Diacon AH, Dawson R, Hanekom M, Narunsky K, Venter A, Hittel N, Geiter LJ, Wells CD, Paccaly AJ, Donald PR. Early bactericidal activity of delamanid (OPC-67683) in smear-positive pulmonary tuberculosis patients. Int J Tuberc Lung Dis. 2011 Jul;15(7):949-54.
This week, we review a recent article published in the July issue of IJTLD on the TB drug candidate OPC-67683 whose new generic name is delamanid. Diacon, et al., present data showing that delamanid is safe, well-tolerated with significant early bactericidal activity.
The results reported are from the Phase IIa Early Bactericidal Activity (EBA) study which evaluates a drug candidates short-term potency when given as a single drug and at different doses. These studies are now generally 14-days and look at the log reduction of colony forming units (CFU) of M. tuberculosis in sputum collections from patients.
Highlights from the article are:
- 54 patients were randomized with 96% completing study treatment. The two patients that did not complete treatment were withdrawn on day one of treatment due to protocol violation and insufficient sputum production.
- 4 doses were evaluated: 100 mg, 200 mg, 300 mg, 400 mg. For first 2 days averaging all dosages, the EBA was similar to rifabutin, streptomycin and amikacin; higher than pyrazinamide; and lower than isoniazid, ethambutol, linezolid, rifampin and rifapentine. A greater proportion of patients achieved a reduction in CFU of ≥0.9 log10 in the 200 mg and 300 mg treatment arms compared to 100 mg.
- The was no apparent dose response with plasma concentrations plateauing at 300 mg. It was noted that delamanid is poorly soluble in water and has limited absorption at higher dosages.
- Results were optimistic and delamanid is currently undergoing evaluation in MDR-TB patients.
Additional TB R&D News Updates: