A Phase 3, double-blind, multicenter, placebo-controlled study of PledOx used on top of modified FOLFOX6 (5 FU/FA and Oxaliplatin) to prevent chemotherapy induced peripheral neuropathy (CIPN) in patients with first-line metastatic colorectal cancer - POLAR-M

开始日期2018-05-09

申办/合作机构-

NCT03430999

/ Completed临床1期

SUNCIST: A Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending, Single-Dose Study to Assess the Safety, Tolerability, Pharmacokinetics of Intravenous Administration of Calmangafodipir in Healthy Japanese and Caucasian Subjects

Randomized, double-bline, placebo-controlled, single dose study comparing the pharmacokinetics (PK) and safety of PP095-01 in Japanese and non-Asian (eg, Caucasian) subjects.

开始日期2017-11-07

申办/合作机构

Egetis Therapeutics AB

NCT03177395

/ Completed临床1期

A Randomised Open Label Exploratory, Safety and Tolerability Study With PP100-01 in Patients Treated With the 12-hour Regimen of N-Acetylcysteine for Paracetamol/Acetaminophen Overdose (The POP Trial)

Investigate the safety and tolerability of PP100-01 add-on treatment to the 12hr NAC treatment regime in patients treated for paracetamol/acetaminophen overdose (POD) when NAC treatment is initiated before 24hours post POD.

开始日期2017-06-08

申办/合作机构

Egetis Therapeutics AB

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100 项与 Calmangafodipir 相关的临床结果

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100 项与 Calmangafodipir 相关的转化医学

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100 项与 Calmangafodipir 相关的专利（医药）

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项与 Calmangafodipir 相关的文献（医药）

2025-01-01·JOURNAL OF PHARMACOLOGICAL SCIENCES

Paclitaxel-induced peripheral neuropathy in male rats attenuated by calmangafodipir, a superoxide dismutase mimetic

Article

作者: Nagahama, Fumiko ; Kawashiri, Takehiro ; Kobayashi, Daisuke ; Koura, Yusuke ; Mori, Kohei ; Mine, Keisuke ; Ishida, Haruna ; Yao, Kozo ; Fujita, Shunsuke ; Ueda, Mami ; Shimazoe, Takao ; Mori, Yusuke

Paclitaxel induces peripheral neuropathy, which is considered a dose-limiting factor. However, appropriate prophylactic agents are currently unavailable. We investigated the prophylactic effects of calmangafodipir, a superoxide dismutase mimetic, on paclitaxel-induced peripheral neuropathy using a male rat model. Repeated administration of paclitaxel (6 mg/kg, intraperitoneal, once weekly for 4 weeks) resulted in mechanical allodynia in the von Frey test and axonal degeneration in the sciatic nerve. Conversely, calmangafodipir (1-10 mg/kg, intravenous, thrice weekly for 4 weeks) prevented mechanical allodynia and axonal degeneration induced by paclitaxel. These results suggest that calmangafodipir may inhibit paclitaxel-induced peripheral neuropathy.

2024-02-01·Bioorganic chemistry

Synthesis, molecular docking and biological evaluation of 1,2,4-oxadiazole based novel non-steroidal derivatives against prostate cancer

Article

作者: Wadhwa, Pankaj ; Kumar, Shubham

Prostate cancer is one of the most prevalent cancers in men leading to second most death causing cancer in men. Despite the availability of multiple treatment still the prevalence is high for prostate cancer. Steroidal antagonists associated with poor bioavailability, side effects while non-steroidal antagonists show serious side effects like gynecomastia. Therefore, there is a need of potential candidate for the treatment of prostate cancer with better bioavailability, good therapeutic effect and minimal side effects. In the same context, we have designed the series, SP1-SP25 based 3-phenyl-5-styryl-1,2,4-oxadiazole as the core structure. We successfully synthesized all 25 molecules in this series and characterized them using ¹H, ¹³C NMR, and mass spectroscopy. Subsequently, we conducted MTT assays using PC-3 cells and observed that all the compounds exhibited a dose-dependent decrease in cell viability. Notably, compounds SP04, SP16, and SP19 demonstrated a significant decrease in cell viability and exhibited potent activity compared to the other synthesized molecules and standard drug bicalutamide. Among them, SP04 emerged as the one of the most potent compounds with an IC₅₀ value of 238.13 nM and an 89.99 % inhibition of PC-3 cells, compared to synthesized molecules and standard drug bicalutamide. Furthermore, we conducted ROS assays and androgen receptor inhibition assays using the potent compound SP04 and bicalutamide. The results indicated that SP04 increased ROS production and decreased androgen receptor expression dose-dependent manner. Additionally, we conducted a docking study to analyse the interaction patterns within the active site of the androgen receptor. ADMET analysis revealed that all the compounds exhibited favorable physicochemical properties and manageable toxicity profiles.

