Clinical trial NCT00388505: Safety of Tobramycin Inhalation Powder (TIP) vs Tobramycin Solution for Inhalation in Patients With Cystic Fibrosis
Official title: A Randomized, Open-label Multicentre Phase 3 Trial to Assess the Safety of Tobramycin Inhalation Powder Compared to Tobramycin Solution for Inhalation in Cystic Fibrosis Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: tobramycin
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-10-17
Enrollment: 517
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study compares the safety of the tobramycin solution for inhalation with the tobramycin dry powder formulation, used with a simple inhaler


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of cystic fibrosis
* Male and female patients at least 6 years of age at the time of screening.
* Forced expiratory volume in one second (FEV1) at screening must be at least 25% and less than or equal to 75% of normal predicted values for age, sex, and height based on Knudson criteria.
* Pseudomonas aeruginosa, a type of bacteria, must be present in a sputum/deep-throat cough swab culture (or bronchoalveolar lavage \[BAL\]) within 6 months prior to screening and in the sputum/ deep-throat cough swab culture at the screening visit.
* Able to comply with all protocol requirements.
* Clinically stable in the opinion of the investigator.
* Use of an effective means of contraception in females of childbearing potential.
* Provide written informed consent, Health Authority Portability and Accountability Act (HIPAA) authorization (where applicable), and assent (as appropriate) prior to the performance of any study-related procedure.

Exclusion Criteria:

* History of sputum culture or deep-throat cough swab (or BAL) culture yielding Burkholderia cepacia (B cepacia), a type of bacteria, within 2 years prior to screening and/or sputum culture yielding B cepacia at screening.
* Coughing up more than 60 cc of blood from the respiratory tract at any time within 30 days prior to study drug administration.
* Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.
* Females who are pregnant (positive pregnancy test), lactating, or are planning to become pregnant during the study.
* History of hearing loss or chronic ringing in the ears deemed clinically significant by the investigator.
* Use of systemic or inhaled antipseudomonal antibiotics within 28 days prior to study drug administration.
* Use of loop diuretics within 7 days prior to study drug administration.
* Use of any investigational treatment within 28 days prior to study drug administration.
* Initiation of treatment with chronic macrolide therapy, dornase alpha treatment or inhaled corticosteroids within 28 days prior to study drug administration (patients may be taking these therapies at the time of enrollment, but they must have initiated treatment more than 28 days prior to study drug administration).

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: 25 weeks
Secondary outcomes:
measure: Serum Tobramycin Concentrations
timeFrame: Weeks 1, 5, 17 and 21
measure: Percentage of Participants With a Decrease From Baseline in Auditory Acuity
timeFrame: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21)
measure: Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1)
timeFrame: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)
measure: Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
timeFrame: Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21).
measure: Change From Baseline in Pseudomonas Aeruginosa Sputum Density
timeFrame: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25).
measure: Change From Baseline in Tobramycin Minimum Inhibitory Concentration
timeFrame: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)
measure: Antipseudomonal Antibiotic Usage During the Study
timeFrame: 25 Weeks
measure: Hospitalization Due to Respiratory Events During the Study
timeFrame: 25 Weeks
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Novartis Investigative Site
state: Connecticut
city: Atlanta
country: United States
facility: Emory University CF Center
state: Georgia
city: Chicago
country: United States
facility: Rush University Center
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Lebanon
country: United States
facility: Novartis Investigative Site
state: New Hampshire
city: Livingston
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Long Branch
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Morristown
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Somerset
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Albany
country: United States
facility: Novartis Investigative Site
state: New York
city: Buffalo
country: United States
facility: Novartis Investigative Site
state: New York
city: New Hyde Park
country: United States
facility: Novartis Investigative Site
state: New York
city: New York City
country: United States
facility: Novartis Investigative Site
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Stony Brook
country: United States
facility: Novartis Investigative Site
state: New York
city: Syracuse
country: United States
facility: Novartis Investigative Site
state: New York
city: Valhalla
country: United States
facility: Novartis Investigative Site
state: New York
city: Hershey
country: United States
facility: Penn State College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Burlington
country: United States
facility: Novartis Investigative Site
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University Health Sciences Center
state: West Virginia
city: South Brisbane
country: Australia
facility: Novartis Investigative Site
city: Calgary
country: Canada
facility: Novartis Investigative Site
city: Hamilton
country: Canada
facility: Novartis Investigative Site
city: Ste-Foy
country: Canada
facility: Novartis Investigative Site
city: Vancouver
country: Canada
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Baranquilla
country: Colombia
facility: Novartis Investigative Site
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Cali
country: Colombia
facility: Novartis Investigative Site
city: Medellin
country: Colombia
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Rouen
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Klinikum der Johann-Wolfgang-Goethe-Universitaet
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Munich
country: Germany
facility: Ludwig-Maximilians-Universitaet
city: Hungary
country: Hungary
facility: Novartis Investigative Site
city: Kaposvar
country: Hungary
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Petach-Tikva
country: Israel
facility: Novartis Investigative Site
city: Genoa
country: Italy
facility: Novartis Investigator Site
city: Palermo
country: Italy
facility: Novartis Investigative Site
city: Potenza
country: Italy
facility: Novartis Investigative Site
city: Roma
country: Italy
facility: Novartis Investigative Site
city: Monterrey Nuevo Leon
country: Mexico
facility: Novartis Investigative Site
city: Groesbeek
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Baracaldo
country: Spain
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Belfast
country: United Kingdom
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Cambridge
country: United Kingdom
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Sheffield
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: University Hospitals Cleveland Medical Center
name: Michael Konstan, MD
role: PRINCIPAL_INVESTIGATOR
References: