Improving Treatment of Nontuberculous Mycobacterial Infection in Cystic Fibrosis

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT02372383
• Collaborator: Cystic Fibrosis Foundation (Other), Colorado Clinical & Translational Sciences Institute (Other)
• Enrollment: 31
• Location: 1
• Arms: 3
• Actual Duration (Months): 20
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine antimycobacterial drug pharmacokinetics (PK) and pharmacodynamics (PD) in patients with cystic fibrosis (CF) to improve treatment of nontuberculous mycobacterial (NTM) lung disease.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Ethambutol; Drug: Rifampin; Drug: Azithromycin; Drug: Pancrelipase	N/A

Detailed Description

The purpose of this study is to determine antimycobacterial drug pharmacokinetics (PK) and pharmacodynamics (PD) in patients with cystic fibrosis (CF) to improve treatment of nontuberculous mycobacterial (NTM) lung disease.

Aim 1: Determine the PK profile of 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, compared to healthy controls.

Aim 2: Begin to investigate the influence of inflammation, host characteristics, and drug metabolism on the PK of the antimycobacterial drugs.

Aim 3: Estimate an optimized dosing regimen for the antimycobacterial drugs against Mycobacterium avium complex (MAC) using historic minimum inhibitory concentration (MIC) data and models of Mycobacterium tuberculosis or MAC infection.

The central goal of this study is to improve treatment of NTM infection in CF. Upon completion of this study the investigators will determine if and why PK of the antimycobacterial drugs are altered in CF. More importantly, the investigators will develop CF-specific guidelines to achieve therapeutic goals with recommendations for drug dosing (including dose, dose frequency and timing in relation to meals and supplemental pancreatic enzymes) and timing of therapeutic monitoring to be used for future treatment of NTM lung disease in CF.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacokinetic Evaluation of Nontuberculous Mycobacterial Antibiotics in Cystic Fibrosis Versus Controls
• Actual Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fasting 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	Drug: Ethambutol; Anti-mycobacterial oral drug; Other Names: Myambutol ; Drug: Rifampin; Anti-mycobacterial oral drug; Other Names: Rifadin ; Drug: Azithromycin; Anti-mycobacterial oral drug; Other Names: Zithromax
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	Drug: Ethambutol; Anti-mycobacterial oral drug; Other Names: Myambutol ; Drug: Rifampin; Anti-mycobacterial oral drug; Other Names: Rifadin ; Drug: Azithromycin; Anti-mycobacterial oral drug; Other Names: Zithromax ; Drug: Pancrelipase; Pancreatic enzyme replacement therapy; Other Names: Creon Zenpep Pertzye
Active Comparator: Healthy Controls 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	Drug: Ethambutol; Anti-mycobacterial oral drug; Other Names: Myambutol ; Drug: Rifampin; Anti-mycobacterial oral drug; Other Names: Rifadin ; Drug: Azithromycin; Anti-mycobacterial oral drug; Other Names: Zithromax

Outcome Measures

Primary Outcome Measures

1. Median Maximal Drug Concentration (Cmax) [0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose]

   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.

Secondary Outcome Measures

1. Other PK Measures: Median Time to Maximal Drug Concentration (Tmax) [0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose]

   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

2. Other PK Measures: Half-life (t1/2) [0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose]

   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

3. Other PK Measures: Drug Clearance [0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose]

   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.

4. Other PK Measures: Volume of Distribution (Vd) [0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose]

   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

5. Covariates of PK Measures: C-reactive Protein (CRP) [baseline]

   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.

6. Covariates of PK Measures: Circulating Neutrophil Count [baseline]

   Circulating neutrophil count. Begin to investigate the influence of inflammation, host characteristics, and drug metabolism on the PK of the antimycobacterial drugs

7. Covariates of PK Measures: Body Mass Index [baseline]

   Body mass index (BMI). Begin to investigate the influence of inflammation, host characteristics, and drug metabolism on the PK of the antimycobacterial drugs

8. Covariates of PK Measures: Creatinine [baseline]

   Creatinine. Begin to investigate the influence of inflammation, host characteristics, and drug metabolism on the PK of the antimycobacterial drugs

9. Area Under the Curve (AUC) [0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post dose]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

CF Subject Inclusion Criteria:

• CF diagnosis defined as a sweat chloride >60mEq/L and/or the presence of two disease-causing CFTR mutations.

• Ages 16 years and above.

• Pancreatic insufficient status defined as previous fecal pancreatic elastase <100mcg/g stool and/or having 2 disease-causing CFTR mutations known to be associated with pancreatic insufficiency, and taking supplemental pancreatic enzymes between 1000-2500 lipase units/kg/meal.

• No positive NTM cultures in the last 2 years.

• Pulmonary function: Most recent FEV1 > 40% predicted.

• Willing to participate in and comply with the study procedures, and willingness of a parent or legally authorized representative to provide written informed consent for those subjects less than 18 years of age.

Healthy Control Inclusion Criteria:

• Ages 18 years and above.

• BMI below 30 to best match CF body type.

• Willing to participate in and comply with the study procedures, and willingness of a parent or legally authorized representative to provide written informed consent for those subjects less than 18 years of age.

CF Subject Exclusion Criteria:

• Allergy or intolerance to rifampin, ethambutol, or azithromycin.

• Hepatic insufficiency defined as having an AST or ALT greater than three times the upper limit of normal at the screening appointment.

• Previous surgical bowel resection.

• Previous lung transplant.

• Use of medications known to interact with the antimycobacterial drug levels; of note, the most common interactions in CF patients are the use of itraconazole, voriconazole, and ivacaftor. We will have subjects hold H2 blockers and proton pump inhibitors for 3 days prior to each PK study day.

• Inability to hold azithromycin: Subjects will not be excluded if they are on chronic azithromycin for immunomodulatory purposes; however, we will ask that the subjects hold the azithromycin starting at the screening visit, through a 2 week wash-out period prior to Visit 2, and remain off through the end of Visit 3 (about 4 weeks total).

• Acute exacerbations: exclusion if any addition of oral, IV, or inhaled antibiotics, or an acute gastrointestinal illness with vomiting or diarrhea in the 2 weeks prior to each visit. No exclusion for previously prescribed alternating chronic inhaled or oral antibiotics.

• We will also exclude pregnant women (urine pregnancy test will be performed for females on the day of each PK study) and decisionally challenged subjects.

Healthy Control Exclusion Criteria:

• Allergy or intolerance to rifampin, ethambutol, or azithromycin.

• Hepatic insufficiency defined as having an AST or ALT greater than three times the upper limit of normal at the screening appointment.

• Previous chronic GI disease or surgical bowel resection.

• Use of medications known to interact with the antimycobacterial drug levels. We will have subjects hold H2 blockers and proton pump inhibitors for 3 days prior to the PK study day.

• Acute illness: exclusion if respiratory illness requiring antibiotics or gastrointestinal illness with vomiting or diarrhea in the 2 weeks prior to the PK visit.

• We will also exclude pregnant women (urine pregnancy test will be performed on the day of PK study) and decisionally challenged subjects.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Colroado	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver
• Cystic Fibrosis Foundation
• Colorado Clinical & Translational Sciences Institute

Investigators

• Principal Investigator: Stacey Martiniano, MD, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT02372383
• Other Study ID Numbers: 14-1043; UL1TR001082
• First Posted: Feb 26, 2015
• Last Update Posted: Feb 11, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of Colorado, Denver: Cystic Fibrosis; Pharmacokinetics; Pharmacodynamics; Nontuberculous Mycobacteria; Treatment
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Azithromycin; Rifampin; Ethambutol; Pancrelipase; Pancreatin

