Phase 3, Decentralized, Randomized, Double-Blind, Placebo Controlled, Parallel Design, Randomized Withdrawal, and Long-term Safety Study to Evaluate the Efficacy and Safety of Ulixacaltamide (PRAX-944) in Adults With Essential Tremor

The goal of this clinical study is to compare ulixacaltamide and placebo treatment in essential tremor. The main question it aims to answer is:
• Is ulixacaltamide a safe and efficacious treatment for patients with essential tremor?
Participants will be asked to participate in one of two clinical studies where they will be treated with either ulixacaltamide or placebo for a period of up to 12 weeks. After the controlled study completion, they will be eligible to participate in a long-term, open-label safety study and be treated with ulixacaltamide.

Start Date02 Nov 2023

Sponsor / Collaborator

Praxis Precision Medicines, Inc.

NCT05021991

/ CompletedPhase 2

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Range Finding Clinical Trial to Evaluate the Efficacy, Tolerability, and Safety of PRAX-944 in the Treatment of Adults With Essential Tremor

This multi-center, randomized, double-blinded, placebo-controlled, dose-range-finding clinical trial (with an optional Extension comprised of an Extension Double-blind (DB) Lead in Period followed by an Extension Open-label (OL) Period) that will assess the efficacy, safety, and tolerability of PRAX 944 in participants aged 18 years or older who have a diagnosis of Essential Tremor (ET) and have had symptoms for at least 3 years.

Start Date14 Oct 2021

Sponsor / Collaborator

Praxis Precision Medicines, Inc.

ACTRN12622000408785

/ RecruitingPhase 2

A Phase 2 Clinical Trial Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of PRAX-944 in Adults with Essential Tremor - Part B

Start Date05 Aug 2021

Sponsor / Collaborator

Praxis Precision Medicines, Inc.

100 Clinical Results associated with Ulixacaltamide

100 Translational Medicine associated with Ulixacaltamide

100 Patents (Medical) associated with Ulixacaltamide

Literatures (Medical) associated with Ulixacaltamide

03 Mar 2025·ChemMedChem

Eco‐friendly Synthesis and Molecular Modelling of 2‐Phenylimidazo[1,2‐b]pyridazine Derivatives: In Vitro and In Vivo Studies for Lead Optimization

Article

Author: Cinque, Pierfrancesco ; Persico, Marco ; Santagada, Vincenzo ; De Caro, Carmen ; Meli, Rosaria ; Comella, Federica ; Rimoli, Maria Grazia ; Tkachuk, Oleh ; Albrizio, Stefania ; Billi, Chiara ; Grillo, Giorgio ; Frecentese, Francesco ; Russo, Emilio ; Schiano, Marica Erminia ; Sodano, Federica ; Fattorusso, Caterina

Abstract7‐methyl‐2‐phenylimidazo[1,2‐b]pyridazin‐3‐carboxylic acid (DM1) and 6‐methoxy‐2‐phenylimidazo[1,2‐b]pyridazin‐3‐carboxylic acid (DM2) have been shown to act as human (h) Cav3.1 voltage‐gated calcium channel blockers with promising in vivo anti‐absence activity, positioning them as potential antiepileptic drugs. The primary aim of this work was to develop cost‐effective and environmentally friendly synthetic procedures for preparing 2‐phenylimidazo[1,2‐b]pyridazine derivatives. After optimizing the synthesis of this compound class using efficient and green techniques such as microwaves and ultrasound irradiation, we further evaluated the antiepileptic effects of DM1 and DM2 in two animal models: CD‐1 ICR mice after pentylenetetrazol administration and DBA/2 mice with seizures induced by audiogenic stimuli. Their neuroprotective effect against oxidative stress were assessed using C6 rat brain glioma cells. DM1 and DM2 exhibited potent anti‐seizure effects in both animal models and demonstrated significant in vitro neuroprotective activity by reducing reactive oxygen species release. To lay the groundwork for the future rational optimization of this promising class of compounds, the molecular bases of DM1 and DM2 activity were investigated by modelling their interaction with hCav3.1 channels. The calculated binding modes of DM1 and DM2 to hCav3.1 channels partially mirrored that of the selective Cav3.1 blocker Z944, paving the way for future lead optimization.

