A single-center, randomized, single-blind, controlled clinical trial of combined celecoxib with ketotifen fumarate to inhibit the recurrence of stiffness after release surgery for post-traumatic elbow stiffness

Start Date15 Dec 2023

Sponsor / Collaborator

Nanjing Drum Tower Hospital

NCT05815758 / CompletedNot Applicable

A Multi-Center, Double-Masked, Randomized, Vehicle-Controlled, Parallel-Group Study Evaluating the Safety and Pharmacokinetics of Brimonidine Tartrate 0.025%/Ketotifen Fumarate 0.035% Combination Ophthalmic Solution, Used Two Times Daily in Healthy Adult Subjects and in Pediatric Subjects With a History or Family History of Atopic Disease (Including Allergic Conjunctivitis)

To compare the safety and tolerability of brimonidine tartrate 0.025%/ketotifen fumarate 0.035% combination ophthalmic solution versus its vehicle in healthy adult subjects and in pediatric subjects.

Start Date20 Apr 2023

Sponsor / Collaborator

Bausch & Lomb, Inc.

NCT05616442 / Not yet recruitingPhase 4IIT

Ketotifen in Non-Alcoholic Fatty Liver Disease Patients

The aim of this study is to investigate the safety and efficacy of using ketotifen in patients with NAFLD patients without cirrhosis

Start Date01 Dec 2022

Sponsor / Collaborator

Tanta University

100 Clinical Results associated with Ketotifen Fumarate

100 Translational Medicine associated with Ketotifen Fumarate

100 Patents (Medical) associated with Ketotifen Fumarate

210

Literatures (Medical) associated with Ketotifen Fumarate

01 Jun 2024·Biomedicine & Pharmacotherapy

Ketotifen counteracts cisplatin-induced acute kidney injury in mice via targeting NF-κB/NLRP3/Caspase-1 and Bax/Bcl2/Caspase-3 signaling pathways

Article

Author: Mohtadi, Shokooh ; Khorsandi, Layasadat ; Salehcheh, Maryam ; Khodayar, Mohammad Javad ; Tabandeh, Mohammad Reza

Cisplatin (CIS) stands as one of the most effective chemotherapy drugs currently available. Despite its anticancer properties, the clinical application of CIS is restricted due to nephrotoxicity. Our research aimed to specify the impact of ketotifen fumarate (KET) against nephrotoxicity induced by CIS in mice. Male NMRI mice were treated with KET (0.4, 0.8, and 1.6 mg/kg, ip) for seven days. On the fourth day of the study, a single dose of CIS (13 mg/kg, ip) was administered, and the mice were sacrificed on the eighth day. The results indicated that administration of KET attenuated CIS-induced elevation of BUN and Cr in the serum, as well as renal KIM-1 levels. This improvement was accompanied by a significant reduction in kidney tissue damage, which was supported by histopathological examinations. Likewise, the decrease in the ratio of GSH to GSSG and antioxidant enzyme activities (CAT, SOD, and GPx), and the increase in lipid peroxidation marker (TBARS) were reversed in KET-treated mice. The ELISA results revealed that KET-treated mice ameliorated CIS-induced elevation in the renal levels of TNF-α, IL-1β, and IL-18. Western blot analysis exhibited that KET suppressed the activation of the transcription factor NF-κB and the NLRP3 inflammasome in the kidney of CIS-treated mice. Moreover, KET treatment reversed the changes in the protein expression of markers related to apoptosis (Bax, Bcl2, Caspase-3, and p53). Interestingly, KET significantly enhanced the cytotoxicity of CIS in HeLa cells. In conclusion, this study provides valuable insights into the promising effects of KET in mitigating CIS-induced nephrotoxicity.

