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| Name | Class |
|---|---|
| Chiltern International Inc. | INDUSTRY |
| ClinPhone, Inc. | INDUSTRY |
| Covance | INDUSTRY |
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The purpose of this study was to assess the comparative safety and effectiveness of aztreonam for inhalation solution versus tobramycin inhalation solution in adult and pediatric patients with cystic fibrosis (CF) and pulmonary Pseudomonas aeruginosa (PA) infection.
Number of Subjects Planned: Approximately 240 randomized patients
Target Population: CF patients >= 6 years of age with stable pulmonary disease, who at study entry had a recent positive sputum culture for PA and had been previously treated with aerosolized antibiotics without demonstration of drug intolerance.
The randomized phase of this study, used for hypotheses testing, enrolled participants from both the United States (US) and EU. An open-label, single-arm extension was available for participants in the EU who completed at least one course of AZLI or TIS during the randomized portion of the study. These participants were eligible to receive 3 additional cycles of AZLI in a 28-day, intermittent, repeating treatment regimen. Results of the extension phase will be available the first quarter (Q1) of 2012.
Randomized Phase Study Design (US and EU): This was an open-label, multicenter, randomized, parallel group study. The study design consisted of 2 treatment arms of 28-day, intermittent, repeating treatment regimens: aztreonam for inhalation solution (AZLI) or tobramycin inhalation solution (TIS). The total study period was 26 weeks. The study schedule included 9 visits - Screening, Baseline, Day 14, Day 28, followed by visits every 28 days through the end of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AZLI 75 mg 3 times a day (TID) | Experimental |
| |
| TIS 300 mg 2 times a day (BID) | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aztreonam for Inhalation Solution (AZLI) | Drug | Aztreonam for inhalation solution (75 mg) was administered 3 times a day (TID) for 28 days for each treatment cycle via the PARI eFlow electronic nebulizer. |
| Measure | Description | Time Frame |
|---|---|---|
| Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted at Day 28 | Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the relative change from baseline in FEV1 percent predicted at Day 28 (Visit 4) was tested using an analysis of covariance (ANCOVA) model-based method. | Baseline and end of treatment Course 1 (Day 28) |
| Mean Actual Change From Baseline in FEV1 Percent Predicted Across 3 Treatment Courses | Spirometry was performed according to ATS guidelines at each visit. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the average adjusted means for the actual change in FEV1 percent predicted at Visits 4, 6, and 8 (Weeks 4, 12, and 20) was tested by mixed-effect model repeated measures (MMRM) analysis using the ITT population analysis set. | Baseline, and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20) |
| Measure | Description | Time Frame |
|---|---|---|
| Relative Change From Baseline in FEV1 Percent Predicted at Day 28 in Subjects Who Received Inhaled Tobramycin for >= 84 Days in the 12 Months Prior to Randomization | Spirometry was performed according to ATS guidelines. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the relative change from baseline in FEV1 percent predicted at Day 28 (Visit 4) was tested using an ANCOVA model-based method, using the population of participants with prior inhaled tobramycin use of >= 84 days in the previous 12 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Actual Change From Baseline in CF Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score at Day 28 | The CFQ-R is a validated patient-reported outcome tool measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The endpoint was change in respiratory symptoms (e.g., coughing, congestion, wheezing) from baseline, assessed with the CFQ-R RSS (range of scores [units]: 0-100; higher scores indicate fewer symptoms). |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark Bresnik, MD | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Anchorage | Alaska | 99508 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22985692 | Derived | Assael BM, Pressler T, Bilton D, Fayon M, Fischer R, Chiron R, LaRosa M, Knoop C, McElvaney N, Lewis SA, Bresnik M, Montgomery AB, Oermann CM; AZLI Active Comparator Study Group. Inhaled aztreonam lysine vs. inhaled tobramycin in cystic fibrosis: a comparative efficacy trial. J Cyst Fibros. 2013 Mar;12(2):130-40. doi: 10.1016/j.jcf.2012.07.006. Epub 2012 Sep 15. |
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Of the 274 participants enrolled in the study, 273 were randomized between 07 August 2008 and 12 November 2009. One subject experienced a serious adverse event (SAE) between Visits 1 and 2; this subject did not receive study drug. A total of 268 participants received study drug (136 AZLI; 132 TIS).