01 Dec 2024·British Journal of Pharmacology

Contribution of T‐type calcium channel isoforms to cold and mechanical sensitivity in naïve and oxaliplatin‐treated mice of both sexes

Article

Author: Snutch, Terrance P. ; Hildebrand, Michael ; David, Laurence S. ; Antunes, Flavia T. T. ; Gandini, Maria A. ; Santin, José Roberto ; Zamponi, Gerald W. ; Gadotti, Vinicius M. ; Souza, Ivana A. ; Quintão, Nara Lins Meira

Background and PurposeThe chemotherapy agent oxaliplatin can give rise to oxaliplatin‐induced peripheral neuropathy (OIPN). Here, we investigated whether T‐type calcium channels (Cav3) contribute to OIPN.Experimental ApproachWe chronically treated mice with oxaliplatin and assessed pain responses and changes in expression of Cav3.2 calcium channels. We also tested the effects of T‐type channel blockers on cold sensitivity in wild‐type and Cav3.2 null mice.Key ResultsOxaliplatin treatment led to mechanical and cold hypersensitivity in male and female mice. Mechanical hypersensitivity persisted in Cav3.2 null mice of both sexes. Intraperitoneal or intrathecal delivery of pan T‐type channel inhibitors attenuated mechanical hypersensitivity in wild‐type but not Cav3.2 null mice. Remarkably cold hypersensitivity occurred in female but not male Cav3.2 null mice even without oxaliplatin treatment. Unexpectedly, intrathecal, intraplantar or intraperitoneal delivery of T‐type channel inhibitors Z944 or TTA‐P2 transiently induced cold hypersensitivity in both male and female wild‐type mice. Acute knockdown of specific Cav3 isoforms revealed that the depletion of Cav3.1 in males and depletion of either Cav3.1 or Cav3.2 in females triggered cold hypersensitivity. Finally, reducing Cav3.2 expression by disrupting the interactions between Cav3.2 and the deubiquitinase USP5 with the small organic molecule II‐2 reversed oxaliplatin‐induced mechanical and cold hypersensitivity and importantly did not trigger cold allodynia.Conclusion and ImplicationsAltogether, our data indicate that T‐type channels differentially contribute to the regulation of cold and mechanical hypersensitivity, and raise the possibility that T‐type channel blockers could promote cold allodynia.

01 Apr 2024·Chemistry & Biodiversity

Discovery of α‐Obscurine Derivatives as Novel Ca_v3.1 Calcium Channel Blockers

Article

Author: Wang, Lei ; Yuan, Zai‐Feng ; Zhao, Qin‐Shi ; Li, Wen‐Yan

AbstractVoltage‐gated calcium channels (VGCCs), particularly T‐type calcium channels (TTCCs), are crucial for various physiological processes and have been implicated in pain, epilepsy, and cancer. Despite the clinical trials of TTCC blockers like Z944 and MK8998, none are currently available on the market. This study investigates the efficacy of Lycopodium alkaloids, particularly as natural product‐based TTCC blockers. We synthesized eighteen derivatives from α‐obscurine, a lycodine‐type alkaloid, and identified five derivatives with significant Cav3.1 blockade activity. The most potent derivative, compound 7, exhibited an IC50 value of 0.19±0.03 μM and was further analyzed through molecular docking, revealing key interactions with Cav3.1. These findings provide a foundation for the structural optimization of Cav3.1 calcium channel blockers and present compound 7 as a promising lead compound for drug development and a tool for chemical biology research.

News (Medical) associated with Ulixacaltamide

02 Mar 2025

·medcitynews.com

Praxis Presses Forward in Essential Tremor Despite Futility Finding From Trial Observers - MedCity News

