DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Pharmacokinetics and Safety of Moxifloxacin

Information source: University Medical Center Groningen
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Tuberculosis

Intervention: Moxifloxacin (Drug)

Phase: Phase 4

Status: Terminated

Sponsored by: University Medical Center Groningen

Official(s) and/or principal investigator(s):
Jos GW Kosterink, PharmD, PhD, Study Chair, Affiliation: Univeristy Medical Center Groningen
Jan-Willem C Alffenaar, PharmD, PhD, Principal Investigator, Affiliation: University Medical Center Groningen

Summary

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.

Clinical Details

Official title: Pharmacokinetics and Safety of Moxifloxacin; a Dose Escalation in Patients With Tuberculosis

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Bound area under the plasma concentration-time curve (AUC0-24h) relative to the minimal inhibitory concentration (MIC)

Unbound AUC0-24h/MIC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis

Bound AUC0-24h/Mutant Prevention Concentration (MPC) ratio

Unbound AUC0-24h/MPC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis and suppression of MFX resistance

% of patients having adverse effects, including QT interval prolongation, hypersensitive reactions, diarrhoea, vomiting and hepatic or renal injury

Bound area under the plasma concentration-time curve (AUC0-24h) relative to the minimal inhibitory concentration (MIC)

Bound area under the plasma concentration-time curve (AUC0-24h) relative to the minimal inhibitory concentration (MIC)

Unbound AUC0-24h/MIC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis

Unbound AUC0-24h/MIC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis

Bound AUC0-24h/Mutant Prevention Concentration (MPC) ratio

Bound AUC0-24h/Mutant Prevention Concentration (MPC) ratio

Unbound AUC0-24h/MPC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis and suppression of MFX resistance

Unbound AUC0-24h/MPC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis and suppression of MFX resistance

Secondary outcome:

Evaluation of the predictive performance of the limited sampling strategies based on a pharmacokinetic population model to calculate AUC0-24h. Several limited sampling points will be evaluated.

Correlation between MFX concentration (mg/L) and QT interval (msec)

Correlation of drug exposure (AUC) and adverse effects

Correlation between the genetic risk score and MFX induced QT prolongation

Evaluation of the predictive performance of the limited sampling strategies based on a pharmacokinetic population model to calculate AUC0-24h. Several limited sampling points will be evaluated.

Evaluation of the predictive performance of the limited sampling strategies based on a pharmacokinetic population model to calculate AUC0-24h. Several limited sampling points will be evaluated.

Correlation between MFX concentration (mg/L) and QT interval (msec)

Correlation between MFX concentration (mg/L) and QT interval (msec)

Detailed 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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Locations and Contacts

University Medical Center Groningen, Groningen, Netherlands
Additional Information

Starting date: May 2011
Last updated: July 2, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017