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Improving Treatment of Nontuberculous Mycobacterial Infection in Cystic Fibrosis

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ClinicalTrials.gov Identifier: NCT02372383
Recruitment Status : Completed
First Posted : February 26, 2015
Results First Posted : February 11, 2021
Last Update Posted : February 11, 2021
Sponsor:
Collaborators:
Cystic Fibrosis Foundation
Colorado Clinical & Translational Sciences Institute
Information provided by (Responsible Party):
University of Colorado, Denver

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Drug: Ethambutol
Drug: Rifampin
Drug: Azithromycin
Drug: Pancrelipase
Enrollment 31
Recruitment Details 20 CF subjects and 10 Healthy controls will be studied
Pre-assignment Details  
Arm/Group Title Healthy Controls (Fasting Only) CF Patients, Fasting, Then Food CF Patients, Food Then Fasting
Hide Arm/Group Description

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

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

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

Period Title: First Intervention (1 Day)
Started 10 11 10
Completed 10 10 10
Not Completed 0 1 0
Reason Not Completed
Unable to collect blood             0             1             0
Period Title: Washout (14 Days)
Started 10 10 10
Completed 10 10 10
Not Completed 0 0 0
Period Title: Second Intervention (1 Day)
Started 10 10 10
Completed 10 10 10
Not Completed 0 0 0
Arm/Group Title CF Subjects Healthy Controls (Fasting Only) Total
Hide Arm/Group Description

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 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 of all reporting groups
Overall Number of Baseline Participants 20 10 30
Hide Baseline Analysis Population Description
One patient was unable to participate at day 1 from the CF Subjects arm, and baseline data was not collected. Baseline demographics data was not stratified between the "Fasting, then Food" versus "Food, then Fasting" sequences. Baseline data was only collected for Healthy Controls versus CF subjects.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 10 participants 30 participants
<=18 years
1
   5.0%
0
   0.0%
1
   3.3%
Between 18 and 65 years
19
  95.0%
10
 100.0%
29
  96.7%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 20 participants 10 participants 30 participants
18.3
(16.1 to 24.8)
25.3
(18.2 to 30.7)
20.6
(16.1 to 30.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 10 participants 30 participants
Female
7
  35.0%
6
  60.0%
13
  43.3%
Male
13
  65.0%
4
  40.0%
17
  56.7%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants
0
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants 10 participants 30 participants
20 10 30
1.Primary Outcome
Title Median Maximal Drug Concentration (Cmax)
Hide Description 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.
Time Frame 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Healthy Controls CF Fasting CF Food
Hide Arm/Group Description:

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

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).

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).

Overall Number of Participants Analyzed 10 20 20
Median (Full Range)
Unit of Measure: mg/L
Rifampin
16.56
(10.2 to 27.0)
12.5
(6.6 to 21.9)
11.2
(4.7 to 14.5)
Ethambutol
3.0
(2.3 to 4.7)
4.2
(1.1 to 6.8)
4.3
(1.0 to 5.7)
Azithromycin
1.1
(0.6 to 2.1)
2.0
(0.1 to 5.3)
2.2
(0.1 to 4.1)
2.Secondary Outcome
Title Other PK Measures: Median Time to Maximal Drug Concentration (Tmax)
Hide Description Tmax 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
Time Frame 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Healthy Controls CF Patients, Fasting CF Patients, Food
Hide Arm/Group Description:

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

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).

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).

Overall Number of Participants Analyzed 10 20 20
Median (Full Range)
Unit of Measure: hours
Rifampin
1.5
(1 to 4)
1.5
(1 to 3)
2.5
(1 to 6)
Ethambutol
2.3
(1 to 4)
2.3
(1 to 4)
2.0
(1 to 4)
Azithromycin
2.0
(1 to 3)
2.0
(1 to 4)
2.0
(1 to 4)
3.Secondary Outcome
Title Other PK Measures: Half-life (t1/2)
Hide Description t1/2 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
Time Frame 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Healthy Controls CF Fasting CF Food
Hide Arm/Group Description:

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

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).

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).

Overall Number of Participants Analyzed 10 20 20
Median (Full Range)
Unit of Measure: hours
Rifampin
3.8
(2.6 to 7.0)
3.4
(2.2 to 5.9)
3.4
(2.3 to 8.0)
Ethambutol
5.3
(3.3 to 6.0)
4.3
(3.1 to 7.2)
4.7
(3.0 to 15.1)
Azithromycin
6.2
(3.3 to 7.0)
5.2
(2.5 to 14.0)
6.6
(2.5 to 14.4)
4.Secondary Outcome
Title Other PK Measures: Drug Clearance
Hide Description

drug 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.

Time Frame 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Healthy Controls CF Fasting CF Food
Hide Arm/Group Description:

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

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).

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).

