Early Bactericidal Activity (EBA) Study of Tuberculosis Regimens With and Without INH and Moxifloxacin

Inclusion Criteria:

• Absence of HIV-1 infection within 30 days prior to study entry OR
• HIV-1 infection
• Confirmed sputum positive for acid fast bacilli (AFB) by smear-microscopy ≥1+ within 1 day prior to study entry.
• Body weight: 40 kg to 90 kg, inclusive
• Age ≥ 18 years at study entry.
• Certain laboratory values, as defined in section 4.1.5 in the protocol, obtained within 30 days prior to entry
• For HIV-positive candidates only: CD4+ cell count of > 100 cells/mm3, obtained within 7 days prior to study entry at a DAIDS approved laboratory.
• For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to entry.
• Female participants who are participating in sexual activity that could lead to pregnancy must agree to use one reliable non-hormonal form of contraceptive (ie, condoms, with a spermicidal agent; a diaphragm, or cervical cap with spermicide; or an IUD) while receiving study medications.
• If a chest x-ray has not been performed within 14 days prior to entry, or the results of such an x-ray are not available, then a chest x-ray must be performed as part of screening.
• Ability and willingness of subject or legal guardian/representative to provide informed consent.
• Willingness to be hospitalized for approximately 16 days.

Exclusion Criteria:

• Receipt of INH prophylaxis or tuberculosis therapy for more than 7 cumulative days in the last 6 months, or of any fluoroquinolone in the 1 month prior to entry.
• Currently or within 30 days on anti-retroviral treatment (ART) or expected to initiate ART within 2 weeks after study entry.
• Breastfeeding.
• Known intolerance to any of the study drugs.
• Resistance to rifampicin determined by GeneXpert within 7 days prior to study entry.
• Known history of resistance to isoniazid or rifampin or known close exposure (i.e., household exposure) to someone with MDR TB or known study candidate default on previous TB treatment (ie, the study candidate was diagnosed with TB, started TB treatment but did not complete that treatment).
• Known allergy to any fluoroquinolone antibiotic.
• History of prolonged QT syndrome or a QTc of > 450 ms.
• Current or planned therapy with quinidine, procainamide, amiodarone, sotalol, or ziprasidone during the first 2 months of tuberculosis treatment.
• Current or prior diagnosis of pulmonary silicosis.
• Advanced disease as defined by Karnofsky score ≤ 70 at entry.

• Any of the following current comorbidities, complications, or underlying medical conditions:

  • poorly controlled diabetes (definition: patients with random plasma glucose > 180 mg/dL within 2 days prior to study entry)
  • uncontrolled hypertension (definition: requiring acute medical treatment or immediate hospitalization)
  • miliary TB
  • neurological TB (including TB of the spine, TB meningitis)
  • peripheral neuropathy ≥ Grade 2 according to the December 2004 (Clarification, August 2009) Division of AIDS (DAIDS) Toxicity Table, within 90 days prior to study entry
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Estimated overnight sputum production of < 10 mL.
• Requirement for concomitant medications that may potentially interact with study drugs.