Other Clinical Trial - Pharmacometrics to Advance Novel Regimens for

Status Recruiting

Clinical Trial Summary

PandrTB is a study of the pharmacokinetics(PK) and pharmacodynamics(PD) of bedaquiline, delamanid, clofazimine, linezolid, moxifloxacin, levofloxacin and pyrazinamide used in novel combinations to treat multidrug-resistant tuberculosis(MDR-TB).

Clinical Trial Description

PandrTB is an observational study nested in the endTB (a randomized study that will evaluate five 9-month, injectable-sparing regimens) and endTB-Q (and RCT evaluating a 4 drug oral regimen given for 6 or 9 months) trials. These trials are providing evidence to support the transformation of MDR-TB treatment. As part of PandrTB: the plasma concentrations of the experimental arm drugs (the new and repurposed drugs bedaquiline, delamanid, clofazimine and linezolid, as well as levofloxacin, moxifloxacin and pyrazinamide) will be measured; MICs will be determined in baseline isolates; and MGIT cultures, additional to those in the endTB study, will be performed at weeks 6 and 10. Nonlinear mixed-effects models will describe the population PK of the drugs and a pharmacodynamic (PD) model of treatment response of Mycobacterium tuberculosis(Mtb) load over time. Recursive partitioning methods will evaluate baseline MICs and PK measures as drivers of treatment response (as described by the parameters of the PD model of initial treatment response of Mtb load over time, and the endTB trial endpoints: time to culture conversion, longer-term outcomes, and acquisition of phenotypic resistance). Thus the key drugs and plasma drug exposure thresholds for activity will be defined, and exposure-dependent synergy or antagonism identified. The risks of toxicities (as assessed in the endTB study) will be estimated, by plasma drug exposure and important comorbidity (including HIV infection). In this way, the PK-efficacy and PK-toxicity analyses will allow definition of target plasma drug exposures. Simulations will predict optimal doses. To advance the understanding of drug penetration, we will develop approaches to measure free drug plasma concentrations. Drug-drug interactions will be described. Thus PandrTB will inform how best to use these new and repurposed drugs in combination, to create the most effective and least toxic regimens while minimizing the development of further drug resistance. ;

Study Design

Related Conditions & MeSH terms

Multi-drug Resistant Tuberculosis
Tuberculosis
Tuberculosis, Multidrug-Resistant

Clinical Trial Details

NCT number	NCT03827811
Study type	Observational
Source	University of Cape Town
Contact	Helen McIlleron, PhD
Phone	27214066779
Email	helen.mcilleron@uct.ac.za
Status	Recruiting
Phase
Start date	January 30, 2020
Completion date	April 30, 2023

View Details

See also
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Withdrawn	`NCT01600963` - A Study to Evaluate the Efficacy and Safety of TMC207 in Patients With Pulmonary Infection With Multi-drug Resistant Mycobacterium Tuberculosis	Phase 3
Recruiting	`NCT03575299` - Clinical Study on Adoptive Treatment of MDR-TB With Allogeneic γδT Cells	Phase 1
Completed	`NCT04342598` - Case Control Study of Vitamin D Status and Adult Multidrug-resistant Pulmonary Tuberculosis in Maharashtra, India
Completed	`NCT04309656` - A Study in Two Panels of Healthy Adult Participants to Assess Single-Dose Immediate-Release and Single-Dose Dispersible Formulations of Pretomanid	Phase 1
Completed	`NCT03822156` - Clinical Analysis of the Patients With Cavitary Pulmonary TB and Endobronchial TB in the PPM-UUH Cohort
Completed	`NCT00425113` - Metronidazole for Pulmonary Tuberculosis (South Korea)	Phase 2
Active, not recruiting	`NCT04081077` - PRACTECAL-PKPD Sub Study	Phase 2/Phase 3
Recruiting	`NCT04397536` - New Genomic Techniques and Management of Multidrug-resistant Tuberculosis
Completed	`NCT00664313` - TBTC Study 30: Safety and Tolerability of Low Dose Linezolid in MDR TB	Phase 1/Phase 2
Completed	`NCT00691392` - Linezolid Pharmacokinetics (PK) in Multi-Drug Resistant (MDR)/Extensively-Drug Resistant (XDR) Tuberculosis (TB)	Phase 1/Phase 2

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

Pharmacometrics to Advance Novel Regimens for Drug-resistant Tuberculosis-PandrTB Tuberculosis — PandrTB

Clinical Trial Summary

Clinical Trial Description

Study Design

Related Conditions & MeSH terms