Trial record 1 of 1 for:
GS-US-205-0117 and cystic fibrosis
Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis, Mild Lung Disease, and P. Aeruginosa (AIR-CF4)
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| ClinicalTrials.gov Identifier: NCT00712166 |
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Recruitment Status :
Completed
First Posted : July 9, 2008
Results First Posted : December 20, 2010
Last Update Posted : December 20, 2010
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Sponsor:
Gilead Sciences
Information provided by:
Gilead Sciences
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Brief Summary:
The purpose of this study was to evaluate the safety and efficacy of a 28-day course of aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis (CF), mild lung disease (forced expiratory volume in 1 second [FEV1] >75% predicted, and Pseudomonas aeruginosa (PA) infection.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cystic Fibrosis Lung Infection Pseudomonas Aeruginosa | Drug: AZLI 75 mg three times daily (TID) Drug: Placebo three times daily (TID) | Phase 3 |
CF patients often have lung infections that occur repeatedly or worsen over time. The lung infections are often caused by a bacteria called Pseudomonas aeruginosa (PA). Treatment with antibiotics can stop or slow down the growth of the bacteria. The antibiotics may be given by mouth, intravenously (IV), or by inhalation as a mist. The purpose of this study was to evaluate the safety and efficacy of AZLI, an investigational formulation of the antibiotic aztreonam and administered three times a day using the PARI eFlow® electronic nebulizer, in CF patients with PA and mild lung disease.
In this study, participant eligibility was assessed at a screening visit that occurred up to 14 days prior to the baseline visit (Day 0). Those participants who met eligibility criteria at Day 0 were randomized and began a 28-day course of blinded study treatment (AZLI or placebo TID). Participants returned for clinic visits at Day 14, an end of treatment visit at Day 28, and a follow up visit 14 days after the last dose of the trial drug (Day 42).
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 160 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Double-Blind, Multicenter, Multinational, Randomized, Placebo-Controlled Trial Evaluating Aztreonam Lysine For Inhalation in Patients With Cystic Fibrosis, Mild Lung Disease, and P. Aeruginosa (AIR-CF4) |
| Study Start Date : | May 2008 |
| Actual Primary Completion Date : | June 2009 |
| Actual Study Completion Date : | August 2009 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Cystic fibrosis
Drug Information available for:
Aztreonam
| Arm | Intervention/treatment |
|---|---|
| Placebo Comparator: Placebo three times daily (TID) |
Drug: Placebo three times daily (TID) |
| Experimental: AZLI 75 mg three times daily (TID) |
Drug: AZLI 75 mg three times daily (TID) |
Primary Outcome Measures :
- Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score at Day 28 [ Time Frame: Day 0 to Day 28 ]The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Days 0, 14, 28, and 42. The endpoint was change in respiratory symptoms (e.g., coughing, congestion, wheezing) from Day 0 (baseline), assessed with the CFQ-R RSS (score range: 0-100; higher scores indicating fewer symptoms, higher health-related quality of life, or better functioning). Baseline CFQ-R RSS and age group (<18 vs. >=18 years) were included as covariates in the analysis.
Secondary Outcome Measures :
- Change From Baseline in CFQ-R RSS Score at Day 14 [ Time Frame: Day 0 to Day 14 ]The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Days 0, 14, 28, and 42. The endpoint was change in respiratory symptoms (e.g., coughing, congestion, wheezing) from Day 0 (baseline), assessed with the CFQ-R RSS (score range: 0-100; higher scores indicating fewer symptoms, higher health-related quality of life, or better functioning). Baseline CFQ-R RSS and age group (<18 vs. >=18 years) were included as covariates in the analysis.
- Change From Baseline in CFQ-R RSS Score at Day 42 [ Time Frame: Day 0 to Day 42 ]The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Days 0, 14, 28, and 42. The endpoint was change in respiratory symptoms (e.g., coughing, congestion, wheezing) from Day 0 (baseline), assessed with the CFQ-R RSS (score range: 0-100; higher scores indicating fewer symptoms, higher health-related quality of life, or better functioning). Baseline CFQ-R RSS and age group (<18 vs. >=18 years) were included as covariates in the analysis.
- Change From Baseline in CFQ-R Physical Functioning Domain Score [ Time Frame: Day 0 to Day 28 ]The CFQ-R contains both general and CF-specific scales. The CFQ-R was administered at Days 0 (baseline), 14, 28, and 42 (the last study visit). The endpoint was change from baseline in the physical functioning domain (e.g., ability to walk and engage in physical activities) of the CFQ-R at Day 28 (range of scores: 0-100; higher scores indicating fewer symptoms, higher health-related quality of life, or better functioning). Baseline CFQ-R physical functioning domain score and age group (<18 vs. >=18 years) were included as covariates in the analysis.
- Number of Participants Using Additional (Nonprotocol-specified) Antipseudomonal Antibiotics During Study [ Time Frame: Day 0 to Day 42 ]The number of participants requiring additional antipseudomonal antibiotics (oral, intravenous [IV], or by inhalation), the time to use of these antibiotics, and the reasons for use was recorded. A binary variable was defined to indicate whether the participants needed any antipseudomonal antibiotics that were non-study drug via the oral, IV, or inhalation route between Day 0 (Baseline Visit) and Day 42 (Visit 5). Fisher's Exact Test was implemented on the intent-to-treat (ITT) and per protocol analysis sets to detect treatment effects on need for additional antipseudomonal antibiotics.
- Number of Participants Hospitalized During Study [ Time Frame: Day 0 to Day 42 ]Hospitalization was defined as any hospital admission lasting for more than 1 calendar day that had been recorded as a serious adverse event (SAE) on the electronic case report form (eCRF). Binary variables were defined to indicate whether participants experienced any hospitalization. Number of hospitalizations was summarized by treatment group.
- Change From Baseline in Log10 Pseudomonas Aeruginosa (PA) Colony Forming Units (CFUs) in Sputum at Day 28 [ Time Frame: Day 0 to Day 28 ]Sputum samples were collected at all study visits for quantitative and qualitative culture for PA. Sputum PA density was quantified by logarithm transformation of the CFU value with base 10. Change from baseline in sputum PA density was calculated as the difference between the log10 CFU values at Day 28 (Visit 4) and the baseline value. Missing data was not imputed. Baseline log10 CFU and age group (<18 vs. >=18 years) were included as covariates in the analysis.
- Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted [ Time Frame: Day 0 to Day 28 ]Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. Treatment effect on the relative change from baseline in FEV1 percent predicted at Day 28 (Visit 4) was tested by the ANCOVA model using the ITT analysis set. Baseline FEV1 percent predicted and age group (<18 vs. >=18 years) were included as covariates in the analysis.
Other Outcome Measures:
- Number of Participants Testing Positive for Other Respiratory Pathogens [ Time Frame: Day 0 to Day 28 ]Sputum/throat swab samples were collected at all visits for quantitative and qualitative culture of Burkholderia species, Stenotrophomonas maltophilia, Achromobacter xylosidans, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive S. aureus (MSSA), and Aspergillus species. One CFU on the culture from either a sputum or throat swab sample was considered presence of the particular organism.
- The Minimum Concentrations of Aztreonam That Inhibit 50% and 90% of All PA Isolates (MIC50 and MIC90, Respectively) [ Time Frame: Day 0 to Day 28 ]Aztreonam susceptibility of PA isolates from expectorated sputum samples (collected at all visits) was assessed. The minimum inhibitory concentration (MIC) is the lowest concentration of antimicrobial agent that inhibits visible growth of a microorganism. The MIC50 and MIC90 for PA is the MIC required to inhibit the growth of 50% or 90% of PA isolates, respectively. Given that there might be multiple PA isolates for each participant, the MIC50 and MIC90 for PA was calculated using the MIC values for all PA isolates. The MIC50 and MIC90 were calculated by treatment group.
