Evaluation of Patient Acceptability of a New Pancreas Powder Formulation in Cystic Fibrosis Patients with Pancreatic Exocrine Insufficiency

The primary objective of this clinical trial is the evaluation of the **acceptability** of a new CREON formulation containing Pancreas Powder gastro-resistant pellets in patients with cystic fibrosis suffering from pancreatic exocrine insufficiency. This is clinically relevant as it aims to assess patient compliance and satisfaction with the new formulation, which could potentially improve treatment adherence and outcomes in managing pancreatic exocrine insufficiency.

Secondary objectives include:

• Evaluation of lipase dose use per main meal, snack, and over the day, including the number of capsules or new formulation used.
• Assessment of the switch potential from CREON capsules to the new formulation or a combination of capsule and new formulation, including situations eligible for switch.
• Evaluation of clinical symptoms such as stool frequency, stool consistency, abdominal pain, and flatulence.
• Assessment of safety and tolerability, including local tolerability.

The clinical trial involves a total of **60 participants** diagnosed with **cystic fibrosis** and suffering from pancreatic exocrine insufficiency. The study population includes both male and female subjects of any ethnic origin, all of whom are at least 18 years of age. Participants were selected based on their current treatment with Pancreatic Enzyme Replacement Therapy (PERT) using CREON capsules, with a stable dose for at least four weeks prior to the study and satisfactory symptom control. The trial does not include a vulnerable population. Participants are required to comply with the study protocol and provide written informed consent. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that the participants are representative of the target population for evaluating the acceptability of a new CREON formulation containing Pancreas Powder gastro-resistant pellets.

The clinical trial is designed as an open-label, single-arm, multicenter study to evaluate the acceptability of a new formulation of **pancreas powder** gastro-resistant pellets in patients with cystic fibrosis suffering from pancreatic exocrine insufficiency. The trial is categorized as a Phase 3 study, with an estimated recruitment start date of March 31, 2024, and an estimated end date of September 30, 2024. The trial involves the administration of the investigational product, Creon, in various formulations, including modified-release capsules and gastro-resistant granules, all intended for oral use. The primary objective is to assess the acceptability of the new formulation, focusing on aspects such as ease of opening the container, taste, tactile sensation, and overall convenience.

Participants will be involved in the study for a maximum treatment period of 9 weeks, depending on the specific formulation used. The study includes several key visits: an initial screening visit to confirm eligibility, followed by a series of follow-up visits to monitor treatment acceptability and safety. The primary endpoint will be assessed at Visit 3, which occurs on Day 8, where various aspects of treatment acceptability will be evaluated. Secondary endpoints include the assessment of lipase dose usage, clinical symptoms such as stool frequency and consistency, and safety and tolerability, including the incidence of adverse events and oral mucosal irritation.

Inclusion criteria for the study require participants to be at least 18 years of age, have a confirmed diagnosis of cystic fibrosis, and be on a stable dose of pancreatic enzyme replacement therapy with Creon for at least 4 weeks prior to the study. Participants must also provide written informed consent and be willing to comply with the study protocol. Conditions that may lead to early termination from the study include non-compliance with the study protocol or the occurrence of significant adverse events. The trial does not include a control group, and all participants will receive the investigational product. The study aims to provide valuable insights into the acceptability and potential benefits of the new Creon formulation for patients with pancreatic exocrine insufficiency.

The clinical trial involves the administration of several formulations of **Creon**, which contain the active substance **pancreas powder**. The primary experimental medication is "Creon 25.000, harde maagsapresistente capsules 25.000 eenheden," a modified-release hard capsule. This formulation is designed for **oral use** and contains a mix of enzymes, including lipase, protease, and others, classified under the ATC code A09AA02. The maximum daily dose is 10 U/g unit(s)/gram, with a total dose not exceeding 80 U/g unit(s)/gram over a maximum treatment period of 8 weeks. Participant compliance is monitored through regular assessments to ensure adherence to the dosing schedule.

Another formulation used in the trial is "Creon 50000 Ph.Eur. lipase units," which is presented as gastro-resistant granules. This formulation is also administered orally and contains the same active substance, **pancreas powder**. The maximum daily dose is set at 10 U/g unit(s)/gram, with a total dose limit of 90 U/g unit(s)/gram over a 9-week period. The granules are designed to resist gastric acid, ensuring the release of enzymes in the intestine.

The trial also includes "Creon 25000 Ph.Eur. lipase units," "Creon 10000 Ph.Eur. lipase units," and "Creon 75000 Ph.Eur. lipase units," all of which are gastro-resistant granules for oral administration. Each of these formulations shares the same active substance and dosing parameters as the "Creon 50000" formulation, with a maximum daily dose of 10 U/g unit(s)/gram and a total dose limit of 90 U/g unit(s)/gram over 9 weeks. These formulations are intended to provide a range of enzyme concentrations to accommodate varying patient needs.

Additionally, "Creon® 10000 Capsules" is included in the study. This formulation is a standard capsule containing **pancreas powder** and is administered orally. The dosing schedule for this formulation is similar to the modified-release capsules, with a maximum daily dose of 10 U/g unit(s)/gram and a total dose limit of 80 U/g unit(s)/gram over an 8-week period. The capsules are designed to deliver enzymes effectively to the digestive tract.

Throughout the trial, participant compliance is monitored through regular follow-ups and assessments to ensure adherence to the prescribed dosing schedules. The trial aims to evaluate the acceptability and efficacy of these formulations in patients with cystic fibrosis suffering from pancreatic exocrine insufficiency.

The efficacy of the clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint focuses on the **acceptability** of the new CREON formulation containing Pancreas Powder gastro-resistant pellets. This will be evaluated at Visit 3 (Day 8) through various parameters, including the ease of opening the container, emptying the dose, taste, tactile sensation, color, time spent taking the dose, general convenience, ease of swallowing, preparation of the final dose, number of dose units ingested, experience of aftertaste, and feeling of fullness after ingestion.

Secondary endpoints will include the lipase dose used per main meal, snack, and over the day, as well as the number of capsules or new formulation used. Clinical symptoms such as stool frequency per day, stool consistency, abdominal pain, and flatulence will also be monitored. Safety and tolerability will be assessed by the incidence of adverse events, stomatitis, oral mucosal irritation, and local tolerability through inspection of the oral cavity and questions regarding pain in the mouth. These assessments will provide comprehensive data on the efficacy and safety of the new formulation in patients with cystic fibrosis suffering from pancreatic exocrine insufficiency.