Cystic Fibrosis
Conditions
Keywords
cystic fibrosis, Pseudomonas aeruginosa
Brief summary
The purpose of this study was to evaluate the safety and efficacy of multiple courses of AZLI in patients with cystic fibrosis (CF) and lung infection due to Pseudomonas aeruginosa (PA).
Detailed description
People with CF often have lung infections that occur repeatedly or worsen over time. The lung infections are often caused by PA. Treatment with antibiotics is used to reduce the presence of the bacteria. The antibiotics may be given orally, intravenously, or inhaled as a mist. The purpose of this study was to evaluate whether AZLI, an investigational formulation of the antibiotic aztreonam, is safe in repeated courses in patients with CF and PA. A course of AZLI treatment in this study comprised 28 days, followed by a 28-day period off treatment. Participants could receive up to 9 courses of AZLI, with a total time on study of up to 18 months. Safety and efficacy results for the 18-month, 9-course period are reported, with efficacy results presented on a by-treatment course basis.
Interventions
DRUGAZLI 75 mg two times a day (BID)/ three times a day (TID)
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Compliance with Studies CP-AI-005 (NCT00104520) or CP-AI-007 (NCT00112359) by taking at least 50% of expected study medication. * Completion of CP-AI-005 or CP-AI-007 or was withdrawn due to need for antipseudomonal antibiotics or for an AE unrelated to study medication tolerance. * Ability to provide written informed consent/assent prior to initiation of study-related procedures. * Ability to perform reproducible pulmonary function tests.
Exclusion criteria
* Use of any investigational medication or device between the last visit of CP-AI-005 or CP-AI-007 and Visit 1 of this study. * Concurrent participation in a study of another investigational drug or device. * Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone/day or 20 mg prednisone every other day. * History of sputum or throat swab culture yielding Burkholderia cepacia in the previous 2 years. * History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night. * Inability to tolerate study medication in CP-AI-005 or CP-AI-007. * Known local or systemic hypersensitivity to aztreonam. * Inability to tolerate inhalation of a short acting beta-2 agonist. * Abnormal renal or hepatic function based on results of most recent test. * Female of child-bearing potential who was pregnant, lactating, or not (in the opinion of the investigator) practicing an acceptable method of birth control. * Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would have interfered with participant treatment, assessment, or compliance with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Chemistry - Concentration of Total Protein | Baseline and end of treatment Course 9 (Week 68) | — |
| Serum Hematology - Number of Red Blood Cells (RBC) | Baseline and end of treatment Course 9 (Week 68) | — |
| Serum Hematology - Hematocrit | Baseline and end of treatment Course 9 (Week 68) | — |
| Serum Hematology - Hemoglobin | Baseline and end of treatment Course 9 (Week 68) | — |
| Serum Hematology - Mean Corpuscular Volume (MCV) | Baseline and end of treatment Course 9 (Week 68) | — |
| Serum Hematology - Mean Corpuscular Hemoglobin (MCH) | Baseline and end of treatment Course 9 (Week 68) | — |
| Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC) | Baseline and end of treatment Course 9 (Week 68) | — |
| Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) | Baseline and end of treatment Course 9 (Week 68) | — |
| Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Baseline and end of treatment Course 9 (Week 68) | — |
| Serum Chemistry - Concentration of Chloride, Potassium, and Sodium | Baseline and end of treatment Course 9 (Week 68) | — |
| Number of Participants Reporting Adverse Events (AEs) | Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug | Participants experiencing at least 1 treatment-emergent AE or at least 1 serious adverse event (SAE) were summarized for the study as a whole. A treatment-emergent AE was any physical or clinical worsening in symptoms or disease experienced by the participant, whether or not the event was considered related to study participation or study procedures. An SAE was any adverse experience that resulted in hospitalization or death. Participants were monitored for AEs and SAEs during all on-treatment and off-treatment intervals throughout the 18-month study period. |
| Number of Subjects With <15% or ≥15% Decline in Forced Expiratory Volume in 1 Second [FEV1] From Pretreatment to 30 Minutes After Treatment With AZLI | Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug | Airway reactivity (percent change in FEV1 from pretreatment to 30 minutes after treatment with AZLI) was assessed at all study visits in which a participant received AZLI treatment. A participant was included in this endpoint if they experienced a decline in FEV1 of ≥15% at any visit in which they received AZLI. |
| Change in Heart Rate (HR) | Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68) | HR was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined. |
| Change in Systolic and Diastolic Blood Pressure (BP) | Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68) | BP was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined. |
| Change in Temperature | Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68) | Temperature was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined. |
| Change in Respiratory Rate (RR) | Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68) | RR was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined. |
| Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Baseline and end of Course 9 (Week 68) | — |
| Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Baseline and end of treatment Course 9 (Week 68) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Other Pathogens | Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72) | Sputum samples were collected at all study visits for qualitative and quantitative culture for Burkholderia cepacia complex (BCC), Stenotrophomonas maltophilia, Achromobacter xylosoxidans, Staphylococcus aureus (including methicillin-sensitive \[MSSA\] and methicillin-resistant \[MRSA\] S.aureus), and fungal organisms. Number of participants with other pathogens at baseline and end of AZLI treatment Courses 1, 3, and 9 are reported. |
| Minimum Inhibitory Concentration (MIC) of Aztreonam | Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72) | The aztreonam susceptibility of PA isolates from expectorated sputum samples (collected at all visits) was assessed. MIC50 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 50% of isolates from a particular organism). MIC90 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 90% of isolates from a particular organism). MIC50 and MIC90 values are single measurements for the entire population and not measured on a per-participant basis. |
| Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68) | Spirometry was performed at each visit. FEV1, FVC, and FEF25-75 were recorded at all visits according to American Thoracic Society (ATS) guidelines. FEV1 = the volume of air exhaled in 1 second. FEV1 % predicted is a normalized value of FEV1 calculated using the Knudson equation, based upon participant age, gender, and height. FVC = (forced vital capacity) the maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration. FEF25-75 = forced expiratory flow from 25% to 75% of the FVC. The percent change from baseline is presented for each endpoint. |
| Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS) | Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68) | The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores: 0-100; higher scores indicate fewer symptoms). The minimal clinically important difference (MCID) corresponds to the smallest change in symptoms that a patient can detect and is a change in score of 4 points. |
| Time to First Hospitalization Due to a Respiratory Event | Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug | Details of all hospitalizations, including the dates of admission and discharge, were recorded on the serious adverse event (SAE) electronic case report form (eCRF). Time to first hospitalization was the number of days from baseline (Visit 1) to the date of first hospitalization or the date of study completion (last visit) /or early withdrawal if censored. |
| Change in Body Weight | Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68) | Weight was measured at all visits and was reported to the nearest 0.1 kg/lb. Percent change in weight from baseline was calculated. |
| Missed School/Work Days Due to CF Symptoms | Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug | Participants were provided with a diary card at each visit to record days of work and/or school missed due to their CF symptoms. The percentage of school/work days missed was calculated as the total number of school/work days missed divided by the total number of on-study days multiplied by 100 across all participants in a treatment group. |
| Time to Intravenous (IV) Antipseudomonal Antibiotics | Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug | Use of IV antipseudomonal antibiotics was compiled from data recorded on the Concomitant Medications eCRF. The time to first IV antipseudomonal antibiotic use was the number of days from baseline (Visit 1) to the date of first IV antipseudomonal antibiotic use or the date of study completion (last visit) /or early withdrawal if censored. |
| Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum | Baseline, and the end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68) | Sputum samples were collected at all participant visits of the study for analysis of microbiology endpoints. Sputum samples were processed for qualitative and quantitative culture of PA (each morphotype). Due to the skewness of the distribution of CFU data, the data were transformed using the base 10 logarithm, in an attempt to normalize the data and allow for parametric tests, before calculating changes. To account for zero values, 1 was added to each CFU measurement before being transformed. Any CFU data values where PA was not isolated from a valid culture were set to zero. |
Countries
Australia, Canada, New Zealand, United States
Participant flow
Recruitment details
Open-label, Phase 3 follow-on study for participants from Studies CP-AI-005 (NCT00104520) and CP-AI-007 (NCT00112359). Participants were enrolled at 71 sites in the United States, Canada, Australia, and New Zealand. The date of first enrollment was 17 August 2005, and the date of database lock was 23 January 2009.
Pre-assignment details
Participants enrolled in this study were required to have previously participated in CP-AI-005 or CP-AI-007. Participants from CP-AI-005 received open-label AZLI (75 mg) in the same regimen (twice daily \[BID\] or three times daily \[TID\]) to which they were previously randomized. Participants from CP-AI-007 received open-label AZLI (75 mg) TID.
Participants by arm
| Arm | Count |
|---|---|
| 75 mg AZLI Two Times a Day (BID) Participants received up to 9 treatment courses of open-label 75 mg AZLI BID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy.
BID = twice daily | 85 |
| 75 mg AZLI Three Times a Day (TID) Participants received up to 9 treatment courses of open-label 75 mg AZLI TID via an investigational nebulizer; each treatment course consisted of 28 days of AZLI and was followed by a 28-day interval off therapy.
TID = three times daily | 189 |
| Total | 274 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | AE related to study | 1 | 4 |
| Overall Study | AE unrelated to study | 2 | 9 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 5 |
| Overall Study | Noncompliance | 0 | 5 |
| Overall Study | Personal or administrative | 10 | 22 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Study drug intolerance (AE) | 2 | 8 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | 75 mg AZLI Two Times a Day (BID) | 75 mg AZLI Three Times a Day (TID) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 19 Participants | 36 Participants | 55 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 65 Participants | 151 Participants | 216 Participants |
| Age Continuous | 27.3 years STANDARD_DEVIATION 11.4 | 29.0 years STANDARD_DEVIATION 13 | 28.5 years STANDARD_DEVIATION 12.5 |
| Aztreonam Minimum Inhibitory Concentration (MIC) for Pseudomonas aeruginosa (PA) Aztreonam MIC > 8 µg/mL | 30 participants | 72 participants | 102 participants |
| Aztreonam Minimum Inhibitory Concentration (MIC) for Pseudomonas aeruginosa (PA) Aztreonam MIC < or = 8 µg/mL | 46 participants | 99 participants | 145 participants |
| Aztreonam Minimum Inhibitory Concentration (MIC) for Pseudomonas aeruginosa (PA) Unknown | 9 participants | 18 participants | 27 participants |
| Body Mass Index (BMI) | 21.30 kg/m^2 STANDARD_DEVIATION 3.25 | 21.44 kg/m^2 STANDARD_DEVIATION 3.96 | 21.40 kg/m^2 STANDARD_DEVIATION 3.75 |
| Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS) | 65.410 Units on a scale STANDARD_DEVIATION 16.896 | 60.332 Units on a scale STANDARD_DEVIATION 18.497 | 61.895 Units on a scale STANDARD_DEVIATION 18.141 |
| Disease severity as defined by FEV1 percent predicted category FEV1 ≤ 50% predicted | 36 Participants | 74 Participants | 110 Participants |
| Disease severity as defined by FEV1 percent predicted category FEV1 > 50% predicted | 49 Participants | 114 Participants | 163 Participants |
| Disease severity as defined by FEV1 percent predicted category Unknown | 0 Participants | 1 Participants | 1 Participants |
| Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted | 56.711 Percent STANDARD_DEVIATION 17.505 | 55.071 Percent STANDARD_DEVIATION 15.428 | 55.582 Percent STANDARD_DEVIATION 16.089 |
| Log10 Pseudomonas aeruginosa (PA) Colony-Forming Units (CFUs) in Sputum | 5.71 log10 CFUs/g STANDARD_DEVIATION 2.249 | 6.16 log10 CFUs/g STANDARD_DEVIATION 1.894 | 6.02 log10 CFUs/g STANDARD_DEVIATION 2.014 |
| Region of Enrollment Australia | 0 participants | 22 participants | 22 participants |
| Region of Enrollment Canada | 0 participants | 8 participants | 8 participants |
| Region of Enrollment New Zealand | 0 participants | 2 participants | 2 participants |
| Region of Enrollment United States | 85 participants | 157 participants | 242 participants |
| Sex: Female, Male Female | 34 Participants | 89 Participants | 123 Participants |
| Sex: Female, Male Male | 51 Participants | 100 Participants | 151 Participants |
| Weight | 59.52 kg STANDARD_DEVIATION 13.28 | 59.28 kg STANDARD_DEVIATION 15.81 | 59.36 kg STANDARD_DEVIATION 15.05 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 83 / 85 | 185 / 189 |
| serious Total, serious adverse events | 38 / 85 | 100 / 189 |
Outcome results
Primary
Change in Heart Rate (HR)
HR was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.
Time frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Change in Heart Rate (HR) | HR, End of Treatment Course 1 | 1.08 beats/minute | Standard Deviation 15.9 |
| 75 mg AZLI Two Times a Day (BID) | Change in Heart Rate (HR) | HR, End of Treatment Course 3 | -0.53 beats/minute | Standard Deviation 13.7 |
| 75 mg AZLI Two Times a Day (BID) | Change in Heart Rate (HR) | HR, End of Treatment Course 9 | 3.87 beats/minute | Standard Deviation 12.9 |
| 75 mg AZLI Three Times a Day (TID) | Change in Heart Rate (HR) | HR, End of Treatment Course 1 | -0.07 beats/minute | Standard Deviation 12.9 |
| 75 mg AZLI Three Times a Day (TID) | Change in Heart Rate (HR) | HR, End of Treatment Course 3 | 0.13 beats/minute | Standard Deviation 14.5 |
| 75 mg AZLI Three Times a Day (TID) | Change in Heart Rate (HR) | HR, End of Treatment Course 9 | -0.06 beats/minute | Standard Deviation 12.5 |
Primary
Change in Respiratory Rate (RR)
RR was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.
