Status:

UNKNOWN

PRACTECAL-PKPD Sub Study

Lead Sponsor:

Medecins Sans Frontieres, Netherlands

Collaborating Sponsors:

London School of Hygiene and Tropical Medicine

Global Alliance for TB Drug Development

Conditions:

Multi-drug Resistant Tuberculosis

Extensively Drug-Resistant Tuberculosis

Eligibility:

All Genders

18+ years

Phase:

PHASE2

PHASE3

Brief Summary

PRACTECAL-PKPD is an exploratory pharmacokinetic and pharmacodynamic sub-study investigating the relationship between the patients' exposure to anti- tuberculosis (TB) drugs in the TB-PRACTECAL trial ...

Detailed Description

PRACTECAL-PKPD is a sub-study of the main TB-PRACTECAL phase II-III trial for the treatment of biologically confirmed pulmonary multi drug or extensively drug-resistant TB (M/XDR-TB). TB-PRACTECAL is ...

Eligibility Criteria

Inclusion

  • Main study inclusion criteria\*:
  • Patients eligible for inclusion in the trial must fulfil all of the following criteria:
  • Male or female subjects aged 15 years of age or above, regardless of HIV status;
  • Microbiological test (molecular or phenotypic) confirming presence of M. tuberculosis;
  • Resistant to at least rifampicin by either molecular or phenotypic drug susceptibility test;
  • Completed informed consent form (ICF);
  • Main study exclusion criteria:
  • Known allergies, hypersensitivity, or intolerance to any of the study drugs;
  • Pregnant or breast-feeding; or unwilling to use appropriate contraceptive measures
  • Liver enzymes \>3 times the upper limit of normal;
  • Any condition (social or medical) which, in the opinion of the investigator, would make study participation unsafe;
  • Taking any medications contraindicated with the medicines in the trial; QTcF \> 450ms;
  • One or more risk factors for QT prolongation (excluding age and gender) or other uncorrected risk factors for TdP;
  • History of cardiac disease, syncopal episodes, symptomatic or asymptomatic arrhythmias (with the exception of sinus arrhythmia);
  • Any baseline biochemical laboratory value consistent with Grade 4 toxicity.
  • Moribund
  • Known resistance to bedaquiline, pretomanid, delamanid or linezolid.
  • Prior use of bedaquiline and/or pretomanid and/or linezolid and/or delamanid for one or more months.
  • Patients not eligible to start a new course of MDR-TB/XDR-TB treatment according to local protocol, including but not limited to:
  • currently on MDR-TB treatment for more than 2 weeks (and not failing)
  • unstable address
  • loss to follow-up in previous treatment with no change in circumstance and motivation.
  • Tuberculous meningoencephalitis, brain abscesses, osteomyelitis or arthritis.
  • \*PKPD inclusion/exclusion:
  • Adult patients (aged 18 years or above) recruited into the investigational arms of the TB-PRACTECAL trial in the approved sites.
  • Willing to sign the sub-study informed consent form after agreeing to the additional blood draws.

Exclusion

    Key Trial Info

    Start Date :

    August 6 2019

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ESTIMATED

    End Date :

    September 30 2022

    Estimated Enrollment :

    240 Patients enrolled

    Trial Details

    Trial ID

    NCT04081077

    Start Date

    August 6 2019

    End Date

    September 30 2022

    Last Update

    May 14 2021

    Active Locations (5)

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    Page 1 of 2 (5 locations)

    1

    Republican Scientific and Practical Centre for Pulmonology and Tuberculosis hospital

    Minsk, Belarus

    2

    Helen Jospeh Hospital

    Johannesburg, Gauteng, South Africa, 2092

    3

    THINK Clinical Trial Unit, Hillcrest

    Durban, KwaZulu-Natal, South Africa, 3650

    4

    King DinuZulu Hospital

    Durban, KwaZulu-Natal, South Africa, 4091