Accelerating the transition of new tuberculosis drug combinations from Phase II to Phase III trials: New technologies and innovative designs

Abstract

Geraint Davies and colleagues discuss the potential for innovative early-phase clinical trial methods and technologies to reduce risk and speed up drug development for tuberculosis.

Fig 1

Elements of critical pathways for clinical development of TB drugs illustrating selected alternatives: (A) Current standard approach, (B) 14+14 IIA design, (C) Dose-ranging 14+14 IIA design incorporating MAD PK in patients, (D) Phase IIC design, (E) Seamless IIB/III design, and (F) IIC design with no monotherapy (‘Mono’) stage. Combo, combination therapy; DDI, drug–drug interaction study; MAD, multiple ascending dose; PK, pharmacokinetic; SAD, single ascending dose; TB, tuberculosis.

Fig 2. Schematic illustration of alternative bacteriological approaches to measurement of elimination of organisms in respiratory specimens over time in clinical trials of TB.

After conversion of cultures to negative in the first weeks of treatment, subsequent stable cure is defined only by the absence of relapse (return of positive cultures). CFU/MGIT, modelling of colony-forming units or mycobacterial growth indicator tube data; TB, tuberculosis.