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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00388505
First received: October 16, 2006
Last updated: June 19, 2012
Last verified: June 2012
  Purpose

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


Condition Intervention Phase
Cystic Fibrosis
Drug: Tobramycin Inhalation Powder
Drug: Tobramycin Solution for Inhalation
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Participants With Treatment-emergent Adverse Events [ Time Frame: 25 weeks ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Serum Tobramycin Concentrations [ Time Frame: Weeks 1, 5, 17 and 21 ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With a Decrease From Baseline in Auditory Acuity [ Time Frame: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) ] [ Designated as safety issue: No ]
    Audiology testing was performed only at selected centers. Auditory acuity was measured from 250 to 8000 Hertz using a standard dual-channel audiometer.

  • Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1) [ Time Frame: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25) ] [ Designated as safety issue: No ]

    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).


  • Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication [ Time Frame: Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21). ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Pseudomonas Aeruginosa Sputum Density [ Time Frame: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25). ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Tobramycin Minimum Inhibitory Concentration [ Time Frame: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25) ] [ Designated as safety issue: No ]
    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.

  • Antipseudomonal Antibiotic Usage During the Study [ Time Frame: 25 Weeks ] [ Designated as safety issue: No ]
    The average number of days patients required antipseudomonal antibiotics during the course of the study.

  • Hospitalization Due to Respiratory Events During the Study [ Time Frame: 25 Weeks ] [ Designated as safety issue: No ]
    The average number of days patients were hospitalized due to respiratory events during the course of the study.


Enrollment: 517
Study Start Date: February 2006
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Tobramycin Inhalation Powder
Tobramycin Inhalation Powder (TIP) capsules for inhalation.
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.
Drug: Tobramycin Solution for Inhalation
Tobramycin solution for inhalation (TOBI), supplied as 300 mg/5mL ampoules administered with a nebulizer

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00388505

  Show 72 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Principal Investigator: Michael Konstan, MD University Hospital Case Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00388505     History of Changes
Other Study ID Numbers: CTBM100C2302
Study First Received: October 16, 2006
Results First Received: June 19, 2012
Last Updated: June 19, 2012
Health Authority: United States: Food and Drug Administration
France: Agence Française de Sécurité Sanitaire des produits de Santé
Germany: Federal Institute for Drugs and Medical Devices
Italy: Agenzia Italiana del Farmaco
Netherlands: College ter beoordeling van geneesmiddelen Medicines Evaluation Board
Spain: Ministerio de Sanidad y Consumo, Agencia Española del Medicamento y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
tobramycin

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Respiratory Aspiration
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Respiration Disorders
Pharmaceutical Solutions
Tobramycin
Therapeutic Uses
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 16, 2014