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, 16 (7), e1002851
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Accelerating the Transition of New Tuberculosis Drug Combinations From Phase II to Phase III Trials: New Technologies and Innovative Designs

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Accelerating the Transition of New Tuberculosis Drug Combinations From Phase II to Phase III Trials: New Technologies and Innovative Designs

Geraint Davies et al. PLoS Med.

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
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
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.

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References

    1. Lienhardt C, Nahid P, Rich ML, Bansbach C, Kendall EA, Churchyard G, González-Angulo L, D'Ambrosio L, Migliori GB, Raviglione M. Target regimen profiles for treatment of tuberculosis: a WHO document. Eur Respir J. 2017;49:pii: 1602352 10.1183/13993003.02352-2016 - DOI - PMC - PubMed
    1. Lienhardt C, Nahid P. Advances in clinical trial design for development of new TB treatments: A call for innovation. PLoS Med. 2019; 16(3): e1002769 10.1371/journal.pmed.1002769 - DOI - PMC - PubMed
    1. Jindani A, Aber V, Edwards E, Mitchison D. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am Rev Respir Dis. 1980;121:939–49. 10.1164/arrd.1980.121.6.939 - DOI - PubMed
    1. Donald P, Sirgel F, Venter A, Parkin D, Seifart H, Wal B van de, et al. Early bactericidal activity of antituberculosis agents. Expert Rev Anti-Infect Ther. 2003;1(1):141–55. - PubMed
    1. Diacon AH, Dawson R, von Groote-Bidlingmaier F, Symons G, Venter A, Donald PR, et al. Bactericidal activity of pyrazinamide and clofazimine alone and in combinations with pretomanid and bedaquiline. Am J Respir Crit Care Med. 2015;191(8):943–53. 10.1164/rccm.201410-1801OC - DOI - PubMed

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Grant support

The authors received no specific funding for this work.
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