2023-03-01·Antioxidants (Basel, Switzerland)

Exacerbated Neuropathy in POLAR A and M Trials Due to Redox Interaction of PledOx-Associated Mn²⁺ and Oxaliplatin-Associated Pt².

Article

作者: Jynge, Per ; Ignarro, Louis J. ; Karlsson, Jan Olof G.

Disappointing results from the POLAR A and M phase III trials involving colorectal cancer patients on chemotherapy with FOLFOX6 in curative (A) and palliative (M) settings have been reported by the principal investigators and the sponsor (PledPharma AB/Egetis Therapeutics AB). FOLFOX6, oxaliplatin in combination with 5-fluorouracil (5-FU), possesses superior tumoricidal activity in comparison to 5-FU alone, but suffers seriously from dose-limiting platinum-associated Chemotherapy-Induced Peripheral Neuropathy (CIPN). The aim of the POLAR trials was to demonstrate that PledOx [calmangafodipir; Ca₄Mn(DPDP)₅] reduced the incidence of persistent CIPN from 40% to 20%. However, this assumption was based on "explorative" data in the preceding PLIANT phase II trial, which did not mirror the expected incidence of unwanted toxicity in placebo patients. In POLAR A and M, the assessment of PledOx efficacy was conducted in patients that received at least six cycles of FOLFOX6, enabling analyses of efficacy in 239 A and 88 M patients. Instead of a hypothesized improvement from 40% to 20% incidence of persistent CIPN in the PledOx group, i.e., a 50% improvement, the real outcome was the opposite, i.e., an about 50% worsening in this bothersome toxicity. Mechanisms that may explain the disastrous outcome, with a statistically significant number of patients being seriously injured after having received PledOx, indicate interactions between two redox active metal cations, Pt²⁺ (oxaliplatin) and Mn²⁺ (PledOx). A far from surprising causal relationship that escaped prior detection by the study group and the sponsor. Most importantly, recently published data (ref 1) unequivocally indicate that the PLIANT study was not suited to base clinical phase III studies on. In conclusion, the POLAR and PLIANT trials show that PledOx and related manganese-containing compounds are unsuited for co-treatment with platinum-containing compounds. For use as a therapeutic adjunct in rescue treatment, like in ischemia-reperfusion of the heart or other organs, or in acetaminophen (paracetamol)-associated liver failure, there is little or nothing speaking against the use of PledOx or other PLED compounds. However, this must be thoroughly documented in more carefully designed clinical trials.

项与 Calmangafodipir 相关的新闻（医药）

2021-05-19

·GlobeNewswire

Emerging Drugs for the Chemotherapy Induced Peripheral

Los Angeles, USA , May 19, 2021 (GLOBE NEWSWIRE) -- Emerging Drugs for the Chemotherapy Induced Peripheral Neuropathy Treatment Will Soon Benefit Patients: A Focus on Recent Clinical Trials Chemotherapy-Induced Peripheral Neuropathy Pipeline Report covers a complete clinical trials analysis of 15+ drugs and 15+ companies, which are developing therapies to change the treatment outlook. DelveInsight’s “Chemotherapy Induced Peripheral Neuropathy (CIPN) Pipeline Insight” report provides comprehensive insights about 15+ companies and 15+ pipeline drugs in the Chemotherapy-Induced Peripheral Neuropathy pipeline landscapes. It comprises CIPN pipeline drug profiles, including clinical and non-clinical stage products. It also includes the Chemotherapy Induced Peripheral Neuropathy therapeutics assessment by product type, stage, route of administration, and molecule type and further highlights the inactive CIPN pipeline products. Some of the key takeaways of the Chemotherapy Induced Peripheral Neuropathy Pipeline Report Get an overview of pipeline landscape @ CIPN Clinical Trials Analysis Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common, dose-dependent adverse effect of many frequently prescribed chemotherapy and biotherapy drugs, including taxanes, platinum-based drugs, vinca alkaloids, thalidomide, bortezomib, and interferon. However, there are currently no approved drugs available to prevent or treat CIPN. Certain chemotherapy drugs are more likely to cause neuropathy. These include platinum drugs, such as oxaliplatin; taxanes, such as docetaxel; vinca alkaloids, such as vincristine; and myeloma treatments, such as bortezomib. Other chemotherapy drugs can also cause neuropathy. Chemotherapy-Induced Peripheral Neuropathy Emerging Drugs PledOx (akacalmangafodipir, SP-04), being developed by Pledpharma (now Egetis Therapeutics AB), is a first in class drug candidate developed for the prevention of nerve damage caused by chemotherapy treatment in colorectal cancer patients. Research and DevelopmentPhase III NCT03654729Phase III (POLAR-M): In October 2018, PledPharma initiated a Phase III, multicenter, double-blind, placebo-controlled study to establish the efficacious dose of PledOx in the prevention of chronic chemotherapy-induced peripheral neuropathy (CIPN) induced by oxaliplatin. This Phase III trial enrolled 291 participants and got completed in August 2020. NCT04034355: Phase III (POLAR-A): In November 2018, PledPharm, in collaboration with Solasia Pharma, initiated a phase III, double-blind, multicenter, placebo-controlled study of PledOx used on top of modified FOLFOX6 (5-FU/FA and Oxaliplatin) to prevent CIPN in the adjuvant treatment of patients with stage III or high-risk stage II colorectal cancer. A total of 301 participants were enrolled in this trial, and this trial was completed in August 2020. ART 123 (recombinant human thrombomodulin alpha, marketed as Recomodulin® in Japan), the company’s lead product candidate, represents a promising new treatment for severe sepsis with coagulopathy. ART-123 is a soluble recombinant human thrombomodulin. ART-123 inhibits the coagulation process by accelerating the activation of protein C by thrombin. The drug is currently in phase 2 of clinical trials for the treatment of Chemotherapy-induced Peripheral Neuropathy Research and DevelopmentPhase IINCT04492436: In July 2021, Asahi Kasei Pharma will initiate a trial titled “A Randomized, Double-blind, Placebo-controlled, Multi-national, Multi-center, Parallel-group, Phase 2b Assessing ART-123's Effect on Preventing Sensory Symptoms of OIPN in Unresectable mCRC Subjects Receiving Oxaliplatin-containing Chemo”. The aim of this study is to compare the efficacy and safety of ART-123 (low and high dose) to placebo on sensory symptoms of oxaliplatin-induced peripheral neuropathy (OIPN) in patients with unresectable metastatic colorectal cancer who receive oxaliplatin-containing chemotherapy. The trial is expected to get completed by July 2024. For further information, refer to the detailed report @ Chemotherapy-Induced Peripheral Neuropathy Pipeline Therapeutics Scope of CIPN Pipeline Drug Insight Key Questions regarding Current Chemotherapy-Induced Peripheral Neuropathy Treatment Landscape and Emerging Therapies Answered in the Pipeline Report Table of Contents Get a customised pipeline report @ Chemotherapy-Induced Peripheral Neuropathy Drugs Pipeline Report Related Reports DelveInsight's CIPN - Market Insights, Epidemiology and Market Forecast - 2030 report provides a detailed overview of the disease and a depth understanding of historical and forecasted epidemiology. DelveInsight's Chemotherapy-Induced Peripheral Neuropathy (CIPN) Epidemiology Forecast 2030 report delivers an in-depth understanding of the disease, historical, and forecasted epidemiology. DelveInsight’s ‘Gene Therapy for Ocular Rare Disease -Market Insights, Competitive Landscape and Market Forecast - 2026’ report delivers an in-depth understanding of the disease. Human Immunodeficiency Virus Type 1 (HIV-1) Infection Pipeline Insights, 2021 report by DelveInsight outlays comprehensive insights of present clinical development scenario and growth prospects. DelveInsight’s Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (HABP/VABP) Market Insights, Epidemiology and Market Forecast - 2030 report provides a detailed overview of the disease. DelveInsight' s IgA Nephropathy (IgAN) - Market Insights, Epidemiology and Market Forecast - 2030 report provides a detailed overview of the disease and a depth understanding of historical and forecasted epidemiology. DelveInsight's IgG4-Related Disease- Market Insights, Epidemiology and Market Forecast - 2030 report provides a detailed understanding of historical and forecasted epidemiology. About DelveInsightDelveInsight is a leading Business Consultant, and Market Research firm focused exclusively on life sciences. It supports Pharma companies by providing comprehensive end-to-end solutions to improve their performance. It also provides Healthcare Consulting services comprising credible market analysis that will help accelerate the business growth and overcome challenges with a practical approach.

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100 项与 Calmangafodipir 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
急性肝功能衰竭	临床3期	-	Egetis Therapeutics AB	2023-06-13
转移性结直肠癌	临床3期	美国	苏爱康制药有限公司	2018-11-07
转移性结直肠癌	临床3期	美国	Egetis Therapeutics AB	2018-11-07
转移性结直肠癌	临床3期	日本	Egetis Therapeutics AB	2018-11-07
转移性结直肠癌	临床3期	日本	苏爱康制药有限公司	2018-11-07
转移性结直肠癌	临床3期	比利时	Egetis Therapeutics AB	2018-11-07
转移性结直肠癌	临床3期	比利时	苏爱康制药有限公司	2018-11-07
转移性结直肠癌	临床3期	捷克	苏爱康制药有限公司	2018-11-07
转移性结直肠癌	临床3期	捷克	Egetis Therapeutics AB	2018-11-07
转移性结直肠癌	临床3期	法国	苏爱康制药有限公司	2018-11-07

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


EUCTR2017-004707-43-GB \| EUCTR2017-004754-42-ES (POLAR M, ESMO_GI2021)	临床3期	周围神经系统疾病一线	486	Calmangafodipir 5μmol/kg	鹹鬱鹽艱齋遞壓醖鹹網(餘製網鬱膚窪艱夢積廠) = There was a total of 14 SAEs on CaM vs 2 SAEs on PLC related to allergic-hypersensitivity reactions 餘餘製範觸範選鏇醖衊 (窪範鏇廠憲壓願築廠憲 )	不佳	2021-07-03
				Placebo
NCT03177395 (POP \| PP100-01 (calmangafodipir) for overdose of paracetamol (The POP trial), CTgov)	临床1期	对乙酰氨基酚过量	24	NAC	鬱構餘襯鏇範窪鬱鬱襯(餘艱網顧遞鏇艱願選醖) = 餘範廠餘築簾壓構鏇壓鏇膚膚積鹽願構齋醖積 (廠觸夢鹹窪糧壓鏇鏇顧, 遞鏇壓範築鏇鬱淵憲餘 ~ 顧壓積鑰膚壓顧鹹壓獵) 更多	-	2019-10-03
NCT03177395 (PP100-01 (calmangafodipir) for overdose of paracetamol (The POP trial), EASL2019)	临床1期	对乙酰氨基酚过量 alanine transaminase (ALT) activity \| full-length keratin-18 (FLK18) \| microRNA-122 (miR-122)	24	NAC alone	膚鹽壓糧壓衊憲壓襯觸(顧範鏇築觸獵醖淵築蓋) = 獵築獵積淵顧淵膚鹽選觸窪積構醖糧鬱鬱簾鬱 (齋膚鏇壓簾範願網艱積, 118 ~ 2606)	积极	2019-04-12
				NAC+PP100-01 (2Âµmol/kg)	膚鹽壓糧壓衊憲壓襯觸(顧範鏇築觸獵醖淵築蓋) = 蓋築鏇襯製糧淵製糧製觸窪積構醖糧鬱鬱簾鬱 (齋膚鏇壓簾範願網艱積, 98 ~ 572)