Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis
LMU Univ Hosp Munich, Div Infect Dis & Trop Med, Munich, Germany.;German Ctr Infect Res DZ, Munich Partner Site, Munich, Germany..
LMU Univ Hosp Munich, Div Infect Dis & Trop Med, Munich, Germany.;German Ctr Infect Res DZ, Munich Partner Site, Munich, Germany..
LMU Univ Hosp Munich, Div Infect Dis & Trop Med, Munich, Germany.;German Ctr Infect Res DZ, Munich Partner Site, Munich, Germany..
LMU Univ Hosp Munich, Div Infect Dis & Trop Med, Munich, Germany.;German Ctr Infect Res DZ, Munich Partner Site, Munich, Germany..
Show others and affiliations
2023 (English)In: Trials, E-ISSN 1745-6215, Vol. 24, no 1, article id 382Article in journal (Refereed) Published
Abstract [en]

Background: Linezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure-response and exposure-toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin.

Methods: Seventy-five participants with drug-sensitive, pulmonary tuberculosis will receive bedaquiline, delamanid and moxifloxacin, and will be randomized to delpazolid dosages of 0 mg, 400 mg, 800 mg, 1200 mg once daily, or 800 mg twice daily, for 16 weeks. The primary efficacy endpoint will be the rate of decline of bacterial load on treatment, measured by MGIT liquid culture time to detection from weekly sputum cultures. The primary safety endpoint will be the proportion of oxazolidinone class toxicities; neuropathy, myelosuppression, or tyramine pressor response. Participants who convert to negative liquid media culture by week 8 will stop treatment after the end of their 16-week course and will be observed for relapse until week 52. Participants who do not convert to negative culture will receive continuation phase treatment with rifampicin and isoniazid to complete a six-month treatment course.

Discussion: DECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages.

Place, publisher, year, edition, pages
BMC , 2023. Vol. 24, no 1, article id 382
Keywords [en]
Uncomplicated pulmonary tuberculosis, Treatment, Delpazolid, Randomized controlled trial, Phase IIb, Oxazolidinone
National Category
Pharmaceutical Sciences Pharmacology and Toxicology Infectious Medicine
Identifiers
URN: urn:nbn:se:uu:diva-507004DOI: 10.1186/s13063-023-07354-5ISI: 001003653200003PubMedID: 37280643OAI: oai:DiVA.org:uu-507004DiVA, id: diva2:1778617
Available from: 2023-07-03 Created: 2023-07-03 Last updated: 2024-01-17Bibliographically approved

Open Access in DiVA

fulltext(1733 kB)115 downloads
File information
File name FULLTEXT01.pdfFile size 1733 kBChecksum SHA-512
a038e77b663622ff9760fa7a8b0b789fe2e0f7979b9cd1a3679c3bb6e26bed3055681d63083d8a940b3873373549f77034000985cfb18f54835b5ab3d98becdf
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records

Svensson, Elin

Search in DiVA

By author/editor
Svensson, Elin
By organisation
Department of Pharmaceutical BiosciencesDepartment of Pharmacy
In the same journal
Trials
Pharmaceutical SciencesPharmacology and ToxicologyInfectious Medicine

Search outside of DiVA

GoogleGoogle Scholar
Total: 115 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 115 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf