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阿斯利康新抗生素药物CAZ-AVI治疗并发性腹腔内感染临床三期研究获得圆满成功

  1. CAZ-AVI
  2. 抗生素
  3. 阿斯利康

来源:生物谷 2014-08-21 10:57

阿斯利康新抗生素药物CAZ-AVI治疗并发性腹腔内感染临床三期研究获得圆满成功

2014年8月21日讯 /生物谷BIOON/ --阿斯利康公司最近宣布公司开发的新型抗生素CAZ-AVI(ceftazidime-avibactam)治疗并发性腹腔内感染(cIAI)的临床三期研究取得令人满意的结果。结果显示CAZ-AVI在治疗cIAI患者(包括由抗头孢他汀菌引起的cIAI)时,与美洛培南同样有效。

本次临床三期研究采用了RECLAIM-1和RECLAIM-2实验设计。CAZ-AVI的有效成分由治疗严重细菌感染的头孢他汀和新型β内酰胺酶抑制剂avibactam构成。CAZ-AVI中的avibactam可以保护头孢他汀不被抗药性菌分泌的β内酰胺酶所分解,从而保持对细菌的毒性。该抗生素主要用于治疗一系列具有抗药性的革兰氏阴性菌。本次临床研究同时评估了不同剂量的CAZ-AVI在临床中的效果与安全性。结果显示CAZ-AVI的临床药效与meropenem,随机分配的患者基本都在给药的28-35天内痊愈。同时其副作用并不高于meropenem,临床中CAZ-AVI表现出的副作用主要有腹泻、呕吐、恶心和发烧。

阿斯利康的研究人员对这一结果表示振奋,同时还透露目前CAZ-AVI针对尿路感染与医院性肺炎的研究也正在有条不紊的进行。

十几年前,由于利润下降以及抗生素品种多样,许多制药巨头包括阿斯利康都纷纷退出抗生素市场。然而最近几年,抗药性细菌在全球呈现井喷态势,使这些制药巨头和各国医药管理部门意识到了严重的危机和机遇,许多制药商纷纷重新回归这一市场,投入精力开发新型抗生素。(生物谷Bioon.com)

详细英文报道:

CAZ-AVI treated patients with cIAI as effectively as meropenem

CAZ-AVI also treated cIAI patients infected with ceftazidime-resistant bacteria as effectively as meropenem

AstraZeneca today announced positive top-line results from RECLAIM-1 and RECLAIM-2, the pivotal Phase III studies investigating the potential of the antibiotic ceftazidime-avibactam (CAZ-AVI) as a treatment for hospitalised adult patients with complicated intra-abdominal infections.

CAZ-AVI consists of a cephalosporin (ceftazidime), an established treatment for serious bacterial infections, and a next generation non-beta lactam beta-lactamase inhibitor (avibactam). CAZ-AVI is being developed to treat a broad range of Gram-negative bacterial infections which are becoming resistant to antibiotics and pose an increasing threat to public health. The addition of avibactam protects ceftazidime from being broken down by beta-lactamases that are produced by resistant bacteria.

The global RECLAIM-1 and RECLAIM-2 Phase III studies both evaluated the safety and efficacy of CAZ-AVI, administered intravenously as a two hour infusion (2000 mg / 500 mg) plus metronidazole, compared to meropenem, administered intravenously as a 30 minute infusion (1 g), in hospitalised adult patients with complicated intra-abdominal infections. Data from the RECLAIM-1 and RECLAIM-2 studies were analysed as a single-pooled dataset with the agreement of the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

In the RECLAIM-1 and RECLAIM-2 Phase III studies, CAZ-AVI met the objective of statistical non-inferiority compared to meropenem. The primary endpoint was a clinical cure rate 28 to 35 days after randomisation (the Test of Cure visit). CAZ-AVI also treated cIAI patients infected with ceftazidime-resistant bacteria as effectively as meropenem.

The adverse event rate for CAZ-AVI in combination with metronidazole was similar to meropenem. The most commonly reported adverse events for CAZ-AVI in combination with metronidazole were diarrhoea, nausea, vomiting and fever, which were not unexpected based on the known safety profiles of ceftazidime and metronidazole.

"We are very encouraged by these results which highlight the potential for CAZ-AVI to provide a much-needed new treatment option for serious and life-threatening intra-abdominal infections, especially where antibiotic resistance poses a threat to treatment," said Briggs Morrison, Executive Vice President, Global Medicines Development & Chief Medical Officer, AstraZeneca.

Studies are also underway for CAZ-AVI in complicated urinary tract infections (cUTI), nosocomial pneumonia and for the treatment of cIAI and cUTI patients with ceftazidime-resistant infections.

The RECLAIM-1 and RECLAIM-2 Phase III studies could form the basis of regulatory submissions seeking approval for a broader range of indications, in line with new EMA guidelines on the evaluation of medicines to treat bacterial infections. EU filing is anticipated in the first quarter of 2015, pending a full analysis of the data from the studies. The results will also be submitted to a scientific meeting in the first half of 2015.

CAZ-AVI is being jointly developed with Forest Laboratories, a wholly-owned subsidiary of Actavis. AstraZeneca holds the global rights to commercialise CAZ-AVI, with the exception of North America where the rights are held by Forest Laboratories.

NOTES TO EDITORS

About RECLAIM

RECLAIM-1 and RECLAIM-2 are Phase III, randomised, multi-centre, double-blind, double-dummy, parallel-group, comparative studies to determine the efficacy, safety, and tolerability of CAZ-AVI administered intravenously as a two hour infusion (2000 mg / 500 mg, every 8 hours), plus metronidazole, administered intravenously as a 60 minute infusion (0.5 g every 8 hours), compared to meropenem, administered intravenously as a 30 minute infusion (1 g every 8 hours). A total of 1,066 patients have been randomised to the RECLAIM-1 and RECLAIM-2 trials from 30 countries.

For the EMA, the co-primary analysis was conducted at the Test of Cure (TOC) in the Modified-Intent-to-Treat (MITT) and Clinically Evaluable (CE) patient populations. The non-inferiority margin was 12.5%; and the lower and upper bounds of the 95% confidence interval were -6.9% and 2.10% respectively for the MITT population and -4.61% and 2.89% for the CE population. For the FDA, the primary analysis was conducted at the TOC in the Microbiological Modified Intent-to-Treat (mMITT) population and the non-inferiority margin was 10%. The lower and upper bounds of the 95% confidence interval were -8.64% and 1.58% respectively.

The MITT population included all enrolled patients who received at least one dose of the study drug; the CE population are the patients who completed their course of treatment without deviation from the study protocol; and the mMITT population are those patients from the MITT group who were identified as carrying a pathogen at the start of treatment.

About CAZ-AVI

CAZ-AVI (ceftazidime-avibactam) is an investigational antibiotic being developed to treat serious Gram-negative bacterial infections. It consists of ceftazidime, a third-generation, antipseudomonal cephalosporin, that is an established treatment for serious Gram-negative bacterial infections, and avibactam, a next generation, non-beta lactam beta-lactamase inhibitor.

The addition of avibactam to ceftazidime protects ceftazidime from breakdown by serine-beta-lactamases. CAZ-AVI offers a differentiated profile versus existing treatment options in serious Gram-negative infections through its activity against a broad range of isolates of carbapenem-resistant Enterobacteriaceae and difficult to treat Pseudomonas aeruginosa combined with robust coverage of extended spectrum beta-lactamase-expressing pathogens.

About cIAI

Most intra-abdominal infections (IAI) are a result of processes involving inflammation and perforations of the gastrointestinal tract, such as appendicitis, peptic ulcer disease, and diverticulitis (a common digestive disease which involves the formation of pouches within the bowel wall). IAI is an important cause of morbidity and mortality and it is the second most commonly identified cause of severe sepsis in the intensive care unit.

From a clinical perspective, IAI are classified in two major categories: complicated and uncomplicated. Complicated intra-abdominal infections (cIAI) extend beyond the source organ into the peritoneal space (the space between the two membranes that separate the organs in the abdominal cavity from the abdominal wall). They cause peritoneal inflammation, and are associated with localised or diffuse peritonitis.

Antimicrobial therapy is an important part of the clinical management of IAI. The threat of antimicrobial resistance, however, is one of the major challenges associated with the antimicrobial management of cIAI.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please

 

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