An Open-Label, Two-Part, Phase 1/2a, Crossover Study to Determine the Absolute Bioavailability and Pharmacokinetics of Oral Immediate-Release Doses of OCR-002 in Subjects With Varying Degrees of Cirrhosis

This is an open-label Phase 1, 2-part, crossover study in approximately 33 adult subjects (12 subjects in Part 1 and 21 subjects in Part 2), with varying degrees of cirrhosis with analysis of pharmacokinetic (PK) data after Part 1 to guide dose regimen selection and PK sampling time points for OCR-002 in Part 2.

开始日期2016-08-15

申办/合作机构

OCERA Therapeutics LLC

NCT03159390 / Unknown statusN/AIIT

Human Metabolism of Ornithine Phenylacetate: A Study in Healthy Volunteers

Intravenous infusion of stable tracers of ornithine, glutamine, glutamate, and glycine will be performed, and collect blood samples, urine samples, and muscle biopsies to evaluate the effect of a continuous oral intake of phenylacetate salt of ornithine (OP) on its metabolic fate.

开始日期2015-02-01

申办/合作机构

Texas A&M University

[+1]

NCT01966419 / Completed临床2期

Multicenter, Randomized Phase 2B Study to Evaluate the Efficacy, Safety and Tolerability of OCR-002 (Ornithine Phenylacetate) in Hospitalized Patients With Cirrhosis and Associated Hyperammonemia With an Episode of Hepatic Encephalopathy (STOP-HE Study)

The purpose of this study is to determine whether ornithine phenylacetate can speed recovery from an acute hepatic encephalopathy episode requiring hospitalization in cirrhotic patients.

开始日期2014-01-07

申办/合作机构

OCERA Therapeutics LLC

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0 项与 OCERA Therapeutics LLC 相关的专利（医药）

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项与 OCERA Therapeutics LLC 相关的文献（医药）

2023-08-01·International urogynecology journal

Correction to: A digital health program for treatment of urinary incontinence: retrospective review of real‑world user data.

作者: McKinney, Jessica L ; Weinstein, Milena M ; Keyser, Laura E ; Pulliam, Samantha J

2023-05-01·International urogynecology journal

A digital health program for treatment of urinary incontinence: retrospective review of real-world user data

Article

作者: Weinstein, Milena M ; McKinney, Jessica L ; Keyser, Laura E ; Pulliam, Samantha J

Introduction and hypothesis:

To determine the effectiveness of a prescription digital therapeutic (pDTx) in reducing urinary incontinence (UI) symptoms in real-world users.

Methods:

This is a retrospective cohort study of real-world data from users of a pDTx designed to guide pelvic floor muscle training(PFMT) between July 1, 2020–December 31, 2021. The primary outcome was UI symptom change as reported via in-app Urogenital Distress Inventory (UDI-6). Included subjects were female, ≥ 18 years with a diagnosis of stress, urgency, or mixed UI who completed the UDI-6 at baseline and 8 weeks. Demographic, symptom, and adherence data were summarized. Paired t-test and Wilcoxon signed rank test were used to analyze change in outcomes from baseline to 8 weeks across adherence and UI diagnosis groups.

Results:

Of 532 women with UI, 265 (50%) met criteria and were included in the analysis. Mean age was 51.2 ± 11.5 years (range 22–84, N = 265). Mean body mass index (BMI) was 27.3 ± 6.2 kg/m2 (range 15.2–46.9, N = 147). Most participants had stress UI (59%) followed by mixed UI (22%), urgency UI/OAB (11%), and unspecified UI (8%). UDI-6 scores improved by 13.90 ± 15.53 (p ≤ 0.001); 62% met or exceeded MCID. Device-reported PFMT adherence was 72% at 4 weeks and 66% at 8 weeks (100% = 14 uses/week). Participants in each diagnosis category reported significant improvement on UDI-6 score from baseline to 8 weeks. No association between UDI-6 score improvement and adherence category, age, BMI, or UI subtype was identified.

Conclusions:

This study demonstrates effectiveness of a pDTx in reducing UI symptoms in a real-world setting. Users achieved statistically and clinically significant symptom improvement over an 8-week period.

2022-03-01·Journal of women's health (2002)3区 · 医学

Female Urinary Incontinence Evidence-Based Treatment Pathway: An Infographic for Shared Decision-Making

3区 · 医学

Review

作者: Ferzandi, Tanaz R. ; Pulliam, Samantha J. ; McKinney, Jessica L. ; Keyser, Laura E.

Objectives: Urinary incontinence (UI) is a highly prevalent burdensome condition among adult females in the United States, yet rates of care-seeking, evaluation, and treatment are nonoptimal. Components of evaluation and treatment are informed by research and professional society guidelines; however, a visual representation of this guidance does not exist. The objectives of this study are to review the literature regarding female UI care and to synthesize this information into a graphical format to facilitate health education, health care delivery, and shared decision-making. Methods: We reviewed published society guidelines, position statements, and associated references from the American College of Obstetrics and Gynecology, the Women's Preventive Services Initiative, American Academy of Family Physicians, American College of Physicians, the Society of Urodynamics and Female Urology, the American Urological Association, and the American Urogynecologic Society, and searched PubMed for related literature. We synthesized these findings into an evidence-based infographic depicting female UI risk factors, influences on care-seeking and provision, screening, evaluation, and a stepwise treatment approach. Results: This study summarizes current evidence and professional guidelines related to female UI into a compelling visual format and accompanying narrative. The infographic is intended as a tool for patient education, clinical practice, and research to facilitate shared decision-making and health care delivery. Conclusions: Female UI is highly prevalent, yet diagnosis and treatment are suboptimal. Use of an evidence-based infographic may positively impact patient knowledge and certainty about UI treatment and support health care provider counseling and decision-making.

