Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, 410 West Tenth Avenue, Columbus, OH, 43210, USA.
Kangen Pharmaceuticals, America LLC, Kansas City, Kansas, USA.
Trials. 2019 Aug 14;20(1):501. doi: 10.1186/s13063-019-3606-y.
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.
慢性胰腺炎（CP）是一种进行性、纤维炎症性疾病，其特征为酶的自动激活以及随后的腺泡细胞纤维替代。相当一部分患者会出现疼痛，其可能由多种原因引起，包括神经周围炎症、疼痛信号的中枢处理改变、实质结构变化和导管阻塞。目前，CP 相关疼痛尚无批准的医学治疗选择。NI-03（甲磺酸奈莫司他）是一种口服丝氨酸蛋白酶抑制剂，可降低胰腺酶活性，在日本已广泛用于治疗 CP 相关疼痛。本研究将评估 NI-03 在美国用于减轻 CP 相关疼痛的安全性和疗效。
本研究由两部分组成。首先，将进行为期 1 周的单剂量（100、200 或 300mg）给药的 I 期研究，以确定其药代动力学和安全性概况。随后，将进行 II 期研究，包括一项双盲、随机对照试验（RCT）。该 RCT 将评估每日 3 次给予 3 种剂量的 NI-03 与安慰剂在 28 天内的疗效。在双盲阶段之前，将进行为期 7 天的单盲、预试验期，以评估基线疼痛特征。主要疗效结局为研究期间终端 7 天内平均最差每日疼痛评分（0-10 数字评分量表）与基线相比的变化。次要疗效结局包括阿片类药物剂量和生活质量指标的变化以及首次使用静脉内解救镇痛的时间。将记录不良事件。
NI-03 在日本已成功且安全地用于治疗 CP 相关疼痛。本研究的目的是使用美国人群中的严格 RCT 评估 NI-03 的安全性和疗效。本研究可能填补了一个重要的临床空白，为 CP 相关疼痛提供了一种有效的医学治疗选择。
ClinicalTrials.gov，NCT02693093。于 2016 年 2 月 26 日通过美国国立卫生研究院注册。
