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Post-Surgical HypoparathyroidismPhase 2NCT05735015

PTH-independent Effects of Encaleret

A Phase 2 study testing encaleret in people with Post-Surgical Hypoparathyroidism, run by National Institute of Dental and Craniofacial Research (NIDCR) 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
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Trial summary

Background: Parathyroid glands in the neck make a hormone that keeps blood calcium levels stable. Sometimes these glands are damaged or removed during neck surgery. This can lead to a condition called postsurgical hypoparathyroidism (PSH). People with PSH have low levels of calcium in their blood. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Post-Surgical Hypoparathyroidism
What is being tested?
encaleret
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
1 Sep 2023to 12 Aug 2025
Phase
Phase 2
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 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must meet the following criteria for inclusion during screening:
  • Be able to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
  • Age >= 18 years
  • Postmenopausal women are allowed to participate in this study:
  • Women are considered postmenopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks prior to start of the study. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment, shall she be considered not of childbearing potential.
  • Body mass index (BMI) >= 18.5 to < 39 kg/m^2
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  • Have a diagnosis of PSH, either permanent PSH (Cohort 1, surgery >= 12 months ago) or recent PSH (Cohort 2, surgery < 12 months ago).
  • Participants must have achieved an albumin-corrected blood calcium level of 7.8-10.2 mg/dL on conventional therapy without significant symptoms of hypocalcemia or hypercalcemia.
  • Participants being treated with thiazide diuretics may be enrolled if they are willing and able to discontinue thiazides for at least 5 half-lives prior to initiation of encaleret and remain off during the study treatment period. (5 half-lives of hydrochlorothiazide = 75 hours; chlorothiazide = 10 hours; chlorthalidone = 12.5 days). If the thiazide is being used as an antihypertensive, as opposed to use as a urine calcium-lowering drug, alternative therapy will be offered.
  • Participants being treated with strong CYP3A4 inhibitors (including clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir) may be enrolled if they are willing and able to discontinue these medications for at least 5 half-lives prior to initiation of encaleret and remain off during the study treatment period.
  • Participants being treated with magnesium or potassium citrate supplements should discontinue such treatment starting on Day 2.
  • Participants being treated with medications that have impacts on mineral metabolism which investigators believe may impact study endpoints may be enrolled if they are willing and safely able to discontinue the medication for at least 5 half-lives prior to initiation of encaleret and remain off during the study treatment period

