Delving into the Latest Updates on Ripasudil Hydrochloride Hydrate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Ripasudil, Ripasudil hydrochloride hydrate (JAN), Ripasudil hydrocholoride hydrate

+ [5]

Target

ROCK1

Mechanism

ROCK1 inhibitors(Rho-associated protein kinase 1 inhibitors)

Therapeutic Areas

Eye DiseasesCongenital DisordersOther Diseases

Active Indication

GlaucomaFuchs' Endothelial DystrophyCorneal Edema+ [1]

Inactive Indication-

Originator Organization

Kowa Co., Ltd.

Active Organization

Kowa Research Institute, Inc.

Kowa Pharmaceuticals America, Inc.

Kowa Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

JP (26 Sep 2014),

Glaucoma

Regulation-

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Structure

Molecular FormulaC15H21ClFN3O3S

InChIKeyDRZAXKMMRYEBQP-IDMXKUIJSA-N

CAS Registry887375-67-9

The purpose of this research is to investigate the effects of ripasudil administered as an ophthalmic solution in patients with FED after femtosecond laser assisted cataract surgery. The secondary aim is to identity the characteristics of patients who will benefit the most with the use of ripasudil based on the test results obtained from this study.

Start Date01 Oct 2023

Sponsor / Collaborator

Singapore Eye Research Institute

NCT05826353 / RecruitingPhase 3

A Double-Masked, Randomized, Placebo-Controlled, Parallel-Group, 12-Week Administration With Two-Week Gradual Dose Taper Phase and 38-Week Follow-Up Phase, Phase 3 Study to Investigate the Safety and Efficacy of Ripasudil (K-321) Eye Drops After Simultaneous Cataract Surgery and Descemetorhexis in Subjects With Fuchs Endothelial Corneal Dystrophy

A study to assess the safety and efficacy of K-321 in participants with FECD after simultaneous cataract surgery and descemetorhexis.

Start Date11 May 2023

Sponsor / Collaborator

Kowa Research Institute, Inc.

NCT05795699 / RecruitingPhase 3

A Double-Masked, Randomized, Placebo-Controlled, Parallel-Group, 12-Week Administration With Two-Week Gradual Dose Taper Phase and 38-Week Follow-Up Phase, Phase 3 Study to Investigate the Safety and Efficacy of Ripasudil (K-321) Eye Drops After Descemetorhexis in Subjects With Fuchs Endothelial Corneal Dystrophy

A study to assess the safety and efficacy of K-321 in participants with FECD after descemetorhexis.

Start Date30 Mar 2023

Sponsor / Collaborator

Kowa Research Institute, Inc.

100 Clinical Results associated with Ripasudil Hydrochloride Hydrate

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100 Translational Medicine associated with Ripasudil Hydrochloride Hydrate

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100 Patents (Medical) associated with Ripasudil Hydrochloride Hydrate

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172

Literatures (Medical) associated with Ripasudil Hydrochloride Hydrate

01 Feb 2024·Journal of pharmacological sciences

Investigation into the usefulness of cynomolgus monkeys with spontaneously elevated intraocular pressure as a model for glaucoma treatment research

Article

Author: Kabayama, Koji ; Hara, Hideaki ; Nakamura, Shinsuke ; Tsusaki, Hideshi ; Sakata, Megumi ; Otsu, Wataru ; Shimazawa, Masamitsu ; Numata, Yosuke ; Araki, Tomoaki

Many glaucoma treatments focus on lowering intraocular pressure (IOP), with novel drugs continuing to be developed. One widely used model involves raising IOP by applying a laser to the trabecular iris angle (TIA) of cynomolgus monkeys to damage the trabecular meshwork. This model, however, presents challenges such as varying IOP values, potential trabecular meshwork damage, and risk of animal distress. This study investigated whether animals with naturally high IOP (>25 mmHg) could be used to effectively evaluate IOP-lowering drugs, thereby possibly replacing laser-induced models. Relationships between TIA size, IOP, and pupil diameter were also examined. Three representative IOP-lowering drugs (latanoprost, timolol, ripasudil) were administered, followed by multiple IOP measurements and assessment of corneal thickness, TIA, and pupil diameter via anterior segment optical coherence tomography (AS-OCT). There was a positive correlation was noted between IOP and corneal thickness before instillation, and a negative correlation between IOP and TIA before instillation. Our findings suggest animals with naturally high IOP could be beneficial for glaucoma research and development as a viable replacement for the laser-induced model and that measuring TIA using AS-OCT along with IOP yields a more detailed evaluation.

