Evaluation of Safety and Tolerability of Optimized Rifampicin Dosing in Tuberculosis Patients

The primary objective of this study is to assess the **safety** of a higher dose of **rifampicin** by evaluating the incidence of hepatotoxicity compared between treatment arms at the end of the 6-month treatment period. This is clinically relevant as it aims to determine the safety profile of an optimized dose of rifampicin in patients with **tuberculosis**, potentially influencing treatment protocols and improving patient outcomes.

Secondary objectives include:

• Determining the proportion of adverse events overall and graded by severity, assessed to be related or probably related to rifampicin during the 6-month treatment, compared between treatment arms.
• Evaluating the final treatment outcome at the end of treatment according to WHO definitions of cure, compared between treatment arms.
• Assessing the two and three months culture conversion rates, compared between treatment arms.
• Determining the steady-state plasma pharmacokinetic parameters, compared between treatment arms.

The clinical trial involves participants diagnosed with **tuberculosis**, specifically focusing on assessing the safety of a higher dose of rifampicin. The study population includes both male and female subjects aged 18 years and older. Participants are required to have no known allergic reactions or toxicity to rifampicin and must provide informed consent prior to any trial-related procedures. Female participants of childbearing potential must have a negative serum pregnancy test and agree to use effective birth control methods during the study. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are expected to comply with the study schedule, and for those in France, affiliation with a social security system or state medical aid is necessary. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **safety** and tolerability of an optimized dose of **rifampicin** in patients diagnosed with **tuberculosis**. This is a Phase III, randomized, double-blind, controlled trial. The primary endpoint is to assess the incidence of hepatotoxicity between treatment arms over a six-month treatment period. Secondary endpoints include the proportion of adverse events related to rifampicin, final treatment outcomes according to WHO definitions, culture conversion rates at two and three months, and steady-state plasma pharmacokinetic parameters.

Participants will be involved in the study for a maximum of six months, with the trial estimated to conclude by December 31, 2025. The study will commence recruitment on December 1, 2023. The trial includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. Inclusion criteria require participants to be 18 years or older, have a confirmed diagnosis of pulmonary tuberculosis, and provide informed consent. Female participants of childbearing potential must have a negative pregnancy test and agree to use effective contraception. Exclusion criteria include known allergies or toxicity to rifampicin.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The trial will be conducted in accordance with ethical standards and regulatory requirements, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of **Rifampicin**, a chemical compound known for its antibiotic properties, primarily used in the treatment of tuberculosis. The pharmaceutical form of Rifampicin utilized in this study is coded as PHF00170MIG. The medication is administered orally, with a maximum daily dose of 1800 mg. The total maximum dose over the treatment period is 340.2 grams. The treatment duration is set for a maximum of six months. The study aims to evaluate the safety and tolerability of an optimized dose of Rifampicin, with a particular focus on the incidence of hepatotoxicity as the primary endpoint.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The study is designed to assess the effects of the experimental medication alone. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial's objective is to provide insights into the safety profile of a higher dose of Rifampicin in patients with tuberculosis, contributing to the optimization of treatment protocols.

Efficacy in the clinical trial will be assessed through several key endpoints. The primary endpoint is the incidence of **hepatotoxicity**, which will be compared between treatment arms at the end of the 6-month treatment period. Secondary endpoints include the proportion of adverse events overall, graded by severity, and assessed to be related or probably related to **rifampicin**. Additionally, the final treatment outcome will be evaluated at the end of treatment according to WHO definitions of cure. Culture conversion rates at two and three months will also be measured, alongside steady-state plasma pharmacokinetic parameters.