Seventy-three sites in the United States (US) and European Union (EU) enrolled a total of 274 participants in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | AZLI (75 mg TID) | AZLI (75 mg/1 mL aztreonam lysine when reconstituted in diluent [0.17% saline]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day (TID) for 28 days for each treatment cycle using the investigational nebulizer. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| Tobramycin Inhalation Solution (TIS) | Drug | Tobramycin inhalation solution (300 mg) was administered 2 times a day (BID) for 28 days for each treatment cycle via the PARI LC Plus nebulizer with compressor or via another nebulizer compatible with country-specified labeling. |
|
|
| Baseline and end of treatment Course 1 (Day 28) |
| Mean Actual Change From Baseline in FEV1 Percent Predicted Across 3 Treatment Courses in Subjects Who Received Inhaled Tobramycin for >= 84 Days in the 12 Months Prior to Randomization | Spirometry was performed according to ATS guidelines at each visit. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the average adjusted means for the actual change in FEV1 percent predicted at Visits 4, 6, and 8 (Weeks 4, 12, and 20) was tested by MMRM analysis using the population of participants with prior inhaled tobramycin use of >=84 days in the previous 12 months. | Baseline and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20) |
| Time to Need for Intravenous (IV) Antipseudomonal Antibiotics for Respiratory Events | IV antipseudomonal antibiotic use for a respiratory event was determined through the adjudication of events by a sponsor-independent, blinded review committee. Use was compiled from data recorded on the concomitant medications electronic case report form (eCRF) and compared to reported adverse events (AEs) to determine use for a respiratory event. The time to IV antipseudomonal antibiotic use was measured in days from baseline (Visit 2) to the date of first IV antipseudomonal antibiotic use or the date of study completion (last visit)/or early withdrawal if censored. | Day 0 to Day 168 (end of study) |
| Time to First Respiratory Hospitalization | This endpoint was determined through the adjudication of events by a sponsor-independent, blinded review committee. Committee members reviewed all hospitalizations and determined which were related to respiratory events. Details of all hospitalizations, including the dates of admission and discharge, were recorded on the serious adverse event (SAE) eCRF. Time to first respiratory hospitalization was the number of days from baseline (Visit 2) to the date of first respiratory hospitalization or the date of study completion (last visit) /or early withdrawal if censored. | Day 0 to Day 168 (end of study) |
| Baseline and end of treatment Course 1 (Day 28) |
| Mean Actual Change From Baseline in CFQ-R RSS Score Across 3 Treatment Courses | The CFQ-R is a validated patient-reported outcome tool measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The endpoint was the average actual change in respiratory symptoms (e.g., coughing, congestion, wheezing) from baseline, assessed with the CFQ-R RSS (range of scores [units]: 0-100; higher scores indicate fewer symptoms) at the end of each treatment course (Weeks 4, 12, and 20). | Baseline and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20) |
| Treatment Satisfaction Questionnaire for Medication (TSQM) - Global Satisfaction Results at Week 20 | This 14 item questionnaire consists of 3 subscales that gauge participant perceptions of a medication's effectiveness, side effects, and convenience. The measure also contains a global satisfaction scale to evaluate overall participant satisfaction. The global satisfaction score is the endpoint reported here. The range of scores is 0 to 100, with higher scores indicating greater satisfaction. | At Week 20 |
| Total Number of Respiratory Hospitalizations | Respiratory hospitalizations were determined through the adjudication of events by a sponsor-independent, blinded review committee. Committee members reviewed hospitalizations and determined which were related to respiratory events. | Day 0 to Day 168 (end of study) |
| Number of Respiratory Events Requiring IV and/or Inhaled Antipseudomonal Antibiotics (Other Than Randomized Treatment) | Inhaled and/or IV antipseudomonal antibiotic use for respiratory event was determined through event adjudication by a sponsor-independent, blinded review committee. Use of IV and/or inhaled antipseudomonal antibiotics was compiled from data recorded on the concomitant medications eCRF and compared to reported AEs to determine use for a respiratory event. The time to IV and/or inhaled antipseudomonal antibiotic use was measured in days from baseline (Visit 2) to the date of first antipseudomonal antibiotic use or the date of study completion (last visit)/or early withdrawal if censored. | Day 0 through Day 168 (end of study) |
| Time to Need for Inhaled and/or IV Antipseudomonal Antibiotics for Respiratory Event (Other Than Randomized Treatment) | Antipseudomonal antibiotic use for respiratory event was determined through event adjudication by a sponsor-independent, blinded review committee. Use of IV and/or inhaled antibiotics for a respiratory event was compiled from data recorded on the concomitant medications eCRF and compared to reported AEs to determine use for a respiratory event. The time to antibiotic use for a respiratory event was measured in days from baseline (Day 0) to the date of first antibiotic use for a respiratory event or the date of study completion (last visit)/or early withdrawal if censored. | Day 0 to Day 168 (end of study) |
| Phoenix |
| Arizona |
| 85006 |
| United States |
| Tuscon | Arizona | 85724 | United States |
| Orange | California | 92868 | United States |
| Aurora | Colorado | 80045 | United States |
| Denver | Colorado | 80206 | United States |
| Wilmington | Delaware | 19803 | United States |
| Orlando | Florida | 32801 | United States |
| Tampa | Florida | 33606 | United States |
| Chicago | Illinois | 60637 | United States |
| Glenview | Illinois | 60025 | United States |
| Niles | Illinois | 60714 | United States |
| Boston | Massachusetts | 02115 | United States |
| Columbia | Missouri | 65212 | United States |
| Las Vegas | Nevada | 89107 | United States |
| Albany | New York | 12208 | United States |
| New Hyde Park | New York | 11040 | United States |
| Cincinnati | Ohio | 45229 | United States |
| Dayton | Ohio | 45404 | United States |
| Toledo | Ohio | 43606 | United States |
| Oklahoma City | Oklahoma | 73112 | United States |
| Hershey | Pennsylvania | 17033 | United States |
| Philadelphia | Pennsylvania | 19102 | United States |
| Philadelphia | Pennsylvania | 19104 | United States |
| Charleston | South Carolina | 29425 | United States |
| Houston | Texas | 77030 | United States |
| San Antonio | Texas | 78212 | United States |
| Salt Lake City | Utah | 84132 | United States |
| Richmond | Virginia | 23298 | United States |
| Innsbruck | A-6020 | Austria |
| Salzburg | A-5020 | Austria |
| Antwerp | 2650 | Belgium |
| Brussels | 1070 | Belgium |
| Brussels | 1090 | Belgium |
| Ghent | 9000 | Belgium |
| Leuven | 3000 | Belgium |
| Copenhagen | DK-2100 | Denmark |
| Amiens | 80054 | France |
| Bordeaux | 33076 | France |
| Caen | 14000 | France |
| Créteil | 94000 | France |
| Lille | 59037 | France |
| Lisieux | 14100 | France |
| Montpellier | 34295 | France |
| Nice | 06202 | France |
| Paris | 75743 | France |
| Pessac | 33604 | France |
| Rennes | 35033 | France |
| Berlin | 123353 | Germany |
| Berlin | 13125 | Germany |
| Bochum | 44791 | Germany |
| Essen | 45122 | Germany |
| Essen | 45239 | Germany |
| Giessen | 35392 | Germany |
| Hamburg | 22763 | Germany |
| Leipzig | 04103 | Germany |
| Magdeburg | 39120 | Germany |
| Mainz | 55101 | Germany |
| München | 80336 | Germany |
| Dublin | 24 | Ireland |
| Dublin | 4 | Ireland |
| Dublin | 9 | Ireland |
| Dublin | Ireland |
| Galway | Ireland |
| Ancona | 60123 | Italy |
| Catania | 95123 | Italy |
| Milan | 20122 | Italy |
| Naples | 80131 | Italy |
| Palermo | 90134 | Italy |
| Parma | 43100 | Italy |
| Rome | 00161 | Italy |
| Rome | 00165 | Italy |
| Verona | 37126 | Italy |
| Maastricht | 6229 | Netherlands |
| The Hague | 2504 LN | Netherlands |
| Lisbon | 1649-035 | Portugal |
| Porto | 4200 319 | Portugal |
| Madrid | 28009 | Spain |
| Madrid | 28034 | Spain |
| Madrid | 28041 | Spain |
| Madrid | 28046 | Spain |
| Málaga | 29011 | Spain |
| Zurich | CH - 8032 | Switzerland |
| Zurich | CH - 8091 | Switzerland |
| Sheffield | West Yorkshire | S10 2TH | United Kingdom |
| Belfast | BT9 7AB | United Kingdom |
| Cambridge | CB23 3RE | United Kingdom |
| Cardiff | CF64-2XX | United Kingdom |
| Leeds | LS9 7TF | United Kingdom |
| Liverpool | L14 3PE | United Kingdom |
| London | SW3 6NP | United Kingdom |
| Southampton | SO16 6YD | United Kingdom |
| TIS (300 mg BID) |
TIS (300 mg/5 mL) was self-administered by inhalation two times a day (BID) for 28 days for each treatment cycle using the PARI LC PLUS(TM) Nebulizer with Compressor. |
| Treated |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | AZLI (75 mg TID) | AZLI (75 mg/1 mL aztreonam lysine when reconstituted in diluent [0.17% saline]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day (TID) for 28 days for each treatment cycle using the investigational nebulizer. |
| BG001 | TIS (300 mg BID) | TIS (300 mg/5 mL) was self-administered by inhalation two times a day (BID) for 28 days for each treatment cycle using the PARI LC PLUS(TM) Nebulizer with Compressor. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Categorical | Number | participants |
| ||||||||||||||||||
