Safety and Drug Level Study of Isoniazid Inhalation by Wet Nebulization in Adults with Tuberculosis

What this Trial Is About

Researchers are investigating the safety and drug levels of inhaled isoniazid INH delivered by wet nebulization in adults with tuberculosis TB. The study focuses on patients with known drug susceptibility and aims to assess local lung tolerability and systemic drug levels. The rationale is that inhaled INH may offer higher concentrations at the infection site with lower systemic exposure, potentially improving treatment especially for drug-resistant TB, which remains a global health challenge. Participants will receive one intravenous dose of 300 mg INH and three ascending inhaled doses of INH 200 mg, 600 mg, and 1200 mg using an eFlow nebulizer. Each dose is separated by 48 hours to 7 days. Lung function tests and blood samples for pharmacokinetic analysis will be collected before and after each dose. The study team will monitor for adverse events and lung function changes to decide on dose escalation. Participants will be monitored closely during the study through spirometry tests, blood draws, and adverse event recording. The main outcomes include local tolerability assessed by lung function and adverse events, and systemic pharmacokinetics measured by serum drug levels. The study requires 8 adult patients with tuberculosis and known drug susceptibility, and participation involves replacement of usual INH treatment by levofloxacin during the study period for some. Total participation time covers the dosing and observation periods up to 25 hours after each dose.

A Phase I Study Investigating the Local Tolerability and Pharmacokinetics of Isoniazid (INH) Inhalation by Wet Nebulization in Patients With Tuberculosis