Evidence map›Paper›PMID 42183375›Full record

ArticleResearch square2026

PTH-Independent CaSR Inhibition with the Oral Calcilytic Encaleret Improves Calcium Homeostasis in Post-Surgical Hypoparathyroidism: A Phase 2 Open-Label Proof-of-Concept Trial.

Iris Ruth Hartley, Rachel Ilana Gafni, Xiaobai Li, Ashna Grover, Elizabeth A Ferguson, Casey A Moore, Karen A Pozo, Kimberly T Ampuero, Ananth V Sridhar, Arun S Mathew PharmD and 5 more

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Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Iris Ruth HartleyNational Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.ORCID 0000-0003-1029-3284
Rachel Ilana GafniNational Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.
Xiaobai LiBiostatistics and Clinical Epidemiology, Clinical center, NIH, Bethesda, MD, USA.
Ashna GroverNational Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.
Elizabeth A FergusonNational Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.
Casey A MooreNational Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.
Karen A PozoNational Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.
Kimberly T AmpueroNational Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.
Ananth V SridharCalcilytix Therapeutics, Inc, San Francisco, CA, USA.
Arun S Mathew PharmDCalcilytix Therapeutics, Inc, San Francisco, CA, USA.
Mary Scott RobertsCalcilytix Therapeutics, Inc, San Francisco, CA, USA.
Scott H AdlerCalcilytix Therapeutics, Inc, San Francisco, CA, USA.
Edward F NemethMetisMedica, Toronto, ON, Canada.
Kelly L RoszkoNational Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.
Michael T CollinsNational Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The calcium-sensing receptor (CaSR) maintains calcium homeostasis by regulating parathyroid hormone (PTH) secretion and directly modulating renal calcium reabsorption. In the kidney, PTH and renal CaSR signaling exert opposing effects on tubular calcium reabsorption and urinary calcium excretion, complicating efforts to define their independent contributions to overall calcium regulation. To examine the PTH-independent effects of CaSR inhibition on renal calcium handling, we administered a calcilytic (CaSR antagonist) to individuals with post-surgical hypoparathyroidism (PSH). In this open-label, phase 2, proof-of-concept study (NCT0573515), ten adults (26-69y) with chronic PSH were orally administered the calcilytic encaleret for up to 5 days. Calcitriol was discontinued one day prior, and calcium and calcitriol were individually titrated based on blood calcium. Mean fractional excretion of calcium (FECa) decreased by 39±29% (p=0.002) by end of treatment. Albumin-corrected serum calcium increased from 8.5±0.3 mg/dL (mean±SD, normal 8.4-10.2) at time 0 to 9.2±0.6 (p=0.002) at 48 hours while urinary calcium decreased from 405±200 mg/day (m:<250; f:<350) to 180±100 (p=0.0005). Although mean intact PTH increased modestly 30 minutes after the first encaleret dose (7.3±3.1 pg/mL to 12.3±7.9 pg/mL; normal 15-65; p=0.008), levels rapidly returned to baseline without further excursions for the remainder of the study. No serious adverse events (AEs) were reported. Transient mild hypercalcemia and headache in 1 participant were the only treatment-related AEs. In PSH, encaleret reduced urinary Ca and increased serum Ca, demonstrating the PTH-independent role of CaSR signaling in renal calcium handling and supporting further study of encaleret as an oral treatment for patients with PSH.

Identifiers

PMID42183375
PMCPMC13193124

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.