Who cannot join

  • Participants who meet any of the following criteria during Screening will not be eligible to participate in the study:
  • History of treatment with any PTH analog (i.e., PTH 1-84, PTH 1-34, TransCon PTH, etc.) within the previous three (3) months
  • History of prior treatment with encaleret
  • History of hypocalcemic seizure within the past 3 months
  • Blood 25-OH Vitamin D level <25 or >60 ng/mL
  • If subject has a blood 25-OH Vitamin D level < 25 ng/mL at the screening visit, they will be prescribed cholecalciferol or ergocalciferol supplementation. Once the 25-OH Vitamin D level is >= 25 ng/mL, the subject will be eligible to continue to the treatment phase of the study.
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  • If a subject has a blood 25-OH Vitamin D level >60 ng/mL at the screening visit, their vitamin D supplementation will be adjusted. Once the 25-OH Vitamin D level is <=60 ng/mL, the subject will be eligible to continue to the treatment phase of the study.
  • Participants with hemoglobin (Hgb) lower than the lower limit of normal.
  • If subject has a low Hgb at the screening visit due to iron, B12, or folate deficiency, they will be prescribed supplementation. Once the Hgb level within the normal range, the subject will be eligible to continue to the treatment phase of the study.
  • Abnormal laboratory values which in the opinion of the investigator, would make the subject not suitable for participation in the study
  • Estimated glomerular filtration rate (eGFR) < 50 mL/minute/1.73 m^2 using CKD-EPI.
  • Insufficient hepatic function defined as one of the following:
  • Total Bilirubin > 1.5 x ULN OR
  • Aspartate transaminase (AST) > 2x ULN OR
  • Alanine transaminase (ALT) > 2x ULN
  • 12-lead resting electrocardiogram (ECG) with clinically significant abnormalities. Participants with screening QTcF (using the Fridericia equation) > 450 milliseconds (ms) will not be eligible for the treatment phase of the study.
  • If a participant has a prolonged QTcF during screening due to a reversible cause of long QT (for example hypocalcemia or QT-prolonging medications), the subject may be eligible for the treatment phase of the study if the reversible cause can be addressed, and repeat ECG shows QTcF <=450 milliseconds.
  • Clinically significant cardiac disease including any of the following:
  • Congestive heart failure requiring treatment (NY Heart Association grade >= 2)
  • History of clinically significant cardiac arrythmias including ventricular arrhythmias, atrial fibrillation, or conduction abnormalities
  • History of unstable angina pectoris or acute myocardial infarction
  • Participants with positive hepatitis B surface antigen (HBsAg) or Hepatitis A immunoglobulin M (IgM) at the screening visit. Participants who are in complete remission from Hepatitis C (HCV) as evidence by sensitive assay >=12 weeks after completion of HCV therapy are allowed to participate in the study. Participants with human immunodeficiency virus (HIV) infection on a stable dose of anti-retroviral therapy who have an undetectable viral load are allowed to participate in the study.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum human chorionic gonadotropin (hCG) laboratory test
  • Clinically significant abnormalities in thyroid function tests. This does not include participants with non-clinically significant or treated thyroid diseases (e.g. subclinical hypothyroidism, hypothyroidism on treatment, etc.). Participants on thyroid-stimulating hormone (TSH)-suppression therapy for thyroid cancer are allowed to participate in this study regardless of TSH level.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for three (3) months following the discontinuation of study treatment. Highly effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
  • Male sterilization (at least 6 months prior to screening). For female participants on the study the vasectomized male partner should be the sole partner for that subject.
  • Combination of the following (a+c or b+c):
  • Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  • Barrier method of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
  • Sexually active male participants who are unwilling to use a condom during vaginal intercourse while taking the encaleret (study drug) and for 3 months after the last dose of the study drug. Participants should not father a child during active participation in the study starting with the first encaleret dose. Condoms are not required if the subject is vasectomized or if the subject's partner is not a woman of child-bearing potential.
  • Hypersensitivity to any active substance or excipient of encaleret
  • History of drug or alcohol dependency within 12 months preceding the screening visit
  • Current participation in other investigational drug studies
  • Unwillingness to refrain from blood donation within 12 weeks prior to admission visit through one year after the last dose of the study drug. If subject donated blood within 12 weeks of the screening visit, they will need to wait until 12 weeks have passed since blood donation for the admission visit.
  • Participants who have a history of diseases of mineral metabolism other than hypoparathyroidism or hyperparathyroidism which investigators believe may impact study endpoints (for example, X-linked hypophosphatemia, rickets, etc.).
  • Participants with history of the following:
  • Any cancer except for thyroid cancer, basal cell skin cancer or squamous cell cancer in the last 5 years. Subjects with history of thyroid, basal cell or squamous cell cancers should have received definitive treatment for their malignancies prior to enrollment.
  • Skeletal malignancies
  • Bone metastases
  • Irradiation (radiotherapy) to the skeleton
  • Any other disease that increases the likelihood for osteosarcoma (ex. Paget's disease).
  • Unexplained elevations of alkaline phosphatase

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Phase 2 Study of the PTH-Independent Effects of Encaleret on Mineral Homeostasis in Subjects With Post-Surgical Hypoparathyroidism (PSH)

Background:

Parathyroid glands in the neck make a hormone that keeps blood calcium levels stable. Sometimes these glands are damaged or removed during neck surgery. This can lead to a condition called postsurgical hypoparathyroidism (PSH). People with PSH have low levels of calcium in their blood. Calcium and vitamin D pills can help them keep their blood calcium levels steady. But this can increase calcium in the urine and result in kidney problems. New treatments for PSH are needed.

Read more

Objective:

To test a drug (encaleret) in people with PSH.

Eligibility:

People aged 18 or older who have PSH.

Design:

Participants will be in the study for 6 months. They will have a screening visit and a treatment visit.

Screening will take up to 2 days. Participants will have a physical exam. They will have blood and urine tests and tests of their heart function. They will have an ultrasound of their kidneys; they will lie on a table for 15 to 30 minutes while a wand is moved over their back.

Treatment will require participants to stay in the clinic for 7 days and 6 nights. They will take the study drug (encaleret) by mouth twice a day for 5 days. They will have a small, flexible tube inserted into a vein; this will remain in place during the visit. Blood samples will be taken through the tube 4 to 9 times each day. Participants urine will be collected.