A committee of outside clinical trial observers has recommended that Praxis Precision Medicines stop testing its experimental treatment for essential tremor after an interim analysis of one study concluded it is unlikely to succeed. Instead, Praxis is continuing that test and a second one, adding that a decision about an FDA submission will be made after a final analysis of both studies. The two separate and simultaneous studies are part of the Phase 3 trial design for the Praxis drug, ulixacaltamide. Both placebo-controlled studies are evaluating the once-daily pill over the course of 12 weeks. The main efficacy goal is assessing patients according to a composite scale that measures the ability to perform tasks of daily living. Essential tremor leads to involuntary shaking and trembling in arms and hands, though it can also affect a patient’s head and voice. An estimated 7 million patients in the U.S. have the neurological disorder, whose exact cause is unknown. The first line of essential tremor therapies for beta blockers. While such drugs were developed for high blood pressure, they are thought to also block nerve impulses to the muscles. Anti-seizure drugs offer an alternative treatment option. Healthcare Using Data to Help Healthcare Practices Succeed A new report from Relatient, A Data-Driven Guide to Patient Access Succes, highlights how focusing on data accuracy and relevance can enhance the performance of healthcare practices. By Relatient Ulixacaltamide is a small molecule inhibitor of T-type calcium channels. It’s designed to block abnormal neuronal burst firing in the cerebello-thalamo-cortical (CTC) circuit, which is correlated with tremor activity. Boston-based Praxis said Friday that based on the results of a planned interim analysis, the trial’s independent data monitoring committee recommended that Study 1 be stopped for futility, “due to the results being unlikely to meet the primary efficacy endpoint under the parameters set by the statistical model.” The targeted total enrollment of the two studies is 600 participants. Praxis said that given the advanced state of trial enrollment, it has decided to complete both studies. Preliminary results are expected in the third quarter of this year. Praxis added that the committee said some underlying assumptions of the statistical model might have influenced the futility finding and it encouraged the company to explore alternative analysis methods. In the Praxis announcement, CEO Marcio Souza said the company will explore different analysis methods for the final dataset that will be the basis for deciding whether to proceed with a regulatory submission. But investors took a dim view of the Praxis drug’s prospects. The biotech’s stock price tumbled Friday, closing at $38.60, down 40.6% from the Thursday’s closing price. Ulixacaltamide came from Cerebrum, Praxis’s proprietary technology for discovering small molecule drugs with the potential to treat central nervous system disorders. Formerly known as PRAX-944, ulixacaltamide is the most advanced drug candidate in the Praxis pipeline. Other drug candidates are in earlier stages of clinical development for various forms of epilepsy. Health IT Reducing Clinical and Staff Burnout with AI Automation As technology advances, AI-powered tools will increasingly reduce the administrative burdens on healthcare providers. By Dr. Michael Blackman, Chief Medical Officer at Greenway Health In its report of fourth quarter and full year 2024 financial results posted on Friday, Praxis stated it finished 2024 with $469.5 million in capital, a strong cash position that follows stock offerings completed last year. The company expects its cash will support operations into 2028. Image: Getty Images, Iaremenko

Phase 3Financial Statement

28 Feb 2025

·www.fiercebiotech.com

Praxis flouts phase 3 futility finding, forging ahead with tremor trial despite interim setback

Praxis\' share price fell more than 40% to around $38 in premarket trading.\n Praxis Precision Medicines has been blindsided by a recommendation to stop a phase 3 essential tremor trial. Two months after CEO Marcio Souza said the chances of the trial being futile were “less than 3%,” the biotech has learnt the study looks unlikely to meet its primary endpoint at an interim analysis.The phase 3 trial is one of two late-stage studies of ulixacaltamide in essential tremor. Participants in the first trial were randomized to receive the study drug or placebo for 12 weeks. Based on a failed phase 2 trial, the biotech picked a daily living scale as its primary endpoint. The scale captures how the disease is affecting a patient’s ability to perform tasks such as getting dressed.An interim analysis suggests patients on ulixacaltamide are doing no better than their peers on placebo. The independent data monitoring committee that carried out the analysis advised Praxis to stop the trial for futility because it is unlikely to meet its primary endpoint.Despite that, Praxis has chosen to continue both late-stage trials to completion. Praxis is pushing ahead because enrollment in both studies is advanced and in light of feedback from the committee, which told the biotech “some underlying assumptions of the statistical model might have influenced” the futility finding. The committee encouraged Praxis to explore alternative analysis methods. Praxis expects to have topline data from the two trials in the third quarter and will decide whether to file for approval after analyzing its final results. The second trial has a different design that allows Praxis to assess if patients maintain their responses after being randomized to ulixacaltamide or placebo. Praxis previously ran a similar withdrawal trial. Patients in the earlier trial relapsed after stopping therapy.Going into the interim analysis, Praxis was bullish about the prospects of the committee giving it the okay to continue the trial. At the J.P. Morgan Healthcare Conference in January, Praxis CEO Souza said the study had “a priori, less than 3% probability of being futile, the way it was designed.” Praxis chief financial officer Tim Kelly reiterated the message that futility was “very unlikely” at events this month.Souza and Kelly’s confidence was underpinned by knowledge of the options available to the committee. The committee could recommend adding hundreds of participants to the trial in response to the interim analysis, suggesting Praxis had a path to success even if its assumptions about the statistical powering of the study were too aggressive.The failure of the trial to clear the bar for a continuation recommendation spooked investors, who sent the biotech’s share price down more than 40% to around $38 in premarket trading. Praxis ended 2024 with $469.5 million.