01 Jan 2024·BMJ open ophthalmology

Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1): outcome masked, placebo-controlled trial comparing two types of corneal transplant surgeries and effect of rho kinase inhibitors on endothelial cell loss protocol

Article

Author: Abdelrahman, Sarah ; Lietman, Thomas M ; Clover, Jameson ; Jeng, Bennie H ; Rose-Nussbaumer, Jennifer ; Lin, Charles C ; Li, Jennifer Y ; Chamberlain, Winston ; Varnado, Nicole ; Arnold, Benjamin F ; Gensheimer, William

Background:

It remains uncertain which endothelial keratoplasty (EK) technique yields the best outcomes while maintaining safety, particularly in eyes with coexisting ocular conditions. Moreover, the impact of endothelial cell loss (ECL) on long-term graft survival requires further investigation. Adjuvant ripasudil, a rho kinase inhibitor, may address the challenge of ECL in corneal transplantation. This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1), a multicentre, outcome-masked, randomised, placebo-controlled, four-arm clinical trial.

Methods:

A total of 160 eligible patients with endothelial dysfunction will be enrolled from five participating sites in the USA. The patients will be randomly assigned in a 2×2 factorial design to one of the following treatment groups: group 1—ultrathin Descemet stripping endothelial keratoplasty (UT-DSAEK) plus topical ripasudil 0.4%; group 2—UT-DSAEK plus topical placebo; group 3—Descemet membrane endothelial keratoplasty (DMEK) plus topical ripasudil 0.4% and group 4—DMEK plus topical placebo. Primary outcomes include the best spectacle-corrected visual acuity at 12 months and ECL at 12 months. Secondary outcomes include visual acuity at different time points, vision-related quality of life, endothelial cell morphology and cost-effectiveness.

Results:

The study outcomes will be analysed using mixed effects linear regression models, taking into account the treatment arms and relevant covariates. Adverse events, including rebubble procedures, graft failure and graft rejection, will be documented and analysed using appropriate statistical methods.

Conclusion:

DETECT I aims to provide evidence on the comparative effectiveness of UT-DSAEK and DMEK, as well as the potential benefits of adjuvant topical ripasudil in reducing ECL. The results of this trial will contribute to optimising corneal transplantation techniques and improving long-term graft survival, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation.

Ethics and dissemination:

A data and safety monitoring committee (DSMC) has been empaneled by the NEI.All study protocols will be subject to review and approval by WCG IRB as the single IRB of record.This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request.

01 Jan 2024·Acta pharmacologica Sinica

Myeloid-derived growth factor suppresses VSMC dedifferentiation and attenuates postinjury neointimal formation in rats by activating S1PR2 and its downstream signaling

Article

Author: Liu, Xue ; Cao, Shi-Feng ; Feng, Min ; Tian, Jia-Ying ; Liu, Qian ; Wang, Zheng-Kai ; Chen, Yi ; Li, Hou-Wei ; Zhao, Yu ; Wang, Zhi-Qi ; Yang, Shuang ; Zhan, Ting-Ting ; Jin, Lu-Ying ; Ren, Jing ; Jiang, Wen-Yu ; Zhao, Yi-Xiu ; Ma, Chun-Yue ; Li, Xue ; Zhang, Yan

