PTH-independent Effects of Encaleret

NCT05735015 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 10001085001085-D
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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

Conditions

Post-Surgical Hypoparathyroidism

Keywords

Hypoparathyroidism; Hypocalcemia; Post-Surgical Hypoparathyroidism; Calcilytix; Encaleret

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (1)

• Proportion of Participants With Concomitant Normal Blood and Urine Calcium

  Day 1-5 while on treatment

Study Arms (1)

Participants with Permanent hypoparathyroidism

EXPERIMENTAL

Participants with permanent post-surgical hypoparathyroidism (\>1 year after surgery) received encaleret 162 mg orally twice daily for up to five days.

Drug: encaleret

Interventions

encaleret DRUG

Encaleret 162 mg orally

Participants with Permanent hypoparathyroidism

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• a. 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
• 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

You may not qualify if:

• 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.
• 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.
• a. 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

Sponsors & Collaborators

• National Institute of Dental and Craniofacial Research (NIDCR): lead
• Calcilytix Therapeutics, Inc., a BridgeBio company: collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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.

  PMID: 31063613 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hypoparathyroidism; Hypocalcemia

Condition Hierarchy (Ancestors)

Parathyroid Diseases; Endocrine System Diseases; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Water-Electrolyte Imbalance

Results Point of Contact

• Title: Dr. Iris Hartley
• Organization: National Institute of Dental and Craniofacial Research

iris.hartley@nih.gov

+1 301 594 5555

Study Officials

• Iris R Hartley, M.D.

  National Institute of Dental and Craniofacial Research (NIDCR)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2023
• First Posted: February 21, 2023
• Study Start: September 1, 2023
• Primary Completion: May 21, 2025
• Study Completion: August 12, 2025
• Last Updated: March 11, 2026
• Results First Posted: March 11, 2026

Record last verified: 2026-02-18

Data Sharing

• IPD Sharing: Will share
• Time Frame: starting 6 months after publication in peer-reviewed journals
• Access Criteria: Anonymized data will be shared on reasonable request to the principal investigator.

Locations

US (1)