Trial Outcomes & Findings for Improving Treatment of Nontuberculous Mycobacterial Infection in Cystic Fibrosis (NCT NCT02372383)
NCT ID: NCT02372383
Last Updated: 2021-02-11
Results Overview
Cmax of the oral antimycobacterial drugs (azithromycin, rifampin and ethambutol) under both fasting conditions and when taken with food plus supplemental pancreatic enzymes in subjects with pancreatic insufficient CF, compared to healthy controls.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
31 participants
Primary outcome timeframe
0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Results posted on
2021-02-11
Participant Flow
20 CF subjects and 10 Healthy controls will be studied
Participant milestones
| Measure |
Healthy Controls (Fasting Only)
Healthy subjects without CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
|
CF Patients, Fasting, Then Food
Fasting for 1 day, then washout for 2 weeks, then Food for 1 day.
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg) Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg) Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg) Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Experimental: Food/Enzymes Subjects with CF will be given the antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg) Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg) Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg) Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
|
CF Patients, Food Then Fasting
Food for 1 day, then washout for 2 weeks, then Fasting for 1 day.
Subjects with CF will be given the antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg) Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg) Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg) Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg) Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg) Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg) Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
|
|---|---|---|---|
|
First Intervention (1 Day)
STARTED
|
10
|
11
|
10
|
|
First Intervention (1 Day)
COMPLETED
|
10
|
10
|
10
|
|
First Intervention (1 Day)
NOT COMPLETED
|
0
|
1
|
0
|
|
Washout (14 Days)
STARTED
|
10
|
10
|
10
|
|
Washout (14 Days)
COMPLETED
|
10
|
10
|
10
|
|
Washout (14 Days)
NOT COMPLETED
|
0
|
0
|
0
|
|
Second Intervention (1 Day)
STARTED
|
10
|
10
|
10
|
|
Second Intervention (1 Day)
COMPLETED
|
10
|
10
|
10
|
|
Second Intervention (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Healthy Controls (Fasting Only)
Healthy subjects without CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
|
CF Patients, Fasting, Then Food
Fasting for 1 day, then washout for 2 weeks, then Food for 1 day.
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg) Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg) Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg) Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Experimental: Food/Enzymes Subjects with CF will be given the antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg) Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg) Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg) Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
|
CF Patients, Food Then Fasting
Food for 1 day, then washout for 2 weeks, then Fasting for 1 day.
Subjects with CF will be given the antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg) Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg) Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg) Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg) Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg) Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg) Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
|
|---|---|---|---|
|
First Intervention (1 Day)
Unable to collect blood
|
0
|
1
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
CF Subjects
n=20 Participants
Fasting State Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
Food/Enzymes State Subjects with CF will then cross-over and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase). CF subjects will be randomized to either receive the medications in the Fasting or Food/Enzymes state first.
|
Healthy Controls (Fasting Only)
n=10 Participants
Healthy subjects without CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=20 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=30 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
19 Participants
n=20 Participants
|
10 Participants
n=10 Participants
|
29 Participants
n=30 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=20 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=30 Participants
|
|
Age, Continuous
|
18.3 years
n=20 Participants
|
25.3 years
n=10 Participants
|
20.6 years
n=30 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=20 Participants
|
6 Participants
n=10 Participants
|
13 Participants
n=30 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=20 Participants
|
4 Participants
n=10 Participants
|
17 Participants
n=30 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
20 participants
n=20 Participants
|
10 participants
n=10 Participants
|
30 participants
n=30 Participants
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post doseCmax of the oral antimycobacterial drugs (azithromycin, rifampin and ethambutol) under both fasting conditions and when taken with food plus supplemental pancreatic enzymes in subjects with pancreatic insufficient CF, compared to healthy controls.
Outcome measures
| Measure |
Healthy Controls
n=10 Participants
Healthy subjects without CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
|
CF Fasting
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
CF Food
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
|---|---|---|---|
|
Median Maximal Drug Concentration (Cmax)
Rifampin
|
16.56 mg/L
Interval 10.2 to 27.0
|
12.5 mg/L
Interval 6.6 to 21.9
|
11.2 mg/L
Interval 4.7 to 14.5
|
|
Median Maximal Drug Concentration (Cmax)
Ethambutol
|
3.0 mg/L
Interval 2.3 to 4.7
|
4.2 mg/L
Interval 1.1 to 6.8
|
4.3 mg/L
Interval 1.0 to 5.7
|
|
Median Maximal Drug Concentration (Cmax)
Azithromycin
|
1.1 mg/L
Interval 0.6 to 2.1
|
2.0 mg/L
Interval 0.1 to 5.3
|
2.2 mg/L
Interval 0.1 to 4.1
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post doseTmax of the oral antimycobacterial drugs (azithromycin, rifampin and ethambutol) under both fasting conditions and when taken with food plus supplemental pancreatic enzymes in subjects with pancreatic insufficient CF, compared to healthy controls
Outcome measures
| Measure |
Healthy Controls
n=10 Participants
Healthy subjects without CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
|
CF Fasting
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
CF Food
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
|---|---|---|---|
|
Other PK Measures: Median Time to Maximal Drug Concentration (Tmax)
Rifampin
|
1.5 hours
Interval 1.0 to 4.0
|
1.5 hours
Interval 1.0 to 3.0
|
2.5 hours
Interval 1.0 to 6.0
|
|
Other PK Measures: Median Time to Maximal Drug Concentration (Tmax)
Ethambutol
|
2.3 hours
Interval 1.0 to 4.0
|
2.3 hours
Interval 1.0 to 4.0
|
2.0 hours
Interval 1.0 to 4.0
|
|
Other PK Measures: Median Time to Maximal Drug Concentration (Tmax)
Azithromycin
|
2.0 hours
Interval 1.0 to 3.0
|
2.0 hours
Interval 1.0 to 4.0
|
2.0 hours
Interval 1.0 to 4.0
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post doset1/2 of the oral antimycobacterial drugs (azithromycin, rifampin and ethambutol) under both fasting conditions and when taken with food plus supplemental pancreatic enzymes in subjects with pancreatic insufficient CF, compared to healthy controls
Outcome measures
| Measure |
Healthy Controls
n=10 Participants
Healthy subjects without CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
|
CF Fasting
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
CF Food
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
|---|---|---|---|
|
Other PK Measures: Half-life (t1/2)
Azithromycin
|
6.2 hours
Interval 3.3 to 7.0
|
5.2 hours
Interval 2.5 to 14.0
|
6.6 hours
Interval 2.5 to 14.4
|
|
Other PK Measures: Half-life (t1/2)
Rifampin
|
3.8 hours
Interval 2.6 to 7.0
|
3.4 hours
Interval 2.2 to 5.9
|
3.4 hours
Interval 2.3 to 8.0
|
|
Other PK Measures: Half-life (t1/2)
Ethambutol
|
5.3 hours
Interval 3.3 to 6.0
|
4.3 hours
Interval 3.1 to 7.2
|
4.7 hours
Interval 3.0 to 15.1
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dosedrug clearance of the oral antimycobacterial drugs (azithromycin, rifampin and ethambutol) under both fasting conditions and when taken with food plus supplemental pancreatic enzymes in subjects with pancreatic insufficient CF, compared to healthy controls Reported here are the Median (range) CL in the CF fasting state compared to HC for Rifampin.
Outcome measures
| Measure |
Healthy Controls
n=10 Participants
Healthy subjects without CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
|
CF Fasting
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
CF Food
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
|---|---|---|---|
|
Other PK Measures: Drug Clearance
Rifampin
|
5.1 L/h
Interval 3.8 to 8.5
|
7.9 L/h
Interval 3.6 to 15.7
|
7.6 L/h
Interval 4.4 to 19.5
|
|
Other PK Measures: Drug Clearance
Ethambutol
|
45.3 L/h
Interval 34.3 to 61.8
|
42.4 L/h
Interval 23.6 to 156.6
|
37.3 L/h
Interval 27.7 to 185.2
|
|
Other PK Measures: Drug Clearance
Azithromycin
|
88.6 L/h
Interval 40.3 to 190.9
|
73.6 L/h
Interval 31.9 to 978.8
|
82.8 L/h
Interval 41.7 to 567.5
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post doseVd of the oral antimycobacterial drugs (azithromycin, rifampin and ethambutol) under both fasting conditions and when taken with food plus supplemental pancreatic enzymes in subjects with pancreatic insufficient CF, compared to healthy controls
Outcome measures
| Measure |
Healthy Controls
n=10 Participants
Healthy subjects without CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
|
CF Fasting
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
CF Food
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
|---|---|---|---|
|
Other PK Measures: Volume of Distribution (Vd)
Rifampin
|
31.3 L
Interval 16.4 to 39.0
|
39.7 L
Interval 21.3 to 67.5
|
37.4 L
Interval 25.9 to 105.6
|
|
Other PK Measures: Volume of Distribution (Vd)
Ethambutol
|
352.8 L
Interval 162.0 to 453.0
|
274.6 L
Interval 139.7 to 1045.9
|
354.3 L
Interval 147.3 to 1866.4
|
|
Other PK Measures: Volume of Distribution (Vd)
Azithromycin
|
717.0 L
Interval 406.1 to 1083.4
|
549.2 L
Interval 201.5 to 9503.5
|
621.3 L
Interval 249.3 to 8608.7
|
SECONDARY outcome
Timeframe: baselinePopulation: This Outcome Measure was only analyzed at the Fasting period and was not collected during the Food period of the study. Therefore, 0 participants are analyzed for the "CF Food" arm for this Outcome Measure.
Median Concentration of C-reactive Protein. Begin to investigate the influence of inflammation, host characteristics, and drug metabolism on the PK of the antimycobacterial drugs.