Time frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Change in Respiratory Rate (RR) | RR, End of Treatment Course 1 | -0.07 breaths/minute | Standard Deviation 2.8 |
| 75 mg AZLI Two Times a Day (BID) | Change in Respiratory Rate (RR) | RR, End of Treatment Course 3 | -0.03 breaths/minute | Standard Deviation 3.3 |
| 75 mg AZLI Two Times a Day (BID) | Change in Respiratory Rate (RR) | RR, End of Treatment Course 9 | 0.02 breaths/minute | Standard Deviation 3.8 |
| 75 mg AZLI Three Times a Day (TID) | Change in Respiratory Rate (RR) | RR, End of Treatment Course 1 | 0.17 breaths/minute | Standard Deviation 3.9 |
| 75 mg AZLI Three Times a Day (TID) | Change in Respiratory Rate (RR) | RR, End of Treatment Course 3 | 0.02 breaths/minute | Standard Deviation 3.7 |
| 75 mg AZLI Three Times a Day (TID) | Change in Respiratory Rate (RR) | RR, End of Treatment Course 9 | 0.33 breaths/minute | Standard Deviation 3.3 |
Primary
Change in Systolic and Diastolic Blood Pressure (BP)
BP was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.
Time frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Change in Systolic and Diastolic Blood Pressure (BP) | Systolic BP, End of Treatment Course 3 | -0.67 mm Hg | Standard Deviation 13.1 |
| 75 mg AZLI Two Times a Day (BID) | Change in Systolic and Diastolic Blood Pressure (BP) | Diastolic BP, End of Treatment Course 1 | 0.49 mm Hg | Standard Deviation 8.4 |
| 75 mg AZLI Two Times a Day (BID) | Change in Systolic and Diastolic Blood Pressure (BP) | Systolic BP, End of Treatment Course 1 | 0.75 mm Hg | Standard Deviation 11 |
| 75 mg AZLI Two Times a Day (BID) | Change in Systolic and Diastolic Blood Pressure (BP) | Diastolic BP, End of Treatment Course 3 | -1.64 mm Hg | Standard Deviation 8.7 |
| 75 mg AZLI Two Times a Day (BID) | Change in Systolic and Diastolic Blood Pressure (BP) | Systolic BP, End of Treatment Course 9 | -1.06 mm Hg | Standard Deviation 13.2 |
| 75 mg AZLI Two Times a Day (BID) | Change in Systolic and Diastolic Blood Pressure (BP) | Diastolic BP, End of Treatment Course 9 | -0.40 mm Hg | Standard Deviation 9.4 |
| 75 mg AZLI Three Times a Day (TID) | Change in Systolic and Diastolic Blood Pressure (BP) | Systolic BP, End of Treatment Course 9 | -0.33 mm Hg | Standard Deviation 11 |
| 75 mg AZLI Three Times a Day (TID) | Change in Systolic and Diastolic Blood Pressure (BP) | Systolic BP, End of Treatment Course 1 | 1.19 mm Hg | Standard Deviation 11.7 |
| 75 mg AZLI Three Times a Day (TID) | Change in Systolic and Diastolic Blood Pressure (BP) | Systolic BP, End of Treatment Course 3 | 0.29 mm Hg | Standard Deviation 11.9 |
| 75 mg AZLI Three Times a Day (TID) | Change in Systolic and Diastolic Blood Pressure (BP) | Diastolic BP, End of Treatment Course 9 | -0.76 mm Hg | Standard Deviation 10 |
| 75 mg AZLI Three Times a Day (TID) | Change in Systolic and Diastolic Blood Pressure (BP) | Diastolic BP, End of Treatment Course 1 | 0.05 mm Hg | Standard Deviation 8.2 |
| 75 mg AZLI Three Times a Day (TID) | Change in Systolic and Diastolic Blood Pressure (BP) | Diastolic BP, End of Treatment Course 3 | -0.89 mm Hg | Standard Deviation 8.3 |
Primary
Change in Temperature
Temperature was recorded at all visits. Change from baseline at the end of AZLI treatment Courses 1 (Visit 2), 3 (Visit 4), and 9 (Visit 19) was determined.
Time frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20) and 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Change in Temperature | Temperature (Celsius) End of Treatment Course 1 | -0.05 degrees Celsius | Standard Deviation 0.4 |
| 75 mg AZLI Two Times a Day (BID) | Change in Temperature | Temperature (Celsius) End of Treatment Course 3 | -0.09 degrees Celsius | Standard Deviation 0.4 |
| 75 mg AZLI Two Times a Day (BID) | Change in Temperature | Temperature (Celsius) End of Treatment Course 9 | 0.04 degrees Celsius | Standard Deviation 0.6 |
| 75 mg AZLI Three Times a Day (TID) | Change in Temperature | Temperature (Celsius) End of Treatment Course 1 | 0.00 degrees Celsius | Standard Deviation 0.5 |
| 75 mg AZLI Three Times a Day (TID) | Change in Temperature | Temperature (Celsius) End of Treatment Course 3 | 0.01 degrees Celsius | Standard Deviation 0.5 |
| 75 mg AZLI Three Times a Day (TID) | Change in Temperature | Temperature (Celsius) End of Treatment Course 9 | 0.05 degrees Celsius | Standard Deviation 0.5 |
Primary
Number of Participants Reporting Adverse Events (AEs)
Participants experiencing at least 1 treatment-emergent AE or at least 1 serious adverse event (SAE) were summarized for the study as a whole. A treatment-emergent AE was any physical or clinical worsening in symptoms or disease experienced by the participant, whether or not the event was considered related to study participation or study procedures. An SAE was any adverse experience that resulted in hospitalization or death. Participants were monitored for AEs and SAEs during all on-treatment and off-treatment intervals throughout the 18-month study period.
Time frame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Number of Participants Reporting Adverse Events (AEs) | Participants Reporting at least One Related AE | 30 participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants Reporting Adverse Events (AEs) | Number of Participants Reporting at Least One AE | 83 participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants Reporting Adverse Events (AEs) | Number of Participants Reporting at Least One SAE | 38 participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants Reporting Adverse Events (AEs) | Participants with Study Drug Withdrawn due to AE | 7 participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants Reporting Adverse Events (AEs) | Number of Participants who Died on Study | 1 participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants Reporting Adverse Events (AEs) | Number of Participants who Died on Study | 0 participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants Reporting Adverse Events (AEs) | Participants with Study Drug Withdrawn due to AE | 38 participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants Reporting Adverse Events (AEs) | Number of Participants Reporting at Least One SAE | 100 participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants Reporting Adverse Events (AEs) | Number of Participants Reporting at Least One AE | 185 participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants Reporting Adverse Events (AEs) | Participants Reporting at least One Related AE | 79 participants |
Primary
Number of Subjects With <15% or ≥15% Decline in Forced Expiratory Volume in 1 Second [FEV1] From Pretreatment to 30 Minutes After Treatment With AZLI
Airway reactivity (percent change in FEV1 from pretreatment to 30 minutes after treatment with AZLI) was assessed at all study visits in which a participant received AZLI treatment. A participant was included in this endpoint if they experienced a decline in FEV1 of ≥15% at any visit in which they received AZLI.