Participants will have follow-up blood tests one (1) week after leaving the clinic. They will have three (3) follow-up phone calls.

Read the detailed description

Study Description:

This will be a single-site, proof-of-principle, open-label study to explore the PTH-independent effects of encaleret on calcium homeostasis in participants with low or undetectable PTH levels as a result of neck surgery (PSH).

Objectives:

Primary Objective:

-Evaluate the PTH-independent effects of encaleret on renal calcium handling in participants with PSH.

Secondary Objectives:

-Evaluate the ability of encaleret to normalize blood calcium while maintaining a normal urinary calcium in participants with PSH.

Primary Endpoint:

-- Percent change in Fractional Excretion of Calcium (FECa) from baseline (Day -1) to the final day of treatment (Day 6 or the last measurement while on encaleret). FECa calculated using fasting blood levels and spot urine collection.

Secondary Endpoints:

-- Proportion of participants who achieve a concomitant normal or elevated fasting blood calcium (albumin-corrected calcium>8.5 mg/dL) and a normal 24-hour urinary calcium level (<250 mg/24 hours for women, <300 mg/24 hours for men) on encaleret at any point between day 1 and day 5.

Being tested
encaleret
Keywords
Hypoparathyroidism, Hypocalcemia, Post-Surgical Hypoparathyroidism, Calcilytix, Encaleret
Medical subject headings
Hypoparathyroidism, Hypocalcemia

What participants receive

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

  • encaleretDrug

    Encaleret 162 mg orally

Study groups in NCT05735015
Study groupRoleWhat they receive
Participants with Permanent hypoparathyroidismExperimentalParticipants with permanent post-surgical hypoparathyroidism (>1 year after surgery) received encaleret 162 mg orally twice daily for up to five days.
Receives: Drug: encaleret

What is being measured

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

  1. Percent Change in Fractional Excretion of Calcium (FECa)

    The percentage change in Fractional Excretion of Calcium (FECa) from baseline (24 hours before first dose of encaleret) to the last measurement while on encaleret (12 hours after last dose of encaleret). FECa is calculated using fasting blood levels and spot urine collection of calcium and creatinine. Percent change = (last measurement - baseline)/baseline x 100.

    Measured: Last measurement (12 hours after last dose of encaleret), baseline (24 hours before first dose of encaleret)

Secondary outcomes (1)

  1. Proportion of Participants With Concomitant Normal Blood and Urine Calcium

    Proportion of participants who achieve a concomitant normal or elevated fasting blood calcium (albumin-corrected calcium>8.5 mg/dL) and a normal 24-hour urinary calcium level (<250 mg/24 hours for women, <300 mg/24 hours for men) on encaleret at any point between day 1 and day 5 while on treatment.

    Measured: Day 1-5 while on treatment

Timeline

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

  1. First posted21 Feb 2023
  2. Study start1 Sep 2023
  3. Primary completion21 May 2025
  4. Study completion12 Aug 2025

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 2
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05735015
Sponsor's protocol ID
10001085
Other IDs
001085-D
Status last verified
18 Feb 2026
First submitted
17 Feb 2023
Last updated
11 Mar 2026
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All anonymized individual participant data (IPD) that underlie results in a publication

Publications

  • Roberts MS, Gafni RI, Brillante B, Guthrie LC, Streit J, Gash D, Gelb J, Krusinska E, Brennan SC, Schepelmann M, Riccardi D, Bin Khayat ME, Ward DT, Nemeth EF, Rosskamp R, Collins MT. Treatment of Autosomal Dominant Hypocalcemia Type 1 With the Calcilytic NPSP795 (SHP635). J Bone Miner Res. 2019 Sep;34(9):1609-1618. doi: 10.1002/jbmr.3747. Epub 2019 Jul 26.

    PubMed 31063613

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing encaleret in people with Post-Surgical Hypoparathyroidism, run by National Institute of Dental and Craniofacial Research (NIDCR) 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 45 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 11 Mar 2026. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 11 Mar 2026). 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?

Percent Change in Fractional Excretion of Calcium (FECa) (time frame: Last measurement (12 hours after last dose of encaleret), baseline (24 hours before first dose of encaleret)). 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 NCT05735015, which also lists 1 linked publication.

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 11 Mar 2026.

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