Restenosis after angioplasty is caused usually by neointima formation characterized by aberrant vascular smooth muscle cell (VSMC) dedifferentiation. Myeloid-derived growth factor (MYDGF), secreted from bone marrow-derived monocytes and macrophages, has been found to have cardioprotective effects. In this study we investigated the effect of MYDGF to postinjury neointimal formation and the underlying mechanisms. Rat carotid arteries balloon-injured model was established. We found that plasma MYDGF content and the level of MYDGF in injured arteries were significantly decreased after balloon injury. Local application of exogenous MYDGF (50 μg/mL) around the injured vessel during balloon injury markedly ameliorated the development of neointimal formation evidenced by relieving the narrow endovascular diameter, improving hemodynamics, and reducing collagen deposition. In addition, local application of MYDGF inhibited VSMC dedifferentiation, which was proved by reversing the elevated levels of osteopontin (OPN) protein and decreased levels of α-smooth muscle actin (α-SMA) in the left carotid arteries. We showed that PDGF-BB (30 ng/mL) stimulated VSMC proliferation, migration and dedifferentiation in vitro; pretreatment with MYDGF (50-200 ng/mL) concentration-dependently eliminated PDGF-BB-induced cell proliferation, migration and dedifferentiation. Molecular docking revealed that MYDGF had the potential to bind with sphingosine-1-phosphate receptor 2 (S1PR2), which was confirmed by SPR assay and Co-IP analysis. Pretreatment with CCG-1423 (Rho signaling inhibitor), JTE-013 (S1PR2 antagonist) or Ripasudil (ROCK inhibitor) circumvented the inhibitory effects of MYDGF on VSMC phenotypic switching through inhibiting S1PR2 or its downstream RhoA-actin monomers (G-actin) /actin filaments (F-actin)-MRTF-A signaling. In summary, this study proves that MYDGF relieves neointimal formation of carotid arteries in response to balloon injury in rats, and suppresses VSMC dedifferentiation induced by PDGF-BB via S1PR2-RhoA-G/F-actin-MRTF-A signaling pathway. In addition, our results provide evidence for cross talk between bone marrow and vasculature.

1

News (Medical) associated with Ripasudil Hydrochloride Hydrate

14 Dec 2022

·www.prnewswire.com

Capstone Announces FDA Approval and EU Authorization of Doxorubicin Hydrochloride Liposome Injection

ROSEMONT, Ill., Dec. 14, 2022 /PRNewswire/ -- Capstone Development Services Company LLC ("Capstone") announced today that it has received approval from the U.S. Food and Drug Administration (FDA), as well as authorization from the European Commission for doxorubicin hydrocholoride liposomal injection. Authorized as a treatment for multiple types of cancer, the product was developed by Capstone in partnership with a leading medical products company. Continue Reading Doxorubicin Hydrochloride Liposome Injection is indicated for treatment of ovarian cancer, acquired immune deficiency syndrome (AIDS)-related Kaposi's Sarcoma and multiple myeloma. It also is authorized in the EU for treatment of metastatic breast cancer. The product is an anthracycline topoisomerase inhibitor encapsulated in liposomes for intravenous use. These approvals are a testament to our team's expertise in complex formulations. - Dan Robins, Ph.D., president, Capston Tweet this The authorizations mark the 19th and 20thth regulatory approvals Capstone has gained for products developed since its founding in 2013. Capstone funded, developed and led the regulatory approval process of the product. After gaining approvals, it transferred ownership of the product to its medical products partner. Dan Robins, Ph.D., president, Capstone, said: "These approvals are a testament to our team's expertise in complex formulations. We are thrilled to have led the development and regulatory process to bring this important product to market on behalf of our global partner." For more details about doxorubicin hydrocholoride liposomal injection, including the boxed warning for cardiomyopathy and infusion-related reactions, see full prescribing information. Doxorubicin Hydrochloride Liposome Injection , USP Important Safety Information WARNING Doxorubicin hydrochloride liposomal infusion can cause myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy was 11% when the cumulative anthracycline dose was between 450mg/m2 to 550mg/m2. Assess left ventricular cardiac function prior to initiation of doxorubicin hydrochloride liposomal infusion, during treatment, and after treatment. Serious, life-threatening, and fatal infusion-related reactions can occur. Acute infusion-related reaction occurred in 11% of patient with solid tumors. Withhold doxorubicin hydrochloride liposomal infusion for infusion-related reactions and resume at a reduced rate. Discontinue doxorubicin hydrochloride liposomal infusion for serious or life-threatening infusion-related reactions. About Capstone Capstone was founded in 2013 by Water Street Healthcare Partners, a strategic investor focused exclusively on health care. The company leads development, manages regulatory services and achieves timely approval of health care products through partnerships with global pharmaceutical and medical companies. To date, Capstone has developed and gained regulatory approvals on 20 products in the U.S., EU and Canada. The company supports its partners with bringing new and affordable health care products to market. For more information, visit capstonedevservices.com. SOURCE Capstone

Drug Approval

100 Deals associated with Ripasudil Hydrochloride Hydrate

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External Link

KEGG	Wiki	ATC	Drug Bank
D10463	Ripasudil Hydrochloride Hydrate	S01EX	DB13165

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Glaucoma	JP	Kowa Co., Ltd.	26 Sep 2014

