Evaluation of Prednisone Efficacy and Safety in Patients with Idiosyncratic Hepatotoxicity: A Phase II Clinical Trial

The primary objective of this study is to evaluate the efficacy and safety of **prednisone** in the treatment of idiosyncratic **hepatotoxicity**. Specifically, the study aims to determine if oral prednisone, compared to placebo, administered over five weeks, is beneficial in terms of decreasing total bilirubin (TBL) levels. This is measured by a reduction of the peak TBL by at least 50% at 14 days or a reduction in the time to normalization of TBL values. Additionally, the study seeks to assess the safety and tolerability of prednisone in patients with acute moderate to severe drug-induced liver injury (DILI). The clinical relevance of this objective lies in potentially providing a therapeutic option for managing hepatotoxicity, which can lead to significant liver damage and complications.

Secondary objectives include: - Assessing if oral prednisone reduces peak alanine aminotransferase (ALT), aspartate aminotransferase (AST), and international normalized ratio (INR) values by at least 50% at day 7 or reduces the time to normalization. - Evaluating whether prednisone decreases the proportion of patients progressing to acute liver failure. - Investigating changes in health-related quality of life with prednisone treatment compared to placebo.

The clinical trial focuses on evaluating the effects of oral prednisone in patients with **hepatotoxicity**. The study population includes both female and male participants aged 18 years and older. Participants are required to have been diagnosed with drug-induced liver injury (DILI) by an expert committee, with moderate to severe DILI characterized by elevations of ALT or AST levels at least five times the upper limit of normal (ULN) and serum total bilirubin (TBL) levels of at least 2.5 mg/dL. Additionally, participants must not show a 15% reduction in ALT values or must have increasing TBL levels 5-10 days after the recognition of liver damage despite the withdrawal of the offending drug. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **efficacy** and safety of **prednisone** in the treatment of **hepatotoxicity**. This is a randomized, double-blind, placebo-controlled trial, conducted over a period of five weeks. The trial involves the administration of oral prednisone, with a maximum daily dose of 40 mg and a total dose not exceeding 60 mg, compared to a placebo. The primary objective is to assess the reduction in total bilirubin (TBL) levels by at least 50% at 14 days or the time to normalization of TBL values. Secondary objectives include evaluating changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and international normalized ratio (INR) levels, as well as quality of life scores.

Participants will be involved in the study for a total of five weeks, with the trial expected to conclude by June 2027. The study includes several key visits: an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and efficacy, and a final end-of-study visit to assess overall outcomes. Inclusion criteria require participants to be adults aged 18 years or older, diagnosed with drug-induced liver injury (DILI) with moderate to severe symptoms, and not showing improvement after withdrawal of the causative drug. Exclusion criteria are not specified in the provided data.

Participants may be withdrawn from the study if they experience adverse events (AEs) or serious adverse events (SAEs) that necessitate premature termination. The primary endpoints focus on the proportion of patients achieving significant reductions in TBL and the time to normalization of TBL values. Secondary endpoints include the proportion of patients with significant reductions in ALT, AST, and INR, as well as the incidence of acute liver failure or the need for liver transplantation. The trial aims to provide comprehensive data on the safety and therapeutic potential of prednisone in managing hepatotoxicity.

The clinical trial involves the administration of **PREDNISONE**, marketed under the name Decortin 5 mg tablete, as the experimental medication. This pharmaceutical is presented in the form of a tablet and is administered orally. The dosage regimen includes a maximum daily dose of 40 mg, with a total maximum dose of 60 mg over the treatment period. The treatment duration is set for a maximum of five weeks. The primary objective is to evaluate the efficacy and safety of prednisone in the treatment of idiosyncratic hepatotoxicity. The study aims to determine if prednisone can reduce the peak of total bilirubin levels by at least 50% at 14 days or decrease the time to normalization of total bilirubin values. Participant compliance will be monitored throughout the study to ensure adherence to the dosing schedule.

In addition to the experimental treatment, a **PLACEBO** is utilized as a comparator in this study. The placebo is also administered in tablet form and taken orally, mirroring the administration route and schedule of the experimental medication. The placebo serves as a control to assess the true efficacy and safety profile of prednisone by providing a baseline for comparison. The use of a placebo is critical in determining the actual therapeutic benefit of the experimental treatment, as it helps to eliminate bias and placebo effects in the study outcomes.

**MICROCRYSTALLINE CELLULOSE** is included as an inactive ingredient in the formulation of the placebo tablets. It is a chemically derived substance used to mimic the appearance and administration characteristics of the active treatment, ensuring blinding in the study. The inclusion of microcrystalline cellulose ensures that the placebo tablets are indistinguishable from the active treatment tablets, maintaining the integrity of the double-blind study design. The administration of the placebo follows the same dosing schedule as the active treatment, with a maximum daily dose of 40 mg and a total maximum dose of 60 mg over the five-week treatment period.

The efficacy of prednisone in the treatment of **idiosyncratic hepatotoxicity** will be assessed through a series of primary and secondary endpoints. The primary endpoints include the proportion of patients achieving a decrease of at least 50% in the peak value of total bilirubin (TBL) by day 14, the time taken for TBL values to return to normal, and the proportion of adverse events (AEs), serious adverse events (SAEs), fatalities, and premature terminations due to AEs. Secondary endpoints will evaluate the proportion of patients achieving a decrease of at least 50% in the peak values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and international normalized ratio (INR) by day 7, the time for these values to return to normal, and the proportion of patients developing acute liver failure, requiring liver transplantation, or experiencing liver-related death by day 28. Additionally, changes in scores from the SF-36 quality of life questionnaire will be assessed at the start of treatment (day 1) and at the end of treatment (day 35).

Measurements will be collected at specified time points, including day 7, day 14, and day 28, with the SF-36 questionnaire administered at visit 1 and visit 6. The analysis will involve comparing the outcomes between the prednisone and placebo groups to determine the efficacy of prednisone in reducing TBL and other liver function markers. The trial will ensure rigorous data collection and analysis to provide reliable results on the efficacy and safety of prednisone in this patient population.