Overall Number of Participants Analyzed 10 20 20
Median (Full Range)
Unit of Measure: L/h
Rifampin
5.1
(3.8 to 8.5)
7.9
(3.6 to 15.7)
7.6
(4.4 to 19.5)
Ethambutol
45.3
(34.3 to 61.8)
42.4
(23.6 to 156.6)
37.3
(27.7 to 185.2)
Azithromycin
88.6
(40.3 to 190.9)
73.6
(31.9 to 978.8)
82.8
(41.7 to 567.5)
5.Secondary Outcome
Title Other PK Measures: Volume of Distribution (Vd)
Hide Description Vd 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
Time Frame 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Healthy Controls CF Fasting CF Food
Hide Arm/Group Description:

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

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).

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).

Overall Number of Participants Analyzed 10 20 20
Median (Full Range)
Unit of Measure: L
Rifampin
31.3
(16.4 to 39.0)
39.7
(21.3 to 67.5)
37.4
(25.9 to 105.6)
Ethambutol
352.8
(162.0 to 453.0)
274.6
(139.7 to 1045.9)
354.3
(147.3 to 1866.4)
Azithromycin
717.0
(406.1 to 1083.4)
549.2
(201.5 to 9503.5)
621.3
(249.3 to 8608.7)
6.Secondary Outcome
Title Covariates of PK Measures: C-reactive Protein (CRP)
Hide Description 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.
Time Frame baseline
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Healthy Controls CF Fasting CF Food
Hide Arm/Group Description:

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

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).

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).

Overall Number of Participants Analyzed 10 20 0
Median (Full Range)
Unit of Measure: mg/dL
0.2
(0.0 to 5.1)
0.8
(0.2 to 9)
7.Secondary Outcome
Title Covariates of PK Measures: Circulating Neutrophil Count
Hide Description Circulating neutrophil count. Begin to investigate the influence of inflammation, host characteristics, and drug metabolism on the PK of the antimycobacterial drugs
Time Frame baseline
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Healthy Controls CF Fasting CF Food
Hide Arm/Group Description:

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

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).

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).

Overall Number of Participants Analyzed 10 20 0
Median (Full Range)
Unit of Measure: 10^3 cells/uL
3.0
(1.4 to 7.2)
3.8
(2.5 to 7.7)
8.Secondary Outcome
Title Covariates of PK Measures: Body Mass Index
Hide Description Body mass index (BMI). Begin to investigate the influence of inflammation, host characteristics, and drug metabolism on the PK of the antimycobacterial drugs
Time Frame baseline
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Healthy Controls CF Fasting CF Food
Hide Arm/Group Description:

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

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).

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).

Overall Number of Participants Analyzed 10 20 0
Median (Full Range)
Unit of Measure: kg/m^2
23.0
(18.9 to 25.1)
21.9
(18.0 to 26.6)
9.Secondary Outcome
Title Covariates of PK Measures: Creatinine
Hide Description Creatinine. Begin to investigate the influence of inflammation, host characteristics, and drug metabolism on the PK of the antimycobacterial drugs
Time Frame baseline
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Healthy Controls CF Fasting CF Food
Hide Arm/Group Description:

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

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).

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).

Overall Number of Participants Analyzed 10 20 0
Median (Full Range)
Unit of Measure: mg/dL
1.0
(0.8 to 1.2)
0.9
(0.7 to 1.1)
10.Secondary Outcome
Title Area Under the Curve (AUC)
Hide Description AUC 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.
Time Frame 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Healthy Controls CF Fasting CF Food
Hide Arm/Group Description:

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

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).

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).

Overall Number of Participants Analyzed 10 20 20
Median (Full Range)
Unit of Measure: mg*h/L
Rifampin
118.3
(70.5 to 156)
76
(38.1 to 167.5)
79.2
(30.8 to 136.7)
Ethambutol
21.4
(16.2 to 30.4)
21.8
(6.4 to 38.2)
23.6
(5 to 36)
Azithromycin
5.6
(2.6 to 12.4)
6.8
(0.5 to 15.7)
6
(0.9 to 12)
Time Frame During the time of participation in the study, about 6 weeks.
Adverse Event Reporting Description Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research. One participant is included in the Fasting arm who dropped out immediately after, prior to the Food period.
 
Arm/Group Title Healthy Controls CF Patients, Fasting CF Patients, Food
Hide Arm/Group Description

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

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).

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).

All-Cause Mortality
Healthy Controls CF Patients, Fasting CF Patients, Food
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/21 (0.00%)   0/20 (0.00%) 
Hide Serious Adverse Events
Healthy Controls CF Patients, Fasting CF Patients, Food
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/21 (0.00%)   0/20 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Healthy Controls CF Patients, Fasting CF Patients, Food
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/21 (0.00%)   0/20 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Stacey Martiniano
Organization: UColorado
Phone: 7207776181
EMail: stacey.martiniano@childrenscolorado.org
Layout table for additonal information
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02372383    
Other Study ID Numbers: 14-1043
UL1TR001082 ( U.S. NIH Grant/Contract )
First Submitted: June 20, 2014
First Posted: February 26, 2015
Results First Submitted: November 26, 2019
Results First Posted: February 11, 2021
Last Update Posted: February 11, 2021