Trial Outcomes & Findings for Drug Interaction Study Between Linezolid and Clarithromycin in Tuberculosis Patients (NCT NCT01521364)
NCT ID: NCT01521364
Last Updated: 2013-07-01
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
7 participants
Primary outcome timeframe
At week 1 (baseline), week 3 (250mg clarithromycin), and week 5(500mg clarithromycin).
Results posted on
2013-07-01
Participant Flow
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.
Not applicatble.
Participant milestones
| Measure |
0mg, 250mg and 500mg Claritromycin
Patients receive 300mg linezolid twice a day during entire study.
|
|---|---|
|
Linezolid Without Clarithromycin (1 wk)
STARTED
|
7
|
|
Linezolid Without Clarithromycin (1 wk)
COMPLETED
|
7
|
|
Linezolid Without Clarithromycin (1 wk)
NOT COMPLETED
|
0
|
|
Linezolid + 250mg Claritromycin (wk 2&3)
STARTED
|
7
|
|
Linezolid + 250mg Claritromycin (wk 2&3)
COMPLETED
|
6
|
|
Linezolid + 250mg Claritromycin (wk 2&3)
NOT COMPLETED
|
1
|
|
Linezolid + 500mg Claritromycin (wk 4&5)
STARTED
|
6
|
|
Linezolid + 500mg Claritromycin (wk 4&5)
COMPLETED
|
5
|
|
Linezolid + 500mg Claritromycin (wk 4&5)
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
0mg, 250mg and 500mg Claritromycin
Patients receive 300mg linezolid twice a day during entire study.
|
|---|---|
|
Linezolid + 250mg Claritromycin (wk 2&3)
Protocol Violation
|
1
|
|
Linezolid + 500mg Claritromycin (wk 4&5)
Withdrawal by Subject
|
1
|
Baseline Characteristics
Drug Interaction Study Between Linezolid and Clarithromycin in Tuberculosis Patients
Baseline characteristics by cohort
| Measure |
Clarithromycin
n=5 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
35 years
STANDARD_DEVIATION 17 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
5 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
0mg Claritrhomycin
n=5 Participants
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.
|
250mg Clarithromycin
n=5 Participants
|
500mg Clarithromycin
n=5 Participants
|
|---|---|---|---|
|
Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Plasma After Addition of 0mg, 250mg, or 500mg Clarithromycin (CLA).
|
36.3 mg*h/L
Interval 33.2 to 46.3
|
61.0 mg*h/L
Interval 34.6 to 63.9
|
67.2 mg*h/L
Interval 66.9 to 76.0
|
SECONDARY outcome
Timeframe: At week 1 (baseline), week 3 (250mg clarithromycin), and week 5 (500mg clarithromycin) and week 6 (baseline).Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to week 6Population: No serious adverse events
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.
Outcome measures
| Measure |
0mg Claritrhomycin
n=5 Participants
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.
|
250mg Clarithromycin
n=5 Participants
|
500mg Clarithromycin
n=5 Participants
|
|---|---|---|---|
|
Number of Patients With Adverse Events (AEs)
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: At week 1 (baseline), week 3 (250mg clarithromycin) and week 5 (500mg clarithromycin)Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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.
Outcome measures
Outcome data not reported
Adverse Events
0mg Claritromycin
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
250mg Clarithromycin
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
500mg Clarithromycin
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
0mg Claritromycin
n=5 participants at risk
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.
|
250mg Clarithromycin
n=5 participants at risk
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.
|
500mg Clarithromycin
n=5 participants at risk
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.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/5
|
0.00%
0/5
|
20.0%
1/5 • Number of events 1
|
Additional Information
Dr. J.W.C. Alffenaar
University of Groningen, University Medical Center Groningen
Phone: +31-50-3614070
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place