PRACTECAL-PKPD Sub Study (PRACTECAL-PKPD)
Multi-drug Resistant Tuberculosis, Extensively Drug-Resistant Tuberculosis, Pulmonary Tuberculosis
About this trial
This is an interventional treatment trial for Multi-drug Resistant Tuberculosis focused on measuring Pharmacokinetics, Pharmcogenomics, Pharmacodynamics, Bedaquiline, Pretomanid, Linezolid, Clofazimine, Moxifloxacin
Eligibility Criteria
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.
Sites / Locations
- Republican Scientific and Practical Centre for Pulmonology and Tuberculosis hospital
- Helen Jospeh Hospital
- Doris Goodwin Hospital
- THINK Clinical Trial Unit, Hillcrest
- King DinuZulu Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Regimen 1: Bedaquiline, Pretomanid, Linezolid, Moxifloxacin
Regimen 2:Bedaquiline, Pretomanid, Linezolid, Clofazimine
Regimen 3: Bedaquiline, Pretomanid, Linezolid
Bedaquiline: 400 mg once daily for 2 weeks followed by 200 mg 3 times per week for 22 weeks Pretomanid: 200mg once daily for 24 weeks Moxifloxacin: 400 mg once daily for 24 weeks Linezolid: 600mg daily for 16 weeks then 300mg daily (or 600mg x3/wk) for the remaining 8 weeks or earlier when moderately tolerated
Bedaquiline: 400 mg once daily for 2 weeks followed by 200 mg 3 times per week for 22 weeks Pretomanid: 200mg once daily for 24 weeks Linezolid: 600mg daily for 16 weeks then 300mg daily (or 600mg x3/wk) for the remaining 8 weeks or earlier when moderately tolerated Clofazimine: 50 mg (less than 33 kg), 100 mg (more than 33 kg) for 24 weeks
Bedaquiline: 400 mg once daily for 2 weeks followed by 200 mg 3 times per week for 22 weeks Pretomanid: 200mg once daily for 24 weeks Linezolid: 600mg daily for 16 weeks then 300mg daily (or 600mg x3/wk) for the remaining 8 weeks or earlier when moderately tolerated)