01 Mar 2024·European Journal of Pharmacology

Involvement of peripheral mast cells in a fibromyalgia model in mice

Article

Author: Fialho, Maria Fernanda Pessano ; Becker, Gabriela ; Oliveira, Sara Marchesan ; Brum, Evelyne da Silva ; Nogueira, Cristina Wayne

Fibromyalgia is a painful disorder of unknown aetiology that presents activation and recruitment of innate immune cells, including mast cells. Efforts have been made to understand its pathogenesis to manage it better. Thus, we explored the involvement of peripheral mast cells in an experimental model of fibromyalgia induced by reserpine. Reserpine (1 mg/kg) was subcutaneously (s.c.) injected once daily in the back of male Swiss mice for three consecutive days. We analysed mechanical and cold allodynia, muscle fatigue and number of mast cell in plantar tissue. The fibromyalgia induction produced mast cell infiltration (i.e., mastocytosis) in the mice's plantar tissue. The depletion of mast cell mediators with the compound 48/80 (0.5-4 mg/kg, intraperitoneal (i.p.)) or the mast cell membrane stabilizer ketotifen fumarate (10 mg/kg, oral route (p.o.) widely (80-90 %) and extensively (from 1 up to 10 days) prevented reserpine-induced mechanical and cold allodynia and muscle fatigue. Compound 48/80 also prevented the reserpine-induced mastocytosis. Finally, we demonstrated that PAR-2, 5-HT_2A, 5-HT₃, H₁, NK1 and MrgprB2 receptors, expressed in neuronal or mast cells, seem crucial to mediate fibromyalgia-related cardinal symptoms since antagonists or inhibitors of these receptors (gabexate (10 mg/kg, s.c.), ENMD-1068 (10 mg/kg, i.p.), ketanserin (1 mg/kg, i.p.), ondansetron (1 mg/kg, p.o.), promethazine (1 mg/kg, i.p.), and L733,060 (5 mg/kg, s.c.), respectively) transiently reversed the reserpine-induced allodynia and fatigue. The results indicate that mast cells mediate painful and fatigue behaviours in this fibromyalgia model, representing potential therapy targets to treat fibromyalgia syndrome.

01 Feb 2024·Medical Engineering & Physics

Selectively coated contact lenses by nanoelectrospray (nES) to fabricate drug-eluting contact lenses for treating ocular diseases

Article

Author: Alexander, Matthew S ; Tam, Chak Hin ; Sanderson, Julie ; Qi, Sheng

Drug-eluting contact lenses (DECLs) incorporated with poly(lactic-co-glycolic acid) (PLGA) and various model drugs (ketotifen fumarate, bimatoprost and latanoprost) were fabricated using nanoelectrospray (nES) approach. The resulting DECLs demonstrated outstanding optical transmittance within the optical zone, indicating that the employed coating procedure did not compromise visual acuity under the prescribed spraying parameters. In vitro drug release assessments of the model drugs (ketotifen fumarate (KF), bimatoprost (BIM), and latanoprost (LN)) revealed a strong correlation between the model drug's hydrophobicity and the duration of drug release. Changing the drug loading of the more hydrophilic model drugs, BIM and KF, showed no impact on the drug release kinetics of DECLs loaded with BIM and KF. However, for the hydrophobic model drug, LN, the highest LN loading led to the most extended drug release. The conventional steam sterilisation method was found to damage the PLGA coating on the DECLs fabricated by nES. An alternative sterilisation strategy, such as radiation sterilisation may need to be investigated in the future study to minimise potential harm to the coating.

News (Medical) associated with Ketotifen Fumarate

23 Sep 2024

·www.globenewswire.com

AB Science provides an update on the development of masitinib in progressive forms of multiple sclerosis post ECTRIMS 2024

