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).

BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02693093 . Registered through the National Institutes of Health on 26 February 2016.

Effect and cost of treatment for acute pancreatitis with or without gabexate mesylate: a propensity score analysis using a nationwide administrative database.

OBJECTIVES: Despite a lack of evidence, gabexate mesylate (GM) is routinely used for the treatment of acute pancreatitis (AP) in some countries. The present study examined the effect and cost of GM for AP treatment using the Japanese Diagnosis Procedure Combination database. METHODS: We performed a propensity score analysis to compare inhospital mortality, length of stay (LOS), and total costs between patients with AP treated with GM and those without GM in 2010. RESULTS: We identified 2483 patients treated with GM and 890 patients without GM. Overall, 77% of the patients treated with GM were nonsevere AP cases. The propensity-matched 707 pairs showed no significant difference between GM users and nonusers in inhospital mortality or median length of stay in nonsevere AP (1.0% vs 1.2%, P = 0.789; 10 vs 10 days, P = 0.160) and severe AP (8.4% vs 5.0%, P = 0.438; 12 vs 14 days, P = 0.487) cases. Total costs were significantly different between the GM users and the nonusers in nonsevere AP cases (US$4982 vs US$4373, P < 0.001), but not in severe AP cases ($6605 vs $6490, P = 0.764). CONCLUSIONS: Using GM for nonsevere AP cannot be justified because of higher costs without significant effects. Gabexate mesylate use is also not justifiable for severe AP because it does not reduce mortality or length of stay.