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Drug Interaction Study Between Linezolid and Clarithromycin in Tuberculosis Patients

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ClinicalTrials.gov Identifier: NCT01521364
Recruitment Status : Completed
First Posted : January 30, 2012
Results First Posted : July 1, 2013
Last Update Posted : July 1, 2013
Sponsor:
Information provided by (Responsible Party):
JWC Alffenaar, University Medical Center Groningen

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Multidrug-resistant Tuberculosis
Extensively Drug-resistant Tuberculosis
Intervention Drug: Addition of different doses of clarithromycin.
Enrollment 7
Recruitment Details

The study was performed at the Tuberculosis Centre Beatrixoord (University of Groningen, University Medical Center Groningen, Haren, The Netherlands).

Dates of recruitment: from december 2011 to november 2012.

Pre-assignment Details Not applicatble.
Arm/Group Title 0mg, 250mg and 500mg Claritromycin
Hide Arm/Group Description Patients receive 300mg linezolid twice a day during entire study.
Period Title: Linezolid Without Clarithromycin (1 wk)
Started 7
Completed 7
Not Completed 0
Period Title: Linezolid + 250mg Claritromycin (wk 2&3)
Started 7
Completed 6
Not Completed 1
Reason Not Completed
Protocol Violation             1
Period Title: Linezolid + 500mg Claritromycin (wk 4&5)
Started 6
Completed 5
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
Arm/Group Title Clarithromycin
Hide Arm/Group Description

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.

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.

Overall Number of Baseline Participants 5
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
<=18 years
0
   0.0%
Between 18 and 65 years
5
 100.0%
>=65 years
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants
35  (17)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Female
1
  20.0%
Male
4
  80.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Netherlands Number Analyzed 5 participants
5
1.Primary Outcome
Title Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Plasma After Addition of 0mg, 250mg, or 500mg Clarithromycin (CLA).
Hide Description

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).

Time Frame At week 1 (baseline), week 3 (250mg clarithromycin), and week 5(500mg clarithromycin).
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 0mg Claritrhomycin 250mg Clarithromycin 500mg Clarithromycin
Hide Arm/Group Description:

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.

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.

[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 5 5 5
Median (Inter-Quartile Range)
Unit of Measure: mg*h/L
36.3
(33.2 to 46.3)
61.0
(34.6 to 63.9)
67.2
(66.9 to 76.0)
2.Secondary Outcome
Title Linezolid (LIN) and Clarithromycin (CLA) Pharmacokinetic Parameters, e.g. Tmax, Cmax, Cmin, T1/2, Cl.
Hide Description [Not Specified]
Time Frame At week 1 (baseline), week 3 (250mg clarithromycin), and week 5 (500mg clarithromycin) and week 6 (baseline).
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Number of Patients With Adverse Events (AEs)
Hide Description 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.
Time Frame Up to week 6
Hide Outcome Measure Data
Hide Analysis Population Description
No serious adverse events
Arm/Group Title 0mg Claritromycin 250mg Clarithromycin 500mg Clarithromycin
Hide Arm/Group Description:

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.

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.

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.

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.

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.

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.

Overall Number of Participants Analyzed 5 5 5
Measure Type: Number
Unit of Measure: participants
0 0 0
4.Secondary Outcome
Title 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.
Hide Description [Not Specified]
Time Frame At week 1 (baseline), week 3 (250mg clarithromycin) and week 5 (500mg clarithromycin)
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Saliva.
Hide Description The data will be used to clinically validate the analysis linezolid in saliva as surrogate marker for linezolid in plasma.
Time Frame At week 3 (after co-administration of 250mg clarithromycin)
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 0mg Claritromycin 250mg Clarithromycin 500mg Clarithromycin
Hide Arm/Group Description

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.

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.

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.

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.

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.

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.

All-Cause Mortality
0mg Claritromycin 250mg Clarithromycin 500mg Clarithromycin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
0mg Claritromycin 250mg Clarithromycin 500mg Clarithromycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/5 (0.00%)      0/5 (0.00%)      0/5 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
0mg Claritromycin 250mg Clarithromycin 500mg Clarithromycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/5 (0.00%)      0/5 (0.00%)      1/5 (20.00%)    
Gastrointestinal disorders       
Nausea *  0/5 (0.00%)  0 0/5 (0.00%)  0 1/5 (20.00%)  1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. J.W.C. Alffenaar
Organization: University of Groningen, University Medical Center Groningen
Phone: +31-50-3614070 ext 40378
Responsible Party: JWC Alffenaar, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT01521364     History of Changes
Other Study ID Numbers: NL35534.042.11
2011-000513-39 ( EudraCT Number )
First Submitted: September 13, 2011
First Posted: January 30, 2012
Results First Submitted: January 17, 2013
Results First Posted: July 1, 2013
Last Update Posted: July 1, 2013