PRESS RELEASE AB SCIENCE PROVIDES AN UPDATE ON THE DEVELOPMENT OF MASITINIB IN PROGRESSIVE FORMS OF MULTIPLE SCLEROSIS POST ECTRIMS 2024 Paris, 23 September 2024, 5.45pm CET AB Science SA (Euronext - FR0010557264 - AB) today provides an update on the development of masitinib in progressive forms of multiple sclerosis (MS), following the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2024 conference. The development of masitinib in progressive forms of multiple sclerosis is based on the MAXIMS study (AB20009), a randomized, double-blind, phase 3 study of masitinib 4.5 mg/kg/day in patients with primary progressive multiple sclerosis (PPMS) and non-active secondary progressive multiple sclerosis (nSPMS). The study enrolls patients with Expanded Disability Status Scale (EDSS) score between 3.0 to 6.0, progression of disease for the last 2 years and absence of T1 Gadolinium-enhancing brain lesions. The primary endpoint of the study is the effect of masitinib on time to confirmed disability progression. The recent results of tolebrutinib in non-active secondary progressive MS presented at the ECTRIMS 2024 conference, reinforce the scientific hypothesis that targeting microglia in nSPMS is a valid approach. Tolebrutinib belongs to a class of drugs that target microglia through an enzymatic target called BTK (Bruton Tyrosine Kinase). Masitinib also targets microglia but through a different enzymatic target called M-CSFR1 (Macrophage Colony Stimulating Factor Receptor-1) and generated positive results in phase 2B (AB07002) [1], which are consistent with tolebrutinib data. EDSS progression confirmed at 3 months was reduced by 37% with masitinib in study AB07002 and by 23% with tolebrutinib in the Hercules study (although the reduction in study AB07002 did not reach the conventional 5% p-value since the study was not powered to detect a significant effect in this secondary endpoint, having 300 patients in the masitinib 4.5 or placebo arms as compared with 1100 patients in the Hercules trial).EDSS progression confirmed at 6 months was reduced by 32% with masitinib and by 31% with tolebrutinib. Importantly, Masitinib significantly improved manual dexterity measured by 9-hole Peg test, in study AB07002 (-4,28 ; p=0,0388).Masitinib has shown the ability to decrease serum neurofilament light chain (NfL) concentration in an animal model of MS, and by extension therefore, possibly neuronal damage [2].Masitinib not only targets microglia but also mast cells, which play a crucial role in progressive MS and in the experimental autoimmune encephalomyelitis (EAE) model of MS, as shown by numerous publications [3-13]. Masitinib benefits from a large safety database with long-term exposure across various indications. In non-oncology indications, around 2,200 patients have received at least one dose of masitinib, more than 1,300 patients have received masitinib for more than six months and close to 1,000 patients have received masitinib for more than one year. BTK safety profiles shows increase in liver injury, hypertension and infections which seem to be a class effect, leaving room for alternative drugs. As a conclusion, masitinib represents a potential credible alternative to BTK inhibitors in the development of new drugs both in primary and non-active secondary progressive MS. Professor Patrick Vermersch, MD, principal investigator of the MAXIMS study, Director of the Doctoral School Biology-Health of the University of Lille, commented: “Tolebrutinib data are important and pave the way to a series of new drugs in progressive forms of MS. Along with BTK inhibitors, masitinib represents a serious potential alternative in the two forms of progressive MS, primary and non-active secondary progressive MS, which remain the two unmet medical needs. The role of mast cells is not to be neglected in MS”. This new development fits well the strategy currently implemented for masitinib, as it further strengthens the scientific rationale for the development of masitinib in progressive forms of MS as well as the plausibility of the results generated with phase 2B/3 study AB07002. About the results of the previous phase 2B/3 study AB07002Study AB07002 met its primary analysis endpoint, demonstrating a statistically significant reduction in cumulative change on EDSS with masitinib 4.5 mg/kg/day (p=0.0256) [1]. This treatment-effect was consistent for PPMS and nSPMS. In addition, masitinib significantly reduced the risk of first disability progression by 42% and the risk of confirmed (3 months) disability progression by 37%. Masitinib also significantly reduced the risk of reaching an EDSS score of 7.0, corresponding to disability severe enough that the patient is restricted to a wheelchair (p=0.0093). The product's safety was consistent with the known risk profile of masitinib, with no elevated risk of infection. [References] [1] Vermersch P, Brieva-Ruiz L, Fox RJ, et al. Efficacy and Safety of Masitinib in Progressive Forms of Multiple Sclerosis: A Randomized, Phase 3, Clinical Trial. Neurol Neuroimmunol Neuroinflamm. 