A5409/RAD-TB is a Phase 2, randomized, controlled, open-label, dose-ranging adaptive platform protocol to evaluate the safety and efficacy of multidrug regimens for the treatment of adults with drug-susceptible pulmonary tuberculosis (TB). A5409 hypothesizes that novel regimens for the treatment of pulmonary tuberculosis will result in superior early efficacy, as determined by time-to-positivity (TTP) measurements of mycobacterial longitudinal growth indicator tube (MGIT) liquid culture during the first 6 weeks of treatment, and will have acceptable safety and tolerability over 8 weeks of treatment compared to standard treatment [(SOC) isoniazid/rifampicin/pyrazinamide/ethambutol (HRZE)]. The study will last 52 weeks, including 26 weeks of TB treatment consisting of 8 weeks of experimental or SOC treatment (based on treatment arm assignment) followed by 18 weeks of SOC treatment with 45 participants in each experimental treatment arm and at least 90 participants in the SOC arm.