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

NCT00388505 | Completed Phase 3 Results

• 1 other identifier: CTBM100C2302
• Study Type: interventional
• Target: 517
• Locations: 14 countries
• Sites: 72

Brief Summary

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

Conditions

Cystic Fibrosis

Keywords

tobramycin

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (8)

• Serum Tobramycin Concentrations

  Weeks 1, 5, 17 and 21

• Percentage of Participants With a Decrease From Baseline in Auditory Acuity

  Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21)

• Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1)

  Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)

• Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication

  Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21).

• Change From Baseline in Pseudomonas Aeruginosa Sputum Density

  Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25).

Study Arms (2)

Tobramycin inhalation powder (TIP)

EXPERIMENTAL

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.

Drug: Tobramycin Inhalation Powder

Tobramycin solution for inhalation (TOBI)

ACTIVE COMPARATOR

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.

Drug: Tobramycin Solution for Inhalation

Interventions

Tobramycin Inhalation Powder DRUG

Tobramycin Inhalation Powder (TIP) capsules for inhalation.

Tobramycin inhalation powder (TIP)

Tobramycin Solution for Inhalation DRUG

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

Tobramycin solution for inhalation (TOBI)

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (72)

Novartis Investigative Site

Hartford, Connecticut, 06102, United States

Location

Emory University CF Center

Atlanta, Georgia, 30322, United States

Location

Rush University Center

Chicago, Illinois, 60612, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02115, United States

Location

Novartis Investigative Site

Lebanon, New Hampshire, 03756, United States

Location

Novartis Investigative Site

Livingston, New Jersey, 07039, United States

Location

Novartis Investigative Site

Long Branch, New Jersey, 07740, United States

Location

Novartis Investigative Site

Morristown, New Jersey, 07967, United States

Location

Novartis Investigative Site

Somerset, New Jersey, 08873, United States

Location

Novartis Investigative Site

Albany, New York, 12208, United States

Location

Novartis Investigative Site

Buffalo, New York, 14222, United States

Location

Novartis Investigative Site

New Hyde Park, New York, 11040, United States

Location

Novartis Investigative Site

New York, New York, 10011, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Novartis Investigative Site

Stony Brook, New York, 11794, United States

Location

Novartis Investigative Site

Syracuse, New York, 13210, United States

Location

Novartis Investigative Site

Valhalla, New York, 10595, United States

Location

Penn State College of Medicine

Hershey, Pennsylvania, 17033, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Novartis Investigative Site

Burlington, Vermont, 05401, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

Location

West Virginia University Health Sciences Center

Morgantown, West Virginia, 26506, United States

Location

Novartis Investigative Site

South Brisbane, Australia

Location

Novartis Investigative Site

Calgary, Canada

Location

Novartis Investigative Site

Hamilton, Canada

Location

Novartis Investigative Site

Ste-Foy, Canada

Location

Novartis Investigative Site

Vancouver, Canada

Location

Novartis Investigative Site

Santiago, Chile

Location

Novartis Investigative Site

Baranquilla, Colombia

Location

Novartis Investigative Site

Bogotá, Colombia

Location

Novartis Investigative Site

Cali, Colombia

Location

Novartis Investigative Site

Medellín, Colombia

Location

Novartis Investigative Site

Montpellier, France

Location

Novartis Investigative Site

Paris, France

Location

Novartis Investigative Site

Rouen, France

Location

Novartis Investigative Site

Berlin, Germany

Location

Novartis Investigative Site

Bochum, Germany

Location

Novartis Investigative Site

Bonn, Germany

Location

Novartis Investigative Site

Cologne, Germany

Location

Novartis Investigative Site

Essen, Germany

Location

Klinikum der Johann-Wolfgang-Goethe-Universitaet

Frankfurt, 60596, Germany

Location

Novartis Investigative Site

Frankfurt, Germany

Location

Novartis Investigative Site

Hamburg, Germany

Location

Novartis Investigative Site

Hanover, Germany

Location

Ludwig-Maximilians-Universitaet

Munich, 80337, Germany

Location

Novartis Investigative Site

München, Germany

Location

Novartis Investigative Site

Hungary, Hungary

Location

Novartis Investigative Site

Kaposvár, Hungary

Location

Novartis Investigative Site

Haifa, Israel

Location

Novartis Investigative Site

Jerusalem, Israel

Location

Novartis Investigative Site

Petah Tikva, Israel

Location

Novartis Investigator Site

Genoa, Italy

Location

Novartis Investigative Site

Palermo, Italy

Location

Novartis Investigative Site

Potenza, Italy

Location

Novartis Investigative Site

Roma, Italy

Location

Novartis Investigative Site

Monterrey Nuevo Leon, Mexico

Location

Novartis Investigative Site

Groesbeek, Netherlands

Location

Novartis Investigative Site

Rotterdam, Netherlands

Location

Novartis Investigative Site

Barakaldo, Spain

Location

Novartis Investigative Site

Barcelona, Spain

Location

Novartis Investigative Site

Madrid, Spain

Location

Novartis Investigative Site

Málaga, Spain

Location

Novartis Investigative Site

Seville, Spain

Location

Novartis Investigative Site

Valencia, Spain

Location

Novartis Investigative Site

Belfast, United Kingdom

Location

Novartis Investigative Site

Birmingham, United Kingdom

Location

Novartis Investigative Site

Cambridge, United Kingdom

Location

Novartis Investigative Site

Leeds, United Kingdom

Location

Novartis Investigative Site

London, United Kingdom

Location

Novartis Investigative Site

Sheffield, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Inhalation

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Michael Konstan, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2006
• First Posted: October 17, 2006
• Study Start: February 1, 2006
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: July 24, 2012
• Results First Posted: July 24, 2012

Record last verified: 2012-06

Locations

CL (1); DE (11); IT (4); ME (1); ES (6); US (24); IL (3); NL (2); FR (3); CA (4); HU (2); GB (6); AU (1); CO (4)