Exocrine Pancreatic Insufficiency (EPI)

Background: Chronic pancreatitis (CP) is a progressive inflammatory disorder causing irreversible pancreatic damage, eventually resulting in pancreatic exocrine insufficiency (PEI). This may lead to malabsorption, malnutrition, weight loss, and impaired quality of life. Pancreatic enzyme replacement therapy (PERT) is the standard treatment for PEI and is predominantly derived from porcine sources. However, religious, ethical, dietary, and supply-related concerns highlight the need for effective non-porcine alternatives. Microbial (fungal)-based pancreatic enzymes have shown promising safety and efficacy in preliminary studies, but evidence in CP remains limited. Objective: To compare the efficacy and safety of non-porcine microbial (fungal)-based pancreatin with standard porcine-based pancreatin in patients with PEI secondary to CP. Methods: This investigator-initiated, randomized, double-blind, single-center, non-inferiority trial will enroll 134 adults with CP-associated PEI (defined as having a fecal elastase \<100 µg/g). After a two-week washout period, participants will be randomized 1:1 to receive either microbial-based or porcine-based pancreatin for 12 weeks. The primary outcome is the change from baseline in the Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q) score at 12 weeks. Secondary outcomes include nutritional status, anthropometric measures, gastrointestinal symptoms, pain scores, stool consistency, glycaemic parameters, laboratory markers, and quality of life. Discussion: This study aims to evaluate whether microbial-based pancreatin is non-inferior to porcine-based therapy and may provide a culturally acceptable and sustainable alternative for managing CP-related PEI.

In this study, ANG003, a pancreatic enzyme replacement therapy (PERT; commonly called "enzymes"), is being investigated as a potential treatment for exocrine pancreatic insufficiency (EPI). People with EPI due to Cystic Fibrosis (CF) may be eligible to participate in this study. The primary objective of this study is to evaluate the safety of ANG003 and see if it works as well compared to Creon, an approved PERT.

This research aims to improve the management of exocrine pancreatic insufficiency (EPI), a condition that can develop after pancreatitis, a painful inflammation of the pancreas. EPI occurs when the pancreas does not produce enough enzymes to help the body properly digest food. While pancreatic enzyme replacement therapy (PERT) is commonly used to manage EPI symptoms, it can be challenging for people who rely on feeding tubes. RELiZORB, could help these patients by simplifying the delivery of the enzymes they need. However, RELiZORB has only been studied in people with EPI caused by cystic fibrosis, so its effectiveness in pancreatitis patients remains unknown. This study aims to determine whether RELiZORB is effective for individuals requiring feeding tube support after pancreatitis.

The purpose of this study is to measure the safety and explore the efficacy of 4 different doses of the new lipase NHS7108 in participants with EPI. In this study, all participants will take NHS7108 daily for 14 days and a matching dose of standard-of-care, pancrelipase (Zenpep®) for 14 days according to Treatment Sequence assignment. Both NHS7108 and Zenpep® are oral capsules that will be taken with each of the daily 3 meals and 2 snacks. Participants will interrupt all of their usual pancrelipase/pancreatin treatment for up to 8 days during screening and for the entire 2 treatment periods, where participants will take either the new lipase NHS7108 or a matching dose of the standard-of-care pancrelipase (Zenpep®). Participants will be asked to stay in a setting that allows controlled diet and 72-hour stool collection for approximately 7 days during the screening period and again for approximately 7 days at the end of each treatment period. During these 3 supervised periods, participants will receive a standardized diet with a predefined amount of fat and protein, stools will be collected in special containers and during the last day of the treatment period, blood samples will be obtained to measure fat absorption. These are essential to ensure valid assessment of participants' fat and protein absorption. Outside the 3 supervised periods, participants will be provided with guidelines and recommendations to create their own home-controlled meals and snacks according to their preferences for the remainder of the study duration. Number of Participants: The aim is to have 56 participants completing the study. Assuming approximately 14% drop-out rate, approximately 66 participants will be randomized to study intervention. Study Arms and Duration: The total study duration for each participant will be about 100 days (approximately 14 weeks), including: * A screening period of up to approximately 28 days (might be extended up to a total of 56 days) prior to the first dose administration. * A crossover treatment period (2 treatment periods: approximately 14 days each, with no washout in between). For each treatment period, study intervention will be administered 5 times a day (with 3 main meals and 2 snacks). After completion of Treatment Period 1, the participant will receive and start the new treatment for Treatment Period 2. * An end of treatment/early discontinuation visit within approximately 7 days of the last study intervention dose. * An end-of-study safety follow-up visit at 14 (±2) days after the last dose administration. Very low dose group: 10 mg NHS7108 (approximately 25,000 LU)/main meal and snack; 25,000 LU Zenpep/main meal and snack (50 mg NHS7108 \[approximately 125,000 LU\] per day; 125,000 LU Zenpep per day) Low dose group: 20 mg NHS7108 (approximately 50,000 LU)/main meal and 10 mg NHS7108 (approximately 25,000 LU)/snack; 50,000 LU Zenpep/main meal and 25,000 LU Zenpep/snack (80 mg NHS7108 \[approximately 200,000 LU\] per day; 200,000 LU Zenpep per day) Medium dose group: 40 mg NHS7108 (approximately 100,000 LU)/main meal and 20 mg (approximately 50,000 LU) NHS7108/snack; 100,000 LU Zenpep/main meal and 50,000 LU Zenpep/snack (160 mg \[approximately 400,000 LU\] NHS7108 per day; 400,000 LU Zenpep per day) High dose group: 60 mg NHS7108 (approximately 150,000 LU)/main meal and 30 mg NHS7108 (approximately 75,000 LU)/snack; 150,000 LU Zenpep/main meal and 75,000 LU Zenpep/snack (240 mg NHS7108 \[approximately 600,000 LU\] per day; 600,000 LU Zenpep per day). The dose for participants \< 60 kg who are assigned to the high dose group will need to be weight-adjusted to ensure that they receive no more than 10,000 LU/kg/day.

The goal of this observational study is to better understand how the pancreas works in adults with type 2 diabetes. The study focuses on both hormone production (endocrine function) and digestive function (exocrine function) of the pancreas. The main questions it aims to answer are: * Can problems with the pancreas help identify a different type of diabetes called pancreatogenic diabetes? * How are blood markers and pancreas structure related to pancreatic function? Participants will: * Have blood tests to measure glucose, insulin, and other markers * Provide a stool sample to assess digestive function * Undergo an ultrasound examination of the pancreas * Answer questions about digestive symptoms The study will take place during a single visit in outpatient clinics.