AzTrials
AzTrials

HypoparathyroidismPhase 3NCT01199614

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

A Phase 3 study testing open-label PTH(1-84) in people with Hypoparathyroidism, run by Columbia University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Hypoparathyroidism
What is being tested?
open-label PTH(1-84)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
1 siteUnited States
Study dates
Dec 2009to 26 Jun 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • 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.
Show all 12Show fewer
  • 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.

Who cannot join

  • failure to have completed either of the inclusionary studies
  • For New Participants (20 anticipated):
  • 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).
Show all 24Show fewer
  • Patients dependent on regular parenteral calcium infusions (e.g. calcium gluconate) to maintain calcium homeostasis.
  • Patients that have undergone gastric resection or have active peptic ulcer disease requiring medical therapy.
  • Use of prohibited medications such as, raloxifene hydrochloride, lithium, methotrexate, or systemic corticosteroids within the last 6 months.
  • Treatment with PTH-like drugs, including PTH(1-84), PTH(1-34) or other N terminal fragments or analogs of PTH or PTH-related protein within the last 6 months.
  • Other drugs known to influence calcium and bone metabolism, such as calcitonin, sodium fluoride, or cinacalcet hydrochloride within the last 6 months.
  • Use of oral bisphosphonates within the previous 6 months or IV bisphosphonate preparations within the previous 12 months prior to screening.
  • Seizure disorder/epilepsy and a history of a documented seizure within the previous 6 months.
  • In regard to participants between 18 and 21 years of age: Presence of open epiphyses as determined by x-ray.
  • Radiotherapy to the skeleton within 5 years.
  • Serum 25-hydroxyvitamin D levels greater than 1.5-fold the laboratory upper limit of normal. (i.e., > 150 ng/mL)
  • Any disease or condition in the opinion of the Investigator that has a high probability of precluding the patient from completing the study or where the patient cannot or will not appropriately comply with study requirements.
  • Participation in any other investigational trial in which receipt of investigational drug or device occurred within 6 months prior to screening for this study.
  • Pregnant or lactating women.
  • History of diagnosed drug or alcohol dependence within the previous 3 years.
  • Clinical history of renal calculi within the past 6 months.
  • Any condition that negatively affects gastrointestinal absorption, including but not limited to short bowel syndrome, bowel resection, tropical sprue, celiac disease, ulcerative colitis, and Crohn's disease.
  • Chronic/severe cardiac disease including but not limited to cardiac insufficiency, arrhythmias, bradycardia (resting heart rate < 60 beats/minute), or hypotension (systolic and diastolic blood pressures < 100 and 60 mmHg, respectively).
  • History of cerebrovascular accident (CVA) in the past 5 years or earlier, if there is residual impairment that would affect participation in the study.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Columbia University Medical Center

    New York, New York, 10032

Other trials in United States

About this study

Official title: HEXT: The Hypoparathyroidism Studies, EXTended: The Effect of PTH on the Skeleton in Hypoparathyroidism

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.

Read the detailed description

Hypoparathyroidism is a rare disorder in which parathyroid hormone (PTH) is markedly decreased or absent from the circulation. It is the only remaining hormone deficiency state for which replacement with the missing hormone has been heretofore unavailable. The hypoparathyroid state is due either to autoimmune destruction of the parathyroid glands or to loss of parathyroid function after neck surgery. Without PTH, calcium homeostasis is markedly abnormal, the most salient clinical feature of which is a reduced serum calcium concentration. The hypocalcemia is associated with other important abnormalities such as markedly reduced parameters of bone turnover. PTH(1-84) is the ideal therapeutic approach to hypoparathyroidism. The current mainstay of therapy, calcium and vitamin D, has important clinical limitations. Large doses of calcium and vitamin D are required and often associated with hypercalciuria and vitamin D toxicity. Moreover, this approach does not correct the skeletal deficiencies resident in the bones themselves due to lack of PTH. In contrast, PTH(1-84) replaces precisely what is missing in this disorder. The research question is: What are the long-term safety and efficacy parameters of PTH(1-84) therapy in hypoparathyroidism?

Preliminary data suggest that treatment with PTH(1-84) for up to 4 years improves control of the serum and urine calcium concentration safely. Since hypoparathyroidism is a chronic disorder, it is important to know whether these salutary effects continue to be seen beyond 4 years. There is a need to determine the safety and efficacy treatment of PTH(1-84) in hypoparathyroidism beyond 4 years.

Being tested
open-label PTH(1-84)
Keywords
Hypoparathyroidism, Hypopara, HPTH, Hypocalcemia, Hypercalciuria, PTH, PTH(1-84)
Medical subject headings
Hypoparathyroidism, Hypocalcemia, Hypercalciuria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • open-label PTH(1-84)Drug

    Also called rhPTH1-84, rhPTH(1-84), PTH1-84, PTH(1-84)

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

Study groups in NCT01199614
Study groupRoleWhat they receive
open-label PTH(1-84)Experimentalopen-label PTH(1-84) / variable dosing: 25mcg every other day, 25mcg every day, 50mcg every day, 75mcg every day, 100mcg every day
Receives: Drug: open-label PTH(1-84)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Dose of Calcium Supplementation

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

    Measured: Baseline, up to 4 years

Secondary outcomes (1)
  1. Percent Change in BMD by DXA

    Bone Mineral Density (BMD) as measured by Dual Energy X-Ray Absorptiometry (DXA)

    Measured: Baseline, up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2010 (estimated)
  2. Study startDec 2009
  3. Primary completion26 Jun 2017
  4. Study completion26 Jun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01199614
Sponsor's protocol ID
AAAE0544
Status last verified
Jul 2024
First submitted
9 Sep 2010
Last updated
5 Jul 2024
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 20485912
  • 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.

    PubMed 20094706
  • 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.

    PubMed 19782782
  • 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.

    PubMed 18684087
  • 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.

    PubMed 25705243
  • 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.

    PubMed 24978675
  • 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.

    PubMed 24445125
  • 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.

    PubMed 23596139
  • 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.

    PubMed 23162103
  • 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.

    PubMed 22883080
  • 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.

    PubMed 22311174
  • 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.

    PubMed 21735476
  • 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.

    PubMed 20881259
  • 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.

    PubMed 36018496

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing open-label PTH(1-84) in people with Hypoparathyroidism, run by Columbia University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Dose of Calcium Supplementation (time frame: Baseline, up to 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01199614, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2024.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in