| Age Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
| |||||||||||||||||
| Inhaled Tobramycin Use in the Previous 12 Months | Number | participants |
| ||||||||||||||||||
| Disease Severity | Forced Expiratory Volume (FEV1) percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. This baseline measure indicates the number of participants with FEV1 greater than 50% and less than or equal to 50% of the predicted value based on age, gender, and height at screening. | Number | participants |
| |||||||||||||||||
| Forced Expiratory Volume (FEV1) Percent Predicted | FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. | Mean | Standard Deviation | percent |
| ||||||||||||||||
| Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score | The CFQ-R is a validated, patient-reported outcome tool measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. Respiratory symptoms (e.g., coughing, congestion, wheezing) are assessed with the CFQ-R Respiratory Symptoms Scale (RSS). The range of scores (units) is 0 to 100 with higher scores indicating fewer symptoms. | Mean | Standard Deviation | units on a scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted at Day 28 | Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the relative change from baseline in FEV1 percent predicted at Day 28 (Visit 4) was tested using an analysis of covariance (ANCOVA) model-based method. | Analysis was based on ITT population (all participants randomized to treatment who received at least part of one dose of study drug). The last observation carried forward (LOCF) method was used to impute missing data. | Posted | Least Squares Mean | Standard Error | percent change in FEV1 percent predicted | Baseline and end of treatment Course 1 (Day 28) |
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| Primary | Mean Actual Change From Baseline in FEV1 Percent Predicted Across 3 Treatment Courses | Spirometry was performed according to ATS guidelines at each visit. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the average adjusted means for the actual change in FEV1 percent predicted at Visits 4, 6, and 8 (Weeks 4, 12, and 20) was tested by mixed-effect model repeated measures (MMRM) analysis using the ITT population analysis set. | Analysis was based on ITT population (all participants randomized to treatment who received at least part of one dose of study drug). | Posted | Least Squares Mean | Standard Error | actual change in FEV1 percent predicted | Baseline, and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20) |
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| Secondary | Relative Change From Baseline in FEV1 Percent Predicted at Day 28 in Subjects Who Received Inhaled Tobramycin for >= 84 Days in the 12 Months Prior to Randomization | Spirometry was performed according to ATS guidelines. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the relative change from baseline in FEV1 percent predicted at Day 28 (Visit 4) was tested using an ANCOVA model-based method, using the population of participants with prior inhaled tobramycin use of >= 84 days in the previous 12 months. | Analysis was based on participants with previous inhaled tobramycin use of >= 84 days within the previous 12 months using the ITT analysis set. The last observation carried forward (LOCF) method was used to impute missing data for statistical analyses. | Posted | Least Squares Mean | Standard Error | percent change in FEV1 percent predicted | Baseline and end of treatment Course 1 (Day 28) |
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| Secondary | Mean Actual Change From Baseline in FEV1 Percent Predicted Across 3 Treatment Courses in Subjects Who Received Inhaled Tobramycin for >= 84 Days in the 12 Months Prior to Randomization | Spirometry was performed according to ATS guidelines at each visit. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the average adjusted means for the actual change in FEV1 percent predicted at Visits 4, 6, and 8 (Weeks 4, 12, and 20) was tested by MMRM analysis using the population of participants with prior inhaled tobramycin use of >=84 days in the previous 12 months. | Analysis was based on participants with prior inhaled tobramycin use >= 84 days in the previous 12 months using the ITT analysis set. | Posted | Least Squares Mean | Standard Error | actual change in FEV1 percent predicted | Baseline and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20) |
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| Secondary | Time to Need for Intravenous (IV) Antipseudomonal Antibiotics for Respiratory Events | IV antipseudomonal antibiotic use for a respiratory event was determined through the adjudication of events by a sponsor-independent, blinded review committee. Use was compiled from data recorded on the concomitant medications electronic case report form (eCRF) and compared to reported adverse events (AEs) to determine use for a respiratory event. The time to IV antipseudomonal antibiotic use was measured in days from baseline (Visit 2) to the date of first IV antipseudomonal antibiotic use or the date of study completion (last visit)/or early withdrawal if censored. | Analysis was based on ITT population (all participants randomized to treatment who received at least part of one dose of study drug). | Posted | Median | 95% Confidence Interval | days | Day 0 to Day 168 (end of study) |
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| Secondary | Time to First Respiratory Hospitalization | This endpoint was determined through the adjudication of events by a sponsor-independent, blinded review committee. Committee members reviewed all hospitalizations and determined which were related to respiratory events. Details of all hospitalizations, including the dates of admission and discharge, were recorded on the serious adverse event (SAE) eCRF. Time to first respiratory hospitalization was the number of days from baseline (Visit 2) to the date of first respiratory hospitalization or the date of study completion (last visit) /or early withdrawal if censored. | Analysis was based on ITT population (all participants randomized to treatment who received at least part of one dose of study drug). | Posted | Median | 95% Confidence Interval | days | Day 0 to Day 168 (end of study) |
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| Other Pre-specified | Actual Change From Baseline in CF Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score at Day 28 | The CFQ-R is a validated patient-reported outcome tool measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The endpoint was change in respiratory symptoms (e.g., coughing, congestion, wheezing) from baseline, assessed with the CFQ-R RSS (range of scores [units]: 0-100; higher scores indicate fewer symptoms). | Analysis was based on ITT population (all participants randomized to treatment who received at least part of one dose of study drug). LOCF method was used to impute missing data for statistical analyses. | Posted | Least Squares Mean | Standard Error | Units on a scale | Baseline and end of treatment Course 1 (Day 28) |
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| Other Pre-specified | Mean Actual Change From Baseline in CFQ-R RSS Score Across 3 Treatment Courses | The CFQ-R is a validated patient-reported outcome tool measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The endpoint was the average actual change in respiratory symptoms (e.g., coughing, congestion, wheezing) from baseline, assessed with the CFQ-R RSS (range of scores [units]: 0-100; higher scores indicate fewer symptoms) at the end of each treatment course (Weeks 4, 12, and 20). | Analysis was based on ITT population (all participants randomized to treatment who received at least part of one dose of study drug). The LOCF method was used to impute missing data for statistical purposes. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20) |
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| Other Pre-specified | Treatment Satisfaction Questionnaire for Medication (TSQM) - Global Satisfaction Results at Week 20 | This 14 item questionnaire consists of 3 subscales that gauge participant perceptions of a medication's effectiveness, side effects, and convenience. The measure also contains a global satisfaction scale to evaluate overall participant satisfaction. The global satisfaction score is the endpoint reported here. The range of scores is 0 to 100, with higher scores indicating greater satisfaction. | Analysis was based on ITT population (all participants randomized to treatment who received at least part of one dose of study drug). | Posted | Least Squares Mean | Standard Error | units on a scale | At Week 20 |
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| Other Pre-specified | Total Number of Respiratory Hospitalizations | Respiratory hospitalizations were determined through the adjudication of events by a sponsor-independent, blinded review committee. Committee members reviewed hospitalizations and determined which were related to respiratory events. | Analysis was based on ITT population (all participants randomized to treatment who received at least part of one dose of study drug). | Posted | Number | hospitalizations | Day 0 to Day 168 (end of study) |
|
