Evaluation of Pancreatic Enzyme Replacement Therapy with Pancreas Powder in Pancreatic Exocrine Insufficiency Post-Pancreatectomy

The primary objective of this study is to investigate the percentage of patients with **Pancreatic Exocrine Insufficiency (PEI)**, following pancreatic surgery, who require doses of Pancreatic Enzyme Replacement Therapy (PERT) higher than 70,000 units per main meal. This is clinically relevant as it helps determine the appropriate dosing of PERT, specifically Creon® 35,000, to manage PEI effectively, ensuring optimal digestion and nutrient absorption in affected patients.

Secondary objectives include observing the effect of different doses of Creon on disease-related PEI symptoms, nutritional parameters, and diabetes parameters over time. These observations are crucial for understanding the broader impact of PERT on patient health and quality of life, as well as for optimizing treatment regimens.

The clinical trial involves **male and female** participants aged between 18 and 85 years who have undergone a total pancreatectomy and are experiencing **Pancreatic Exocrine Insufficiency (PEI)**. The sponsor has not provided the total number of participants. The study population includes individuals of any ethnic origin, and participants must have had their surgery at least two weeks prior to the study's commencement. Those with a history of pancreatic cancer may be included even if they are receiving adjuvant cancer treatments such as chemotherapy or radiation therapy. Participants are required to exhibit symptoms related to PEI, as evaluated by the investigator, and must be on treatment with Proton Pump Inhibitors. The trial population is characterized by a willingness and ability to comply with the study protocol, including the completion of an electronic diary throughout the study. Participants must provide written informed consent and have an estimated life expectancy consistent with the study duration. The trial includes a vulnerable population, and lifestyle considerations such as diet and physical activity are not specified in the provided data.

The clinical trial is designed as an open-label, multicenter, prospective, interventional study to evaluate the efficacy of **pancreatic enzyme replacement therapy** (PERT) in patients with **pancreatic exocrine insufficiency** (PEI) following pancreatic surgery. The trial will involve adult participants aged 18 to 85 years who have undergone a total pancreatectomy. The primary objective is to determine the percentage of patients requiring doses higher than 70,000 units per main meal. The study will also assess secondary endpoints, including clinical symptoms, nutritional laboratory parameters, and quality of life improvements.

The trial will commence with a screening visit to confirm eligibility based on inclusion criteria, such as previous total pancreatectomy and the presence of PEI symptoms. Participants will be required to provide written informed consent and demonstrate the ability to comply with study requirements, including the use of an electronic diary. The trial will span approximately 196 days, with participants receiving oral administration of the investigational product, Kreon 35,000, in the form of gastro-resistant capsules.

Study visits will be scheduled at regular intervals to monitor treatment efficacy and safety. These visits will include assessments of clinical symptoms, nutritional status, and any adverse events. The end-of-study visit will involve a comprehensive evaluation of the primary and secondary endpoints. Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety.

The trial is expected to conclude by October 2025, with recruitment starting in September 2024. Participants' involvement will last for the duration of the treatment period, with the possibility of early termination based on predefined criteria. The study aims to provide valuable insights into the management of PEI in post-pancreatectomy patients, contributing to the optimization of PERT dosing regimens.

The clinical trial involves the administration of **Kreon 35,000 Ph. Eur. Lipase Einheiten**, a **gastro-resistant capsule, hard** formulation, containing the active substance **pancreas powder**. This experimental medication is designed for **oral use** and is intended to provide pancreatic enzyme replacement therapy (PERT) in patients with pancreatic exocrine insufficiency (PEI) following pancreatic surgery. The maximum daily dose of Kreon 35,000 is 560,000 U units, with a total maximum dose of 104,370,000 U units over the course of the treatment period, which can extend up to 196 days. The primary objective of the study is to assess the percentage of patients requiring doses higher than 70,000 U per main meal. The product is manufactured by Viatris Healthcare GmbH and is not a pediatric formulation.

In addition to the experimental treatment, the study may involve the use of a **mix of enzymes** as a non-experimental treatment. This comparator treatment serves as a standard-of-care therapy to evaluate the efficacy and safety of the experimental medication. The administration of the comparator treatment will follow the same oral route as the experimental medication. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed treatment regimen. The trial is open-label and interventional, allowing for the direct observation of the effects of the treatment on the participants.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the percentage of patients treated with doses higher than the approved final treatment doses of **Pancreatic Enzyme Replacement Therapy (PERT)**, specifically Creon® 35,000, in patients with **Pancreatic Exocrine Insufficiency (PEI)** following pancreatic surgery. Secondary endpoints include a comprehensive evaluation of various parameters: Clinical Global Impression (CGI) as assessed by the investigator, nutritional laboratory parameters, diabetes-related parameters such as glucose and HbA1c levels, and insulin doses. Additionally, clinical symptoms including abdominal pain, flatulence, stool consistency, and stool frequency will be monitored through patient diaries, with a focus on average daily stool frequency during the treatment period.

Further secondary endpoints involve the assessment of Body Mass Index (BMI) and body weight, improvement in Quality of Life (QoL) as measured by the Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q), and changes from baseline to the end of treatment. Vital signs will be evaluated, and the incidence of PERT-related adverse events will be recorded. These efficacy parameters will be collected and analyzed at various timepoints throughout the study, ensuring a thorough assessment of the treatment's impact on the patients' condition.