Evaluation of Atorvastatin in Modulating Bile Acid Synthesis in Patients with Moderate to Severe Bile Acid Diarrhoea: A Dose-Response Study

The primary objective of this study is to evaluate whether **atorvastatin** treatment can reduce the synthesis of bile acids in patients with moderate to severe **bile acid diarrhoea**. This will be assessed by measuring the bile acid synthesis marker C4 in a dose-response manner. Clinically, this is significant as it may offer a therapeutic approach to managing bile acid diarrhoea, a condition characterized by excessive bile acid production leading to chronic diarrhea and associated symptoms.

Secondary objectives include investigating the effects of atorvastatin on symptoms, hepatobiliary markers, metabolic markers, glycaemic control markers, stool samples, and safety in the same patient population. These secondary outcomes will provide a comprehensive understanding of the broader impacts of atorvastatin treatment beyond bile acid synthesis, potentially informing its safety and efficacy profile in managing bile acid diarrhoea.

The clinical trial focuses on patients diagnosed with **bile acid diarrhoea**, specifically those with moderate to severe conditions confirmed by a SeHCAT test result of ≤ 10%. The study population includes both male and female participants, with an age range that encompasses adults and older adults. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on their confirmed diagnosis, and no specific lifestyle considerations such as diet or physical activity were highlighted as part of the selection criteria.

The clinical trial is designed to evaluate the efficacy of **atorvastatin** in reducing bile acid synthesis in patients with moderate to severe **bile acid diarrhoea**. This study is a randomized, double-blind, placebo-controlled trial. Participants will be randomly assigned to receive either atorvastatin or a placebo, administered orally in the form of film-coated tablets. The trial will span an estimated duration from August 2025 to December 2026, with participant involvement lasting up to 10 weeks.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on a SeHCAT test result of ≤ 10%. Following randomization, participants will undergo a series of follow-up visits to monitor the primary endpoint, which is the ratio of geometric mean concentration of 7alpha-Hydroxy-4-cholesten-3-on (C4) at the end of the 80 mg atorvastatin treatment period compared to the placebo period. Secondary endpoints include differences in mean C4 concentration, mean daily stools, and mean daily watery stools, assessed through a 7-day stool diary.

The end-of-study visit will conclude the trial for each participant, assessing the final outcomes and ensuring participant safety. Participants may be withdrawn from the study early if they experience adverse effects, fail to adhere to the study protocol, or withdraw consent. The trial is conducted under strict regulatory guidelines to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **Atorvastatin Viatris 40 mg Filmtabletten**, which is a **film-coated tablet** containing the active substance **atorvastatin**. This medication is administered orally. The maximum daily dose is 80 mg, with a total maximum dose of 4200 mg over the course of the study. The treatment period for atorvastatin is set at a maximum of 10 weeks. The primary objective of the trial is to assess the effect of atorvastatin on bile acid synthesis in patients with moderate to severe bile acid diarrhea. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen.

The study also includes a **placebo** group, where participants receive a **tablet** identical in appearance to the atorvastatin film-coated tablet but without the active substance. The placebo is administered orally, with a maximum treatment period of 4 weeks. The placebo serves as a control to evaluate the efficacy of atorvastatin in reducing bile acid synthesis. Participants' adherence to the placebo regimen will be monitored similarly to those receiving atorvastatin. The use of a placebo is essential to establish a baseline for comparison and to validate the results of the experimental treatment.

Efficacy in the clinical trial titled "Treatment of Bile Acid Diarrhoea with Atorvastatin (BASTA)" will be assessed using both primary and secondary endpoints. The primary endpoint is the ratio of the geometric mean concentration of **7alpha-Hydroxy-4-cholesten-3-on (C4)** at the end of the 80 mg atorvastatin treatment period compared to the end of the placebo treatment period. This endpoint will evaluate the effect of atorvastatin on bile acid synthesis in patients with moderate-severe bile acid diarrhoea.

Secondary endpoints include the difference in mean concentration of **7alpha-Hydroxy-4-cholesten-3-on (C4)** in µg/L at the end of the 80 mg atorvastatin treatment period compared to the end of the placebo treatment period. Additionally, the trial will assess the difference in mean daily stools and mean daily watery stools during the last week of the 80 mg atorvastatin treatment period compared to the last week of the placebo treatment period. These stool-related endpoints will be measured using a 7-day stool diary, with watery stools classified as 6 or 7 on the Bristol Stool Chart.