Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles

Study Overview
=================
Brief Summary
-----------------
To provide efficacy and safety data comparing two dosing schedules of Tobramycin Inhalation Powder (TIP) for the treatment of pulmonary Pseudomonas aeruginosa in patients with cystic fibrosis.

Official Title
-----------------
A 24-week, Open-label, Parallel-group, Interventional Phase IV Study Comparing Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles for the Treatment of Pulmonary Pseudomonas Aeruginosa in Patients With Cystic Fibrosis

Conditions
-----------------
Cystic Fibrosis

Intervention / Treatment
-----------------
* Drug: Tobramycin Inhalation Powder


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provide written informed consent, HIPPA (Health Insurance Portability and Accountability Act) authorization (where applicable), and assent (as appropriate) prior to the performance of any study-related procedure. Confirmed diagnosis of CF FEV1 at screening (Visit 1) ≥25% and ≤ 80% of normal predicted values for age, sex, and height P. aeruginosa must be present within 6 months prior to screening and at screening Able to comply with all protocol requirements Clinically stable in the opinion of the investigator Exclusion Criteria: History of Burkholderia cenocepacia (Bcc) complex within 2 years prior to screening and/or Bcc complex at screening Hemoptysis more than 60 cc at any time within 30 days prior to study drug administration History of hearing loss or chronic tinnitus deemed clinically significant by the investigator Serum creatinine 2 mg/dL or greater, BUN 40 mg/dL or greater, or an abnormal urinalysis defined as 2+ or greater proteinuria at screening Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics Patients who are unable to discontinue previously received inhaled antibiotic regimen(s) (inhaled antibiotics are not allowed other than study drug) Use of inhaled aminoglycosides within 28 days prior to study drug administration (Visit 2) Use of systemic anti-pseudomonal antibiotics within 28 days prior to study drug administration Use of loop diuretics within 7 days prior to study drug administration Administration of any investigational drug within 30 days prior to enrollment or 5 half-lives, whichever is longer Signs and symptoms of acute pulmonary disease, e.g , pneumonia, pneumothorax Hospitalization during the baseline visit History of malignancy Patients with clinically significant laboratory abnormalities (not associated with the study indication) at screening Patients with other clinically significant conditions (not associated with the study indication) which might interfere with the assessment of this study Patients or caregivers with a history of noncompliance to medical regimens and patients or caregivers who are considered potentially unreliable Pregnant or nursing (lactating) women Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Tobramycin Inhalation Powder (112 mg) once daily during 168 days | Drug: Tobramycin Inhalation Powder<br>* Tobramycin Inhalation Powder 112 mg (four 28-mg capsules) taken via inhaler once or twice a day, depending on study arm<br>|
| Active Comparator: Arm 2<br>Tobramycin Inhalation Powder (112 mg) twice daily on days 1-28, days 57-84 and days 113-140 | Drug: Tobramycin Inhalation Powder<br>* Tobramycin Inhalation Powder 112 mg (four 28-mg capsules) taken via inhaler once or twice a day, depending on study arm<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Forced Expiratory Volume in 1 Second ( FEV1) Percent Predicted | The Forced Expiratory Volume in 1 second (FEV1) percent predicted expresses FEV1 as a percentage of the predicted values for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 percent predicted indicates improvement in lung function. | Baseline and Day 168 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted | The Forced Expiratory Volume in 1 second (FEV1) percent predicted expresses FEV1 as a percentage of the predicted values for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 percent predicted indicates improvement in lung function. | Baseline and Day 168 | 
| Percent Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted | Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC will be assessed via spirometry. A positive change from baseline in FVC indicates improvement in lung function. | Baseline and Day 168 | 
| Percent Change From Baseline in Forced Expiratory Flow (FEF) 25%-75% Predicted | The Forced Expiratory Flow (FEF) 25%-75% measurement describes the amount of air expelled from the lungs during the middle half (25% - 75%) of the forced vital capacity test and is measured using spirometry. A positive change from baseline in FEF indicates improvement in lung function. The predicted percent will be assessed. | Baseline and day 168 | 
| Change From Baseline in Pseudomonas Aeruginosa Sputum Density | Change from baseline in Pseudomonas aeruginosa sputum density will be measured by log10 colony forming units per gram of sputum. | Baseline and day 168 | 
| Time to First Hospitalization Due to Respiratory-related Events | Time to the first hospitalization due to respiratory-related events (number of days) per patient. | Day 1 to day 168 | 
| Percentage of Patients With Hospitalizations Due to Respiratory-related Events | Percentage of patients with hospitalization due to respiratory-related events | Day 1 to day 168 | 
| Length of Hospital Stay Due to Respiratory-related Events | The number of days in length of hospital stay per patient due to respiratory-related events will be measured. | Day 1 to day 168 | 
| Time to First Usage of Anti-pseudomonal Antibiotic | Time to first usage of anti-pseudomonal antibiotic per patient will be assessed by number of days | Day 1 to day 168 | 
| Percentage of Patients Who Use Anti-pseudomonal Antibiotic | Percentage of patients who use anti-pseudomonal antibiotic will be assessed. | Day 1 to day 168 | 
| Duration of Use of Anti-pseudomonal Antibiotic | Number of days of use of anti-pseudomonal antibiotic per patient will be assessed. | Day 1 to day 168 | 
| Change From Baseline in Tobramycin Minimal Inhibitory Concentration for Pseudomonas Aeruginosa | Change from baseline in tobramycin minimal inhibitory concentration for Pseudomonas aeruginosa will be measured by laboratory testing. | Baseline and day 168 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CF, Cystic Fibrosis