Pharmacokinetics and Safety of Moxifloxacin (MFX468)

University Medical Center Groningen (UMCG)

Status and phase

Terminated

Phase 4

Conditions

Tuberculosis

Treatments

Drug: Moxifloxacin

Study type

Interventional

Funder types

Other

Identifiers

NCT01329250

MFX468

Details and patient eligibility

About

The main objective of this prospective clinical trial is to compare pharmacokinetics and safety and tolerability of a standard dose (400 mg) with an escalated dose (600 mg; 800 mg) of moxifloxacin (MFX). This clinical trial will provide important safety information on MFX in a higher dosage in TB patients.

Full description

Moxifloxacin (MFX) is a fluoroquinolone with a high in vitro and in vivo bactericidal activity against Mycobacterium tuberculosis. A daily dose of 600-800 mg MFX should be considered for optimal killing of the involved mycobacteria and suppression of drug resistance, which is higher than the currently used dose of 400 mg once daily. In general, safety data to support switching to the suggested higher dose are limited.

For this purpose, twenty tuberculosis patients will start on a standard dose of MFX 400 mg once daily. After 8 days the dose will be increased to 600 mg once daily and on the 15th day of treatment, the dose of MFX will be escalated to 800 mg. In patients who have been treated with rifampicin (RIF) in the past three weeks prior to start of MFX treatment an additional washout period of 3 weeks to reduce the rifampicin induced enzymatic activity will precede the dose escalation.

Enrollment

9 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with TB, with Mycobacterium tuberculosis (or M. africanum) by culture
Starting treatment with MFX in a dose of 400 mg as part of their TB treatment

Exclusion criteria

Contra-indication for MFX
Baseline QTc-interval > 450 msec
History of resuscitation
History of ventricular tachycardia (including Torsades de Pointes)
Family history of sudden cardiac death or Torsades de Pointes
Additional risk factors for Torsades de Pointes (including known heart failure, Left ventricular hypertrophy)
Use of concomitant treatment with QT/QTc prolonging drugs (including anti-dysrhythmics class IA and III, antipsychotics, tricyclic antidepressants or the antihistaminic drug terfenadine)
Abnormal electrolytes (K, Mg, Na, Ca)
Abnormal cardiac repolarisation on screening/baseline ECG
History of adverse events to fluoroquinolones
HIV co-infection
RIF treatment during last 3 weeks before start of the study. After a washout period of 3 weeks the patient can be included.