Korean Stroke Cohort for functioning and rehabilitation (KOSCO)-II is a large, multi-centre prospective cohort study for all acute first-ever stroke patients admitted to participating hospitals in nine distinct areas of Korea. This study is designed as a 10-year, longitudinal follow-up investigating the residual disabilities, activity limitations, and quality of life issues arising in patients suffering from first-ever stroke as previous similar stroke cohort with KOSCO. The main objectives of this study are to identify and compare the factors that influence residual disability and long-term quality of life in first-ever acute stroke patients with KOSCO. The secondary objectives of this study are to determine and compare the risk of mortality and recurrent vascular events in first-ever acute stroke patients with KOSCO. Investigators will investigate longitudinal health behaviors and patterns of healthcare utilization, including stroke rehabilitation care. Investigators will also investigate the long-term health status, mood, and quality of life in stroke patient caregivers. In addition, investigators will identify baseline and ongoing characteristics that are associated with secondary outcomes.

Start Date01 Jan 2020

Sponsor / Collaborator

Samsung Medical Center

NL-OMON46715 / RecruitingPhase 3IIT

Distal pancreatectomy, minimally invasive or open, for malignancy (DIPLOMA) - DIPLOMA-trial

Start Date03 May 2018

Sponsor / Collaborator-

100 Clinical Results associated with Sitaxentan Sodium

100 Translational Medicine associated with Sitaxentan Sodium

100 Patents (Medical) associated with Sitaxentan Sodium

200

Literatures (Medical) associated with Sitaxentan Sodium

01 Oct 2024·Biochemical Pharmacology

Role of endothelin ETA receptors in the hypertension induced by the VEGFR-2 kinase inhibitors axitinib and lenvatinib in conscious freely-moving rats

Article

Author: Van Daele, Marieke ; Groenen, Marleen ; Wragg, Edward S ; Woolard, Jeanette ; Hill, Stephen J ; March, Julie ; Cooper, Samantha L ; Pannucci, Patrizia

Receptor tyrosine kinase inhibitors (RTKIs) suppress tumour growth by targeting vascular endothelial growth factor receptor 2 (VEGFR-2) which is an important mediator of angiogenesis. Here, we demonstrate that two potent RTKIs, axitinib and lenvatinib, are associated with hypertensive side effects. Doppler flowmetry was used to evaluate regional haemodynamic profiles of axitinib and lenvatinib. Male Sprague Dawley rats (350-500 g) were instrumented with Doppler flow probes (renal and mesenteric arteries and descending abdominal aorta) and catheters (jugular vein and distal abdominal aorta, via the caudal artery). Rats were dosed daily with axitinib (3 or 6 mg.kg^-1) or lenvatinib (1 or 3 mg.kg^-1) and regional haemodynamics were recorded over a maximum of 4 days. Both RTKIs caused significant (p < 0.05) increases in mean arterial pressure (MAP), which was accompanied by significant (p < 0.05) vasoconstriction in both the mesenteric and hindquarters vascular beds. To gain insight into the involvement of endothelin-1 (ET-1) in RTKI-mediated hypertension, we also monitored heart rate (HR) and MAP in response to axitinib or lenvatinib in animals treated with the ET_A receptor selective antagonist sitaxentan (5 mg.kg^-1) or the mixed ET_A/ET_B receptor antagonist bosentan (15 mg.kg^-1) over two days. Co-treatment with bosentan or sitaxentan markedly reduced the MAP effects mediated by both RTKIs (p < 0.05). Bosentan, but not sitaxentan, also attenuated ET-1 mediated increases in HR. These data suggest that selective antagonists of ET_A receptors may be appropriate to alleviate the hypertensive effects of axitinib and lenvatinib.