2022 Feb 21;9(3):e1148. [2] Hermine O, Vermersch P, et al. Masitinib limits neuronal damage, as measured by serum neurofilament light chain concentration, in a model of neuroimmune-driven neurodegenerative disease. Preprint. bioRxiv 2024.03.07.583695; doi: https://doi-org.libproxy1.nus.edu.sg/10.1101/2024.03.07.583695 [3] Sandhu JK, Kulka M. Decoding Mast Cell-Microglia Communication in Neurodegenerative Diseases. Int J Mol Sci. 2021 Jan 22;22(3):1093. [4] Pinke KH, et al. Should mast cells be considered therapeutic targets in multiple sclerosis? Neural Regen Res. 2020 Nov;15(11):1995-2007. [5] Pinke KH, et al. Calming Down Mast Cells with Ketotifen: A Potential Strategy for Multiple Sclerosis Therapy? Neurotherapeutics. 2020 Jan;17(1):218-234. [6] Brown MA, Weinberg RB. Mast Cells and Innate Lymphoid Cells: Underappreciated Players in CNS Autoimmune Demyelinating Disease. Front Immunol. 2018;9:514. [7] Skaper SD, Facci L, Zusso M, Giusti P. An Inflammation-Centric View of Neurological Disease: Beyond the Neuron Front Cell Neurosci. 2018;12:72. [8] Hendriksen E, et al. Mast cells in neuroinflammation and brain disorders Neurosci Biobehav Rev. 2017;79:119-133. [9] Elieh-Ali-Komi D, Cao Y. Role of Mast Cells in the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis. Clin Rev Allergy Immunol. 2017;52(3):436-445. [10] Conti P, Kempuraj D. Important role of mast cells in multiple sclerosis. Mult Scler Relat Disord. 2016;5:77-80. [11] Skaper SD, Facci L, Giusti P. Mast cells, glia and neuroinflammation: partners in crime?. Immunology. 2014;141(3):314-327. [12] Skaper SD, et al. Microglia and mast cells: two tracks on the road to neuroinflammation. FASEB J. 2012;26(8):3103-3117. [13] Zappulla JP, Arock M, Mars LT, Liblau RS. Mast cells: new targets for multiple sclerosis therapy?. J Neuroimmunol. 2002;131(1-2):5-20. About AB ScienceFounded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unmet medical needs, often lethal with short term survival or rare or refractory to previous line of treatment. AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, inflammatory diseases and viral diseases. The company is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB). Further information is available on AB Science’s website: www.ab-science.com. Forward-looking Statements - AB ScienceThis press release contains forward-looking statements. These statements are not historical facts. These statements include projections and estimates as well as the assumptions on which they are based, statements based on projects, objectives, intentions and expectations regarding financial results, events, operations, future services, product development and their potential or future performance. These forward-looking statements can often be identified by the words "expect", "anticipate", "believe", "intend", "estimate" or "plan" as well as other similar terms. While AB Science believes these forward-looking statements are reasonable, investors are cautioned that these forward-looking statements are subject to numerous risks and uncertainties that are difficult to predict and generally beyond the control of AB Science and which may imply that results and actual events significantly differ from those expressed, induced or anticipated in the forward-looking information and statements. These risks and uncertainties include the uncertainties related to product development of the Company which may not be successful or to the marketing authorizations granted by competent authorities or, more generally, any factors that may affect marketing capacity of the products developed by AB Science, as well as those developed or identified in the public documents published by AB Science. AB Science disclaims any obligation or undertaking to update the forward-looking information and statements, subject to the applicable regulations, in particular articles 223-1 et seq. of the AMF General Regulations. For additional information, please contact: AB ScienceFinancial Communication & Media Relations investors@ab-science.com Attachment CP UPDATE ECTRIMS 2024. VEng VF

