Clinical trial NCT01519661: Long Term Safety of Tobramycin Inhalation Powder in Patients With Cystic Fibrosis
Official title: A Single Arm, Open-label, Multicenter, Phase IV Trial to Assess Long Term Safety of Tobramycin Inhalation Powder (TIP) in Patients With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Infections
Pseudomonas Aeruginosa in Cystic Fibrosis
Keywords: Tobramycin Inhalation powder
Cystic fibrosis
Lung disease
Anti-bacterial agents
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-01-27
Enrollment: 157
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study assessed the long term safety data for the use of tobramycin inhalation powder in patients suffering from cystic fibrosis who have a chronic pulmonary infection with Pseudomonas aeruginosa.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of Cystic Fibrosis
* FEV1 at screening must be between 25 and 75 percent of normal predicted values for age, sex and height based on the Knudson equation
* Pseudomonas aeruginosa must be present in a sputum / deep cough throat swab culture or bronchoalveolar lavage within 6 months prior to screening and in the sputum/deep-throat cough swab culture at screening

Exclusion Criteria:

* History of sputum culture or deep cough throat swab culture yielding Burkholderia cenocepacia complex within 2 years prior to screening and /or sputum culture yielding Burkholderia cenocepacia at screening
* Hemoptysis more than 60mL at any time within 30 days prior to study drug administration
* History of hearing loss or chronic tinnitus deemed clinically significant
* Serum creatinine 2mg/dl or more, BUN 40mg/dl or more, 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 regularly receiving more than 1 class of inhaled anti-pseudomonal antibiotic
* Any use of inhaled or systemic anti-pseudomonal antibiotic within 28 days prior to study drug administration
* Use of loop diuretics within 7 days prior to study drug administration

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With Treatment Emergent Adverse Events, Serious Adverse Events (SAEs) and Deaths
timeFrame: 337 days
Secondary outcomes:
measure: Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted
timeFrame: Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period.
measure: Relative Change From Baseline in FVC Percent Predicted
timeFrame: Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period.
measure: Relative Change From Baseline in FEF Rate Over 25 to 75 Percent of Vital Capacity Predicted
timeFrame: Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period.
measure: Change From Baseline in Pseudomonas Aeruginosa Colony Forming Units in Sputum
timeFrame: Baseline, day 1, day 29, day 85, day 141, day 197, day 253, day 309, day 337
measure: Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa
timeFrame: Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337
measure: Percentage of Participants Hospitalized Due to Serious Respiratory-related Adverse Events
timeFrame: Day 337
measure: Number of Hospitalization Days Due to Serious Respiratory-related Adverse Events
timeFrame: Day 337
measure: Time to First Hospitalization Due to Serious Respiratory-related Adverse Events
timeFrame: Day 337
measure: Percentage of Participants Who Used New Anti-pseudomonal Antibiotics
timeFrame: Day 337
measure: Number of Days of New Anti-pseudomonal Antibiotic Use
timeFrame: Day 337
measure: Time to Use of New Anti-pseudomonal Antibiotic
timeFrame: Day 337
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: Denver
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Jacksonville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: St. Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Omaha
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Las Vegas
country: United States
facility: Novartis Investigative Site
state: Nevada
city: Morristown
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Akron
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Cleveland
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Charleston
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Fort Worth
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Tacoma
country: United States
facility: Novartis Investigative Site
state: Washington
city: Madison
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Milwaukee
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Córdoba
country: Argentina
facility: Novartis Investigative Site
state: Cordoba
city: Paraná
country: Argentina
facility: Novartis Investigative Site
state: Entre Rios
city: New Lambton Heights
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Clayton
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Giens Cedex
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Reims
country: France
facility: Novartis Investigative Site
city: Roscoff
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Messina
country: Italy
facility: Novartis Investigative Site
state: ME
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Palermo
country: Italy
facility: Novartis Investigative Site
city: Roma
country: Italy
facility: Novartis Investigative Site
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
state: Nuevo León
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Sommerwerck U, Virella-Lowell I, Angyalosi G, Viegas A, Cao W, Debonnett L. Long-term safety of tobramycin inhalation powder in patients with cystic fibrosis: phase IV (ETOILES) study. Curr Med Res Opin. 2016 Nov;32(11):1789-1795. doi: 10.1080/03007995.2016.1211516. Epub 2016 Sep 9.