Safety of Tobramycin Inhalation Powder (TIP) vs Tobramycin Solution for Inhalation in Patients With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

— EAGER  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00388505
• Other study ID #: CTBM100C2302
• Status: Completed
• Phase: Phase 3
• First received: October 16, 2006
• Last updated: June 19, 2012
• Start date: February 2006
• Est. completion date: March 2009

Study information

• Verified date: June 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationFrance: Agence Française de Sécurité Sanitaire des produits de SantéGermany: Federal Institute for Drugs and Medical DevicesItaly: Agenzia Italiana del FarmacoNetherlands: College ter beoordeling van geneesmiddelen Medicines Evaluation BoardSpain: Ministerio de Sanidad y Consumo, Agencia Española del Medicamento y Productos SanitariosUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 517
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Tobramycin Inhalation Powder
Tobramycin Inhalation Powder (TIP) capsules for inhalation.
• Tobramycin Solution for Inhalation
Tobramycin solution for inhalation (TOBI), supplied as 300 mg/5mL ampoules administered with a nebulizer

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	South Brisbane
Canada	Novartis Investigative Site	Calgary
Canada	Novartis Investigative Site	Hamilton
Canada	Novartis Investigative Site	Ste-Foy
Canada	Novartis Investigative Site	Vancouver
Chile	Novartis Investigative Site	Santiago
Colombia	Novartis Investigative Site	Baranquilla
Colombia	Novartis Investigative Site	Bogota
Colombia	Novartis Investigative Site	Cali
Colombia	Novartis Investigative Site	Medellin
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Rouen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Essen
Germany	Klinikum der Johann-Wolfgang-Goethe-Universitaet	Frankfurt
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Muenchen
Germany	Ludwig-Maximilians-Universitaet	Munich
Hungary	Novartis Investigative Site	Hungary
Hungary	Novartis Investigative Site	Kaposvar
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Petach-Tikva
Italy	Novartis Investigator Site	Genoa
Italy	Novartis Investigative Site	Palermo
Italy	Novartis Investigative Site	Potenza
Italy	Novartis Investigative Site	Roma
Mexico	Novartis Investigative Site	Monterrey Nuevo Leon
Netherlands	Novartis Investigative Site	Groesbeek
Netherlands	Novartis Investigative Site	Rotterdam
Spain	Novartis Investigative Site	Baracaldo
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga
Spain	Novartis Investigative Site	Sevilla
Spain	Novartis Investigative Site	Valencia
United Kingdom	Novartis Investigative Site	Belfast
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Cambridge
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Sheffield
United States	Novartis Investigative Site	Albany	New York
United States	Emory University CF Center	Atlanta	Georgia
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Buffalo	New York
United States	Novartis Investigative Site	Burlington	Vermont
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Rush University Center	Chicago	Illinois
United States	Novartis Investigative Site	Hartford	Connecticut
United States	Penn State College of Medicine	Hershey	Pennsylvania
United States	Novartis Investigative Site	Lebanon	New Hampshire
United States	Novartis Investigative Site	Livingston	New Jersey
United States	Novartis Investigative Site	Long Branch	New Jersey
United States	University of Louisville	Louisville	Kentucky
United States	West Virginia University Health Sciences Center	Morgantown	West Virginia
United States	Novartis Investigative Site	Morristown	New Jersey
United States	Novartis Investigative Site	New Hyde Park	New York
United States	Novartis Investigative Site	New York City	New York
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Rochester	Rochester	New York
United States	Novartis Investigative Site	Somerset	New Jersey
United States	Novartis Investigative Site	Stony Brook	New York
United States	Novartis Investigative Site	Syracuse	New York
United States	Novartis Investigative Site	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Chile,  Colombia,  France,  Germany,  Hungary,  Israel,  Italy,  Mexico,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	25 weeks	Yes
Secondary	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).	Weeks 1, 5, 17 and 21	No
Secondary	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.	Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21)	No
Secondary	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).	Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)	No
Secondary	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.	Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21).	No
Secondary	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.	Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25).	No
Secondary	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.	Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)	No
Secondary	Antipseudomonal Antibiotic Usage During the Study	The average number of days patients required antipseudomonal antibiotics during the course of the study.	25 Weeks	No
Secondary	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.	25 Weeks	No