Time frame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Number of Subjects With <15% or ≥15% Decline in Forced Expiratory Volume in 1 Second [FEV1] From Pretreatment to 30 Minutes After Treatment With AZLI | Participants with <15% decline | 76 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Subjects With <15% or ≥15% Decline in Forced Expiratory Volume in 1 Second [FEV1] From Pretreatment to 30 Minutes After Treatment With AZLI | Participants with >=15% decline | 9 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Subjects With <15% or ≥15% Decline in Forced Expiratory Volume in 1 Second [FEV1] From Pretreatment to 30 Minutes After Treatment With AZLI | Participants with <15% decline | 175 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Subjects With <15% or ≥15% Decline in Forced Expiratory Volume in 1 Second [FEV1] From Pretreatment to 30 Minutes After Treatment With AZLI | Participants with >=15% decline | 14 Participants |
Primary
Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT)
Time frame: Baseline and end of treatment Course 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) | ALT, Baseline | 31.21 U/L | Standard Deviation 22.343 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) | ALT, End of Treatment Course 9 | 30.78 U/L | Standard Deviation 24.045 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) | AST, Baseline | 27.83 U/L | Standard Deviation 14.856 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) | AST, End of Treatment Course 9 | 26.84 U/L | Standard Deviation 14.588 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) | GGT, Baseline | 35.49 U/L | Standard Deviation 48.215 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) | GGT, End of Treatment Course 9 | 40.83 U/L | Standard Deviation 57.471 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) | GGT, Baseline | 29.64 U/L | Standard Deviation 41.862 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) | ALT, Baseline | 26.65 U/L | Standard Deviation 18.982 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) | AST, End of Treatment Course 9 | 26.22 U/L | Standard Deviation 15.24 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) | ALT, End of Treatment Course 9 | 27.81 U/L | Standard Deviation 21.794 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) | GGT, End of Treatment Course 9 | 32.39 U/L | Standard Deviation 39.662 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-glutamlytransferase (GGT) | AST, Baseline | 25.77 U/L | Standard Deviation 15.556 |
Primary
Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen
Time frame: Baseline and end of treatment Course 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Calcium (EDTA), Baseline | 9.67 mg/dL | Standard Deviation 0.406 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Calcium (EDTA), End of Treatment Course 9 | 9.43 mg/dL | Standard Deviation 0.385 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Creatinine, Baseline | 0.80 mg/dL | Standard Deviation 0.202 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Creatinine, End of Treatment Course 9 | 0.80 mg/dL | Standard Deviation 0.207 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Direct bilirubin, Baseline | 0.14 mg/dL | Standard Deviation 0.076 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Direct bilirubin, End of Treatment Course 9 | 0.16 mg/dL | Standard Deviation 0.081 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Total bilirubin, Baseline | 0.42 mg/dL | Standard Deviation 0.237 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Total bilirubin, End of Treatment Course 9 | 0.51 mg/dL | Standard Deviation 0.294 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Serum glucose, Baseline | 115.46 mg/dL | Standard Deviation 55.211 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Serum glucose, End of Treatment Course 9 | 121.11 mg/dL | Standard Deviation 57.47 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | BUN, Baseline | 14.65 mg/dL | Standard Deviation 4.258 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | BUN, End of Treatment Course 9 | 13.83 mg/dL | Standard Deviation 4.764 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | BUN, Baseline | 14.32 mg/dL | Standard Deviation 5.698 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Calcium (EDTA), Baseline | 9.56 mg/dL | Standard Deviation 0.416 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Total bilirubin, Baseline | 0.43 mg/dL | Standard Deviation 0.298 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Calcium (EDTA), End of Treatment Course 9 | 9.47 mg/dL | Standard Deviation 0.427 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Serum glucose, End of Treatment Course 9 | 116.40 mg/dL | Standard Deviation 65.046 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Creatinine, Baseline | 0.81 mg/dL | Standard Deviation 0.317 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Total bilirubin, End of Treatment Course 9 | 0.49 mg/dL | Standard Deviation 0.377 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Creatinine, End of Treatment Course 9 | 0.82 mg/dL | Standard Deviation 0.295 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | BUN, End of Treatment Course 9 | 14.49 mg/dL | Standard Deviation 4.805 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Direct bilirubin, Baseline | 0.13 mg/dL | Standard Deviation 0.064 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Serum glucose, Baseline | 111.53 mg/dL | Standard Deviation 49.485 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Calcium, Creatinine, Direct Bilirubin, Total Bilirubin, Serum Glucose, and Blood Urea Nitrogen | Direct bilirubin, End of Treatment Course 9 | 0.14 mg/dL | Standard Deviation 0.072 |
Primary
Serum Chemistry - Concentration of Chloride, Potassium, and Sodium
Time frame: Baseline and end of treatment Course 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Chloride, Potassium, and Sodium | Serum chloride, Baseline | 102.17 mEq/L | Standard Deviation 2.904 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Chloride, Potassium, and Sodium | Serum chloride, End of Treatment Course 9 | 101.81 mEq/L | Standard Deviation 2.61 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Chloride, Potassium, and Sodium | Serum potassium, Baseline | 4.20 mEq/L | Standard Deviation 0.354 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Chloride, Potassium, and Sodium | Serum potassium, End of Treatment Course 9 | 4.19 mEq/L | Standard Deviation 0.388 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Chloride, Potassium, and Sodium | Serum sodium, Baseline | 139.18 mEq/L | Standard Deviation 2.984 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Chloride, Potassium, and Sodium | Serum sodium, End of Treatment Course 9 | 138.64 mEq/L | Standard Deviation 2.608 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Chloride, Potassium, and Sodium | Serum sodium, Baseline | 139.23 mEq/L | Standard Deviation 2.618 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Chloride, Potassium, and Sodium | Serum chloride, Baseline | 102.22 mEq/L | Standard Deviation 2.943 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Chloride, Potassium, and Sodium | Serum potassium, End of Treatment Course 9 | 4.25 mEq/L | Standard Deviation 0.372 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Chloride, Potassium, and Sodium | Serum chloride, End of Treatment Course 9 | 102.16 mEq/L | Standard Deviation 2.977 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Chloride, Potassium, and Sodium | Serum sodium, End of Treatment Course 9 | 138.88 mEq/L | Standard Deviation 2.694 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Chloride, Potassium, and Sodium | Serum potassium, Baseline | 4.29 mEq/L | Standard Deviation 0.37 |
Primary
Serum Chemistry - Concentration of Total Protein
Time frame: Baseline and end of treatment Course 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Total Protein | Total protein, Baseline | 7.63 g/dL | Standard Deviation 0.588 |
| 75 mg AZLI Two Times a Day (BID) | Serum Chemistry - Concentration of Total Protein | Total protein, End of Treatment Course 9 | 7.47 g/dL | Standard Deviation 0.425 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Total Protein | Total protein, Baseline | 7.58 g/dL | Standard Deviation 0.536 |
| 75 mg AZLI Three Times a Day (TID) | Serum Chemistry - Concentration of Total Protein | Total protein, End of Treatment Course 9 | 7.53 g/dL | Standard Deviation 0.56 |
Primary
Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets
Time frame: Baseline and end of Course 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI. Results obtained at the end of a 28-day treatment period are presented for selected timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Lymphocytes, Baseline | 2.00 number of cells x10^3/µL | Standard Deviation 0.623 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Basophils, Baseline | 0.05 number of cells x10^3/µL | Standard Deviation 0.037 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Monocytes, Baseline | 0.47 number of cells x10^3/µL | Standard Deviation 0.19 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Lymphocytes, End of Treatment Course 9 | 1.99 number of cells x10^3/µL | Standard Deviation 0.801 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Monocytes, End of Treatment Course 9 | 0.50 number of cells x10^3/µL | Standard Deviation 0.157 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Eosinophils, Baseline | 0.18 number of cells x10^3/µL | Standard Deviation 0.111 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Neutrophils, Baseline | 6.54 number of cells x10^3/µL | Standard Deviation 3.295 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | WBCs, End of Treatment Course 9 | 9.47 number of cells x10^3/µL | Standard Deviation 3.998 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Neutrophils, End of Treatment Course 9 | 6.68 number of cells x10^3/µL | Standard Deviation 3.481 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Basophils, End of Treatment Course 9 | 0.05 number of cells x10^3/µL | Standard Deviation 0.034 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Platelets, Baseline | 293.11 number of cells x10^3/µL | Standard Deviation 85.681 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Eosinophils, End of Treatment Course 9 | 0.21 number of cells x10^3/µL | Standard Deviation 0.209 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Platelets, End of Treatment Course 9 | 290.43 number of cells x10^3/µL | Standard Deviation 106.903 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | WBCs, Baseline | 9.28 number of cells x10^3/µL | Standard Deviation 3.692 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Platelets, End of Treatment Course 9 | 311.39 number of cells x10^3/µL | Standard Deviation 98.37 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Basophils, Baseline | 0.06 number of cells x10^3/µL | Standard Deviation 0.144 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Basophils, End of Treatment Course 9 | 0.05 number of cells x10^3/µL | Standard Deviation 0.033 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Eosinophils, Baseline | 0.19 number of cells x10^3/µL | Standard Deviation 0.152 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Lymphocytes, Baseline | 2.17 number of cells x10^3/µL | Standard Deviation 0.732 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | WBCs, Baseline | 10.11 number of cells x10^3/µL | Standard Deviation 3.635 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | WBCs, End of Treatment Course 9 | 9.53 number of cells x10^3/µL | Standard Deviation 3.562 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Eosinophils, End of Treatment Course 9 | 0.17 number of cells x10^3/µL | Standard Deviation 0.144 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Lymphocytes, End of Treatment Course 9 | 2.13 number of cells x10^3/µL | Standard Deviation 0.719 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Monocytes, Baseline | 0.54 number of cells x10^3/µL | Standard Deviation 0.241 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Monocytes, End of Treatment Course 9 | 0.52 number of cells x10^3/µL | Standard Deviation 0.21 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Neutrophils, Baseline | 7.09 number of cells x10^3/µL | Standard Deviation 3.227 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Neutrophils, End of Treatment Course 9 | 6.63 number of cells x10^3/µL | Standard Deviation 3.345 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Concentration of White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets | Platelets, Baseline | 340.19 number of cells x10^3/µL | Standard Deviation 106.749 |
Primary
Serum Hematology - Hematocrit
Time frame: Baseline and end of treatment Course 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Hematocrit | Hematocrit, Baseline | 43.43 percent | Standard Deviation 4.037 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Hematocrit | Hematocrit, End of treatment course 9 | 42.00 percent | Standard Deviation 3.317 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Hematocrit | Hematocrit, Baseline | 42.45 percent | Standard Deviation 4.142 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Hematocrit | Hematocrit, End of treatment course 9 | 41.63 percent | Standard Deviation 4.056 |
Primary
Serum Hematology - Hemoglobin
Time frame: Baseline and end of treatment Course 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Hemoglobin | Hemoglobin, Baseline | 14.06 g/dL | Standard Deviation 1.406 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Hemoglobin | Hemoglobin, End of treatment course 9 | 13.89 g/dL | Standard Deviation 1.195 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Hemoglobin | Hemoglobin, Baseline | 13.70 g/dL | Standard Deviation 1.448 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Hemoglobin | Hemoglobin, End of treatment course 9 | 13.71 g/dL | Standard Deviation 1.475 |
Primary
Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC)
Time frame: Baseline and end of treatment Course 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC) | MCHC, Baseline | 32.41 g/dL | Standard Deviation 1.032 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC) | MCHC, End of treatment course 9 | 33.13 g/dL | Standard Deviation 1.272 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC) | MCHC, Baseline | 32.34 g/dL | Standard Deviation 1.228 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Mean Corpuscular Hemoglobin Concentration (MCHC) | MCHC, End of treatment course 9 | 32.99 g/dL | Standard Deviation 1.288 |
Primary
Serum Hematology - Mean Corpuscular Hemoglobin (MCH)
Time frame: Baseline and end of treatment Course 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Mean Corpuscular Hemoglobin (MCH) | MCH, Baseline | 27.43 pg | Standard Deviation 1.824 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Mean Corpuscular Hemoglobin (MCH) | MCH, End of treatment course 9 | 28.35 pg | Standard Deviation 2.282 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Mean Corpuscular Hemoglobin (MCH) | MCH, Baseline | 27.84 pg | Standard Deviation 2.09 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Mean Corpuscular Hemoglobin (MCH) | MCH, End of treatment course 9 | 28.89 pg | Standard Deviation 2.05 |
Primary
Serum Hematology - Mean Corpuscular Volume (MCV)
Time frame: Baseline and end of treatment Course 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Mean Corpuscular Volume (MCV) | MCV, Baseline | 84.33 fL | Standard Deviation 4.88 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Mean Corpuscular Volume (MCV) | MCV, End of treatment course 9 | 85.38 fL | Standard Deviation 5.232 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Mean Corpuscular Volume (MCV) | MCV, Baseline | 86.08 fL | Standard Deviation 5.56 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Mean Corpuscular Volume (MCV) | MCV, End of treatment course 9 | 87.72 fL | Standard Deviation 5.45 |
Primary
Serum Hematology - Number of Red Blood Cells (RBC)
