Encaleret for Hypoparathyroidism

Overseen by Iris R Hartley, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Institute of Dental and Craniofacial Research (NIDCR)

Must not be taking: PTH analogs, Encaleret

Disqualifiers: Hypocalcemic seizure, Cardiac disease, Cancer, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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. 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 1 week after leaving the clinic. They will have 3 follow-up phone calls.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. If you are on thiazide diuretics or strong CYP3A4 inhibitors, you must stop them for a specific time before starting the study drug and remain off them during the trial. Also, if you take magnesium or potassium citrate supplements, you should stop them two days before the study begins.

How is the drug Encaleret different from other treatments for hypoparathyroidism?

Encaleret is unique because it is a calcilytic, which means it works by blocking the calcium-sensing receptor to increase parathyroid hormone (PTH) levels, potentially offering a new approach compared to traditional treatments that focus on calcium and vitamin D supplementation. ^{1 2 3 4 5}

Research Team

Iris R Hartley, M.D.

Principal Investigator

National Institute of Dental and Craniofacial Research (NIDCR)

Eligibility Criteria

Adults with postsurgical hypoparathyroidism (PSH) can join this study. They must have stable blood calcium levels on current treatments, a BMI between 18.5 and <39 kg/m2, and normal or managed thyroid function. Pregnant women, those at childbearing age not using contraception, people with recent substance dependency, certain heart conditions, liver issues or severe kidney problems cannot participate.

Inclusion Criteria

Body mass index (BMI) must be between 18.5 to < 39 kg/m2

I can stop taking strong CYP3A4 inhibitors before starting the study treatment.

I have been diagnosed with PSH and had surgery either more or less than a year ago.

Exclusion Criteria

My liver isn't working well.

Unwillingness to refrain from blood donation within specific timeframes

I have had a seizure caused by low calcium in the last 3 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 days

1 visit (in-person)

Treatment

Participants receive encaleret by mouth twice a day for 5 days while staying in the clinic

7 days

1 visit (in-patient stay)

Follow-up

Participants have follow-up blood tests and phone calls to monitor safety and effectiveness after treatment

1 week

1 visit (in-person), 3 phone calls

Treatment Details

Interventions

• Encaleret (Calcium-Sensing Receptor Antagonist)

Trial Overview The trial is testing encaleret for PSH patients to manage their blood calcium without causing kidney issues. Participants will take encaleret orally twice daily for five days during a week-long clinic stay where they'll undergo frequent blood tests and urine collection followed by follow-up checks.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

All participants given 5 days of encaleret twice daily

Who Is Running the Clinical Trial?

National Institute of Dental and Craniofacial Research (NIDCR)

Lead Sponsor

Trials

312

Recruited

853,000+

Janice S. Lee

National Institute of Dental and Craniofacial Research (NIDCR)

Clinical Director

DDS, MD, MS

Jennifer Webster-Cyriaque

National Institute of Dental and Craniofacial Research (NIDCR)

Acting Director

DDS, PhD

Findings from Research

Cinacalcet was successfully used to manage a newborn with neonatal severe hyperparathyroidism (NSHPT) caused by a genetic mutation, effectively controlling calcium, phosphorus, and parathyroid hormone levels.

The treatment was well-tolerated, showing no side effects over the course of one year, suggesting that cinacalcet could be a safe alternative to traditional treatments for NSHPT in infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cinacalcet therapy in an infant with an R185Q calcium-sensing receptor mutation causing hyperparathyroidism: a case report and review of the literature. Forman, TE., Niemi, AK., Prahalad, P., et al.[2021]

The Hypoparathyroid Patient Questionnaire (HPQ 40/28) effectively identified and quantified specific symptoms in patients with postsurgical hypoparathyroidism (HypoPT), highlighting significant complaints such as pain, cramps, and neurovegetative symptoms.

The calcium-phosphate product (CPP) was found to be the main contributor to the severity of symptoms in HypoPT patients, correlating with various complaints including loss of vitality and memory problems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantification of Symptom Load by a Disease-Specific Questionnaire HPQ 28 and Analysis of Associated Biochemical Parameters in Patients With Postsurgical Hypoparathyroidism. Wilde, D., Wilken, L., Stamm, B., et al.[2020]

In a study involving 24 adults with postsurgical chronic hypoparathyroidism, calcium citrate (Ca-Cit) was found to significantly reduce urinary oxalate excretion compared to calcium carbonate (CaCO3), which may lower the risk of kidney stones (nephrolithiasis).

Both Ca-Cit and CaCO3 maintained similar serum calcium and phosphorus levels, but Ca-Cit was associated with less constipation, suggesting it may be a better option for patients who have difficulty tolerating CaCO3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium Citrate Versus Calcium Carbonate in the Management of Chronic Hypoparathyroidism: A Randomized, Double-Blind, Crossover Clinical Trial. Naciu, AM., Tabacco, G., Bilezikian, JP., et al.[2023]

The calcilytic AXT914 effectively increased serum parathyroid hormone (PTH) and calcium levels while decreasing phosphorus levels and urinary calcium excretion in rat models of postsurgical hypoparathyroidism, indicating its potential as a treatment option.

AXT914 not only corrected calcium and phosphorus imbalances but also improved the functional recovery of autotransplanted parathyroid tissues, suggesting a beneficial mechanism of action in managing postsurgical hypoparathyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Therapeutic Approach Using a Calcilytic (AXT914) for Postsurgical Hypoparathyroidism in Female Rats. Lim, YS., You, BH., Kim, HB., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Cinacalcet therapy in an infant with an R185Q calcium-sensing receptor mutation causing hyperparathyroidism: a case report and review of the literature. [2021]

2. Italy pubmed.ncbi.nlm.nih.gov

Multicenter retro-prospective observational study on chronic hypoparathyroidism and rhPTH (1-84) treatment. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Quantification of Symptom Load by a Disease-Specific Questionnaire HPQ 28 and Analysis of Associated Biochemical Parameters in Patients With Postsurgical Hypoparathyroidism. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Calcium Citrate Versus Calcium Carbonate in the Management of Chronic Hypoparathyroidism: A Randomized, Double-Blind, Crossover Clinical Trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

A New Therapeutic Approach Using a Calcilytic (AXT914) for Postsurgical Hypoparathyroidism in Female Rats. [2021]