Evidence map›Paper›PMID 39181887›Full record

ArticleNature communications2024

Dose optimization of TBI-223 for enhanced therapeutic benefit compared to linezolid in antituberculosis regimen.

Natasha Strydom, Jacqueline P Ernest, Marjorie Imperial, Belén P Solans, Qianwen Wang, Rokeya Tasneen, Sandeep Tyagi, Heena Soni, Andrew Garcia, Kristina Bigelow and 8 more

5 registry-linked trialsAbstract readComparative StudyClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00396084 phase1 / phase2completednot on this map

Randomized, Open Label, Multiple Dose Phase I Study of the Early Bactericidal Activity of Linezolid, Gatifloxacin, Levofloxacin, and Moxifloxacin in HIV-non-infected Adults With Initial Episodes of Sputum Smear-Positive Pulmonary Tuberculosis

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2004 to 2007Enrolled70ConditionsTuberculosisArmsGatifloxacin, Isoniazid, Levofloxacin, Linezolid, Moxifloxacin
NCT00816426 phase1completednot on this map

Pharmacokinetics of Standard First and Second Line Anti-TB Drugs in the Lung and Lesions of Subjects Elected for Resection Surgery

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2008 to 2017Enrolled19ConditionsTuberculosisArmsRifampicin, Isoniazid, Pyrazinamide, Kanamycin, Moxifloxacin
NCT02333799 phase3completednot on this map

A Phase 3 Open-label Trial Assessing the Safety and Efficacy of Bedaquiline Plus PA-824 Plus Linezolid in Participants With Pulmonary Infection of Either XDR-TB or Treatment Intolerant / Non-responsive MDR-TB.

TypeinterventionalSponsorGlobal Alliance for TB Drug DevelopmentRan2015 to 2020Enrolled109ConditionsPulmonary TuberculosisArmsBedaquiline, PA-824, Linezolid
NCT03086486 phase3completednot on this map

A Phase 3 Partially-blinded, Randomized Trial Assessing the Safety and Efficacy of Various Doses and Treatment Durations of Linezolid Plus Bedaquiline and Pretomanid in Participants With Pulmonary Infection of Either Extensively Drug-resistant Tuberculosis (XDR-TB), Pre-XDR-TB or Treatment Intolerant or Non-responsive Multi-drug Resistant Tuberculosis (MDR-TB)

TypeinterventionalSponsorGlobal Alliance for TB Drug DevelopmentRan2017 to 2022Enrolled181ConditionsTuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Tuberculosis, MDR, TuberculosisArmsPretomanid, Linezolid, Bedaquiline, Placebo Linezolid
NCT03758612 phase1completednot on this map

A Phase 1, Partially-Blinded, Placebo-Controlled, Randomized, Single Ascending Dose (SAD) With a Food Effect Cohort Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBI-223 in Healthy Adult Participants.

TypeinterventionalSponsorGlobal Alliance for TB Drug DevelopmentRan2019 to 2020Enrolled86ConditionsTuberculosis, Tuberculosis, PulmonaryArmsTBI-223 oral suspension, TBI-223 enteric capsule, TBI-223 SR Tablet Prototype 1, TBI-223 SR Tablet Prototype 2, TBI-223 SR Tablet Prototype 3
3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. REVOLUTIONIZING TUBERCULOSIS REGIMEN DEVELOPMENT.Transactions of the American Clinical and Climatological Association · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Natasha StrydomDepartment of Bioengineering and Therapeutic Sciences, Schools of Pharmacy, University of California, San Francisco, CA, USA.ORCID 0000-0002-0929-0783
Jacqueline P ErnestDepartment of Bioengineering and Therapeutic Sciences, Schools of Pharmacy, University of California, San Francisco, CA, USA.
Marjorie ImperialDepartment of Bioengineering and Therapeutic Sciences, Schools of Pharmacy, University of California, San Francisco, CA, USA.
Belén P SolansDepartment of Bioengineering and Therapeutic Sciences, Schools of Pharmacy, University of California, San Francisco, CA, USA.ORCID 0000-0003-4621-5480
Qianwen WangDepartment of Bioengineering and Therapeutic Sciences, Schools of Pharmacy, University of California, San Francisco, CA, USA.
Rokeya TasneenCenter for Tuberculosis Research, Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Sandeep TyagiCenter for Tuberculosis Research, Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Heena SoniCenter for Tuberculosis Research, Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Andrew GarciaCenter for Tuberculosis Research, Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Kristina BigelowCenter for Tuberculosis Research, Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Martin GengenbacherCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.ORCID 0000-0002-0208-5920
Matthew ZimmermanCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.
Min XieCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.ORCID 0000-0002-9770-5351
Jansy P SarathyCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.ORCID 0000-0002-1532-146X
Tian J YangTB Alliance, New York, NY, USA.ORCID 0000-0001-7392-6398
Véronique DartoisCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.ORCID 0000-0001-9470-5009
Eric L NuermbergerCenter for Tuberculosis Research, Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-1440-9889
Radojka M SavicDepartment of Bioengineering and Therapeutic Sciences, Schools of Pharmacy, University of California, San Francisco, CA, USA. rada.savic@ucsf.edu.ORCID 0000-0003-3143-5579

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

TBI-223, a novel oxazolidinone for tuberculosis, is designed to provide improved efficacy and safety compared to linezolid in combination with bedaquiline and pretomanid (BPaL). We aim to optimize the dosing of TBI-223 within the BPaL regimen for enhanced therapeutic outcomes. TBI-223 is investigated in preclinical monotherapy, multidrug therapy, and lesion penetration experiments to describe its efficacy and safety versus linezolid. A translational platform incorporating linezolid and BPaL data from preclinical experiments and 4 clinical trials (NCT00396084, NCT02333799, NCT03086486, NCT00816426) is developed, enabling validation of the framework. TBI-223 preclinical and Phase 1 data (NCT03758612) are applied to the translational framework to predict clinical outcomes and optimize TBI-223 dosing in combination with bedaquiline and pretomanid. Results indicate that daily doses of 1200-2400 mg TBI-223 may achieve efficacy comparable to the BPaL regimen, with >90% of patients predicted to reach culture conversion by two months.

Indexed as

Antitubercular AgentsDiarylquinolinesLinezolidOxazolidinonesAdultAnimalsDose-Response Relationship, DrugDrug Therapy, CombinationFemaleHumansMaleMiceMiddle AgedMycobacterium tuberculosisNitroimidazolesTreatment OutcomeAntitubercular AgentsbedaquilineDiarylquinolinesLinezolidNitroimidazolesOxazolidinonespretomanid

Identifiers

PMID39181887
PMCPMC11344811

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.