Bedaquiline: Phase II data

Researchers at Stellenbosch University and colleagues reported data from the double-blind, South African Phase II NC-001 trial in 85 treatment-naïve, drug-susceptible patients with uncomplicated pulmonary TB infection showing that PA-824 plus moxifloxacin and pyrazinamide led to a significantly higher mean 14-day EBA measured as the rate of daily change in log CFUs in sputum (0.233 log10 CFU/mL of sputum per day), the primary endpoint, vs. bedaquiline alone (0.061 log10 CFU/mL of sputum per day), bedaquiline plus pyrazinamide (0.131 log10 CFU/mL of sputum per day) and bedaquiline plus PA-824 (0.114 log10 CFU/mL of sputum per day) (p<0.001 for all). PA-824 plus moxifloxacin and pyrazinamide was comparable to standard treatment Rifafour rifampicin/isoniazid/ethambutol/pyrimethamine (0.14 log10 CFU/mL of sputum per day) on the endpoint and non-significantly greater than PA-824 plus pyrazinamide (0.154 log10 CFU/mL of sputum per day).

Treatments were well tolerated and appeared safe. There were 7 withdrawals due to adverse events including 5 patients with increased alanine aminotransferase levels in excess of 3 times the upper limit of normal. Additionally, 1 patient receiving PA-824 plus moxifloxacin and pyrazinamide had an increase of >=60 ms in QT intervals on day 5 and 1 patient had an episode of altered consciousness due to newly diagnosed neurocysticercosis. Patients received bedaquiline alone (700 mg on day, 1,500 mg on day 2 and 400 mg on days 3-14); bedaquiline plus pyrazinamide; bedaquiline plus once-daily 200 mg PA-824; PA-824 plus pyrazinamide; PA-824 plus pyrazinamide and once-daily 400 mg moxifloxacin; or Rifafour as an active comparator. Data were published in The Lancet and presented at the International AIDS meeting in Washington. The TB Alliance funded the trial. ...