Safety of Tobramycin Inhalation Powder (TIP) vs Tobramycin Solution for Inhalation in Patients With Cystic Fibrosis (EAGER)
|Cystic Fibrosis||Drug: Tobramycin Inhalation Powder Drug: Tobramycin Solution for Inhalation||Phase 3|
|Study Design:||Allocation: Randomized
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|
- Number of Participants With Treatment-emergent Adverse Events [ Time Frame: 25 weeks ]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.
- Serum Tobramycin Concentrations [ Time Frame: Weeks 1, 5, 17 and 21 ]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) ]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) ]
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). ]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). ]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) ]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 ]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 ]The average number of days patients were hospitalized due to respiratory events during the course of the study.
|Study Start Date:||February 2006|
|Study Completion Date:||March 2009|
|Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00388505
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|Principal Investigator:||Michael Konstan, MD||University Hospitals Cleveland Medical Center|