Intervention: Moxifloxacin
Trial phase: Phase 1 | Phase 2
ATC code: J01MA14 | S01AE07
SMILES: [H][C@@]12CCCN[C@]1([H])CN(c1c(F)cc3c(=O)c(C(=O)O)cn(C4CC4)c3c1OC)C2
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 98
Group description: A Moxifloxacin-containing oral regimen of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Moxifloxacin (M), substituting Moxifloxacin for Ethambutol.

The intervention arm substituted moxifloxacin for ethambutol (moxifloxacin group), and consisted of daily doses of moxifloxacin, rifampicin, isoniazid and pyrazinamide for 8 weeks, followed by daily doses of moxifloxacin, rifampicin and isoniazid for 16 weeks.

Participants in the moxifloxacin arm received daily 400 mg of moxifloxacin (Avelox®, Bayer Healthcare), weight-based rifampicin at 450 or 600 mg, and 225 or 300 mg of isoniazid, for participants 38-54 and ≥55 kg, respectively, during the 2-month intensive phase and 4-month continuation phase of TB treatment. During the intensive phase of treatment, pyrazinamide was used at 1500 and 2000mg in participants between 38-54 and ≥55 kg, respectively.
Eligibility criteria:
Inclusion Criteria:

Adults ≥ 18 years of age
Previous history of anti-TB chemotherapy
HIV status: HIV infected and uninfected patients are allowed in the study:
All patients must agree to HIV testing to confirm HIV status.
Patients already on ARVs will be allowed in the study provided that the ART regimen is not contraindicated with any of the study agents .
HIV infected patients at any CD4 count irrespective of ART commencement and duration will be included in the study
Smear positive or Gene Xpert positive pulmonary tuberculosis
Rifampicin susceptible as determined by Gene Xpert at screening. Gene Xpert will be used to determine rifampicin resistance, hence the study team will made aware of resistance within 48 hours and prior to study enrolment.
Karnofsky score greater than 70
Female candidates of reproductive potential must agree to use two reliable methods of contraception while on study: a barrier method of contraception (condoms or cervical cap) together with another reliable form of contraceptive (condoms with a spermicidal agent, a diaphragm or cervical cap with spermicide, an Intrauterine Device (IUD), or hormone-based contraceptive)
A negative pregnancy test

Laboratory parameters done at, or 14 days prior to, screening:

Haemoglobin level of at least 7.0 g/dL
Serum aspartate transaminase (AST) and alanine transaminase (ALT) activity less than 3 times the upper limit of normal
Serum total bilirubin level less than 2.5 times upper limit of normal
Creatinine clearance (CrCl) level greater than 60 mls/min
Platelet count of at least 50 x109cells/L
Serum potassium greater than 3.0 mmol/L

Exclusion Criteria:

Patients on a Nevirapine (NVP)-containing ART regimen at screening
Pregnant or breastfeeding
Received an antibiotic active against M. tuberculosis in the last 14 days (e.g. fluoroquinolones, macrolides, standard anti-tuberculosis drugs).
Patients with known M. tuberculosis resistance to any of the study drugs at screening
History of prolonged QT syndrome or current or planned therapy with quinidine, procainamide, amiodarone, sotalol, or ziprasidone during the intensive phase of tuberculosis treatment.
Known allergies or intolerance to any of the study drugs.