Phase 2Phase 3

28 Feb 2025

·endpts.com

Praxis says its essential tremor drug failed a Phase 3 readout but plans to complete study

Praxis reported that its lead small molecule program failed a Phase 3 study on Friday morning, sending its stock price $PRAX down roughly 40%. The company was studying whether an experimental drug called ulixacaltamide could treat patients with essential tremor, a nervous system disorder that causes involuntary shaking. Typically, patients are treated with beta blockers or antipsychotic medications like Xanax, but ulixacaltamide is designed to inhibit T-type calcium channels. In a press release, Praxis said the trial’s independent data monitoring committee recommended the study stop early due to a high likelihood of futility. The primary endpoint was unlikely to be reached, the company said. But Praxis said it intends to complete the study, as well as another Phase 3 looking at the randomized withdrawal of ulixacaltamide, because the committee also “indicated that some underlying assumptions of the statistical model might have influenced this outcome.” Topline results for both trials are expected in the third quarter, after which Praxis will make a decision about whether to file for approval with the FDA. It wasn’t immediately clear what such underlying assumptions were or how they might have influenced the data. Praxis didn’t immediately return a request for comment. In a note to investors last month, TD Cowen analyst Ritu Baral said Praxis had intended to complete the trial regardless of the data committee’s findings. A futility finding likely would indicate “minimal to no separation” between ulixacaltamide and placebo, she added. Despite Friday’s fail, Praxis’ small molecule platform will continue to produce data readouts this year. The company is expecting open-label data for the epilepsy program vormatrigine in the first half of 2025, as well as Phase 2/3 data in the second half of the year.

Phase 3

100 Deals associated with Ulixacaltamide

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Essential Tremor	Phase 3	United States	Praxis Precision Medicines, Inc.	02 Nov 2023
Parkinson Disease	Phase 2	United States	Praxis Precision Medicines, Inc.	09 Feb 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05021978 (PRAX-944-221, CTgov)	Phase 2	Essential Tremor	24	OLT+PRAX-944 (Part A: PRAX-944 20mg to 40mg OLT)	bntfzsmmju(qvatnwectv) = wpzbjchahn bvvjkdwdpw (vpabrgfnio, wrwzrtuogs - mudveejwop) View more	-	01 Mar 2024
				PRAX-944 (Part B: PRAX-944 20mg to 120mg OLT)	sepxcpqbfm(qyxxabkkrn) = vmpyiyizlr brwvcidpnw (vwxoidhnow, dteyplkqnd - fsgycmzddt) View more
NCT05021991 (Essential1, NEWS) Manual	Phase 3	Essential Tremor	65	ulixacaltamide	nbekisjuua(tqbezywlho) = zwgtpikqvb ywsqhwqgrn (pxdjbidwhw, 2.38 - 7.23) View more	Positive	08 Aug 2023
				Placebo+ulixacaltamide	nbekisjuua(tqbezywlho) = ybqwrtnzkw ywsqhwqgrn (pxdjbidwhw, 1.68 - 7.05) View more
NCT05021978 (PRAX-944-221, AAN 12022 \| AAN 22022) Manual	Phase 2	Essential Tremor	7	PRAX-944	angmeqsmjh(mqkwofnsxo) = xtrrbjmgfr kodhloaphg (undbepucck )	Positive	03 May 2022

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