A Phase 1, Single Dose PK and Safety Study With NI-03 Followed by a Phase 2, Randomized, Double-Blind, Parallel-Group Dose-Ranging Study to Evaluate the Safety and Efficacy of NI-03 When Compared to Placebo in Subjects With Chronic Pancreatitis
The purpose of this study is to determine the safety and efficacy of NI-03.
100 项与 NI-03 相关的临床结果
100 项与 NI-03 相关的专利（医药）
项与 NI-03 相关的文献（医药）
2022-12-17·International journal of molecular sciences
Extracellular Vesicles as Mediators of Nickel-Induced Cancer Progression.
作者: Shan Liu ; Angelica Ortiz ; Aikaterini Stavrou ; Angela R Talusan ; Max Costa
Emerging evidence suggests that extracellular vesicles (EVs), which represent a crucial mode of intercellular communication, play important roles in cancer progression by transferring oncogenic materials. Nickel (Ni) has been identified as a human group I carcinogen; however, the underlying mechanisms governing Ni-induced carcinogenesis are still being elucidated. Here, we present data demonstrating that Ni exposure generates EVs that contribute to Ni-mediated carcinogenesis and cancer progression. Human bronchial epithelial (BEAS-2B) cells and human embryonic kidney-293 (HEK293) cells were chronically exposed to Ni to generate Ni-treated cells (Ni-6W), Ni-transformed BEAS-2B cells (Ni-3) and Ni-transformed HEK293 cells (HNi-4). The signatures of EVs isolated from Ni-6W, Ni-3, HNi-4, BEAS-2B, and HEK293 were analyzed. Compared to their respective untreated cells, Ni-6W, Ni-3, and HNi-4 released more EVs. This change in EV release coincided with increased transcription of the EV biogenesis markers CD82, CD63, and flotillin-1 (FLOT). Additionally, EVs from Ni-transformed cells had enriched protein and RNA, a phenotype also observed in other studies characterizing EVs from cancer cells. Interestingly, both epithelial cells and human umbilical vein endothelial (HUVEC) cells showed a preference for taking up Ni-altered EVs compared to EVs released from the untreated cells. Moreover, these Ni-altered EVs induced inflammatory responses in both epithelial and endothelial cells and increased the expression of coagulation markers in endothelial cells. Prolonged treatment of Ni-alerted EVs for two weeks induced the epithelial-to-mesenchymal transition (EMT) in BEAS-2B cells. This study is the first to characterize the effect of Ni on EVs and suggests the potential role of EVs in Ni-induced cancer progression.
2019-08-14·Trials4区 · 医学
A phase 1/2 trial to evaluate the pharmacokinetics, safety, and efficacy of NI-03 in patients with chronic pancreatitis: study protocol for a randomized controlled trial on the assessment of camostat treatment in chronic pancreatitis (TACTIC).
4区 · 医学
作者: Mitchell L Ramsey ; Janet Nuttall ; Phil A Hart ; TACTIC Investigative Team
Chronic pancreatitis (CP) is a progressive, fibro-inflammatory disease characterized by enzymatic autoactivation and subsequent fibrotic replacement of acinar cells. A significant proportion of patients develop pain, which may be due to many causes, including perineural inflammation, altered central processing of pain signals, parenchymal structural changes, and ductal obstruction. Currently there are no approved medical treatment options for CP-associated pain. NI-03 (camostat mesilate) is an orally administered serine protease inhibitor that reduces pancreatic enzyme activity and has been widely used for the treatment of CP-associated pain in Japan. The current study will assess the safety and efficacy of NI-03 for reduction of CP-associated pain in the USA.
The current study consists of two phases. First, a phase I study will be performed to establish the pharmacokinetics and safety profile over a 1-week period following a single dose (100, 200, or 300 mg). Subsequently, a phase II study will be performed consisting of a double-blind, randomized, controlled trial (RCT). This RCT will evaluate the efficacy of each of the three doses of NI-03 given three times daily compared to placebo over 28 days. A 7-day, single-blind, run-in period will precede the double-blind phase to assess baseline pain characteristics. The primary efficacy outcome is the average of worst daily pain scores (numeric rating scale of 0-10) over the terminal 7 days of the study period compared to baseline. Secondary efficacy outcomes include change in opioid dose and quality of life measures, and time to first rescue intravenous analgesic. Adverse events will be recorded.
NI-03 has been used successfully and safely in Japan to treat CP-associated pain. The aim of the current study is to assess the safety and efficacy of NI-03 using a rigorous RCT in a population in the USA. This study may fill an important clinical gap to provide an effective medical treatment option for CP-associated pain.
ClinicalTrials.gov, NCT02693093 . Registered through the National Institutes of Health on 26 February 2016.
2016-08-04·Wei sheng wu xue bao = Acta microbiologica Sinica
[Effects of nisin on in vitro fermentation, methanogenesis and functional microbial populations of the rumen].
This study was conducted to evaluate the effects of nisin on in vitro fermentation, methanogenesis and functional microbial populations of the rumen.
The negative control did not contain any additives. Monensin (5 μmol/L) was added as positive control. Nisin was added at 3 doses:3 (NI-3), 9 (NI-9), and 27 mg/100 mL (NI-27). Each treatment contained 4 replicates. Gas and methane production was measured at 0, 3, 6, 9, 12, and 24 h after incubation. Samples of culture were collected at 24 h, and used to measure rumen fermentation parameters and functional microbial populations.
Compared with negative control, both nisin and monensin addition dramatically reduced gas and methane production (P<0.05). Nisin addition had no effect on pH, dry matter degradability, and organic matter degradability (P0.05). Ammonia concentration was reduced by NI-9 (P<0.05), but was not influenced by NI-3 and NI-27 (P0.05). In contrast, monensin addition significantly lowered dry matter degradability, organic matter degradability, and ammonia concentration (P<0.05), but had no influence on pH (P0.05). Compared with negative control, both nisin and monensin addition significantly reduced acetate concentration and acetate-propionate ratio (P<0.05), and increased propionate concentration (P<0.05). Quantitative real-time PCR results showed that both nisin and monensin addition had no effects on the populations of total bacteria and Bacteroides (P0.05). Compared with negative control, the populations of protozoa, methanogens, fungi and Firmicutes were not influenced by nisin (P0.05), but were significantly reduced by monensin addition (P<0.05). Both nisin and monensin addition significantly increased the populations of sulfur-reducing bacteria and Clostridium aminophilum (P<0.05), but had no influence on the population of Clostridium sticklandii (P0.05).
Appropriate nisin addition could reduce methanogenesis and ammoniagenesis, while had no adverse effect on feed digestion. These effects are probably associated with the variation of rumen functional microbial populations and communities.