Study Results

Participant Flow

Recruitment Details	20 CF subjects and 10 Healthy controls will be studied

Arm/Group Title	Healthy Controls (Fasting Only)	CF Patients, Fasting, Then Food	CF Patients, Food Then Fasting
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
Period Title: First Intervention (1 Day)
STARTED	10	10	10
COMPLETED	10	10	10
NOT COMPLETED	0	0	0
Period Title: First Intervention (1 Day)
STARTED	10	10	10
COMPLETED	10	10	10
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	CF Subjects	Healthy Controls (Fasting Only)	Total
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 Participants	20	10	30
Age (Count of Participants)
<=18 years	1 5%	0 0%	1 3.3%
Between 18 and 65 years	19 95%	10 100%	29 96.7%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	18.3	25.3	20.6
Sex: Female, Male (Count of Participants)
Female	7 35%	6 60%	13 43.3%
Male	13 65%	4 40%	17 56.7%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	20 100%	10 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Median Maximal Drug Concentration (Cmax)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy Controls	CF Fasting	CF Food
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).
Measure Participants	10	20	20
Rifampin	16.56	12.5	11.2
Ethambutol	3.0	4.2	4.3
Azithromycin	1.1	2.0	2.2

2. Secondary Outcome

Title	Other PK Measures: Median Time to Maximal Drug Concentration (Tmax)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy Controls	CF Patients, Fasting	CF Patients, Food
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).
Measure Participants	10	20	20
Rifampin	1.5	1.5	2.5
Ethambutol	2.3	2.3	2.0
Azithromycin	2.0	2.0	2.0

3. Secondary Outcome

Title	Other PK Measures: Half-life (t1/2)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy Controls	CF Fasting	CF Food
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).
Measure Participants	10	20	20
Rifampin	3.8	3.4	3.4
Ethambutol	5.3	4.3	4.7
Azithromycin	6.2	5.2	6.6

4. Secondary Outcome

Title	Other PK Measures: Drug Clearance
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy Controls	CF Fasting	CF Food
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).
Measure Participants	10	20	20
Rifampin	5.1	7.9	7.6
Ethambutol	45.3	42.4	37.3
Azithromycin	88.6	73.6	82.8

5. Secondary Outcome

Title	Other PK Measures: Volume of Distribution (Vd)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy Controls	CF Fasting	CF Food
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).
Measure Participants	10	20	20
Rifampin	31.3	39.7	37.4
Ethambutol	352.8	274.6	354.3
Azithromycin	717.0	549.2	621.3

6. Secondary Outcome

Title	Covariates of PK Measures: C-reactive Protein (CRP)
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

Outcome Measure Data

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
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).
Measure Participants	10	20	0
Median (Full Range) [mg/dL]	0.2	0.8

7. Secondary Outcome

Title	Covariates of PK Measures: Circulating Neutrophil Count
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

Outcome Measure Data

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
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).
Measure Participants	10	20	0
Median (Full Range) [10^3 cells/uL]	3.0	3.8

8. Secondary Outcome

Title	Covariates of PK Measures: Body Mass Index
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

Outcome Measure Data

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
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).
Measure Participants	10	20	0
Median (Full Range) [kg/m^2]	23.0	21.9

9. Secondary Outcome

Title	Covariates of PK Measures: Creatinine
Description	Creatinine. Begin to investigate the influence of inflammation, host characteristics, and drug metabolism on the PK of the antimycobacterial drugs
Time Frame	baseline

Outcome Measure Data

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
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).
Measure Participants	10	20	0
Median (Full Range) [mg/dL]	1.0	0.9

10. Secondary Outcome

Title	Area Under the Curve (AUC)
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy Controls	CF Fasting	CF Food
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).
Measure Participants	10	20	20
Rifampin	118.3	76	79.2
Ethambutol	21.4	21.8	23.6
Azithromycin	5.6	6.8	6

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/21 (0%)		0/20 (0%)
Serious Adverse Events
	Healthy Controls		CF Patients, Fasting		CF Patients, Food
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/21 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Healthy Controls		CF Patients, Fasting		CF Patients, Food
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/21 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.