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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01HL124053-01A1 | U.S. NIH Grant/Contract | View source | |
| NICHOL15A0 | Other Grant/Funding Number | Cystic Fibrosis Foundation Therapeutics |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| Cystic Fibrosis Foundation | OTHER |
| CF Therapeutics Development Network Coordinating Center | NETWORK |
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This is a study to examine the effect of combining chronic oral azithromycin with inhaled tobramycin in adolescent and adult subjects with cystic fibrosis who are chronically infected with P. aeruginosa.
This study is a prospective, randomized, double-blinded, placebo-controlled trial of azithromycin 500mg taken orally thrice weekly vs. placebo in subjects with cystic fibrosis and chronic airway infection with P. aeruginosa who are utilizing chronic inhaled tobramycin therapy. It will include approximately 120 subjects able to complete a primary 6-week study phase. Subjects will be at least 12 years old with a baseline forced expiratory volume at one second (FEV1) between 25-100% predicted. Subjects will continue to use clinically prescribed inhaled tobramycin cycled on/off every 4 weeks. They will be provided over-encapsulated azithromycin 500mg tablets or placebo during the primary study phase. An optional extension phase will be offered to all subjects completing the primary 6-week study. This 8-week extension phase will include an initial 4 weeks without use of inhaled tobramycin or other inhaled antibiotics, followed by a 4-week period with inhaled tobramycin use. All subjects participating in the extension phase of the study will be provided azithromycin 500mg tablets to be taken thrice weekly for the entire 8-week period.
This study will investigate how use of chronic oral azithromycin affects some of the previously demonstrated benefits to health when using inhaled tobramycin. The primary measurements will focus on lung function. Additional measurements will focus on disease-related quality of life as reported by subjects in the trial. Exploratory outcomes, including measurements of safety, are also planned.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| azithromycin | Active Comparator | azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks |
|
| placebo | Placebo Comparator | encapsulated placebo taken by mouth thrice weekly for 6 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| azithromycin | Drug | 500mg tablet over-encapsulated to match placebo |
|
| Measure | Description | Time Frame |
|---|---|---|
| Relative Change in Lung Function | Relative change in FEV1 volume (L) from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6 | baseline (week 0) to week 6 (6 week period) |
| Measure | Description | Time Frame |
|---|---|---|
| Relative Change in Lung Function | Relative change in FEV1 (L) from the beginning of the 4-week period with inhaled tobramycin at week 2 to the end of the 4-week period with inhaled tobramycin at week 6 | week 2 to week 6 (4 week period) |
| Change in Cystic Fibrosis Respiratory Symptom Diary - Chronic Respiratory Infection Symptom Score (CFRSD-CRISS) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Sputum Pseudomonas Aeruginosa Bacterial Density | Absolute change in log10 transformed quantitative Pseudomonas aeruginosa (Pa) bacterial density as measured by colony forming units (CFUs) per mL of sputum from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. Culture results below the lower limit of detection of 1x10^2 were set to 1/2 of that LLD prior to log transformation. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David P Nichols, MD | National Jewish Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Los Angeles | Los Angeles | California | 90027 | United States | ||
| Stanford University Medical Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | Azithromycin | azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks azithromycin: 500mg tablet over-encapsulated to match placebo inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 11, 2018 | Feb 4, 2021 |
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| placebo (for azithromycin) | Drug |
|
| inhaled tobramycin | Drug | clinically prescribed inhaled tobramycin used by subjects participating in the study |
|
Absolute change in CFRSD-CRISS from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. The Cystic Fibrosis Respiratory Symptoms Diary asks a participant to state the extent of 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest, and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present "a great deal" or "extremely." A summed score (ranging from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where lower scores indicate improvement of symptoms. |
| baseline (week 0) to week 6 (6 week period) |
| Change in Cystic Fibrosis Questionnaire - Revised Respiratory Symptom Score (CFQ-R RSS) | Absolute change in the CFQ-R RSS from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. Age appropriate versions of Cystic Fibrosis Questionnaire - Revised ask a participant from 4 to 6 questions related to respiratory symptoms. The Respiratory Domain Scaled Score is calculated as follows: 100*[sum of {responses-1}] / [{number of responses}*3] only if [number of responses] ≥ [number of possible responses]/2; otherwise the score is set to missing. The scaled score ranges from 0 to 100 and higher scores indicate improvement of symptoms. | baseline (week 0) to week 6 (6 week period) |
| baseline (week 0) to week 6 (6 week period) |
| Palo Alto |
| California |
| 94025 |
| United States |
| Rady Children's Hospital and Health Center at the University of California San Diego | San Diego | California | 92123 | United States |
| National Jewish Health | Denver | Colorado | 80206 | United States |
| Yale University School of Medicine | New Haven | Connecticut | 06520 | United States |
| University of Florida | Gainesville | Florida | 32610 | United States |
| The Nemours Children's Clinic - Orlando | Orlando | Florida | 32806 | United States |
| Nemours Children's Clinic - Pensacola | Pensacola | Florida | 32504 | United States |
| Saint Luke's Cystic Fibrosis Center of Idaho | Boise | Idaho | 83712 | United States |
| Northwestern University | Chicago | Illinois | 60208 | United States |
| Saint Francis Medical Center | Peoria | Illinois | 61637 | United States |
| Riley Hospital for Children | Indianapolis | Indiana | 46202 | United States |
| Maine Medical Partners Pediatric Specialty Care | Portland | Maine | 04102 | United States |
| Johns Hopkins University | Baltimore | Maryland | 21287 | United States |
| Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| University of Massachusetts Memorial Health Care | Worcester | Massachusetts | 01655 | United States |
| University of Michigan Health System | Ann Arbor | Michigan | 48109 | United States |
| Helen DeVos Children's Hospital | Grand Rapids | Michigan | 49503 | United States |
| The Minnesota Cystic Fibrosis Center | Minneapolis | Minnesota | 55455 | United States |
| Children's Mercy Kansas City | Kansas City | Missouri | 64108 | United States |
| Cardinal Glennon Children's Medical Center | St Louis | Missouri | 63104 | United States |
| St. Louis Children's Hospital | St Louis | Missouri | 63110 | United States |
| Monmouth Medical Center | Long Branch | New Jersey | 07740 | United States |
| Beth Israel Medical Center | New York | New York | 10003 | United States |
| Children's Hospital of New York | New York | New York | 10032 | United States |
| University of Rochester Medical Center Strong Memorial | Rochester | New York | 14642 | United States |
| University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| University Hospitals Case Medical Center/Rainbow Babies and Children's Hospital | Cleveland | Ohio | 44106 | United States |
| Dayton Children's Hospital | Dayton | Ohio | 45404 | United States |
| Oregon Health Sciences University | Portland | Oregon | 97239 | United States |
| Hershey Medical Center Pennsylvania State University | Hershey | Pennsylvania | 17033 | United States |
| St. Christopher's Hospital for Children | Philadelphia | Pennsylvania | 19134 | United States |
| Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | 15224 | United States |
| Cook Children's Medical Center | Fort Worth | Texas | 76104 | United States |
| Intermountain Cystic Fibrosis Center | Salt Lake City | Utah | 84113 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98145 | United States |
| University of Washington Medical Center | Seattle | Washington | 98195 | United States |
| Children's Hospital of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| Placebo |
encapsulated placebo taken by mouth thrice weekly for 6 weeks placebo (for azithromycin) inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study |
| Treated | Participants receiving at least one dose of study drug |
|
| COMPLETED |
|
| NOT COMPLETED |
|
Modified intent-to-treat population (m-ITT) defined as all randomized participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Azithromycin | azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks azithromycin: 500mg tablet over-encapsulated to match placebo inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study |
| BG001 | Placebo | encapsulated placebo taken by mouth thrice weekly for 6 weeks placebo (for azithromycin) inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study |
| 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, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Cystic Fibrosis (CF) Genotype | Other refers to participants with either two known, non-F508 del CF mutations, or one known, non-F508 del CF mutation and one unidentified allele which has not been classified as a CF mutation. Unidentified refers to participants with 2 alleles that have not been classified as CF mutations. | Count of Participants | Participants |
| |||||||||||||||
| FEV1 | FEV1 is the forced expiratory volume in one second. | Mean | Standard Deviation | liters |
| ||||||||||||||
| ppFEV1 Category | FEV1 percent of predicted (ppFEV1) is calculated using the Global Lung Initiative multi-ethnic reference equations for ages 3-95. | Count of Participants | Participants |
| |||||||||||||||
| Current Tobramycin Formulation | Count of Participants | Participants |
| ||||||||||||||||
