Losartan and Inflammation in Cystic Fibrosis

• Sponsor: University of Miami (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03206788
• Collaborator: University of Alabama at Birmingham (Other), Children's Hospital Medical Center, Cincinnati (Other), University of Kansas Medical Center (Other), Cystic Fibrosis Foundation (Other)
• Enrollment: 7
• Locations: 4
• Arms: 2
• Actual Duration (Months): 25.6
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to examine if a specific drug called losartan (Cozaar ®), generally used to treat high blood pressure and to protect kidneys from damage in patients suffering from Diabetes Mellitus, will have any effect on the nasal inflammation in patients with cystic fibrosis (CF). The study will be performed at the Pulmonary Division at the University of Miami, Cincinnati Children's Medical Hospital Center, University of Kansas Medical Center and University of Alabama-Birmingham.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Losartan; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Losartan as Anti-inflammatory Therapy to Augment F508del Cystic Fibrosis Transmembrane (CFTR) Recovery
• Actual Study Start Date: Nov 11, 2017
• Actual Primary Completion Date: Oct 24, 2019
• Actual Study Completion Date: Dec 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Losartan group Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Drug: Losartan; 25 mg or 50 mg (based on patient's weight) Losartan tablets taken by mouth daily in the morning for week 1 followed by twice daily (one in the morning and one in the evening) on Weeks 2-12.; Other Names: Cozaar
Placebo Comparator: Placebo group Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.	Drug: placebo; Placebo tablets, matching the Losartan intervention, taken by mouth daily in the morning for week 1 followed by twice daily (one in the morning and one in the evening) on Weeks 2-12.; Other Names: matching placebo twice daily

Outcome Measures

Primary Outcome Measures

1. Change in Nasal Potential Difference (NPD) to Assess CFTR Activity [Baseline, 12 weeks]

   Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activity will be measured as the change in NPD in response to apical perfusion with 0 Cl-/isoproterenol. NPD will be measured at the nasal epithelium via a voltmeter.

Secondary Outcome Measures

1. Change in NPD to Assess CaCC Activity [Baseline, 12 weeks]

   Potential difference of Calcium dependent Chloride Channels (CaCC) will be measured as the change in NPD on on Adenosine Triphosphate (ATP) stimulation. NPD will be measured at the nasal epithelium via a voltmeter.

2. Change in NPD to Assess BK Activity [Baseline, 12 weeks]

   Big Potassium (BK) activity will be measured as the change in NPD on Adenosine Triphosphate (ATP) stimulation. NPD will be assessed from nasal epithelium samples and analyzed via a voltmeter.

3. Change in FEV1 [Baseline, 12 weeks]

   Forced Expiratory Volume in 1 second (FEV1) assessed in liters will be measured using spirometry.

4. Change in Sweat Chloride Concentration [Baseline, 12 weeks]

   Sweat chloride concentration will be analyzed from participant sweat samples analyzed in millimoles per liter (mmol/l)

5. Change in Quality of Life (QoL) Scores as Assessed by the CFQ-R [Baseline, 12 weeks]

   Cystic Fibrosis Questionnaire-Revised (CFQ-R) is a quality of life questionnaire with a total score ranging from 0-100 with a higher score indicating increased quality of life.

6. Change in Cytokine Levels [Baseline, 12 weeks]

   Nasal airway epithelial cells taken by brush will be assessed for cytokine levels including Interleukin IL-1beta, Transforming Growth Factor (TGF-beta) active and total, IL-6, IL-8 and IL-13 in pg/mL.

7. Change in hsCRP [Baseline, 12 weeks]

   Serum samples will be analyzed for High sensitivity C-Reactive Protein (hsCRP) values in mg/L.

8. Change in Blood Count Values [Baseline, 12 weeks]

   Serum blood count values including white blood count (WBC) and Absolute Neutrophil Counts (ANC) will be evaluated in units/uL.

9. Change in %PMN Values [Baseline, 12 weeks]

   Serum samples will be analyzed for % Polymorphonuclear (PMN) cells.

10. Change in SAA Values [Baseline, 12 weeks]

    Serum samples will be analyzed for Serum Amyloid A (SAA) values in mg/L.

11. Change in Calprotectin Values [Baseline, 12 weeks]

    Serum samples will be analyzed for calprotectin values in ug/mg.

12. Change in GM-CSF Values [Baseline, 12 weeks]

    Serum samples will be analyzed for % Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) values in pg/mL.

13. Change in TGF-beta Values [Baseline, 12 weeks]

    Serum samples will be analyzed for TGF-beta values in ng/mL.

14. Change in mRNA Expression [Baseline, 12 weeks]

    Change in messenger ribonucleic acid (mRNA) expression from nasal cells evaluated via quantitative polymerase chain reaction (qPCR) for Leucine Rich Repeating Protein 26 (LRRC26) and TGF-Beta).

15. Change in Losartan Metabolites Levels [Baseline, 12 weeks]

    Change in serum blood levels of Losartan and Losartan metabolites EXP3179 & EXP3174.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• CF patients homozygous for F508del and on current treatment with Orkambi™ for at least 3 months

• Age >12 years

• Forced expiratory volume at one second (FEV1) >/= 40% of predicted

Exclusion Criteria:

• Female patients not willing to adhere to strict birth control (combination of two methods)

• Pregnancy

• History of intolerance to angiotensin receptor blockers (ARBs)

• Treatment with angiotensin converting enzyme (ACE) inhibitor

• NPD response to zero chloride (0Cl)/isoproterenol of > - 6.6 mV at screening (evidence of detectable CFTR activity at baseline)

• Regular use of NSAIDs or potassium supplementation, treatment with aliskiren, on anticoagulation

• Oral corticosteroid use within 6 weeks

• Exacerbation requiring treatment within 6 weeks

• Active treatment for mycobacterial infections

• Significant hypoxemia (oxygen saturation <90% on room air and rest or use of continuous oxygen treatment), chronic respiratory failure by history (pCO2 > 45 mmHg), clinical evidence of cor pulmonale

• Untreated arterial hypertension (systolic blood pressure >140 mm Hg, diastolic blood pressure > 90 mmHg)

• Blood pressure less than 90 mm Hg systolic while standing

• Cardiac, renal (creatinine 1.5 times normal limit), hepatic (LFTs > 3x normal upper limit), neurological, psychiatric, endocrine or neoplastic diseases that are judged to interfere with participation in study

• Known renal artery stenosis

• Concomitant airway disorders other than CF, such as allergic bronchopulmonary aspergillosis (ABPA).

• Subjects with prior thoracic surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	University of Miami, Miller School of Medicine	Miami	Florida	United States	33136
3	University of Kansas	Kansas City	Kansas	United States	66160
4	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

• University of Miami
• University of Alabama at Birmingham
• Children's Hospital Medical Center, Cincinnati
• University of Kansas Medical Center
• Cystic Fibrosis Foundation

Investigators

• Principal Investigator: Matthias Salathe, MD, University of Miami

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 1, 2019

More Information

Publications

None provided.

• Responsible Party: Matthias Salathe, Emeritus Professor, University of Miami
• ClinicalTrials.gov Identifier: NCT03206788
• Other Study ID Numbers: 20170397; 20170333
• First Posted: Jul 2, 2017
• Last Update Posted: Nov 27, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Losartan

Study Results

Participant Flow

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Period Title: Overall Study
STARTED	2	5
COMPLETED	2	2
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	Losartan Group	Placebo Group	Total
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.	Total of all reporting groups
Overall Participants	2	5	7
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	5 100%	7 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	2 40%	2 28.6%
Male	2 100%	3 60%	5 71.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 20%	1 14.3%
Not Hispanic or Latino	2 100%	4 80%	6 85.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	2 100%	5 100%	7 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change in Nasal Potential Difference (NPD) to Assess CFTR Activity
Description	Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activity will be measured as the change in NPD in response to apical perfusion with 0 Cl-/isoproterenol. NPD will be measured at the nasal epithelium via a voltmeter.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	2	2
Mean (Standard Error) [mV]	-4.2 (2.1)	1.59 (2.48)

2. Secondary Outcome

Title	Change in NPD to Assess CaCC Activity
Description	Potential difference of Calcium dependent Chloride Channels (CaCC) will be measured as the change in NPD on on Adenosine Triphosphate (ATP) stimulation. NPD will be measured at the nasal epithelium via a voltmeter.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	2	2
Mean (Standard Error) [mV]	2.14 (1)	-5.43 (7.1)

3. Secondary Outcome

Title	Change in NPD to Assess BK Activity
Description	Big Potassium (BK) activity will be measured as the change in NPD on Adenosine Triphosphate (ATP) stimulation. NPD will be assessed from nasal epithelium samples and analyzed via a voltmeter.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	2	2
Mean (Standard Error) [mV]	2.14 (1)	-5.43 (7.1)

4. Secondary Outcome

Title	Change in FEV1
Description	Forced Expiratory Volume in 1 second (FEV1) assessed in liters will be measured using spirometry.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	2	2
Mean (Standard Error) [Liter]	-0.18 (0.18)	1.85 (0.1)

5. Secondary Outcome

Title	Change in Sweat Chloride Concentration
Description	Sweat chloride concentration will be analyzed from participant sweat samples analyzed in millimoles per liter (mmol/l)
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	2	2
Mean (Standard Error) [mmol/l]	-2.5 (7.5)	-3 (6)

6. Secondary Outcome

Title	Change in Quality of Life (QoL) Scores as Assessed by the CFQ-R
Description	Cystic Fibrosis Questionnaire-Revised (CFQ-R) is a quality of life questionnaire with a total score ranging from 0-100 with a higher score indicating increased quality of life.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Values were not measured for this outcome for all participants.

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	0	0

7. Secondary Outcome

Title	Change in Cytokine Levels
Description	Nasal airway epithelial cells taken by brush will be assessed for cytokine levels including Interleukin IL-1beta, Transforming Growth Factor (TGF-beta) active and total, IL-6, IL-8 and IL-13 in pg/mL.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Values were not measured for this outcome for all participants.

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	0	0

8. Secondary Outcome

Title	Change in hsCRP
Description	Serum samples will be analyzed for High sensitivity C-Reactive Protein (hsCRP) values in mg/L.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Values were not measured for this outcome for all participants.

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	0	0

9. Secondary Outcome

Title	Change in Blood Count Values
Description	Serum blood count values including white blood count (WBC) and Absolute Neutrophil Counts (ANC) will be evaluated in units/uL.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Values were not measured for this outcome for all participants.

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	0	0

10. Secondary Outcome

Title	Change in %PMN Values
Description	Serum samples will be analyzed for % Polymorphonuclear (PMN) cells.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Values were not measured for this outcome for all participants.

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	0	0

11. Secondary Outcome

Title	Change in SAA Values
Description	Serum samples will be analyzed for Serum Amyloid A (SAA) values in mg/L.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Values were not measured for this outcome for all participants.

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	0	0

12. Secondary Outcome

Title	Change in Calprotectin Values
Description	Serum samples will be analyzed for calprotectin values in ug/mg.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Values were not measured for this outcome for all participants.

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	0	0

13. Secondary Outcome

Title	Change in GM-CSF Values
Description	Serum samples will be analyzed for % Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) values in pg/mL.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Values were not measured for this outcome for all participants.

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	0	0

14. Secondary Outcome

Title	Change in TGF-beta Values
Description	Serum samples will be analyzed for TGF-beta values in ng/mL.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Values were not measured for this outcome for all participants.

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	0	0

15. Secondary Outcome

Title	Change in mRNA Expression
Description	Change in messenger ribonucleic acid (mRNA) expression from nasal cells evaluated via quantitative polymerase chain reaction (qPCR) for Leucine Rich Repeating Protein 26 (LRRC26) and TGF-Beta).
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Values were not measured for this outcome for all participants.

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	0	0

16. Secondary Outcome

Title	Change in Losartan Metabolites Levels
Description	Change in serum blood levels of Losartan and Losartan metabolites EXP3179 & EXP3174.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

Values were not measured for this outcome for all participants.

Arm/Group Title	Losartan Group	Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).	Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
Measure Participants	0	0

Adverse Events

Time Frame	16 weeks
Arm/Group Title	Losartan Group		Placebo Group
Arm/Group Description	Participant will receive the Losartan intervention and will take 50 mg losartan orally once daily for week 1, followed by 50 mg orally twice daily on weeks 2-12 (unless weight adjustment needed).		Participant will receive the placebo intervention, matching the Losartan intervention, once daily for week 1, followed by twice daily on weeks 2-12.
All Cause Mortality
	Losartan Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/5 (0%)
Serious Adverse Events
	Losartan Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Losartan Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		5/5 (100%)
General disorders
nose bleed	1/2 (50%)	2	0/5 (0%)	0
Sore throat	1/2 (50%)	1	0/5 (0%)	0
Fatigue	0/2 (0%)	0	1/5 (20%)	1
Musculoskeletal and connective tissue disorders
muscle cramps	1/2 (50%)	2	1/5 (20%)	5
Nervous system disorders
Headache	0/2 (0%)	0	3/5 (60%)	5
Respiratory, thoracic and mediastinal disorders
Nasal congestion	2/2 (100%)	2	0/5 (0%)	0
Pulmonary exacerbation	0/2 (0%)	0	2/5 (40%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.