Evaluation of Early Bactericidal Activity and Safety in Pulmonary Tuberculosis With WX-081
Evaluation of Early Bactericidal Activity and Safety in Pulmonary Tuberculosis With WX-081
This is a multi-center, randomized, parallel, open-label, positive-controlled Phase 2
 clinical trial, which aims to evaluate the early bactericidal activity, safety and
 tolerability of WX-081 in patients with drug-naive&susceptible and drug-resistant
 tuberculosis. Also the efficacy of WX-081 will be explored in participants with
 drug-resistant tuberculosis.
This is a Phase 2, multi-center, randomized, parallel, open-label, positive-controlled
 clinical trial. The objective of this trial is to evaluate the early bactericidal activity,
 safety and tolerability of WX-081 patients with drug-naive&susceptible and drug-resistant
 tuberculosis. and the efficacy in participants with drug-resistant tuberculosis.

 This trial will be divided into core research stage (stage 1) and extended research stage
 (stage 2). During stage 1, a panel of 44 participants with drug-naive&susceptible
 tuberculosis will be randomized to receive either WX-081(including 3 groups:150mg qd, 300mg
 qd, 450mg qd. n=12 per group) or standard treatment (n=8) for 2 weeks, and then followed by a
 follow-up period of 2 weeks. A panel of 40 participants with drug-resistant tuberculosis will
 be randomized to receive either WX-081 (400mg qd, n=20) or bedaquiline (400mg qd, n=20) for 2
 weeks. During stage 2, the 40 participants with drug-resistant tuberculosis will receive
 WX-081(150mg qd) + MBT treatment (ie. multi-drug background treatment) and bedaquiline (200mg
 tiw) +MBT treatment for 6 weeks respectively, and then followed by a follow-up period of 4
 weeks.
Inclusion Criteria:

 1. Male or female, aged between 18 and 65 years.

 2. Body weight between 40 and 90 kg.

 3. Newly-treated drug sensitivity tuberculosis: clinically diagnosed as pulmonary
 tuberculosis, without treatment, sputum smear-positive for acid-fast bacilli (AFB at
 least 1+), and no resistant to rifampicin or isoniazid in the drug sensitivity test.

 4. Drug-resistant tuberculosis: re-treatment pulmonary tuberculosis patients, diagnosed
 as rifampicin resistance (RR-TB) or isoniazid and rifampicin resistance (MDR-TB) by
 molecular biology methods, and sputum smear-positive for acid-fast bacilli. Patients
 must be willing to discontinue all TB drugs to allow 7 days washout.

 5. Patients must consent to HIV-testing, or provide HIV-negative report within 6 months.

 6. Women are not breastfeeding or pregnant, and agree to practice effective contraception
 throughout the trial.

 7. Provide voluntary and written informed consent prior to all trial-related procedures,
 agree to comply with the requirements and restrictions listed in the informed consent
 form and agreement.

 Exclusion Criteria:

 1. Patients with HIV infection.

 2. Patients with miliary tuberculosis or extrapulmonary tuberculosis judged by the
 investigator.

 3. Patients with certain QT/QTc interval characteristics as described in the protocol.

 4. the patients have a history of, or current evidence of clinically relevant unstable or
 severe cardiovascular, kidney, liver, blood, tumor, endocrine and metabolic, mental or
 rheumatic diseases, or any other condition that will not be suitable to participate in
 this study, according to the judgement of the investigator.

 5. Patients who have participated in other clinical studies within 8 weeks prior to trial
 start.

 6. Patients having a known or suspected hypersensitivity or serious adverse reaction to
 drugs used in this trial.

 7. Women who are pregnant, breastfeeding, or planning to become pregnant.

 8. Current or past history of alcohol and/or drug use that, in the investigator's
 opinion, would compromise the participant's safety or compliance to the study protocol
 procedures.