Drug Interaction Study Between Linezolid and Clarithromycin in Tuberculosis Patients
|Multidrug-resistant Tuberculosis Extensively Drug-resistant Tuberculosis||Drug: Addition of different doses of clarithromycin.||Phase 4|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Pharmacokinetic Effect of Clarithromycin on the AUC0-12h of Linezolid in Multidrug-resistant and Extensively Drug-resistant Tuberculosis (MDR/XDR-TB) Patients|
- Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Plasma After Addition of 0mg, 250mg, or 500mg Clarithromycin (CLA). [ Time Frame: At week 1 (baseline), week 3 (250mg clarithromycin), and week 5(500mg clarithromycin). ]
The AUCs of linezolid will be measured at 3 time points after addition of 3 different clarithromycin dosages.
Samples were obtained before doseing and 1h, 2h, 3h, 4h, 8h, and 12h after administration of linezolid (and claritromycin depending on the period).
- Linezolid (LIN) and Clarithromycin (CLA) Pharmacokinetic Parameters, e.g. Tmax, Cmax, Cmin, T1/2, Cl. [ Time Frame: At week 1 (baseline), week 3 (250mg clarithromycin), and week 5 (500mg clarithromycin) and week 6 (baseline). ]
- Number of Patients With Adverse Events (AEs) [ Time Frame: Up to week 6 ]To assess short-term safety and tolerability when combining linezolid (LIN) with clarithromycin (CLA) by monitoring AEs, i.e. gastro-intestinal effects, hyperlactatemia, haematological abnormalities and neuropathy.
- Pharmacokinetic Parameters, e.g. Tmax, T1/2, Cmax, Cmin, Cl, of Anti-TB Drugs That Are Co-administered as Part of the Continued Standard Care. [ Time Frame: At week 1 (baseline), week 3 (250mg clarithromycin) and week 5 (500mg clarithromycin) ]
- Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Saliva. [ Time Frame: At week 3 (after co-administration of 250mg clarithromycin) ]The data will be used to clinically validate the analysis linezolid in saliva as surrogate marker for linezolid in plasma.
|Study Start Date:||December 2011|
|Study Completion Date:||November 2012|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
0mg, 250mg, and 500mg claritromycin
Patients receive 300mg linezolid twice a day during entire study. After one week, 250mg claritromycin once daily is added for a duration of two weeks.
After another two weeks, 250mg claritromycin is replaced by 500mg claritromycin once daily for another two weeks.
After this, there is a wash-out period of one week during which no claritromycine is administered.
Drug: Addition of different doses of clarithromycin.
At week 1, 250mg clarithromycin once a day will be added to linezolid therapy during two weeks.
At week 3, 500mg clarithromycin once a day will be added to linezolid therapy during to weeks.
Other Name: Clarithromycin, 250/500mg (Pharmachemie) RVG 029081/029082
Please refer to this study by its ClinicalTrials.gov identifier: NCT01521364
|Tuberculosis Center Beatrixoord|
|Haren, Groningen, Netherlands|
|Principal Investigator:||Jan-Willem C Alffenaar, PhD, PharmD||University Medical Center Groningen|