PA-824: Phase IIb data

The open-label, South African and Tanzanian Phase IIb NC-002 trial in 181 patients with drug-sensitive TB infection showed that once-daily 200 mg PA-824 in combination with 400 mg moxifloxacin and 1,500 mg pyrazinamide met the primary endpoint of a greater average daily reduction in CFU counts over 8 weeks vs. once-daily Rifafour rifampicin/isoniazid/ethambutol/pyrazinamide (daily log CFU reduction of 0.155 vs. 0.112, p<0.05). In 9 evaluable patients with multidrug-resistant TB (MDR-TB) infection, 200 mg PA-824 plus moxifloxacin and pyrazinamide led to a daily log CFU reduction of 0.117 over 8 weeks. The alliance calls the combination - PA-824, a nitroimidazopyran; moxifloxacin, a fluoroquinolone antibiotic; and pyrazinamide, an off-patent TB drug - the PaMZ TB regimen. A 100 mg dose of PA-824 in combination with 400 mg moxifloxacin and 1,500 mg pyrazinamide missed the primary endpoint vs. Rifafour (daily log CFU reduction of 0.133 vs. 0.112, p=not significant).

In drug-sensitive patients, high-dose PaMZ met the secondary endpoints of reducing median time to conversion to negative growth in solid (28 vs. 35 days) and liquid (49 vs. 56 days) cultures vs. Rifafour. Low-dose PaMZ led to a median time to conversion to negative growth of 28 days in solid culture and of 42 days in liquid culture (p=not significant for both). In MDR-TB patients, median time to conversion to negative growth was 35 days in solid culture and 56 days in liquid culture. ...