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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00388505




Registration number
NCT00388505
Ethics application status
Date submitted
16/10/2006
Date registered
17/10/2006
Date last updated
24/07/2012

Titles & IDs
Public title
Safety of Tobramycin Inhalation Powder (TIP) vs Tobramycin Solution for Inhalation in Patients With Cystic Fibrosis
Scientific 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
Secondary ID [1] 0 0
CTBM100C2302
Universal Trial Number (UTN)
Trial acronym
EAGER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tobramycin Inhalation Powder
Treatment: Drugs - Tobramycin Solution for Inhalation

Experimental: Tobramycin inhalation powder (TIP) - Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.

Active Comparator: Tobramycin solution for inhalation (TOBI) - Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.


Treatment: Drugs: Tobramycin Inhalation Powder
Tobramycin Inhalation Powder (TIP) capsules for inhalation.

Treatment: Drugs: Tobramycin Solution for Inhalation
Tobramycin solution for inhalation (TOBI), supplied as 300 mg/5mL ampoules administered with a nebulizer

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-emergent Adverse Events - An adverse event (AE) is any untoward medical occurrence, including any unfavorable and unintended sign, symptom or disease temporally associated with the use of the study medication that does not necessarily have a causal relationship with study medication. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability, is a congenital anomaly or defect, or is a significant medical event that may jeopardize the patient or require intervention to prevent one of the outcomes listed above.
Timepoint [1] 0 0
25 weeks
Secondary outcome [1] 0 0
Serum Tobramycin Concentrations - Serum tobramycin concentrations were measured in a subset of participants at Week 1 (start of cycle 1), Week 5 (End of Cycle 1), Week 17 (start of cycle 3) and Week 21 (end of cycle 3). Serum samples were collected at pre-dose and post-dose at specified intervals; one specimen between 0 to 2 hours; two additional specimens between 2 and 5 hours (sample times must have been a minimum of 2 hours apart).
Timepoint [1] 0 0
Weeks 1, 5, 17 and 21
Secondary outcome [2] 0 0
Percentage of Participants With a Decrease From Baseline in Auditory Acuity - Audiology testing was performed only at selected centers. Auditory acuity was measured from 250 to 8000 Hertz using a standard dual-channel audiometer.
Timepoint [2] 0 0
Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21)
Secondary outcome [3] 0 0
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1) - Forced expiratory volume in one second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 is then converted to a percentage of normal (percent predicted) based on height, weight, and race. FEV1 was measured at Baseline (prior to beginning study treatment) and predose on Day 28 of Cycles 1, 2 and 3 and at the follow-up visit.
Relative change = 100 * ((Day 28 of Cycle 3 value - Baseline value)/ Baseline value).
Timepoint [3] 0 0
Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)
Secondary outcome [4] 0 0
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication - Patient's self-reported treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM, a validated instrument) which was modified by adding four study-specific questions; the standard fourteen questions of the TSQM were not altered. Responses to nearly all items are rated on a five-point or seven-point rating scale and the items are factored into 4 domains. The TSQM domain scores range from 0 to 100 with higher scores representing higher satisfaction for that domain.
Timepoint [4] 0 0
Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21).
Secondary outcome [5] 0 0
Change From Baseline in Pseudomonas Aeruginosa Sputum Density - Three Pseudomonas aeruginosa biotypes were assessed in patient's sputum; mucoid, dry and small colony variant. Overall density is defined as the sum of all bio-types in Pseudomonas aeruginosa density.
Timepoint [5] 0 0
Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25).
Secondary outcome [6] 0 0
Change From Baseline in Tobramycin Minimum Inhibitory Concentration - The minimum inhibitory concentration (MIC) is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. The MIC of tobramycin against total Pseudomonas aeruginosa colonization was assessed over the course of the study.
Timepoint [6] 0 0
Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)
Secondary outcome [7] 0 0
Antipseudomonal Antibiotic Usage During the Study - The average number of days patients required antipseudomonal antibiotics during the course of the study.
Timepoint [7] 0 0
25 Weeks
Secondary outcome [8] 0 0
Hospitalization Due to Respiratory Events During the Study - The average number of days patients were hospitalized due to respiratory events during the course of the study.
Timepoint [8] 0 0
25 Weeks