| History of Azithromycin Use at Baseline | Current use is defined as use of chronic oral azithromycin for the past 30 days (can be either 3x/week or daily dosing). | Count of Participants | Participants |
|
| 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 in Lung Function | Relative change in FEV1 volume (L) from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6 | Participants in the m-ITT population with spirometry measurements of FEV1 liters at both baseline (week 0) and week 6. | Posted | Mean | Standard Deviation | percent change | baseline (week 0) to week 6 (6 week period) |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Relative Change in Lung Function | Relative change in FEV1 (L) from the beginning of the 4-week period with inhaled tobramycin at week 2 to the end of the 4-week period with inhaled tobramycin at week 6 | Participants in the m-ITT population with spirometry measurements of FEV1 liters at both week 2 and week 6. | Posted | Mean | Standard Deviation | percent change | week 2 to week 6 (4 week period) |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Cystic Fibrosis Respiratory Symptom Diary - Chronic Respiratory Infection Symptom Score (CFRSD-CRISS) | Absolute change in CFRSD-CRISS from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. The Cystic Fibrosis Respiratory Symptoms Diary asks a participant to state the extent of 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest, and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present "a great deal" or "extremely." A summed score (ranging from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where lower scores indicate improvement of symptoms. | Participants in the m-ITT population with CFRSD-CRISS diaries at both baseline (week 0) and week 6. | Posted | Mean | Standard Deviation | score on a scale | baseline (week 0) to week 6 (6 week period) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Cystic Fibrosis Questionnaire - Revised Respiratory Symptom Score (CFQ-R RSS) | Absolute change in the CFQ-R RSS from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. Age appropriate versions of Cystic Fibrosis Questionnaire - Revised ask a participant from 4 to 6 questions related to respiratory symptoms. The Respiratory Domain Scaled Score is calculated as follows: 100*[sum of {responses-1}] / [{number of responses}*3] only if [number of responses] ≥ [number of possible responses]/2; otherwise the score is set to missing. The scaled score ranges from 0 to 100 and higher scores indicate improvement of symptoms. | Participants in the m-ITT population with CFQ-R respiratory symptom scores at both baseline (week 0) and week 6. | Posted | Mean | Standard Deviation | score on a scale | baseline (week 0) to week 6 (6 week period) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change in Sputum Pseudomonas Aeruginosa Bacterial Density | Absolute change in log10 transformed quantitative Pseudomonas aeruginosa (Pa) bacterial density as measured by colony forming units (CFUs) per mL of sputum from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. Culture results below the lower limit of detection of 1x10^2 were set to 1/2 of that LLD prior to log transformation. | Participants in the m-ITT population with Pseudomonas aeruginosa sputum culture results at both baseline (week 0) and week 6. | Posted | Mean | Standard Deviation | log10(CFUs/mL) | baseline (week 0) to week 6 (6 week period) |
|
|
6 weeks
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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 | Azithromycin | azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks azithromycin: 500mg tablet over-encapsulated to match placebo inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study | 0 | 61 | 4 | 61 | 22 | 61 |
| EG001 | Placebo | encapsulated placebo taken by mouth thrice weekly for 6 weeks placebo (for azithromycin) inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study | 0 | 54 | 3 | 54 | 32 | 54 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Forced expiratory volume decreased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (19.0) | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Testicular torsion | Reproductive system and breast disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (19.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Arthur Baines | Seattle Children's Hospital | 2068841431 | arthur.baines@seattlechildrens.org |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 1, 2017 | Feb 5, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| 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 |
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| ID | Term |
|---|---|
| D017963 | Azithromycin |
| ID | Term |
|---|---|
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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| ≥ 18 to < 30 years |
|
| ≥ 30 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Delta F508 Heterozygous |
|
| Other |
|
| Unidentified |
|
| Not Available |
|
| ≥ 50% to < 75% |
|
| ≥ 75% |
|
| Tobramycin Inhaled Powder |
|
| Non-Current User |
|
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| Counts |
|---|
| Participants |
|
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