Clinical ResultPhase 3Phase 2

15 Nov 2021

·www.biospace.com

Bayshore Pharmaceuticals Announces Commercial Launch of ANDA Approved Products

Nov. 15, 2021 11:00 UTC SHORT HILLS, N.J.--(BUSINESS WIRE)-- Bayshore Pharmaceuticals, LLC is pleased to introduce three new FDA-approved products to their expanding portfolio. Metolazone Tablets USP, 2.5mg, 5mg and 10 mg, is the generic equivalent of Zaroxolyn Tablets. It is available by prescription only and is indicated for the treatment of high blood pressure and fluid retention. Etodolac Immediate Release Tablets USP, 400 mg and 500 mg, is the generic equivalent of Lodine Tablets. Etodolac is a nonsteroidal anti-inflammatory drug and only available by prescription. Ketotifen Fumarate Ophthalmic Solution, 0.035% (OTC & RX) is the generic equivalent of Zaditor. It is an antihistamine that is indicated for the treatment of itchy eyes. Ketotifen is Bayshore Pharmaceutical’s first ANDA approved product that is available by prescription or as an OTC in the Bayshore Label. “Bayshore is very proud to bring these internal R&D projects through to FDA approval and commercialization. These efforts further exemplify our focus on balancing internally developed products with our continued partnerships with manufacturing partners such as Beximco Pharmaceuticals, in which we can utilize our trade relationships to market & distribute ANDA’s for those companies not set up do so directly,” says Mark Moshier, President of Bayshore Pharmaceuticals. About Bayshore Pharmaceuticals: Bayshore Pharmaceuticals, LLC was established in 2011 in the centrally located area of Short Hills, NJ. As a full-service Sales & Distribution company focusing on FDA-approved generic pharmaceuticals, Bayshore used its extensive knowledge and experience in global API and Finished Dosage Form manufacturing to differentiate itself from other Generic Pharmaceutical Sales & Marketing organizations. In addition to developing its wholly-owned portfolio of generic products, Bayshore successfully utilized its longstanding industry relationships to augment its business by marketing other pharma manufacturer’s ANDA products under the same Bayshore label. With a strong emphasis on Project Management and Supplier & Customer transparency, Bayshore, along with our global manufacturing partners, maintains the highest level of product quality, in full compliance with current Good Manufacturing Practices (cGMP). This mission has allowed Bayshore to become one of the most service-oriented and reliable supply partners in the industry. View source version on businesswire.com: Contacts Mark Moshier, President (973) 315-1819 Dena Mando, Vice President Sales & Marketing (973) 315-1824 Source: Bayshore Pharmaceuticals View this news release online at:

28 Oct 2021

·www.biospace.com

Eton Pharmaceuticals Announces Acquisition of Approved Orphan Drug Product Carglumic Acid-Product is the first generic alternative to one of the highest priced pharmaceutical products in the world

DEER PARK, Ill., Oct. 28, 2021 (GLOBE NEWSWIRE) --Eton Pharmaceuticals (Nasdaq: ETON), an innovative pharmaceutical company focused on developing and commercializing treatments for rare diseases, today announced that it has acquired U.S. marketing rights to carglumic acid tablets. The product’s Abbreviated New Drug Application, which is owned by Novitium Pharma, was approved by the U.S. Food and Drug Administration on October 13, 2021. The product is an AB-rated, substitutable generic version of Carbaglu®. “We are pleased to be offering patients a lower cost alternative to one of the most expensive treatments in the world,” said Sean Brynjelsen, CEO of Eton Pharmaceuticals. “With our existing orphan drug commercial footprint and robust patient support services, we believe we are well positioned to commercialize this product. We look forward to working with Novitium to bring the product to patients later this year,” Brynjelsen added. Carbaglu® is widely regarded as one of the highest priced pharmaceutical products in the world, with the annual cost of treatment estimated to exceed $1 million for many patients. The introduction of Eton’s lower cost alternative is expected to save patients and the U.S. healthcare system millions of dollars annually. About Eton Pharmaceuticals Eton Pharmaceuticals, Inc. is an innovative pharmaceutical company focused on developing and commercializing treatments for rare diseases. The company currently owns or receives royalties from five FDA-approved products, including ALKINDI® SPRINKLE, Biorphen®, Alaway® Preservative Free, Rezipres®, and carglumic acid, and has five additional products that have been submitted to the FDA. Company Contacts: Eton Pharmaceuticals David Krempa dkrempa@etonpharma.com 612-387-3740

