Rifapentine-containing treatment shortening regimens for pulmonary tuberculosis:

INTERVENTION: Trade Name: Priftin Product Name: RIFAPENTINE Pharmaceutical Form: Tablet INN or Proposed INN: RIFAPENTINE CAS Number: 61379‐65‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150‐ Trade Name: Rifadin Product Name: Rifampicin Pharmaceutical Form: Capsule INN or Proposed INN: RIFAMPICIN CAS Number: 13292‐46‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ Trade Name: Moxifloxacin 400mg Film‐coated Tablets Product Name: Moxifloxacin Pharmaceutical Form: Tablet INN or Proposed INN: MOXIFLOXACIN Other descriptive name: MOXIFLOXACIN Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 400‐ Trade Name: Myambutol Product Name: Ethambutol Pharmaceutical Form: Tablet INN or Proposed INN: ETHAMBUTOL CAS Number: 74‐55‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 400‐ Trade Name: Nicotibine Product Name: Isoniazide Pharmaceutical Form: Tablet INN or Proposed INN: ISONIAZID CAS Number: 54‐85‐3 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ Trade Name: Pyrafat Product Name: Pyrazinamide Pharmaceutical Form: Tablet INN or Proposed INN: PYRAZINAMIDE CAS Number: 98‐96‐4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 500‐ CONDITION: Pulmonary tuberculosis Therapeutic area: Diseases [C] ‐ Respiratory Tract Diseases [C08] PRIMARY OUTCOME: Main Objective: ? To evaluate the efficacy of a rifapentine‐containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug‐susceptible pulmonary tuberculosis; ? To evaluate the efficacy of a rifapentine‐containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug‐susceptible pulmonary tuberculosis Primary end point(s): ? Efficacy: TB disease‐free survival at twelve months after study treatment assignment. ; ? Safety: Proportion of participants with grade 3 or higher adverse events during study drug treatment Secondary Objective: ? To evaluate the safety of the investigational regimens; ? To evaluate the tolerability of the investigational regimens ; ? To collect and assess biospecimens from consenting participants for the purpose of research on discovery and validation of TB biomarkers; ? To determine the correlation of mycobacterial and clinical markers with time to culture conversion, culture status at completion of eight weeks of treatment, treatment failure, and relapse.; ? To conduct a pharmacokinetic/pharmacodynamic (PK/PD) study of the test drugs. The main objectives of the PK/PD study are to characterize study drug PK parameters and to determine relationships between treatment outcomes and PK parameters. ; ? To evaluate the pharmacokinetics of efavirenz‐based antiretroviral treatment among patients with TB/HIV co‐infection taking efavirenz‐based combination antiretroviral therapy and TB treatment with rifapentine Timepoint(s) of evaluation of this end point: Twelve months after study treatment SECONDARY OUTCOME: Secondary end point(s): ? TB disease‐free survival at eighteen months after study treatment assignment; ? Time to stable sputum culture conversion (solid and liquid media considered separately); ? Speed of decline of sputum viable bacilli by automated liquid MGIT culture days to detection; ? Proportion of participants who are culture negative at completion of eight weeks of treatment (solid and liquid media considered separately); ? Sensitivity analyses assuming all participants classified as ?not assessable? have a favorable outcome; ? Discontinuation of assigned treatment for a reason other than microbiological ineligibility; ? Estimated steady state efavirenz PK parameters including mid‐dosing interval concentration Timepoint(s) of evaluation of this end point: Eighteen months after study treatment INCLUSION CRITERIA: A. Suspected pulmonary tuberculosis plus one or both of the following: a) at least one sputum specimen positive for acid‐fast bacilli on smear microscopy OR b) at least one sputum specimen positive for M. tuberculosis by Xpert MTB/RIF testing, with semiquantitative result of ?medium? or ?high? and rifamycin resistance not detected. B. Age twelve (12) years or older C. A verifiable address or residence location that is readily accessible for visiting, and willingness to inform the study team of any change of address during the treatment and follow‐up period. D. Women of child‐bearing potential who are not surgically sterilized must agree to practice an adequate method of contraception (barrier method or non‐hormonal intrauterine device) or abstain from heterosexual intercourse during study drug treatment. E. Documentation of HIV infection status. F. For HIV‐positive individuals, CD4 T cell count greater than or equal to 100 cells/mm3 based on t