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Fuchs' Endothelial Dystrophy	Phase 3	US	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	CA	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	DK	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	DE	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	ES	Kowa Research Institute, Inc.	30 Mar 2023
Fuchs' Endothelial Dystrophy	Phase 3	GB	Kowa Research Institute, Inc.	30 Mar 2023
Corneal Edema	Phase 3	US	Kowa Research Institute, Inc.	04 Aug 2022
Corneal Edema	Phase 3	PR	Kowa Research Institute, Inc.	04 Aug 2022
Ophthalmologic surgical procedures	Phase 3	US	Kowa Research Institute, Inc.	04 Aug 2022
Ophthalmologic surgical procedures	Phase 3	PR	Kowa Research Institute, Inc.	04 Aug 2022

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ARVO2023	Not Applicable	-	-	Ripa	pjokujbrjn(sbrdizkbiy) = rlnqtwffog hzkgpuvojq (qeomgqwhpw )	-	23 Apr 2023
				Lipo-Ripa	pjokujbrjn(sbrdizkbiy) = huecptyysg hzkgpuvojq (qeomgqwhpw )
AAO2022	Not Applicable	Fuchs' Endothelial Dystrophy	23	Topical Ripasudil	oozzqorukq(phmfaswfzr) = lagbuikcsd hfakbpasgv (ppwkxdffrh )	-	29 Sep 2022
ARVO2022	Not Applicable	-	-	Ripasudil ophthalmic solution	zrbafuvasv(faaiwzqwcf) = xzzsitrfhc tphvgixuzq (vtnzjniqqq )	Negative	01 May 2022
				Balanced salt solution (BSS)	zrbafuvasv(faaiwzqwcf) = hrwqwlrqdf tphvgixuzq (vtnzjniqqq )
AAO2021	Not Applicable	Fuchs' Endothelial Dystrophy	-	DMEK+ripasudil	jhwyiqqqit(lcphryomsd) = dkycdrfffl oochazjbyt (threbcvxpu ) View more	-	13 Nov 2021
				Ripasudil	jhwyiqqqit(lcphryomsd) = jvhgusfevw oochazjbyt (threbcvxpu ) View more
ARVO2019	Not Applicable	-	11	Ripasudil	wrwveijpkd(rwnladgtpe) = gtrresgmwx mqakbythbj (vmjmpwoaes ) View more	-	01 Jul 2019
				Control (DMSO)	wrwveijpkd(rwnladgtpe) = zzkqnboehw mqakbythbj (vmjmpwoaes ) View more
2019 ARVO Annual Meeting (ARVO2019)	Not Applicable	-	-	Vehicle	fnycoapwat(ukquxzykum) = ksmrepjham mjegpphvix (vdbholztdt )	-	01 Jul 2019
				NMDA	fnycoapwat(ukquxzykum) = wqtrnyongz mjegpphvix (vdbholztdt )
not available (ARVO2019)	Not Applicable	Glaucoma, Open-Angle	271	Ripasudil 0.4% eye drops	pyctpqqsuw(ocekdbbjjp) = doqeqltaii vehsonfkke (bjeldickpq )	Positive	01 Jul 2019
ARVO2019	Not Applicable	-	-	Placebo	zunxouqzfu(cohftmregp) = szdczorpul zeatthqyvk (wejkctkgup ) View more	-	01 Jul 2019
				Ripasudil 0.04%	zunxouqzfu(cohftmregp) = wxmvkdkzrd zeatthqyvk (wejkctkgup ) View more
2018 ARVO Annual Meeting (ARVO2018)	Not Applicable	Ocular Hypotension	9	Ripasudil 0.4% ophthalmic solution	esrgzysdzs(oeeepywxgs) = sjknkuqweo fmwmlqcjrb (nbzywgxlsf )	Negative	01 Jul 2018
2018 ARVO Annual Meeting (ARVO2018)	Not Applicable	-	20	Placebo instillation	hekwiyrsav(dcyfufgklq) = utazhqvrou xercqbnmmn (cjrcprdamy ) View more	Positive	01 Jul 2018
				0.04% Ripasudil instillation	hekwiyrsav(dcyfufgklq) = qelncvkuyg xercqbnmmn (cjrcprdamy ) View more