Orphan DrugAcquisition

100 Deals associated with Ketotifen Fumarate

External Link

KEGG	Wiki	ATC	Drug Bank
D01332	Ketotifen Fumarate	S01GX08 R06AX17	DB00920

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Eczema	JP	Sun Pharma Japan Ltd.	30 Apr 1986
Pruritus	JP	Sun Pharma Japan Ltd.	30 Apr 1986
Urticaria	JP	Sun Pharma Japan Ltd.	30 Apr 1986
Asthma	CH	Novartis Pharma AG	03 May 1979
Chronic Urticaria	CH	Sandoz International GmbH	03 May 1979
Conjunctivitis, Allergic	CH	Sandoz International GmbH	03 May 1979
Dermatitis, Atopic	CH	Sandoz International GmbH	03 May 1979
Rhinitis, Allergic	CH	Sandoz International GmbH	03 May 1979

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Seasonal allergic conjunctivitis	Phase 3	US	Bausch & Lomb, Inc.	18 Nov 2022
Pruritus	Phase 1	US	Bausch & Lomb, Inc.	07 Apr 2018

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


UEGW	Not Applicable	Mast Cell Activation Disorders	-	Ketotifen	jvvozvliye(mylguseyst) = exsdjzlftz jidjtevyzv (tmnvfuisrq )	-	01 Oct 2018
				Fexofenadine	jvvozvliye(mylguseyst) = nkzirpanim jidjtevyzv (tmnvfuisrq )
AAAAI2012	Not Applicable	Peanut Hypersensitivity eosinophilia	6	Ketotifen	kxowbjkibh(tyuqfgzbeu) = 3 anaphylactic reactions occurred: day-1 placebo patient at 50mg dose (gastrointestinal, cutaneous); day-5 treatment patient at 50mg dose, occurred post exercise, (gastrointestinal, cutaneous, respiratory); day-6 placebo patient at 12mg dose, associated with fever, (gastrointestinal, cutaneous, respiratory), epinephrine was given and patient withdrew from study dxbixpwgyv (foadyzwsst ) View more	Positive	01 Feb 2012
				Placebo
ARVO2004	Not Applicable	Acute conjunctivitis	99	Epinastine HCl 0.05%	(pgeiwibqrd) = Three (5.9%) epinastine patients and 7 (14.6%) ketotifen patients experienced adverse events. Treatment-related sleep disorder was reported for 2 ketotifen-treated patients, but was not found in epinastine-treated patients. yvzqiirvja (tvwucciopc )	-	01 May 2004
				Ketotifen
ARVO2003	Not Applicable	Conjunctivitis, Allergic HLA-DR+ \| CD29+ \| eotaxin+	19	Ketotifen fumarate 0,05%	(itmbkbbfkq) = nxnolghqzl bznkamqnve (dyvfjcqsdi ) View more	Positive	01 May 2003
ARVO2003	Not Applicable	Conjunctivitis, Allergic	92	Ketotifen fumarate 0.025%	gmdxyznbht(krinevhngl) = wxdawahpal iuksxlbdqh (sltghvsins )	-	01 May 2003
				Olopatadine HCl 0.1%	gmdxyznbht(krinevhngl) = istaumpssx iuksxlbdqh (sltghvsins )

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