01 Oct 2024·ESC Heart Failure

Pulmonary artery denervation versus conventional therapies for PAH: a systematic review and updated network meta‐analysis

Review

Author: Chen, Feng ; Wang, Xiang ; Zhang, Longyao ; Wei, Yongyue ; Pan, Zoucheng ; Wu, Xiaoyu ; Kan, Jing ; Chen, Shao‐liang

AbstractAimsA recent guideline presented by the ESC Congress in 2022 had indicated a novel therapy targeted at pulmonary artery hypertension, known as pulmonary artery denervation (PADN), which get inspired from a laboratorial trial that could lowering the pulmonary artery pressure through the intervention on the animals. Our aim is to conduct a network meta‐analysis to compare the efficacy and safety of PADN from six aspects with the current conventional therapies.Methods and resultsAccording to the PRISMA guidance, databases including Ovid, ClinicalTrials.gov, Medline, Embase, and PubMed were searched from inception to 22 August 2023, along with a full assessment of the previous five meta‐analyses. Data were extracted and curated for Bayesian network meta‐analysis. The primary outcome was the change in the 6‐min walking distance (6MWD) from baseline with a secondary outcome called change in mean pulmonary artery pressure (mPAP) from baseline. The four safety outcomes included risk of clinical worsening, hospitalization, mortality and severe adverse events (SAEs). The comparison is structured on a contrast model based on 65 randomized controlled trials (RCTs) on PADN and the other conventional mainstream drugs. PADN had a better effect in improving 6MWD than Placebo (−77.76 m, 95% CI: −102.04 to −54.34 m), Macitentan (−65.32 m, 95% CI: −95.34 to −36.1 m), Bosentan (−64.5 m, 95% CI: −94.7 to −35.07 m), Iloprost (−62.66 m, 95% CI: −99.48 to −27.13 m), Oxygen (−62.42 m, 95% CI: −100.01 to −25.78 m), Treprostinil (−62.01 m, 95% CI: −89.04 to −35.61 m), Riociguat (−60.59 m, 95% CI: −86.11 to −35.98 m), Selexipag (−47.2 m, 95% CI: −85.61 to −10.19 m), Sildenafil (−44.92 m, 95% CI: −74.43 to −16.15 m), or Sitaxsentan (−39.53 m, 95% CI: −78.99 to −0.76 m). PADN had a better antihypertensive effect than placebo and showed statistical significant lower risks to induce clinical worsening and re‐hospitalization than treprostinil, riociguat, and placebo groups. No statistically significant difference in risk of mortality and severe adverse events was observed between PADN versus the other interventions.ConclusionsCompared with 16 types of conventional therapies and Placebo, PADN has advantage over nine single therapies and Placebo in improving 6MWD and appears to be better than two types of dual‐drug combined therapies while with no statistical significance. PADN shows a favourable antihypertensive effect on mPAP and has a lower risk to trigger clinical worsening or hospitalization, while its risk on mortality and severe adverse events is still inconclusive.

30 Oct 2023·Clinical Hemorheology and Microcirculation

Application of ultrasound microbubble contrast to evaluate the effect of sitaxentan on renal microvascular perfusion in beagles undergoing cardiopulmonary bypass

Article

Author: Yang, Lu ; Mo, Liqun ; Li, Fuyu ; Zhu, Fuzu ; Bai, Yiping

BACKGROUND & OBJECTIVE: We aimed to evaluate the effect of sitaxentan on renal microvascular perfusion via application of ultrasound microbubble contrast. METHODS: Male beagles were randomly divided into: Sham, cardiopulmonary bypass (CPB) and sitaxentan-infused (Sit) groups (n = 6). The ascending slope rate (ASR), area under the curve (AUC), derived peak intensity, and time to peak (TTP) were obtained via ultrasound microbubble contrast before CPB (T1), after 1 h CPB (T2), at end of CPB (T3), and 2 h after CPB (T4). RESULTS: Compared with the Sham group, the CPB group had lower ASR of the renal cortex and medulla at T2 - 4, higher AUC and TTP at T3 - 4, and lower derived peak intensity at T4. The ASR at T2 - 4 in the Sit group was lower, TTP was higher at T2 - 4, and AUC was higher at T3 - 4 (P < 0.05). Compared with the CPB group, the Sit group had higher ASR of the renal cortex and medulla at T3 - 4 and AUC and TTP at T3 - 4 (P < 0.05). Compared with that at T1, the ASR of the renal cortex and medulla at T2 - 4 in the CPB group was lower, and AUC and TTP were higher at T3 - 4. The ASR of the renal cortex and medulla at T2 - 4 in the Sit group was lower, TTP was higher at T2 - 4, and AUC was higher at T4 (P < 0.05). CONCLUSIONS: Ultrasound microbubble contrast could be effectively used to evaluate renal microvascular perfusion peri-CPB in beagles, which was prone to decrease and could be improved via pretreatment with sitaxentan.