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| Other Pre-specified | Number of Respiratory Events Requiring IV and/or Inhaled Antipseudomonal Antibiotics (Other Than Randomized Treatment) | Inhaled and/or IV antipseudomonal antibiotic use for respiratory event was determined through event adjudication by a sponsor-independent, blinded review committee. Use of IV and/or inhaled antipseudomonal antibiotics was compiled from data recorded on the concomitant medications eCRF and compared to reported AEs to determine use for a respiratory event. The time to IV and/or inhaled antipseudomonal antibiotic use was measured in days from baseline (Visit 2) to the date of first antipseudomonal antibiotic use or the date of study completion (last visit)/or early withdrawal if censored. | Analysis was based on ITT population (all participants randomized to treatment who received at least part of one dose of study drug). | Posted | Number | events | Day 0 through Day 168 (end of study) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Time to Need for Inhaled and/or IV Antipseudomonal Antibiotics for Respiratory Event (Other Than Randomized Treatment) | Antipseudomonal antibiotic use for respiratory event was determined through event adjudication by a sponsor-independent, blinded review committee. Use of IV and/or inhaled antibiotics for a respiratory event was compiled from data recorded on the concomitant medications eCRF and compared to reported AEs to determine use for a respiratory event. The time to antibiotic use for a respiratory event was measured in days from baseline (Day 0) to the date of first antibiotic use for a respiratory event or the date of study completion (last visit)/or early withdrawal if censored. | Analysis was based on ITT population (all participants randomized to treatment who received at least part of one dose of study drug). | Posted | Median | 95% Confidence Interval | days | Day 0 to Day 168 (end of study) |
|
Treatment-emergent adverse events (AEs) were collected continuously from Day 0 (first dose) through Day 168 (Week 24).
An AE was any physical/clinical worsening in symptoms/disease (including clinically significant change in lab values) experienced by a participant at any time during study, whether or not the AE was considered related to study participation or procedures. Participants were only counted once within a System Organ Class (SOC) and preferred term.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AZLI (75 mg TID) | AZLI (75 mg/1 mL aztreonam lysine when reconstituted in diluent [0.17% saline]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day (TID) for 28 days for each treatment cycle using the investigational nebulizer. | 42 | 136 | 128 | 136 | ||
| EG001 | TIS (300 mg BID) | TIS (300 mg/5 mL) was self-administered by inhalation two times a day (BID) for 28 days for each treatment cycle using the PARI LC PLUS(TM) Nebulizer with Compressor. | 44 | 132 | 127 | 132 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Discomfort | Gastrointestinal disorders | MedDRA (11.1) |
| ||
| Abdominal Distention | Gastrointestinal disorders | MedDRA (11.1) |
| ||
| Abdominal Pain | Gastrointestinal disorders | MedDRA (11.1) |
| ||
| Alcohol Poisoning | Injury, poisoning and procedural complications | MedDRA (11.1) |
| ||
| Anuria | Renal and urinary disorders | MedDRA (11.1) |
| ||
| Atrial Fibrillation | Cardiac disorders | MedDRA (11.1) |
| ||
| Body Temperature Increased | Investigations | MedDRA (11.1) |
| ||
| Breath Sounds Abnormal | Investigations | MedDRA (11.1) |
| ||
| C-Reactive Protein Increased | Investigations | MedDRA (11.1) |
| ||
| Catheter Related Infection | Infections and infestations | MedDRA (11.1) |
| ||
| Chest Discomfort | General disorders | MedDRA (11.1) |
| ||
| Chest Pain | General disorders | MedDRA (11.1) |
| ||
| Chills | General disorders | MedDRA (11.1) |
| ||
| Coma | Nervous system disorders | MedDRA (11.1) |
| ||
| Constipation | Gastrointestinal disorders | MedDRA (11.1) |
| ||
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Cyanosis | Cardiac disorders | MedDRA (11.1) |
| ||
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA (11.1) |
| ||
| Diabetes Mellitus Inadequate Control | Metabolism and nutrition disorders | MedDRA (11.1) |
| ||
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Dyspnoea Exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Exercise Tolerance Decreased | General disorders | MedDRA (11.1) |
| ||
| Fatigue | General disorders | MedDRA (11.1) |
| ||
| Feeding Tube Complication | Injury, poisoning and procedural complications | MedDRA (11.1) |
| ||
| Forced Expiratory Volume Decreased | Investigations | MedDRA (11.1) |
| ||
| Glycosylated Haemoglobin Increased | Investigations | MedDRA (11.1) |
| ||
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Headache | Nervous system disorders | MedDRA (11.1) |
| ||
| Hyperaemia | Vascular disorders | MedDRA (11.1) |
| ||
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Insomnia | Psychiatric disorders | MedDRA (11.1) |
| ||
| Joint Swelling | Musculoskeletal and connective tissue disorders | MedDRA (11.1) |
| ||
| Lethargy | Nervous system disorders | MedDRA (11.1) |
| ||
| Lung Infiltration | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Malaise | General disorders | MedDRA (11.1) |
| ||
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA (11.1) |
| ||
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Nasal Mucosal Disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Nausea | Gastrointestinal disorders | MedDRA (11.1) |
| ||
| Oedema Peripheral | General disorders | MedDRA (11.1) |
| ||
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Oxygen Saturation Decreased | Investigations | MedDRA (11.1) |
| ||
| Pain | General disorders | MedDRA (11.1) |
| ||
| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA (11.1) |
| ||
| Pleuritic Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Poor Quality Sleep | Nervous system disorders | MedDRA (11.1) |
| ||
| Productive Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Pulmonary Function Test Decreased | Investigations | MedDRA (11.1) |
| ||
| Pyrexia | General disorders | MedDRA (11.1) |
| ||
| Rales | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Respiratory Tract Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Rhonchi | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Sinus Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Sinus Headache | Nervous system disorders | MedDRA (11.1) |
| ||
| Sputum Discoloured | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Systemic Candida | Infections and infestations | MedDRA (11.1) |
| ||
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Vein Disorder | Vascular disorders | MedDRA (11.1) |
| ||
| Vertigo | Ear and labyrinth disorders | MedDRA (11.1) |
| ||
| Vomiting | Gastrointestinal disorders | MedDRA (11.1) |
| ||
| Weight Decreased | Investigations | MedDRA (11.1) |
| ||
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | MedDRA (11.1) |
| ||
| Arthalgia | Musculoskeletal and connective tissue disorders | MedDRA (11.1) |
| ||
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (11.1) |
| ||
| Breath Sounds Abnormal | Investigations | MedDRA (11.1) |
| ||
| Chest Discomfort | General disorders | MedDRA (11.1) |
| ||
| Chest Pain | General disorders | MedDRA (11.1) |
| ||
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA (11.1) |
| ||
| Diarrhoea | Gastrointestinal disorders | MedDRA (11.1) |
| ||
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Exercise Tolerance Decreased | General disorders | MedDRA (11.1) |
| ||
| Fatigue | General disorders | MedDRA (11.1) |
| ||
| Forced Expiratory Volume Decreased | Investigations | MedDRA (11.1) |
| ||
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Headache | Nervous system disorders | MedDRA (11.1) |
| ||
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (11.1) |
| ||
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Nausea | Gastrointestinal disorders | MedDRA (11.1) |
| ||
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Pain | General disorders | MedDRA (11.1) |
| ||
| Productive Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Pulmonary Function Test Decreased | Investigations | MedDRA (11.1) |
| ||
| Pyrexia | General disorders | MedDRA (11.1) |
| ||
| Rales | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Respiratory Tract Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Rhinitis | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Sinus Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
| ||
| Vomiting | Gastrointestinal disorders | MedDRA (11.1) |
| ||
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) |
|
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other scholarly media only after the following conditions have been met:
The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
The study has been completed at all study sites for at least 2 years.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mark Bresnik, MD, Director, Clinical Research | Gilead Sciences, Inc. | (650) 522-5934 | mark.bresnik@gilead.com |
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| D011552 | Pseudomonas Infections |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| D001398 | Aztreonam |
| D014031 | Tobramycin |
| C009497 | 2-(4-toluidino)-6-naphthalenesulfonic acid |
| ID | Term |
|---|---|
| D008997 | Monobactams |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013457 | Sulfur Compounds |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D009328 | Nebramycin |
| D007612 | Kanamycin |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
Not provided
Not provided
|
| >= 18 years |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Europe |
|
| >= 84 days |
|
| > 50% predicted |
|
Treatment difference refers to TIS-AZLI. |
| Yes |
| Non-Inferiority or Equivalence |
The treatment difference (TIS-AZLI) and standard error from the ANCOVA model were used to compute the two-sided 95% confidence interval. If the 95% upper boundary was less than the pre-specified non-inferiority margin of 4%, then the null hypothesis was rejected. |
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