Time frame: Baseline and end of treatment Course 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Number of Red Blood Cells (RBC) | RBCs, Baseline | 5.15 number x10^6/µL | Standard Deviation 0.442 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Number of Red Blood Cells (RBC) | RBCs, End of treatment 9 | 4.93 number x10^6/µL | Standard Deviation 0.376 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Number of Red Blood Cells (RBC) | RBCs, Baseline | 4.94 number x10^6/µL | Standard Deviation 0.499 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Number of Red Blood Cells (RBC) | RBCs, End of treatment 9 | 4.77 number x10^6/µL | Standard Deviation 0.492 |
Primary
Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils
Time frame: Baseline and end of treatment Course 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Basophils, End of Treatment Course 9 | 0.59 percent of differential | Standard Deviation 0.393 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Lymphocytes, Baseline | 23.40 percent of differential | Standard Deviation 8.278 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Basophils, Baseline | 0.59 percent of differential | Standard Deviation 0.379 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Lymphocytes, End of Treatment Course 9 | 22.30 percent of differential | Standard Deviation 7.462 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Eosinophils, Baseline | 2.05 percent of differential | Standard Deviation 1.194 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Monocytes, Baseline | 5.32 percent of differential | Standard Deviation 1.919 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Neutrophils, End of Treatment Course 9 | 69.02 percent of differential | Standard Deviation 8.551 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Monocytes, End of Treatment Course 9 | 5.64 percent of differential | Standard Deviation 1.66 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Eosinophils, End of Treatment Course 9 | 2.20 percent of differential | Standard Deviation 1.694 |
| 75 mg AZLI Two Times a Day (BID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Neutrophils, Baseline | 68.39 percent of differential | Standard Deviation 9.331 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Neutrophils, End of Treatment Course 9 | 67.46 percent of differential | Standard Deviation 9.808 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Neutrophils, Baseline | 69.26 percent of differential | Standard Deviation 9.261 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Basophils, Baseline | 0.61 percent of differential | Standard Deviation 0.39 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Basophils, End of Treatment Course 9 | 0.62 percent of differential | Standard Deviation 0.34 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Eosinophils, Baseline | 1.95 percent of differential | Standard Deviation 1.453 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Eosinophils, End of Treatment Course 9 | 1.88 percent of differential | Standard Deviation 1.625 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Lymphocytes, Baseline | 22.74 percent of differential | Standard Deviation 8.265 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Lymphocytes, End of Treatment Course 9 | 24.17 percent of differential | Standard Deviation 8.441 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Monocytes, Baseline | 5.26 percent of differential | Standard Deviation 1.752 |
| 75 mg AZLI Three Times a Day (TID) | Serum Hematology - Percent of Differential for Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Monocytes, End of Treatment Course 9 | 5.77 percent of differential | Standard Deviation 1.977 |
Secondary
Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum
Sputum samples were collected at all participant visits of the study for analysis of microbiology endpoints. Sputum samples were processed for qualitative and quantitative culture of PA (each morphotype). Due to the skewness of the distribution of CFU data, the data were transformed using the base 10 logarithm, in an attempt to normalize the data and allow for parametric tests, before calculating changes. To account for zero values, 1 was added to each CFU measurement before being transformed. Any CFU data values where PA was not isolated from a valid culture were set to zero.
Time frame: Baseline, and the end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum | End of Treatment Course 1 | -0.20 Log10 PA CFUs/g | Standard Deviation 1.5 |
| 75 mg AZLI Two Times a Day (BID) | Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum | End of Treatment Course 3 | -0.43 Log10 PA CFUs/g | Standard Deviation 1.4 |
| 75 mg AZLI Two Times a Day (BID) | Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum | End of Treatment Course 9 | -0.47 Log10 PA CFUs/g | Standard Deviation 1.9 |
| 75 mg AZLI Three Times a Day (TID) | Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum | End of Treatment Course 3 | -0.53 Log10 PA CFUs/g | Standard Deviation 2.1 |
| 75 mg AZLI Three Times a Day (TID) | Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum | End of Treatment Course 9 | -0.60 Log10 PA CFUs/g | Standard Deviation 2.1 |
| 75 mg AZLI Three Times a Day (TID) | Change From Baseline in Pseudomonas Aeruginosa (PA) log10 Colony-forming Units (CFU) Per Gram of Sputum | End of Treatment Course 1 | -0.81 Log10 PA CFUs/g | Standard Deviation 1.8 |
Secondary
Change in Body Weight
Weight was measured at all visits and was reported to the nearest 0.1 kg/lb. Percent change in weight from baseline was calculated.
Time frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Change in Body Weight | End of Treatment Course 1 | 0.58 Percent change from baseline | Standard Error 2.449 |
| 75 mg AZLI Two Times a Day (BID) | Change in Body Weight | End of Treatment Course 3 | 1.31 Percent change from baseline | Standard Error 3.769 |
| 75 mg AZLI Two Times a Day (BID) | Change in Body Weight | End of Treatment Course 9 | 3.24 Percent change from baseline | Standard Error 6.542 |
| 75 mg AZLI Three Times a Day (TID) | Change in Body Weight | End of Treatment Course 1 | 0.85 Percent change from baseline | Standard Error 2.338 |
| 75 mg AZLI Three Times a Day (TID) | Change in Body Weight | End of Treatment Course 3 | 1.38 Percent change from baseline | Standard Error 3.991 |
| 75 mg AZLI Three Times a Day (TID) | Change in Body Weight | End of Treatment Course 9 | 3.55 Percent change from baseline | Standard Error 7.431 |
Secondary
Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS)
The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores: 0-100; higher scores indicate fewer symptoms). The minimal clinically important difference (MCID) corresponds to the smallest change in symptoms that a patient can detect and is a change in score of 4 points.
Time frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS) | End of Treatment Course 1 | 3.53 Units on a scale | Standard Deviation 12.243 |
| 75 mg AZLI Two Times a Day (BID) | Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS) | End of Treatment Course 3 | 0.37 Units on a scale | Standard Deviation 19.296 |
| 75 mg AZLI Two Times a Day (BID) | Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS) | End of Treatment Course 9 | 0.30 Units on a scale | Standard Deviation 15.217 |
| 75 mg AZLI Three Times a Day (TID) | Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS) | End of Treatment Course 1 | 6.83 Units on a scale | Standard Deviation 17.379 |
| 75 mg AZLI Three Times a Day (TID) | Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS) | End of Treatment Course 3 | 7.34 Units on a scale | Standard Deviation 18.518 |
| 75 mg AZLI Three Times a Day (TID) | Change in Clinical Symptoms as Assessed by the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale (CFQ-R RSS) | End of Treatment Course 9 | 6.01 Units on a scale | Standard Deviation 17.943 |
Secondary
Minimum Inhibitory Concentration (MIC) of Aztreonam
The aztreonam susceptibility of PA isolates from expectorated sputum samples (collected at all visits) was assessed. MIC50 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 50% of isolates from a particular organism). MIC90 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 90% of isolates from a particular organism). MIC50 and MIC90 values are single measurements for the entire population and not measured on a per-participant basis.
Time frame: Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC50, End of Treatment Course 9 | 16 µg/mL |
| 75 mg AZLI Two Times a Day (BID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC50, Follow-up | 4 µg/mL |
| 75 mg AZLI Two Times a Day (BID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC90, Baseline | 128 µg/mL |
| 75 mg AZLI Two Times a Day (BID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC90, End of Treatment Course 1 | 256 µg/mL |
| 75 mg AZLI Two Times a Day (BID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC90, End of Treatment Course 3 | 256 µg/mL |
| 75 mg AZLI Two Times a Day (BID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC90, End of Treatment Course 9 | 512 µg/mL |
| 75 mg AZLI Two Times a Day (BID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC90, Follow-up | 128 µg/mL |
| 75 mg AZLI Two Times a Day (BID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC50, End of Treatment Course 3 | 8 µg/mL |
| 75 mg AZLI Two Times a Day (BID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC50, Baseline | 4 µg/mL |
| 75 mg AZLI Two Times a Day (BID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC50, End of Treatment Course 1 | 4 µg/mL |
| 75 mg AZLI Three Times a Day (TID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC50, End of Treatment Course 3 | 8 µg/mL |
| 75 mg AZLI Three Times a Day (TID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC50, End of Treatment Course 9 | 8 µg/mL |
| 75 mg AZLI Three Times a Day (TID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC90, End of Treatment Course 9 | 512 µg/mL |
| 75 mg AZLI Three Times a Day (TID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC50, Follow-up | 8 µg/mL |
| 75 mg AZLI Three Times a Day (TID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC90, Follow-up | 256 µg/mL |
| 75 mg AZLI Three Times a Day (TID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC90, Baseline | 128 µg/mL |
| 75 mg AZLI Three Times a Day (TID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC50, Baseline | 4 µg/mL |
| 75 mg AZLI Three Times a Day (TID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC90, End of Treatment Course 1 | 256 µg/mL |
| 75 mg AZLI Three Times a Day (TID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC50, End of Treatment Course 1 | 8 µg/mL |
| 75 mg AZLI Three Times a Day (TID) | Minimum Inhibitory Concentration (MIC) of Aztreonam | MIC90, End of Treatment Course 3 | 256 µg/mL |
Secondary
Missed School/Work Days Due to CF Symptoms
Participants were provided with a diary card at each visit to record days of work and/or school missed due to their CF symptoms. The percentage of school/work days missed was calculated as the total number of school/work days missed divided by the total number of on-study days multiplied by 100 across all participants in a treatment group.
Time frame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Missed School/Work Days Due to CF Symptoms | 2.00 Percentage of days missed | Standard Deviation 4.04 |
| 75 mg AZLI Three Times a Day (TID) | Missed School/Work Days Due to CF Symptoms | 3.19 Percentage of days missed | Standard Deviation 6.86 |
Secondary
Number of Participants With Other Pathogens
Sputum samples were collected at all study visits for qualitative and quantitative culture for Burkholderia cepacia complex (BCC), Stenotrophomonas maltophilia, Achromobacter xylosoxidans, Staphylococcus aureus (including methicillin-sensitive \[MSSA\] and methicillin-resistant \[MRSA\] S.aureus), and fungal organisms. Number of participants with other pathogens at baseline and end of AZLI treatment Courses 1, 3, and 9 are reported.
Time frame: Baseline; end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68); and at Follow-up (Week 72)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | BCC, End of Treatment Course 1 | 0 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | MRSA, Follow-up | 5 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | S. aureus, Follow-up | 16 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | BCC, Baseline | 0 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | Candida Species, End of Treatment Course 9 | 38 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | MSSA, Baseline | 26 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | BCC, End of Treatment Course 9 | 0 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | A. xylosoxidans, End of Treatment Course 3 | 7 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | BCC, Follow-up | 0 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | MSSA, End of Treatment Course 1 | 27 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | S. maltophilia, Baseline | 13 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | S. aureus, Baseline | 33 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | S. maltophilia, End of Treatment Course 1 | 12 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | MSSA, End of Treatment Course 3 | 31 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | S. maltophilia, End of Treatment Course 3 | 11 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | A. xylosoxidans, End of Treatment Course 9 | 4 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | S. maltophilia, Follow-up | 6 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | MSSA, End of Treatment Course 9 | 10 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | A. xylosoxidans, Baseline | 8 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | S. aureus, End of Treatment Course 1 | 34 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | A. xylosoxidans, End of Treatment Course 1 | 8 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | MSSA, Follow-up | 11 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | S. maltophilia, End of Treatment Course 9 | 5 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | A. xylosoxidans, Follow-up | 4 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | MRSA, Baseline | 7 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | Aspergillus Species, Baseline | 15 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | S. aureus, End of Treatment Course 3 | 41 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | Aspergillus Species, End of Treatment Course 1 | 18 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | MRSA, End of Treatment Course 1 | 7 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | Aspergillus Species, End of Treatment Course 3 | 21 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | Candida Species, End of Treatment Course 1 | 48 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | Aspergillus Species, End of Treatment Course 9 | 9 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | MRSA, End of Treatment Course 3 | 9 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | Aspergillus Species, Follow-up | 10 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | S. aureus, End of Treatment Course 9 | 15 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | Candida Species, Baseline | 51 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | MRSA, End of Treatment Course 9 | 5 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | Candida Species, End of Treatment Course 3 | 55 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | Candida Species, Follow-up | 36 Participants |
| 75 mg AZLI Two Times a Day (BID) | Number of Participants With Other Pathogens | BCC, End of Treatment Course 3 | 0 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | Candida Species, Follow-up | 95 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | BCC, End of Treatment Course 1 | 0 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | S. maltophilia, End of Treatment Course 3 | 15 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | A. xylosoxidans, End of Treatment Course 1 | 11 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | Candida Species, Baseline | 135 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | Candida Species, End of Treatment Course 3 | 125 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | Candida Species, End of Treatment Course 9 | 101 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | S. aureus, Baseline | 65 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | S. aureus, End of Treatment Course 1 | 66 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | S. aureus, End of Treatment Course 3 | 68 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | S. aureus, End of Treatment Course 9 | 51 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | S. aureus, Follow-up | 49 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | MSSA, Baseline | 32 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | MSSA, End of Treatment Course 1 | 32 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | MSSA, End of Treatment Course 3 | 35 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | MSSA, End of Treatment Course 9 | 31 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | MSSA, Follow-up | 32 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | MRSA, Baseline | 25 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | MRSA, End of Treatment Course 1 | 25 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | MRSA, End of Treatment Course 3 | 26 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | MRSA, End of Treatment Course 9 | 19 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | MRSA, Follow-up | 17 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | BCC, Baseline | 1 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | BCC, End of Treatment Course 3 | 1 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | BCC, End of Treatment Course 9 | 0 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | BCC, Follow-up | 1 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | S. maltophilia, Baseline | 14 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | S. maltophilia, End of Treatment Course 1 | 17 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | S. maltophilia, End of Treatment Course 9 | 14 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | S. maltophilia, Follow-up | 12 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | A. xylosoxidans, Baseline | 13 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | A. xylosoxidans, End of Treatment Course 3 | 12 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | A. xylosoxidans, End of Treatment Course 9 | 9 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | A. xylosoxidans, Follow-up | 7 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | Aspergillus Species, Baseline | 41 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | Aspergillus Species, End of Treatment Course 1 | 35 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | Aspergillus Species, End of Treatment Course 3 | 33 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | Aspergillus Species, End of Treatment Course 9 | 27 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | Aspergillus Species, Follow-up | 38 Participants |
| 75 mg AZLI Three Times a Day (TID) | Number of Participants With Other Pathogens | Candida Species, End of Treatment Course 1 | 139 Participants |
Secondary
Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75)
Spirometry was performed at each visit. FEV1, FVC, and FEF25-75 were recorded at all visits according to American Thoracic Society (ATS) guidelines. FEV1 = the volume of air exhaled in 1 second. FEV1 % predicted is a normalized value of FEV1 calculated using the Knudson equation, based upon participant age, gender, and height. FVC = (forced vital capacity) the maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration. FEF25-75 = forced expiratory flow from 25% to 75% of the FVC. The percent change from baseline is presented for each endpoint.
Time frame: Baseline, and end of treatment Courses 1 (Week 4), 3 (Week 20), and 9 (Week 68)
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FVC (L), End of Treatment Course 9 | 1.51 Percent change from baseline | Standard Deviation 14.15 |
| 75 mg AZLI Two Times a Day (BID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEV1 Percent Predicted, End of Treatment Course 3 | 3.46 Percent change from baseline | Standard Deviation 12.504 |
| 75 mg AZLI Two Times a Day (BID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEF25-75 (L/sec), End of Treatment Course 1 | 12.81 Percent change from baseline | Standard Deviation 36.149 |
| 75 mg AZLI Two Times a Day (BID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEV1 (L), End of Treatment Course 9 | 1.31 Percent change from baseline | Standard Deviation 15.924 |
| 75 mg AZLI Two Times a Day (BID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEF25-75 (L/sec), End of Treatment Course 3 | 16.05 Percent change from baseline | Standard Deviation 55.447 |
| 75 mg AZLI Two Times a Day (BID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEV1 Percent Predicted, End of Treatment Course 9 | 1.23 Percent change from baseline | Standard Deviation 15.673 |
| 75 mg AZLI Two Times a Day (BID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEF25-75 (L/sec), End of Treatment Course 9 | 3.24 Percent change from baseline | Standard Deviation 28.506 |
| 75 mg AZLI Two Times a Day (BID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEV1 (L), End of Treatment Course 3 | 3.55 Percent change from baseline | Standard Deviation 12.491 |
| 75 mg AZLI Two Times a Day (BID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEV1 (L), End of Treatment Course 1 | 4.87 Percent change from baseline | Standard Deviation 11.428 |
| 75 mg AZLI Two Times a Day (BID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FVC (L), End of Treatment Course 1 | 3.13 Percent change from baseline | Standard Deviation 11.946 |
| 75 mg AZLI Two Times a Day (BID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FVC (L), End of Treatment Course 3 | 1.77 Percent change from baseline | Standard Deviation 10.948 |
| 75 mg AZLI Two Times a Day (BID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEV1 Percent Predicted, End of Treatment Course 1 | 4.91 Percent change from baseline | Standard Deviation 11.599 |
| 75 mg AZLI Three Times a Day (TID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FVC (L), End of Treatment Course 3 | 5.95 Percent change from baseline | Standard Deviation 13.178 |
| 75 mg AZLI Three Times a Day (TID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEV1 (L), End of Treatment Course 3 | 6.04 Percent change from baseline | Standard Deviation 16.489 |
| 75 mg AZLI Three Times a Day (TID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEV1 (L), End of Treatment Course 9 | 3.98 Percent change from baseline | Standard Deviation 17.899 |
| 75 mg AZLI Three Times a Day (TID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEV1 Percent Predicted, End of Treatment Course 3 | 6.15 Percent change from baseline | Standard Deviation 16.592 |
| 75 mg AZLI Three Times a Day (TID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEV1 Percent Predicted, End of Treatment Course 9 | 4.24 Percent change from baseline | Standard Deviation 17.992 |
| 75 mg AZLI Three Times a Day (TID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FVC (L), End of Treatment Course 1 | 5.59 Percent change from baseline | Standard Deviation 16.533 |
| 75 mg AZLI Three Times a Day (TID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FVC (L), End of Treatment Course 9 | 5.29 Percent change from baseline | Standard Deviation 14.075 |
| 75 mg AZLI Three Times a Day (TID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEF25-75 (L/sec), End of Treatment Course 1 | 14.14 Percent change from baseline | Standard Deviation 36.089 |
| 75 mg AZLI Three Times a Day (TID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEF25-75 (L/sec), End of Treatment Course 3 | 4.81 Percent change from baseline | Standard Deviation 32.579 |
| 75 mg AZLI Three Times a Day (TID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEF25-75 (L/sec), End of Treatment Course 9 | 3.29 Percent change from baseline | Standard Deviation 36.329 |
| 75 mg AZLI Three Times a Day (TID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEV1 Percent Predicted, End of Treatment Course 1 | 7.97 Percent change from baseline | Standard Deviation 16.511 |
| 75 mg AZLI Three Times a Day (TID) | Percent Change in Pulmonary Function (FEV1, FEV1 Percent Predicted, FVC, FEF25-75) | FEV1 (L), End of Treatment Course 1 | 7.98 Percent change from baseline | Standard Deviation 16.512 |
Secondary
Time to First Hospitalization Due to a Respiratory Event
Details of all hospitalizations, including the dates of admission and discharge, were recorded on the serious adverse event (SAE) electronic case report form (eCRF). Time to first hospitalization was the number of days from baseline (Visit 1) to the date of first hospitalization or the date of study completion (last visit) /or early withdrawal if censored.
Time frame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Time to First Hospitalization Due to a Respiratory Event | 359 Days | Full Range 27.6 |
| 75 mg AZLI Three Times a Day (TID) | Time to First Hospitalization Due to a Respiratory Event | 417 Days | Full Range 21.32 |
Secondary
Time to Intravenous (IV) Antipseudomonal Antibiotics
Use of IV antipseudomonal antibiotics was compiled from data recorded on the Concomitant Medications eCRF. The time to first IV antipseudomonal antibiotic use was the number of days from baseline (Visit 1) to the date of first IV antipseudomonal antibiotic use or the date of study completion (last visit) /or early withdrawal if censored.
Time frame: Overall study (72 weeks) included nine 28-day courses of study drug alternating with nine 28-day courses off drug
Population: The analysis population consisted of all enrolled participants who received one or more doses of AZLI.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 75 mg AZLI Two Times a Day (BID) | Time to Intravenous (IV) Antipseudomonal Antibiotics | 276 Days |
| 75 mg AZLI Three Times a Day (TID) | Time to Intravenous (IV) Antipseudomonal Antibiotics | 232 Days |