项与 OCERA Therapeutics LLC 相关的新闻（医药）

2024-01-05

·奇点网

《自然》重磅：等了50年，克星终于来了！罗氏/哈佛团队发现全新抗生素，可抑制内毒素脂多糖外排，让耐药鲍曼不动杆菌自杀丨科学大发现

*仅供医学专业人士阅读参考2017年，世界卫生组织发布了一个“追杀”名单。名单按照紧急程度，列举了多种亟需开发新抗生素的耐药细菌。其中排名第一的是多重/广泛耐药的结核分枝杆菌，排名第二的是耐碳青霉烯鲍曼不动杆菌（CRAB）。虽然鲍曼不动杆菌的知名度不如结核分枝杆菌高，但是对被誉为人类对抗细菌感染“最后一道防线”的碳青霉烯类抗生素因耐药的CRAB，仍让医生胆寒。据估算，侵袭性CRAB感染的死亡率在40%到60%之间，缺少有效治疗方法是其推高死亡率的主要原因之一。更可怕的是，FDA已经有50多年没有批准治疗CRAB感染的新抗生素上市了。好消息是，近日由罗氏Kenneth A. Bradley和Michael A. Lobritz领衔的研究团队，在顶级期刊《自然》上发表了一项突破性研究成果[1]。他们宣布找到了一个以脂多糖转运体为靶点的新型抗生素zosurabalpin，它可以抑制CRAB合成的内毒素脂多糖外排，导致细胞内脂多糖浓度过高，CRAB中毒身亡。论文首页截图值得注意的是，由哈佛大学Daniel Kahne和哈佛医学院Andrew C. Kruse领衔的研究团队，从结构生物学、生物化学和遗传学的角度，详细阐述了zosurabalpin抑制脂多糖转运体外排脂多糖的机制[2]，进一步证实了这一全新机制的存在。据了解，这也是科学家首次发现脂多糖转运体可以作为抗生素的作用靶点。论文首页截图正如前文所言，耐碳青霉烯鲍曼不动杆菌（CRAB）感染导致的超高死亡率是临床医生的噩梦。为了找到对抗CRAB的新型抗生素，Bradley团队对Tranzyme Pharma公司生产的44985种大环肽（MCPs）进行筛选。他们发现其中一个编号为RO7036668的大环肽对鲍曼不动杆菌有活性，但对其他革兰氏阴性菌无活性，对革兰氏阳性菌和酵母菌的活性也非常有限，且没有发现细胞毒性。为了进一步提高这个大环肽的杀菌活性，研究人员对它做了初步改造，得到了先导化合物RO7075573。两种化合物的分子结构在改造之后，RO7075573对一组鲍曼不动杆菌的药效是RO7036668的4到64倍，而且选择性变得更强了。由于RO7075573对抗生素敏感型和多耐药（MDR）型鲍曼不动杆菌的抗菌活性相似，Bradley团队推测RO7075573可能作用于一个新的靶点。基于小鼠模型的研究也证实，RO7075573在体内也有与体外相似的强大抗菌活性。这也促使研究团队有信心进一步开发这个大环肽。体内药代动力学显示，RO7075573具有良好的吸收、分布、代谢和消除特性，但是耐受性似乎不行，会导致血脂异常，进而导致模式动物死亡。于是他们进一步对RO7075573做了改造，降低它的亲脂性，得到了zosurabalpin（ZAB）。研究结果显示，模式动物对zosurabalpin耐受良好。ZAB本尊接下来的工作就是寻找zosurabalpin的作用靶点，以及它在体内的疗效。Bradley团队寻找作用靶点的方法简单粗暴，就是通过不断提升培养基中zosurabalpin的浓度，让鲍曼不动杆菌自己进化出自发耐药，然后通过基因测序分析突变的位点。在汇总测序结果之后，他们发现突变主要发生在编码脂多糖（LPS）转运和生物合成的基因中，尤其是构成脂多糖转运系统的LptB2FGC复合物中的多种蛋白（LptF和LptG等）。显然，zosurabalpin肯定是影响了脂多糖的转运。随后的生化实验证实了zosurabalpin是以内膜LptB2FGC复合物为靶点，阻断了脂多糖的转运，导致这种内毒素在细胞内积累，最终导致细菌的死亡。哈佛大学Daniel Kahne和哈佛医学院Andrew C. Kruse团队，进一步从结构生物学角度证实了上述发现。值得注意的是，这个靶点之前没有被当做抗生素的靶点。作用机制示意图[3]在研究的最后，Bradley团队测试了zosurabalpin治疗严重侵袭性CRAB感染的潜力。他们对分离自患者不同感染部位的129株鲍曼不动杆菌分离株进行了体外活性评估，其中78%是难治性鲍曼不动杆菌，80%属于多耐药鲍曼不动杆菌。体外数据显示，zosurabalpin对这些菌株有极强的抑菌活性。将上述菌株接种到模式小鼠体内之后，zosurabalpin仍有强大的抑菌活性，而且细菌的负担呈剂量依赖性下降。不同剂量zosurabalpin的治疗效果总的来说，Bradley团队发现了一种对耐碳青霉烯鲍曼不动杆菌和泛耐药鲍曼不动杆菌有强力抑菌活性的抗生素，并发现了一个之前不为人所知的新的抗生素靶点LptB2FGC复合物，这也为铜绿假单胞菌、肺炎克雷伯菌和大肠杆菌等革兰氏阴性菌抗生素的开发提供了思路。需要指出的是，虽然zosurabalpin是个作用于全新靶点的抗生素，按理说现阶段临床上不会出现耐药的情况；但是在抗生素的压力之下，几乎所有的抗生素最终都会面临耐药问题，正如在本研究中，Bradley团队自己也筛选出了耐药株。不过，在合理使用的情况下，必定会减轻耐药性的发生。据了解，目前zosurabalpin已经进入临床测试阶段。如果试验顺利，耐碳青霉烯鲍曼不动杆菌给临床医生带来的噩梦有可能就此终结。参考文献：[1].Zampaloni, C., Mattei, P., Bleicher, K. et al. A novel antibiotic class targeting the lipopolysaccharide transporter. Nature. 2024. doi: 10.1038/s41586-023-06873-0[2].Pahil, K.S., Gilman, M.S.A., Baidin, V. et al. A new antibiotic traps lipopolysaccharide in its intermembrane transporter. Nature. 2024. doi: 10.1038/s41586-023-06799-7[3].Gugger MK, Hergenrother PJ. A new type of antibiotic targets a drug-resistant bacterium. Nature. 2024. doi:10.1038/d41586-023-03988-2本文作者丨BioTalker

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药物(靶点)	适应症	全球最高研发状态

炭素 ( NF-κB )	克罗恩病更多	终止
TZP-202 ( GPR38 )	消化不良更多	终止
Ornithine Phenylacetate ( NF-κB x NOS2 )	高氨血症更多	无进展
TZP-102 ( GHSR )	糖尿病性胃轻瘫更多	无进展
TZP-201 ( GPR38 )	消化不良更多	无进展