News (Medical) associated with Sitaxentan Sodium

22 Aug 2024

·www.pharmaceutical-technology.com

Leo Pharma’s Timber bet falls flat following Phase III failure

There is currently no treatment approved for ichthyosis by the FDA. Image credit: Shutterstock / JHVEPhoto. A year after hedging its bets on Timber Pharmaceuticals’ dermatology pipeline, Leo Pharma has reported a Phase III failure for the lead asset it acquired at the time. TMB-001, a topical ointment formulation of isotretinoin, came up short in the late-stage trial for patients with moderate to severe congenital ichthyosis. Ichthyosis is an umbrella term for congenital skin conditions that cause dry and scaly skin. In the Phase III ASCEND trial (NCT05295732), Leo stated the therapy did not demonstrate a statistically significant improvement in patients compared to those treated with a vehicle. This meant the primary and key secondary endpoints were not met. The results do not support US regulatory submission, the Danish privately owned company stated in a 21 August press release. There is currently no treatment approved for ichthyosis by the US Food and Drug Administration (FDA). Instead, the condition is managed by hydrating the skin with creams and lotions. See Also: A comprehensive guide to supply chain management for specialty drugs Codiak BioSciences gets grant for extracellular vesicles for disease treatment and prevention The ASCEND trial had a three-week induction, a nine-week treatment period, and – for eligible patients – a 12-week open-label maintenance regimen. A total of 209 patients aged six years and over were enrolled in the study. Timber’s CEO John Koconis said: “We are disappointed and saddened by the results of the Phase III trial. After encouraging phase 2b results, we observed an unexpectedly high vehicle response in this trial.” A previous Phase IIb trial evaluating the ointment achieved its primary endpoint of a 50% reduction in the Visual Index for Ichthyosis Severity scale score versus baseline. Leo Pharma spent $36m to acquire a bankrupt Timber in August 2023, including a $14m upfront payment. At the time, Timber had received orphan, fast-track, and breakthrough designations from the FDA. Following the acquisition, the company became a fully owned subsidiary of Leo Pharma. Leo Pharma’s chief development officer Kreesten Meldgaard Madsen said the company remains committed to dermatologic diseases but added “as is the case for all pharmaceutical research, not all trials are successful”. Leo Pharma stated the trial results will not impact its 2024 financial results. The company had a regulatory win elsewhere in the dermatology space in June this year, when its single-dose autoinjector for atopic dermatitis Adbry (tralokinumab-ldrm) received FDA approval . Whilst the clinical journey of TMB-001 stutters, Timber also has TMB-003 (sitaxentan) – a topical ET-A receptor antagonist in preclinical testing for sclerotic skin diseases.

Phase 2Phase 3Clinical ResultFast TrackBreakthrough Therapy

12 Jan 2021

·www.biospace.com

Timber Pharmaceuticals Receives Orphan Drug Designation from U.S. FDA for TMB-003 for the Treatment of Systemic Sclerosis

WOODCLIFF LAKE, N.J., Jan. 12, 2021 (GLOBE NEWSWIRE) -- via NewMediaWire -- Timber Pharmaceuticals, Inc. ("Timber" or the “Company”) (NYSE American: TMBR), a biopharmaceutical company focused on the development and commercialization of treatments for rare and orphan dermatologic diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to TMB-003, the company’s locally delivered formulation of sitaxsentan, for the treatment of systemic sclerosis. “People who are living with systemic sclerosis or scleroderma often struggle with their quality of life because the condition can be disfiguring and may cover joints and cause pain that affects movement and mobility,” said John Koconis, Chief Executive Officer of Timber. “Currently there is no FDA approved treatment for any cutaneous symptoms in scleroderma. We are pleased to receive orphan drug designation for our investigational treatment and look forward to advancing into clinical stage research.” The Orphan Drug Designation program provides orphan status to drugs and biologics that are intended for the treatment, prevention or diagnosis of a rare disease or condition that affects less than 200,000 people in the U.S. Systemic sclerosis is a group of rare autoimmune connective tissue disorders (CTD) characterized by inflammation and thickening of the skin and other connective tissues from excessive collagen deposition. Systemic sclerosis leads to abnormalities in the skin, joints, and internal organs. Sitaxsentan is a highly selective endothelin (ET-A) receptor antagonist, which is a class of drugs previously developed in oral form for the treatment of pulmonary arterial hypertension (PAH). TMB-003 is a locally delivered formulation of sitaxsentan that has the potential to reduce collagen while addressing systemic safety concerns associated with oral administration. Timber is in the preclinical stages of evaluating TMB-003 for the treatment of scleroderma and expects to submit an Investigational New Drug (IND) application to the FDA in 2022. About Timber Pharmaceuticals, Inc. Timber Pharmaceuticals, Inc. is a biopharmaceutical company focused on the development and commercialization of treatments for rare and orphan dermatologic diseases. The Company's investigational therapies have proven mechanisms-of-action backed by decades of clinical experience and well-established CMC (chemistry, manufacturing and control) and safety pro The Company is initially focused on developing non-systemic treatments for rare dermatologic diseases including congenital ichthyosis (CI), facial angiofibromas (FAs) in tuberous sclerosis complex (TSC), and scleroderma. For more information, visit . Forward-Looking Statements This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the Company's product development, clinical and regulatory timelines, market opportunity, competitive position, intellectual property rights, possible or assumed future results of operations, business strategies, potential growth opportunities and other statements that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management's current beliefs and assumptions. These statements may be identified by the use of forward-looking expressions, including, but not limited to, "expect," "anticipate," "intend," "plan," "believe," "estimate," "potential, "predict," "project," "should," "would" and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company's Form 10-Q filed on August 18, 2020 and its other filings with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. For more information, contact: Timber Pharmaceuticals, Inc. John Koconis Chief Executive Officer jkoconis@timberpharma.com Investor Relations: Stephanie Prince PCG Advisory (646) 762-4518 sprince@pcgadvisory.com Media Relations: Adam Daley Berry & Company Public Relations (212) 253-8881 adaley@berrypr.com

Orphan Drug

11 Aug 2006

·www.pharmatimes.com

EU opens door to Encysive’s Thelin

US drugmaker Encysive says it has received a nod from European regulators to market its hypertension drug Thelin (sitaxentan sodium), pushing shares in the firm up more than 11% to $4.60 in after-hours trading on the Nasdaq. The news follows the thumbs up by an advisory panel last month, but the company is waiting for a formal letter from the European Commission before it will provide further details, it said in a statement. Encysive’s shares have been on a rollercoaster since March this year, when the US Food and Drug Administration unexpectedly issued its first approvable letter for Thelin instead of the anticipated all clear, a move which swiped around 50% off the group’s share price a the time. This was followed by a second request for further information in July, again pushing shares down as investor confidence in the drug waned further. But Encysive remains confident in the future of Thelin in the US, saying the matter raised by the FDA in its latest 'approvable' letter would not require any additional clinical trials, and that is a matter of judgment that does require negotiations with the agency to see if agreement can be reached. One group basking in Encysive’s misfortune is Actelion, maker of rival drug Tracleer (bosentan), its stock enjoying a nice boost on news of Thelin’s delay. Sales of Tracleer were $335 million in the first half of this year, but had been expected to come under pressure in the second half on competition from Thelin as well as Pfizer's Revatio (sildenafil) and Myogen's ambrisentan, also due for approval in the USA before the end of the year. Thelin has been tipped as a $200 million product at peak.

100 Deals associated with Sitaxentan Sodium

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pulmonary Arterial Hypertension	Phase 3	IS	Pfizer Ltd.	10 Aug 2006
Pulmonary Arterial Hypertension	Phase 3	NO	Pfizer Ltd.	10 Aug 2006
Pulmonary Arterial Hypertension	Phase 3	EU	Pfizer Ltd.	10 Aug 2006

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00810732 (FCRD01, CTgov)	Phase 2	Proteinuria \| Stiffness \| Chronic Kidney Diseases	27	Open (Sitaxsentan)	parmnmqbjz(pkakvmpuao) = zwebzikimn usgbweyenl (zbelphmsio, mzptkemyxa - aljhonhkbc) View more	-	06 Jul 2023
				Placebo (Placebo)	parmnmqbjz(pkakvmpuao) = zdpasvezle usgbweyenl (zbelphmsio, deafetakvj - nqabvgdiea) View more
NCT00303498 (CTgov)	Phase 2	Heart Failure, Diastolic	200	Placebo	xkrrxsbjbc(omrmbkaddv) = wczeppqkmu nchtxtqzhw (nbxdidczfh, dujncxsglj - mpofpcwbrw) View more	-	04 Jan 2023
NCT00838383 (FCAD02, CTgov)	Phase 2	Heart Diseases	29	Placebo	cmzclrwmdv(mlspkcofyj) = ydkktnoure ifijijvdyo (eiltamxxao, mjhclxwooh - uglfwzbwfh) View more	-	08 Sep 2022
NCT00744211 (CTgov)	Not Applicable	Heart Diseases	29	Vehicle (Vehicle)	izqrmfeyml(yywygjigcl) = tjfjcnnyxm hohaycawts (bgnizjnbtv, xrpihshxkt - ecflcqakcm) View more	-	09 Nov 2017
				1mg/kg sitaxsentan sodium (ET-ARA 1mg/kg)	uzfylhmyul(auoodfqebu) = yikvsarghv bplhfddoew (kwfktixexl, kswzhrtosf - zrccqtphhy) View more
NCT00303498 (Pubmed \| JACC Heart Fail)	Phase 2	Heart Failure, Diastolic	192	Sitaxsentan 100 mg/day	tshjujaagf(momuqdtvzs) = bmkjgzwooa qqddfflnwo (zschipzfwz )	Negative	01 Apr 2014
				Placebo	tshjujaagf(momuqdtvzs) = samgcvhwio qqddfflnwo (zschipzfwz )
NCT00811018 (STRIDE-3, CTgov)	Phase 3	Pulmonary Arterial Hypertension	1,192	Sitaxsentan	(xbgjikuvwd) = gspmszsgev abowguzlhx (vobqmdysvj, ahyvlqhfxp - wuiawsivtx) View more	-	24 Apr 2012
NCT00795639 (CTgov)	Phase 3	Pulmonary Arterial Hypertension	183	Sitaxsentan	scbebggqrg(xgjozzofix) = wwomcnnsnv oleqrbmxuf (bmhntogxqp, aisvtrdbgu - fhuxzdfbls) View more	-	01 Mar 2012
NCT00796666 (CTgov)	Phase 3	Pulmonary Arterial Hypertension	131	Sitaxsentan (Sitaxsentan and Placebo)	oehryddmpi(vjiqcvadhm) = qxmdzipabg tctdwprrxl (fgbtnpniwu, ylhzwbomch - eaffrhmrvq) View more	-	29 Feb 2012
				Sitaxsentan (Sitaxsentan and Sildenafil)	oehryddmpi(vjiqcvadhm) = dosbwpuvam tctdwprrxl (fgbtnpniwu, dajkmygwez - vnyvmhqrqn) View more
NCT00796510 (CTgov)	Phase 3	Pulmonary Arterial Hypertension	3	Sitaxsentan (Sitaxsentan)	aepyxrstcr(bhintvammy) = vcjdhdlaah lwkawxifnt (jqwqlmfhoc, vkmuvpcwqb - aoosqipxdc) View more	-	20 Feb 2012
				Sitaxsentan (Sitaxsentan and Sildenafil)	aepyxrstcr(bhintvammy) = dpgikskkyk lwkawxifnt (jqwqlmfhoc, hzsipsvhbr - alyiithuzc) View more
NCT01210443 (CTgov)	Phase 3	Pulmonary Arterial Hypertension	2	Sitaxentan	ixsfnerrlg(kxtyqndkzq) = mhfiavbyqg dzhqwtrzid (kojqyxsadm, xarnodkeha - gixrfrlhwx) View more	-	14 Dec 2011

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