Outcome measures
| Measure |
Healthy Controls
n=10 Participants
Healthy subjects without CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
|
CF Fasting
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
CF Food
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
|---|---|---|---|
|
Covariates of PK Measures: C-reactive Protein (CRP)
|
0.2 mg/dL
Interval 0.0 to 5.1
|
0.8 mg/dL
Interval 0.2 to 9.0
|
—
|
SECONDARY outcome
Timeframe: baselinePopulation: This Outcome Measure was only analyzed at the Fasting period and was not collected during the Food period of the study. Therefore, 0 participants are analyzed for the "CF Food" arm for this Outcome Measure.
Circulating neutrophil count. Begin to investigate the influence of inflammation, host characteristics, and drug metabolism on the PK of the antimycobacterial drugs
Outcome measures
| Measure |
Healthy Controls
n=10 Participants
Healthy subjects without CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
|
CF Fasting
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
CF Food
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
|---|---|---|---|
|
Covariates of PK Measures: Circulating Neutrophil Count
|
3.0 10^3 cells/uL
Interval 1.4 to 7.2
|
3.8 10^3 cells/uL
Interval 2.5 to 7.7
|
—
|
SECONDARY outcome
Timeframe: baselinePopulation: This Outcome Measure was only analyzed at the Fasting period and was not collected during the Food period of the study. Therefore, 0 participants are analyzed for the "CF Food" arm for this Outcome Measure.
Body mass index (BMI). Begin to investigate the influence of inflammation, host characteristics, and drug metabolism on the PK of the antimycobacterial drugs
Outcome measures
| Measure |
Healthy Controls
n=10 Participants
Healthy subjects without CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
|
CF Fasting
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
CF Food
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
|---|---|---|---|
|
Covariates of PK Measures: Body Mass Index
|
23.0 kg/m^2
Interval 18.9 to 25.1
|
21.9 kg/m^2
Interval 18.0 to 26.6
|
—
|
SECONDARY outcome
Timeframe: baselinePopulation: This Outcome Measure was only analyzed at the Fasting period and was not collected during the Food period of the study. Therefore, 0 participants are analyzed for the "CF Food" arm for this Outcome Measure.
Creatinine. Begin to investigate the influence of inflammation, host characteristics, and drug metabolism on the PK of the antimycobacterial drugs
Outcome measures
| Measure |
Healthy Controls
n=10 Participants
Healthy subjects without CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
|
CF Fasting
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
CF Food
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
|---|---|---|---|
|
Covariates of PK Measures: Creatinine
|
1.0 mg/dL
Interval 0.8 to 1.2
|
0.9 mg/dL
Interval 0.7 to 1.1
|
—
|
SECONDARY outcome
Timeframe: 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post doseAUC of the oral antimycobacterial drugs (azithromycin, rifampin and ethambutol) under both fasting conditions and when taken with food plus supplemental pancreatic enzymes in subjects with pancreatic insufficient CF, compared to healthy controls.
Outcome measures
| Measure |
Healthy Controls
n=10 Participants
Healthy subjects without CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
|
CF Fasting
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
CF Food
n=20 Participants
Subjects with CF will be given the antimycobacterial drugs in the fasting state, without supplemental pancreatic enzymes
* Rifampin 10mg/kg oral once daily (max 600mg, round to closest 150mg)
* Ethambutol 15mg/kg oral once daily (max 2500mg, round to nearest 100mg)
* Azithromycin 10mg/kg oral once daily (max 500mg, rounded to the nearest 250mg)
Blood will be drawn at time points 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Ethambutol: Anti-mycobacterial oral drug
Rifampin: Anti-mycobacterial oral drug
Azithromycin: Anti-mycobacterial oral drug
CF subjects will then cross-over following at least a 2 week washout time point and and be given the same dose of the 3 antimycobacterial drugs with a standardized meal plus a typical meal-dose of pancreatic enzymes (Pancrelipase).
|
|---|---|---|---|
|
Area Under the Curve (AUC)
Rifampin
|
118.3 mg*h/L
Interval 70.5 to 156.0
|
76 mg*h/L
Interval 38.1 to 167.5
|
79.2 mg*h/L
Interval 30.8 to 136.7
|
|
Area Under the Curve (AUC)
Ethambutol
|
21.4 mg*h/L
Interval 16.2 to 30.4
|
21.8 mg*h/L
Interval 6.4 to 38.2
|
23.6 mg*h/L
Interval 5.0 to 36.0
|
|
Area Under the Curve (AUC)
Azithromycin
|
5.6 mg*h/L
Interval 2.6 to 12.4
|
6.8 mg*h/L
Interval 0.5 to 15.7
|
6 mg*h/L
Interval 0.9 to 12.0
|
Adverse Events
Healthy Controls
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
CF Patients, Fasting
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
CF Patients, Food
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place