Eligibility
Key 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.
Minimum age
6 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Novartis Investigative Site - South Brisbane
Recruitment postcode(s) [1] 0 0
- South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New Hampshire
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Vermont
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
West Virginia
Country [13] 0 0
Canada
State/province [13] 0 0
Calgary
Country [14] 0 0
Canada
State/province [14] 0 0
Hamilton
Country [15] 0 0
Canada
State/province [15] 0 0
Ste-Foy
Country [16] 0 0
Canada
State/province [16] 0 0
Vancouver
Country [17] 0 0
Chile
State/province [17] 0 0
Santiago
Country [18] 0 0
Colombia
State/province [18] 0 0
Baranquilla
Country [19] 0 0
Colombia
State/province [19] 0 0
Bogota
Country [20] 0 0
Colombia
State/province [20] 0 0
Cali
Country [21] 0 0
Colombia
State/province [21] 0 0
Medellin
Country [22] 0 0
France
State/province [22] 0 0
Montpellier
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Rouen
Country [25] 0 0
Germany
State/province [25] 0 0
Berlin
Country [26] 0 0
Germany
State/province [26] 0 0
Bochum
Country [27] 0 0
Germany
State/province [27] 0 0
Bonn
Country [28] 0 0
Germany
State/province [28] 0 0
Essen
Country [29] 0 0
Germany
State/province [29] 0 0
Frankfurt
Country [30] 0 0
Germany
State/province [30] 0 0
Hamburg
Country [31] 0 0
Germany
State/province [31] 0 0
Hannover
Country [32] 0 0
Germany
State/province [32] 0 0
Koeln
Country [33] 0 0
Germany
State/province [33] 0 0
Muenchen
Country [34] 0 0
Germany
State/province [34] 0 0
Munich
Country [35] 0 0
Hungary
State/province [35] 0 0
Hungary
Country [36] 0 0
Hungary
State/province [36] 0 0
Kaposvar
Country [37] 0 0
Israel
State/province [37] 0 0
Haifa
Country [38] 0 0
Israel
State/province [38] 0 0
Jerusalem
Country [39] 0 0
Israel
State/province [39] 0 0
Petach-Tikva
Country [40] 0 0
Italy
State/province [40] 0 0
Genoa
Country [41] 0 0
Italy
State/province [41] 0 0
Palermo
Country [42] 0 0
Italy
State/province [42] 0 0
Potenza
Country [43] 0 0
Italy
State/province [43] 0 0
Roma
Country [44] 0 0
Mexico
State/province [44] 0 0
Monterrey Nuevo Leon
Country [45] 0 0
Netherlands
State/province [45] 0 0
Groesbeek
Country [46] 0 0
Netherlands
State/province [46] 0 0
Rotterdam
Country [47] 0 0
Spain
State/province [47] 0 0
Baracaldo
Country [48] 0 0
Spain
State/province [48] 0 0
Barcelona
Country [49] 0 0
Spain
State/province [49] 0 0
Madrid
Country [50] 0 0
Spain
State/province [50] 0 0
Malaga
Country [51] 0 0
Spain
State/province [51] 0 0
Sevilla
Country [52] 0 0
Spain
State/province [52] 0 0
Valencia
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Belfast
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Birmingham
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Cambridge
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Leeds
Country [57] 0 0
United Kingdom
State/province [57] 0 0
London
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study compares the safety of the tobramycin solution for inhalation with the tobramycin
dry powder formulation, used with a simple inhaler
Trial website
https://clinicaltrials.gov/show/NCT00388505
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Konstan, MD
Address 0 0
University Hospitals Cleveland Medical Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications