A Randomised, Double-blind, Placebo Controlled, Parallel Group Study in Healthy Adult Volunteers to Determine the Tolerability and Safety of Pyronaridine (PYR) Co-administered With Piperaquine (PQP) Under Fasted Conditions

The study is a clinical trial involving two medicines called piperaquine (PQP) and pyronaridine (PYR) which, in combination with dihydroartemisinin (DHA) and with artesunate (ART) respectively, have been in clinical use for over 20 years to treat acute episodes of malaria. PYR and PQP are both known to be well tolerated and provide effective treatment for malarial infection when administered in their licensed combinations, but have not been administered together in combination before.
This new combination is being considered for development for malaria prevention (i.e. chemoprophylaxis) in sub-Saharan Africa and therefore, the trial participants will be exclusively drawn from a population from that origin.

开始日期2022-02-14

申办/合作机构

MMV Medicines for Malaria Venture

[+1]

100 项与 Pyronalidine tetraphosphate 相关的临床结果

登录后查看更多信息

100 项与 Pyronalidine tetraphosphate 相关的转化医学

登录后查看更多信息

100 项与 Pyronalidine tetraphosphate 相关的专利（医药）

登录后查看更多信息

项与 Pyronalidine tetraphosphate 相关的文献（医药）

2024-09-03·ACS Omega

Oral Pyronaridine Tetraphosphate Reduces Tissue Presence of Parasites in a Mouse Model of Chagas Disease

Article

作者: Ekins, Sean ; Lane, Thomas R. ; Barbosa da Silva, Elany ; Giardini, Miriam A. ; Siqueira-Neto, Jair Lage ; Bernatchez, Jean A. ; Calvet Alvarez, Claudia Magalhaes

The eukaryotic parasite Trypanosoma cruzi (T. cruzi) is responsible for Chagas disease, which results in heart failure in patients. The disease is more common in Latin America, and is an emerging infection with The Centers for Disease Control estimating that greater than 300,000 people are currently infected in the United States. This disease has also spread from South and Central America, where it is endemic to many other countries, including Australia, Japan, and Spain. Current therapy for Chagas disease is inadequate due to limited efficacy in the indeterminate and chronic phases of the disease, in addition to the adverse effects from nifurtimox and benznidazole, which are nitro-containing drugs used for therapy. There is a clear need for new therapies for the Chagas disease. Using a computational machine learning approach, we have previously shown that the antimalarial pyronaridine tetraphosphate is active against T. cruzi Brazil-luc in vitro against parasites infecting a myoblast cell line and is also active in vivo in an acute mouse model of Chagas disease when dosed i.p. We now further evaluated oral pyronaridine as a monotherapy to determine the minimum effective dose to treat acute and chronic models of Chagas disease. Our results for T. cruzi Brazil-luc demonstrated daily oral dosing with pyronaridine from 150 to 600 mg/kg resulted in statistically significant inhibition in the 7 day acute mouse model. Combination therapy with daily dosing of benznidazole and pyronaridine in the acute infection model demonstrated that 300 mg/kg pyronaridine could return statistically significant antiparasitic activity to a subtherapetic 10 mg/kg benznidazole. In contrast, pyronaridine as monotherapy or combined with benznidazole lacked efficacy in the chronic mouse model, whereas 100 mg/kg benznidazole alone demonstrated undetectable parasites in the heart of mice. Pyronaridine requires further assessment in other chronic models to identify if it can be used beyond the acute stage of T. cruzi infection.

2023-10-31·mBio

Pyronaridine tetraphosphate is an efficacious antiviral and anti-inflammatory active against multiple highly pathogenic coronaviruses

Article

作者: Ardanuy, Jeremy ; Johnson, Robert ; Dillen, Carly ; Frieman, Matthew ; Weston, Stuart ; Taylor, Louis ; Hammond, Holly

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), continues to be one of the largest dangers to human health around the world. The need for effective antiviral and anti-inflammatory treatments is still extremely high as newly emerging variants threaten the efficacy of currently used treatment options. Many compounds are effective at inhibiting SARS-CoV-2 infection in vitro but fail to recapitulate that efficacy in vivo . There is a major demand for antiviral drugs that are efficacious and broadly effective for the treatment of highly pathogenic coronaviruses including SARS-CoV-2, and its close relatives SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). One drug with the potential to join the small subset of broadly active antiviral compounds that is both efficacious in vivo and orally bioavailable is pyronaridine triphosphate, which has now been published to show both in vitro and in vivo efficacy in A549 cells and the K18-hACE2 mouse model, respectively, by functioning as a protease inhibitor of the SARS-CoV-2 papain-like protease (PLpro). In our studies, pyronaridine treatment resulted in significant improvements to lung inflammatory pathology, reducing pro-inflammatory cytokine and chemokine levels, and inhibiting weight loss seen in the mouse model associated with the severity of disease in three highly pathogenic coronavirus infection models, SARS-CoV-1, SARS-CoV-2, and MERS-CoV. Additionally, we found that pyronaridine treatment can safely and effectively be combined with currently used therapeutics molnupiravir and nirmatrelvir (main protease inhibitor component of Paxlovid) in a SARS-CoV-2 in vivo model, and there was evidence of a synergistic effect that further reduced viral titers, inflammatory lung pathology, and inflammatory cytokine and chemokine levels. These results indicate that pyronaridine represents an excellent potential therapeutic candidate for COVID-19 treatment individually, or in combination with other approved antivirals as well as a potential therapeutic option for the treatment of highly pathogenic coronaviruses such as SARS-CoV-1, MERS-CoV, and future coronaviruses yet to emerge. IMPORTANCEPyronaridine tetraphosphate is on the WHO Essential Medicine List for its importance as a widely available and safe treatment for malaria. We find that pyronaridine is a highly effective antiviral therapeutic across mouse models using multiple variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the highly pathogenic viruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus responsible for previous coronavirus outbreaks. Additionally, we find that pyronaridine additively combines with current COVID-19 treatments such as nirmatrelvir (protease inhibitor in Paxlovid) and molnupiravir to further inhibit SARS-CoV-2 infections. There are many antiviral compounds that demonstrate efficacy in cellular models, but few that show this level of impact in multiple mouse models and represent a promising therapeutic for the current coronavirus pandemic as well as future outbreaks as well.

2023-10-01·Drug Discovery Today

Learning from COVID-19: How drug hunters can prepare for the next pandemic

Article

作者: Lane, Thomas R ; Puhl, Ana C ; Ekins, Sean

Over 3 years, the SARS-CoV-2 pandemic killed nearly 7 million people and infected more than 767 million globally. During this time, our very small company was able to contribute to antiviral drug discovery efforts through global collaborations with other researchers, which enabled the identification and repurposing of multiple molecules with activity against SARS-CoV-2 including pyronaridine tetraphosphate, tilorone, quinacrine, vandetanib, lumefantrine, cetylpyridinium chloride, raloxifene, carvedilol, olmutinib, dacomitinib, crizotinib, and bosutinib. We highlight some of the key findings from this experience of using different computational and experimental strategies, and detail some of the challenges and strategies for how we might better prepare for the next pandemic so that potential antiviral treatments are available for future outbreaks.

100 项与 Pyronalidine tetraphosphate 相关的药物交易

登录后查看更多信息

研发状态

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05160363 (CTgov)	临床1期	-	37	Piperaquine tetraphosphate+Pyronaridine Tetraphosphate (PYR and PQP Combination)	衊醖鹹鑰繭膚簾製淵製(窪窪鹽築築醖簾艱觸齋) = 憲壓製範鹹選願製糧窪選獵積衊醖鏇餘顧範襯 (夢構襯襯觸鑰糧壓壓衊, 鬱鹹艱築壓廠範築衊窪 ~ 壓膚壓顧鑰觸網範製淵) 更多	-	2024-05-10
				Placebo+Pyronaridine Tetraphosphate (PYR and Placebo Combination)	衊醖鹹鑰繭膚簾製淵製(窪窪鹽築築醖簾艱觸齋) = 艱獵願齋鑰製積齋廠艱選獵積衊醖鏇餘顧範襯 (夢構襯襯觸鑰糧壓壓衊, 廠簾齋願鹹願選廠觸窪 ~ 艱範製衊艱顧顧獵鏇膚) 更多