PRACTECAL-PKPD Sub Study

• Status: Active, not recruiting
• Trial end date: 2022-09-30
• Target enrollment: 0
• Participant gender: All

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 investigational regimens and their respective treatment outcomes.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medecins Sans Frontieres, Netherlands
• Collaborators: Clinical HIV Reserach Unit, Wits Health Consortium; Drugs for Neglected Diseases; eResearch Technology, Inc.; Global Alliance for TB Drug Development; Hackensack Meridian Health; Hackensack University Medical Centre; Liverpool School of Tropical Medicine; London School of Hygiene and Tropical Medicine; London School of Hygiene and Tropical Medicine Clinical Reserach Department; Ministry of Health, Belarus; Ministry of Health, Republic of Uzbekistan; Ministry of Public Health, Republic of Belarus; Minsk Republican Research and Practical Centre for Pulmonology and Tuberculosis; Swiss Tropical & Public Health Institute; TB & HIV Investigative Network (THINK); THINK TB & HIV Investigative Network; University College London Institute for Global Health; University College, London; University of California, San Francisco; University of California, San Francisco (UCSF), USA; University of Liverpool; Wits Health Consortium (Pty) Ltd; World Health Organization
• Treatments: Bedaquiline; Clofazimine; Diarylquinolines; Linezolid; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination

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.