjects not receiving thyroid hormone replacement therapy. For patients on thyroid hormone replacement therapy, the dose must have been stable for at least 3 months prior to screening
• serum creatinine \< 1.5 mg/dL on a single measurement prior to use of study drug
• Physically capable of performing daily subcutaneous (SQ) self-injections, in the thigh, of study medication (or have designee perform injection).
• Willingness and ability to comply with the protocol (prior to screening).
• With regard to female patients: Women of childbearing potential must have a negative pregnancy test at Screening and agree to use two medically acceptable methods of contraception for the duration of the study with pregnancy testing at every scheduled visit.
• Patients who have any of the following during the screening visit are not eligible for enrollment in this study:
• Known history of hypoparathyroidism resulting from an activating mutation in the CaSR gene or impaired responsiveness to PTH (pseudohypoparathyroidism). If unknown, it shall be assumed to be not-present.
• Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism, such as active hyperthyroidism, Paget's disease, insulin-dependent diabetes mellitus (IDDM) or poorly controlled Type II diabetes mellitus (HbA1C \> 8%), severe and chronic cardiac, liver or renal disease, Cushing's syndrome, neuromuscular disease such as rheumatoid arthritis, myeloma, pancreatitis, malnutrition, rickets, recent prolonged immobility, active malignancy, primary or secondary hyperparathyroidism, a history of parathyroid carcinoma, hypopituitarism, acromegaly, or multiple endocrine neoplasia types I and II.
• To be eligible, patients with a history of thyroid cancer must be documented to be disease-free for a period of at least 5 years (or 2 years with evidence of follow up and a doctor's note of clearance).

Sponsors & Collaborators

• Columbia University: lead
• NPS Pharma: collaborator
• Shire: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (14)

• 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.

  PMID: 20485912 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.

  PMID: 20094706 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.

  PMID: 19782782 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.

  PMID: 18684087 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.

  PMID: 25705243 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.

  PMID: 24978675 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.

  PMID: 24445125 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.

  PMID: 23596139 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.

  PMID: 23162103 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.

  PMID: 22883080 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.

  PMID: 22311174 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.

  PMID: 21735476 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.

  PMID: 20881259 BACKGROUND

• 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.

  PMID: 36018496 DERIVED

Related Links

• The Hypoparathyroidism Association

MeSH Terms

Conditions

Hypoparathyroidism; Hypocalcemia; Hypercalciuria

Interventions

Parathyroid Hormone

Condition Hierarchy (Ancestors)

Parathyroid Diseases; Endocrine System Diseases; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Water-Electrolyte Imbalance; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: John P. Bilezikian, MD
• Organization: Columbia University

jpb2@cumc.columbia.edu

212-305-6257

Study Officials

• John P Bilezikian, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2010
• First Posted: September 13, 2010
• Study Start: December 1, 2009
• Primary Completion: June 26, 2017
• Study Completion: June 26, 2017
• Last Updated: July 5, 2024
• Results First Posted: July 5, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)