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| Ages Eligible for Study: | 6 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Participants ≥ 6 years of age
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Documentation of CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:
- Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test
- Two well characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
- Abnormal nasal potential difference
- PA present in expectorated sputum or throat swab culture at Visit 1 OR documented PA in 2 expectorated sputum or throat swab cultures within the 12 months prior to Visit 1 (one of the previous PA positive cultures must have been no more than 3 months prior to Visit 1)
- FEV1 > 75% predicted at Visit 1
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Participants must have exhibited two or more of the following chronic and/or intermittent CF symptoms, for a minimum of 28 days prior to randomization and with no worsening of symptoms within 7 days prior to randomization:
- Chest congestion
- Daily cough
- Productive cough
- Wheezing
- Trouble breathing
- Nocturnal wakening due to coughing
- Participants (and parent/guardian as required) had to be able to provide written informed consent/assent prior to any study related procedures
- Females of childbearing potential had to have a negative urine pregnancy test at Visit 1
- Ability to perform reproducible pulmonary function tests
- In the opinion of the Investigator, the participant did not require immediate antipseudomonal antibiotic intervention to treat an impending exacerbation, and the participant's condition was stable enough to enroll in the study
Exclusion Criteria:
- Administration of any investigational drug or device within 28 days prior to Visit 1 or within 6 half-lives of the investigational drug (whichever was longer)
- Administration of any IV, oral, or inhaled antipseudomonal antibiotic within 28 days prior to Visit 1
- Known local or systemic hypersensitivity to monobactam antibiotics
- Inability to tolerate short-acting bronchodilator (BD) use at least TID
- Changes in or initiation of chronic azithromycin treatment within 28 days prior to Visit 1
- Changes in or initiation of chronic hypertonic saline treatment within 28 days prior to Visit 1
- Changes in or initiation of dornase alfa within 28 days prior to Visit 1
- Changes in antimicrobial, BD, or corticosteroid medications within 7 days prior to Visit 1
- Changes in physiotherapy technique or schedule within 7 days prior to Visit 1
- History of lung transplantation
- History of participation (enrollment) in any prior clinical studies with AZLI
- A chest radiograph at Visit 1 (or within the previous 180 days of Visit 1), with abnormalities indicating a significant acute finding (e.g., lobar infiltrate and atelectasis, pneumothorax, or pleural effusion); a chest radiograph obtained and interpreted between Visits 1 and 2 was also acceptable for determining eligibility
- Positive urine pregnancy test at Visit 1; all women of childbearing potential were to be tested
- Females of childbearing potential who were lactating or were not (in the opinion of the investigator) practicing an acceptable method of birth control; female participants who utilized hormonal contraceptives as their birth control method must have used the same method for at least 3 months before study dosing
- Participant was being assessed at Visit 1 by the investigator for an acute change in respiratory symptoms
- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00712166
Locations
Show 40 study locations
Sponsors and Collaborators
Gilead Sciences
Investigators
| Principal Investigator: | Claire Wainwright, MD | Royal Children's Hospital, Brisbane, QLD, Australia | |
| Principal Investigator: | Ron Gibson, MD | Children's Hospital & Regional Medical Center, Seattle WA, USA |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Mark Bresnik, MD, Director, Clinical Research, Gilead Sciences, Inc. |
| ClinicalTrials.gov Identifier: | NCT00712166 |
| Other Study ID Numbers: |
GS-US-205-0117 |
| First Posted: | July 9, 2008 Key Record Dates |
| Results First Posted: | December 20, 2010 |
| Last Update Posted: | December 20, 2010 |
| Last Verified: | November 2010 |
Keywords provided by Gilead Sciences:
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cystic fibrosis pseudomonas aeruginosa lung infection |
CFQ-R inhaled antibiotic aztreonam lysine |
Additional relevant MeSH terms:
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Cystic Fibrosis Fibrosis Pseudomonas Infections Lung Diseases Infections Pathologic Processes Pancreatic Diseases |
Digestive System Diseases Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Gram-Negative Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses |