Efficacy and Tolerability of Delamanid, Linezolid, Pyrazinamide and Levofloxacin

Summary

The proposed study will randomize adults (18 years of age or older) with pulmonary MDR-TB with sputum that contains M. tuberculosis that is isoniazid and rifampin resistant by MTBDRplus and fluoroquinolone susceptible by MTBDRsl HIV seropositive (with or without antiretroviral therapy) or negative (but not unknown) and Karnofsky score of \>60 at sites in Moldova, Peru, and the Philippines.

Patients with MDR-TB will be randomized to oral regimen of delamanid (DLM), linezolid (LZD), levofloxacin (LFX) and pyrazinamide (PZA) for 24, 32, 40, 48 or 56 weeks or World Health Organization (WHO) standard of care MDR-TB regimen (9-month "modified Bangladesh" regimen or WHO standard MDR-TB regimen).

Primary Objective

1\. Determine the shortest duration of the delamanid-containing oral regimen that is non-inferior to the blended WHO standard regimen.

Secondary Objective

1. Define the safety and tolerability of the oral delamanid, linezolid, levofloxacin and pyrazinamide regimen.
2. Determine if baseline PZA susceptibility is associated with shorter time to non-inferior treatment duration.
3. Identify the relationship between delamanid and linezolid serum drug levels and time to sputum culture conversion among patients on the delamanid-containing oral regimen.
4. Identify the relationship between delamanid and linezolid serum drug levels and occurrence of adverse events among patients on the delamanid-containing oral regimen.

Conditions

• Tuberculosis Multi Drug Resistant Active

Interventions

DRUG

Delamanid

Delamanid is a medication used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, for active multidrug-resistant tuberculosis. It is taken by mouth.

DRUG

Linezolid

Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics.

DRUG

Levofloxacin

Levoflaxacin is an antibiotic used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, urinary tract infections, chronic prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis.

DRUG

Pyrazinamide

Pyrazinamide is a medication used in combination with other drugs such as isoniazid and rifampicin in the treatment of Mycobacterium tuberculosis.

DRUG

WHO MDR-TB regimen

The WHO guidelines recommend the following 5-agent treatment regimen for MDR-TB: pyrazinamide; a fluoroquinolone; a parenteral agent (typically amikacin or kanamycin); ethionamide (or prothionamide); and either cycloserine or para-aminosalicylic acid, with preference for cycloserine. Short (9 mos) or longer (20-24 mos) treatment schedules can be used.

Sponsors & Collaborators

• Westat

  collaborator OTHER

• University of Florida

  collaborator OTHER

• Boston University

  lead OTHER

Principal Investigators

• C. Robert Horsburgh, MD · Boston University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-08-31

Primary Completion

2021-08-31

Completion

2022-08-31

FDA Drug

Yes