Trial Outcomes & Findings for Safety Study of Aztreonam Lysine for Inhalation (AZLI) in the Treatment of Early Bronchiolitis Obliterans Syndrome (BOS) (NCT NCT01469364)
NCT ID: NCT01469364
Last Updated: 2016-01-29
Results Overview
Within-subject change to absolute FEV1 month 1 vs. 0. FEV1 was measured 14-35 days after the start of months 1 AZLI courses and compared to study month 0 (baseline/prior to 1st dose).
COMPLETED
PHASE4
30 participants
Baseline, month 1
2016-01-29
Participant Flow
Subjects were recruited from two lung transplant centers, Duke and UCLA, and 30 subjects enrolled in the study from April 2013 to July 2014.
Participant milestones
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
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|---|---|
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Overall Study
STARTED
|
30
|
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Overall Study
COMPLETED
|
28
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
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|---|---|
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Overall Study
Adverse Event
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Safety Study of Aztreonam Lysine for Inhalation (AZLI) in the Treatment of Early Bronchiolitis Obliterans Syndrome (BOS)
Baseline characteristics by cohort
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
n=30 Participants
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
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|---|---|
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Age, Continuous
|
64 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
28 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
2 participants
n=5 Participants
|
|
Region of Enrollment
United States
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30 participants
n=5 Participants
|
|
FEV1
|
1.87 liters
n=5 Participants
|
|
FVC
|
2.68 liters
n=5 Participants
|
|
FEF 25-75
|
1.18 liters
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, month 1Within-subject change to absolute FEV1 month 1 vs. 0. FEV1 was measured 14-35 days after the start of months 1 AZLI courses and compared to study month 0 (baseline/prior to 1st dose).
Outcome measures
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
n=30 Participants
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
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|---|---|
|
Change in Pulmonary Function, as Measured by Serial Forced Expiratory Volume in 1 Second (FEV1) on Spirometry
|
-0.04 Liter
Interval -0.22 to 0.12
|
PRIMARY outcome
Timeframe: Baseline, month 5Within-subject change to absolute FEV1 month 5 vs 0.
Outcome measures
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
n=26 Participants
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
|
|---|---|
|
Change in Pulmonary Function, as Measured by Serial Forced Expiratory Volume in 1 Second (FEV1) on Spirometry
|
-0.02 Liter
Interval -0.25 to 0.1
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PRIMARY outcome
Timeframe: Baseline, month 1Population: subjects with completed SF-36 surveys at month 1 and month 0 (n=28)
The SF-36 is a commonly used, well validated measure of global health related quality of life. The survey was self-administered. There are 8 subscales which combine to form a Physical Component Score (PCS) and a Mental Component Score (MCS). We analyzed within subject changes to the PCS and MCS at month 1 vs. 0. MCS and PCS scores are relative to a US population mean of 50. The higher the score, the better one perceives his quality of life. A change in score of 4 points or more is considered clinically meaningful. Scores represent Median Absolute Difference. The SF-36 was completed 14-35 days after the start of months 1 AZLI courses and compared to study month 0 (baseline/prior to 1st dose).
Outcome measures
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
n=28 Participants
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
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|---|---|
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Change in Global Health Related Quality of Life, Measured by Serially Self-administered Short Form 36 Health Survey Questionnaire (SF-36) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1
PCS: month 1 vs. Baseline (n=28)
|
-1.52 units on a scale
Interval -4.21 to 2.71
|
|
Change in Global Health Related Quality of Life, Measured by Serially Self-administered Short Form 36 Health Survey Questionnaire (SF-36) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1
MCS: month 1 vs. Baseline (n-28)
|
0.78 units on a scale
Interval -0.96 to 5.42
|
PRIMARY outcome
Timeframe: Baseline, month 5Population: subjects with completed SF-36 surveys at month 5 and 0 (n=26) time-points.
The SF-36 is a commonly used, well validated measure of global health related quality of life. The survey was self-administered. There are 8 subscales which combine to form a Physical Component Score (PCS) and a Mental Component Score (MCS). We analyzed within subject changes to the PCS and MCS at month 5 vs 0. MCS and PCS scores are relative to a US population mean of 50. The higher the score, the better one perceives his quality of life. A change in score of 4 points or more is considered clinically meaningful. Scores represent Median Absolute Difference. The SF-36 was completed 14-35 days after the start of months 1 and 5 AZLI courses and compared to study month 0 (baseline/prior to 1st dose).
Outcome measures
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
n=26 Participants
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
|
|---|---|
|
Change in Global Health Related Quality of Life, Measured by Serially Self-administered Short Form 36 Health Survey Questionnaire (SF-36) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1 and Month 5.
PCS: month 5 vs. Baseline (n=26)
|
1.62 units on a scale
Interval -1.42 to 5.3
|
|
Change in Global Health Related Quality of Life, Measured by Serially Self-administered Short Form 36 Health Survey Questionnaire (SF-36) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1 and Month 5.
MCS: month 5 vs. Baseline (n-26)
|
-1.24 units on a scale
Interval -6.51 to 4.71
|
PRIMARY outcome
Timeframe: Baseline, month 1Population: subjects with completed SF-36 surveys at month 1 and month 0 (n=28) time-points.
The SRGQ measures activities, symptoms, and impacts of living with a pulmonary condition. We analyzed the change to the within-subject Total score month 1 vs. 0. Total score ranges from 0-100 with a smaller value representing better respiratory-specific QOL. A change in score of 4 points or more is considered clinically meaningful. Scores represent Median Absolute Difference in the Total Score. The SGRQ was completed 14-35 days after the start of months 1 AZLI courses and compared to study month 0 (baseline/prior to 1st dose).
Outcome measures
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
n=28 Participants
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
|
|---|---|
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Change in Respiratory-specific Health Related Quality of Life, Measured by Serially Self Administered St. George's Respiratory Questionnaire (SGRQ) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1
|
0.82 units on a scale
Interval -6.53 to 8.2
|
PRIMARY outcome
Timeframe: Baseline, month 5Population: subjects with completed SF-36 surveys at month 5 and 0 (n=26) time-points.
The SRGQ measures activities, symptoms, and impacts of living with a pulmonary condition. We analyzed the change to the within-subject Total score month 5 vs 0. Total score ranges from 0-100 with a smaller value representing better respiratory-specific QOL. A change in score of 4 points or more is considered clinically meaningful. Scores represent Median Absolute Difference in theTotal Score. The SGRQ was completed 14-35 days after the start of month 5 AZLI courses and compared to study month 0 (baseline/prior to 1st dose).
Outcome measures
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
n=26 Participants
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
|
|---|---|
|
Change in Respiratory-specific Health Related Quality of Life, Measured by Serially Self Administered St. George's Respiratory Questionnaire (SGRQ) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 5.
|
0.15 units on a scale
Interval -5.21 to 6.19
|
PRIMARY outcome
Timeframe: Baseline, month 5Within-subject change to absolute FEF 25-75 month 5 vs 0. FEF 25-75 was measured 14-35 days after the start of months 5
Outcome measures
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
n=26 Participants
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
|
|---|---|
|
Change in Pulmonary Function, as Measured by Serial Forced Expiratory Flow (FEF25-75) on Spirometry at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 5.
|
-0.015 Liter
Interval -0.36 to 0.17
|
PRIMARY outcome
Timeframe: Baseline, month 1Within-subject change to absolute FEF 25-75 month 1 vs. 0. FEF 25-75 was measured 14-35 days after the start of months 1
Outcome measures
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
n=30 Participants
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
|
|---|---|
|
Change in Pulmonary Function, as Measured by Serial Forced Expiratory Flow (FEF25-75) on Spirometry at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1
|
-0.025 Liter
Interval -0.19 to 0.13
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SECONDARY outcome
Timeframe: At Study Months 2 and 4Population: Partial data for this outcome measure was collected on 4 participants and due to not having complete data set analyzation was not completed.
This will be compared to study month 0 (baseline, when obtained as standard of care (SOC).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At study months 2 or 4Population: Partial data for this outcome measure was collected on 4 participants and due to not having a complete data set the analyzation was not completed.
This will be compared to study month 0 (baseline), when obtained at standard of care visit (SOC)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, month 1Population: The statistical analysis was unable to be performed due to insufficient number of paired observations. Only 9 of 30 enrolled had baseline microbiology data, 3 were cultured positive for Pseudomonas Aeruginosa. Only 1 of the 3 had a subsequent SOC BAL sample collected. Therefore, only raw data is entered for the one subject.
Microbiology data was collected when performed for SOC purposes on BAL or sputum samples. Baseline and 1 month value represents the culture final report value (0,1+, 2+, 3+, 4+) of Pseudomonas aeruginosa. A value of zero represents no Pseudomonas aeruginosa sputum or bronchoalveolar fluid. A value of 4 represents high amounts of Pseudomonas aeruginosa sputum or bronchoalveolar fluid.
Outcome measures
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
n=1 Participants
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
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|---|---|
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Among Patients Colonized With Pseudomonas Aeruginosa, Change in Infection Burden as Measured by the Culture Final Report (0,1+, 2+, 3+, 4+) of in Pseudomonas Aeruginosa Sputum or Bronchoalveolar Fluid.
Culture value at Baseline
|
4 culture value of Pseudomonas aeruginosa
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Among Patients Colonized With Pseudomonas Aeruginosa, Change in Infection Burden as Measured by the Culture Final Report (0,1+, 2+, 3+, 4+) of in Pseudomonas Aeruginosa Sputum or Bronchoalveolar Fluid.
Culture value at one month
|
0 culture value of Pseudomonas aeruginosa
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SECONDARY outcome
Timeframe: Baseline - defined as a within 90 days of enrollment and After Treatment (5 months)Population: Participants with paired SOC bronchoalveolar lavage fluid cell differential counts performed within 90 days of AZLI month 1 (baseline timepoint) and \>=15 days after AZLI dose 1 through the completion of dose 3 (study month 5) were included in the analysis (n=5).
The study team is measuring the change in neutrophils AFTER treatment. They will compare a SOC BAL taken after AZLI with the BAL taken within 90 days of AZLI initiation (pre or baseline measure). The post AZLI BAL measurement time range is 15 days after first course of AZLI up to last day of the 3rd and final course of AZLI (over a period of 5 consecutive months).
Outcome measures
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
n=5 Participants
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
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|---|---|
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Bronchoalveolar Lavage Fluid (BALF) Neutrophilia After Treatment, When Performed as Part of Clinical Care (SOC).
|
7.80 mean percentage of neutrophils
Standard Deviation 25.43
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Adverse Events
Aztreonam Lysine for Inhalation (AZLI)
Serious adverse events
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
n=30 participants at risk
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
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|---|---|
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Respiratory, thoracic and mediastinal disorders
Left pneumothorax
|
3.3%
1/30 • Adverse events were collected on study day 1, day 7 and at the end of study month 1 and 5.
|
Other adverse events
| Measure |
Aztreonam Lysine for Inhalation (AZLI)
n=30 participants at risk
Patients to received Aztreonam Lysine(AZLI)
Aztreonam Lysine for Inhalation (AZLI): The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)
Status Post Lung Transplant: Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care.
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|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough during or after administration
|
43.3%
13/30 • Adverse events were collected on study day 1, day 7 and at the end of study month 1 and 5.
|
|
General disorders
Dry mouth during administration
|
6.7%
2/30 • Adverse events were collected on study day 1, day 7 and at the end of study month 1 and 5.
|
|
Respiratory, thoracic and mediastinal disorders
Increased dyspnea
|
6.7%
2/30 • Adverse events were collected on study day 1, day 7 and at the end of study month 1 and 5.
|
|
Respiratory, thoracic and mediastinal disorders
Increased sputum production
|
6.7%
2/30 • Adverse events were collected on study day 1, day 7 and at the end of study month 1 and 5.
|
|
Reproductive system and breast disorders
Thinned out mucous
|
3.3%
1/30 • Adverse events were collected on study day 1, day 7 and at the end of study month 1 and 5.
|
|
Gastrointestinal disorders
Nausea
|
3.3%
1/30 • Adverse events were collected on study day 1, day 7 and at the end of study month 1 and 5.
|
|
General disorders
Dysphonia
|
3.3%
1/30 • Adverse events were collected on study day 1, day 7 and at the end of study month 1 and 5.
|
|
Psychiatric disorders
Irritability
|
3.3%
1/30 • Adverse events were collected on study day 1, day 7 and at the end of study month 1 and 5.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place