Delving into the Latest Updates on Casopitant Mesylate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Casopitant, Casopitant mesylate (USAN), Rezonic

+ [4]

Target

NK1R

Mechanism

NK1R antagonists(Neurokinin 1 receptor antagonists)

Therapeutic Areas

Other DiseasesNeoplasmsNervous System Diseases+ [2]

Active Indication-

Inactive Indication

Anxiety DisordersChemotherapy-induced nausea and vomitingDepressive Disorder, Major+ [13]

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

GSK Plc

Drug Highest PhaseDiscontinuedNDA/BLA

First Approval Date-

Regulation-

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Structure

Molecular FormulaC31H39F7N4O5S

InChIKeyYRFKYVWDPCOSTE-REWBLLDVSA-N

CAS Registry414910-30-8

View All Structures (2)

This is a phase III study designed to demonstrate the superiority of single-dose 90 mg intravenous (IV) casopitant over placebo, each in combination with ondansetron and dexamethasone, for the prevention of emesis over the first 0-120 hours (overall phase) following initiation of the cisplatin infusion in the first cycle of highly emetogenic chemotherapy (HEC). Eligibility is limited to subjects who are scheduled to receive their first cycle of chemotherapy which includes at least 60 mg/m2 of cisplatin administered on Day 1 only of a 21 day or 28 day cycle. All subjects will receive IV ondansetron and oral dexamethasone on Day 1 prior to initiation of the cisplatin infusion, followed by oral dexamethasone on Days 2-4. Additionally, subjects will be randomized to receive single-dose 90 mg IV casopitant or matching placebo prior to initiation of a cisplatin-based HEC regimen.

Start Date01 Sep 2009

Sponsor / Collaborator

GSK Plc

NCT00601172 / CompletedPhase 3

A Study of Single Dose Intravenous Casopitant in Combination With Ondansetron and Dexamethasone for the Prevention of Oxaliplatin Induced Nausea and Vomiting.

This a Phase III trial designed to determine if IV casopitant plus dexamethasone and ondansetron is more effective in the prevention of vomiting and nausea then dexamethasone and ondansetrone alone following the administration of moderately emetogenic oxaliplatin-based chemotherapy.

Start Date10 Mar 2008

Sponsor / Collaborator

GSK Plc

EUCTR2007-005169-36-IT / Not yet recruitingNot Applicable

A Study of Single Dose Intravenous Casopitant in Combination with Ondansetron and Dexamethasone for the Prevention of Oxaliplatin-Induced Nausea and Vomiting - Casopitant in prevention of nausea and vomiting

Start Date05 Feb 2008

Sponsor / Collaborator

GlaxoSmithKline Research & Development Ltd.

100 Clinical Results associated with Casopitant Mesylate

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100 Translational Medicine associated with Casopitant Mesylate

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100 Patents (Medical) associated with Casopitant Mesylate

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51

Literatures (Medical) associated with Casopitant Mesylate

01 Feb 2024·Biotechnology and Applied Biochemistry

Homology modeling, virtual screening, molecular docking, and ADME approaches to identify a potent agent targeting NK2R protein

Article

Author: Soltani, Arash ; Hashemy, Seyed Isaac

AbstractNeurokinin/tachykinin receptors are classified as the G‐protein coupled receptor superfamily. The neurokinin 2 receptor (NK2R) is widely expressed in different tissues. NK2R is associated with a range of biological events, such as inflammation, smooth muscle contraction, intestinal motor functions, and asthma. Despite these diverse activities, no approved drugs targeting NK2R have been developed yet. Our study focuses on finding potential inhibitors for NK2R using virtual screening, molecular docking, and ADME (absorption, distribution, metabolism, and excretion) approaches. We used a homology modeling approach and AlphaFold DB to obtain the three‐dimensional structure of mouse and human NK2R proteins, respectively. The homology model of NK2R was predicted using MODELLER v10.3 and further refined and validated using the 3Drefine tool and RAMPAGE server, respectively. Molecular docking was performed using a library of 910 structurally similar molecules to four NK1R antagonists: aprepitant, casopitant, fosaprepitant, and rolapitant. Molecular docking revealed six small molecules that displayed high Chemscore fitness scores, and binding energies with desirable ligand–NK2R interactions. The evaluation of the in silico ADME profile, solubility, and permeability of the ligand molecules has revealed that the small molecules are potentially nontoxic and have the chance of exhibiting biological activity after oral administration. Further experimental studies (in vitro and in vivo assays) are required to evaluate the effectiveness of these inhibitors as therapeutic targets.

01 Jul 2022·Pharmacopsychiatry

Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry

Review

Author: Tani, Hideaki ; Sakurai, Hitoshi ; Yonezawa, Kengo ; Uchida, Hiroyuki ; Mimura, Masaru ; Bauer, Michael

Abstract Introduction There is an imminent need for faster-acting and more effective antidepressants beyond the monoaminergic hypothesis. Methods We systematically searched the US Clinical Trials registry for antidepressant compounds with completed phase II and III trials. Compounds that demonstrated significant superiority over placebo in the primary outcome measure in the latest phase of phase II and III trials were identified. The collateral information was gathered via a PubMed search and press releases. Results Nine compounds were identified. AXS-05 (a combination of dextromethorphan and bupropion) and ansofaxine hydrochloride showed a positive result over placebo in a phase III study for major depressive disorder or treatment-resistant depression. MIJ821, nitrous oxide, psilocybin, ayahuasca, facial injection of botulinum toxin A, prasterone, and casopitant demonstrated at least one positive result in phase II trials. Ayahuasca showed a greater response rate than placebo at week one, indicating the rapid antidepressant effect. Discussion These new compounds with novel mechanisms of action are expected to provide a greater variety of treatment options for depression if preliminary positive results are confirmed.

01 May 2018·The OncologistQ2 · MEDICINE

Olanzapine-Based Triple Regimens Versus Neurokinin-1 Receptor Antagonist-Based Triple Regimens in Preventing Chemotherapy-Induced Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy: A Network Meta-Analysis

Q2 · MEDICINE

Review

Author: Gao, Fangfang ; Zhao, Hongyun ; Yang, Yunpeng ; Huang, Yan ; Zhang, Yaxiong ; Zhang, Li ; Hong, Shaodong ; Chen, Likun ; Chen, Xi ; Zhang, Zhonghan ; Ma, Shuxiang ; Zhou, Ningning ; Chen, Gang ; Luo, Fan ; Ma, Yuxiang ; Hou, Xue ; Xue, Cong ; Zhou, Ting ; Fang, Wenfeng ; Zhan, Jianhua ; Zhao, Yuanyuan

AbstractBackgroundThe current antiemetic prophylaxis for patients treated with highly emetogenic chemotherapy (HEC) included the olanzapine-based triplet and neurokinin-1 receptor antagonists (NK-1RAs)-based triplet. However, which one shows better antiemetic effect remained unclear.Materials and MethodsWe systematically reviewed 43 trials, involving 16,609 patients with HEC, which compared the following antiemetics at therapeutic dose range for the treatment of chemotherapy-induced nausea and vomiting: olanzapine, aprepitant, casopitant, fosaprepitant, netupitant, and rolapitant. The main outcomes were the proportion of patients who achieved no nausea, complete response (CR), and drug-related adverse events. A Bayesian network meta-analysis was performed.ResultsOlanzapine-based triple regimens showed significantly better no-nausea rate in overall phase and delayed phase than aprepitant-based triplet (odds ratios 3.18, 3.00, respectively), casopitant-based triplet (3.78, 4.12, respectively), fosaprepitant-based triplet (3.08, 4.10, respectively), rolapitant-based triplet (3.45, 3.20, respectively), and conventional duplex regimens (4.66, 4.38, respectively). CRs of olanzapine-based triplet were roughly equal to different NK-1RAs-based triplet but better than the conventional duplet. Moreover, no significant drug-related adverse events were observed in olanzapine-based triple regimens when compared with NK-1RAs-based triple regimens and duplex regimens. Additionally, the costs of olanzapine-based regimens were obviously much lower than the NK-1RA-based regimens.ConclusionOlanzapine-based triplet stood out in terms of nausea control and drug price but represented no significant difference of CRs in comparison with NK-1RAs-based triplet. Olanzapine-based triple regimens should be an optional antiemetic choice for patients with HEC, especially those suffering from delayed phase nausea.Implications for PracticeAccording to the results of this study, olanzapine-based triple antiemetic regimens were superior in both overall and delayed-phase nausea control when compared with various neurokinin-1 receptor antagonists-based triple regimens in patients with highly emetogenic chemotherapy (HEC). Olanzapine-based triplet was outstanding in terms of nausea control and drug price. For cancer patients with HEC, especially those suffering from delayed-phase nausea, olanzapine-based triple regimens should be an optional antiemetic choice.

100 Deals associated with Casopitant Mesylate

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External Link

KEGG	Wiki	ATC	Drug Bank
D06574	Casopitant Mesylate	-	DB06634

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Vomiting	NDA/BLA	IE	GSK Plc	01 Mar 2006
Vomiting	NDA/BLA	BE	GSK Plc	01 Mar 2006
Vomiting	NDA/BLA	BE	GSK Plc	01 Mar 2006
Vomiting	NDA/BLA	IE	GSK Plc	01 Mar 2006
Chemotherapy-induced nausea and vomiting	NDA/BLA	US	GSK Plc	-
Chemotherapy-induced nausea and vomiting	NDA/BLA	US	GSK Plc	-
Chemotherapy-induced nausea and vomiting	NDA/BLA	EU	GSK Plc	-
Chemotherapy-induced nausea and vomiting	NDA/BLA	EU	GSK Plc	-
Postoperative Nausea and Vomiting	NDA/BLA	EU	GSK Plc	-
Postoperative Nausea and Vomiting	NDA/BLA	EU	GSK Plc	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00601172 (CTgov)	Phase 3	Nausea \| Chemotherapy-induced nausea and vomiting \| Vomiting	710	placebo+casopitant+Ondansetron+dexamethasone (Placebo)	xekryxeclk(hazqpkvbjb) = zhkonbnwgb yctiebblgl (bnteruhbub, lsdckgpooi - aqynjucqza) View more	-	17 Jan 2018
				Casopitant (Casopitant 90 mg)	xekryxeclk(hazqpkvbjb) = valkczrthr yctiebblgl (bnteruhbub, zwhzcrapba - wmzxdrvvep) View more
ASCO2011	Phase 3	Drug-induced nausea and vomiting	710	Casopitant 90 mg	(geypqduwvf) = pscknoensg dwceulzknc (ykeisfuneb )	-	20 May 2011
				Placebo	(geypqduwvf) = ymfmlcdejw dwceulzknc (ykeisfuneb )
Pubmed \| Anesth Analg	Phase 2	Postoperative Nausea and Vomiting	702	Ondansetron 4 mg	(smfrzmabub) = headache, dizziness, and constipation were the most frequently reported adverse events gevaagoscm (fclvdeqflc ) View more	Positive	01 Jul 2010
				Casopitant 0 mg
NCT00104403 (Pubmed \| Cancer)	Phase 2	Neoplasms	723	Casopitant 50 mg	(yrvksthcuh) = jcjiaaovpc zjkdzqcotz (njvwtuqmzu ) View more	Positive	15 Dec 2009
				Casopitant 100 mg	(yrvksthcuh) = fcmxshlizx zjkdzqcotz (njvwtuqmzu ) View more
NCT00366834 (Pubmed \| J Urol)	Phase 3	Chemotherapy-induced nausea and vomiting	1,840	Control	(nqhndrqtfe) = vwdkbrlsfy pglxcjwjap (tgqvppblyd )	Positive	10 Nov 2009
				Single-dose oral casopitant	(nqhndrqtfe) = njmpkuuuxb pglxcjwjap (tgqvppblyd )
NCT00431236 (Pubmed \| Lancet Oncol)	Phase 3	Chemotherapy-induced nausea and vomiting	810	Casopitant mesylate (single oral dose)	(ftrgrqefmj) = hxxyexuptk tifwolpfnr (wqbqapewxe )	Positive	01 Jun 2009
				Casopitant mesylate (3-day intravenous plus oral)	(ftrgrqefmj) = wovmsoqvub tifwolpfnr (wqbqapewxe )
ASCO2006	Phase 2	Chemotherapy-induced nausea and vomiting	493	Placebo control	(jgiykwfeka) = yzflqvgxap jblapdbqws (iybvpkusoe ) View more	-	20 Jun 2006
				Casopitant 50mg	(jgiykwfeka) = bkdcqzgvds jblapdbqws (iybvpkusoe ) View more
ASCO2006	Phase 2	Chemotherapy-induced nausea and vomiting	719	Casopitant mesylate 50mg	(sdaulmdakq) = dighsuuetj ujqhduwskg (qefpdchaqg )	-	20 Jun 2006
				Casopitant mesylate 100mg	(sdaulmdakq) = jecrfieunq ujqhduwskg (qefpdchaqg )