Second Open Label Extension to Bridging Study CTBM100C2303

Study Overview
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Brief Summary
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This was an open-label, single arm (uncontrolled) study in participants suffering from cystic fibrosis, who have completed their study participation in CTBM100C2303 and extension study one CTBM100C2303E1 (all visits), who were proven infected with Pseudomonas aeruginosa at enrollment into CTBM100C2303.

Official Title
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A Phase III Open-Label Extension Study to Assess the Safety and Efficacy of Tobramycin Inhalation Powder After Manufacturing Process Modifications (TIPnew) in Cystic Fibrosis (CF) Patients Who Successfully Completed Participation in Study CTBM100C2303E1

Conditions
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Pulmonary Infections, Pseudomonas Aeruginosa

Intervention / Treatment
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* Drug: Tobramycin inhalation powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed all visits in study CTBM100C2303 and CTBM100C2303E1, and visit 11 of study CTBM100C2303E1 took place not more than 5 days before enrollment into this study. Confirmed diagnosis of cystic fibrosis participants with P. aeruginosa infection. Forced Expiratory Volume in one second (FEV1) at screening (at start of study CTBM100C2303) must be between 25% and 80% of normal predicted values. Exclusion Criteria: Any use of inhaled anti-pseudomonal antibiotics between the termination of the trial CTMB100C2303E1 and the enrollment into this study. Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tobramycin Inhalation Powder (TIPnew)<br>Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles. | Drug: Tobramycin inhalation powder<br>* Tobramycin dry powder for inhalation in capsules administered by the T-326 inhaler.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. | From time of first administration of study drug until study completion (up to 169 days) | 
| Number of Participants With Serious Adverse Events (SAEs) | A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the participant or require medical or surgical intervention to prevent one of the aforementioned outcomes. | From time of consent to 4 weeks after study completion (up to 199 days) | 
| Percentage of Participants With a Decrease of ≥20% in Forced Expiratory Value in One Second (FEV1) Percent (%) Predicted From Pre-dose to 30-minute Post-dose | Airway Reactivity >= 20% relative decrease in FEV1% predicted from pre-dose to 30 minutes post-dose. Relative Change = 100 * (30 minutes Post-dose - Pre-dose)/Pre-dose assessed by the number and percentage of participants with a decrease of ≥ 20% in FEV1 % predicted from pre-dose to 30 minutes post-dose. | Pre-dose and post-dose of Day 1 and Day 29 of every Cycle (5, 6, 7) | 
| Percentage of Participants With Frequency Decrease From Baseline in the Post-baseline Audiology Tests | Auditory acuity of participants was measured using a standard dual-channel audiometer at frequencies from 250 to 8000 Hertz, and an audiogram (pure-tone air conduction) and tympanogram were performed by an audiologist. The categories reported includes >= 10dB decrease in 3 consecutive frequencies in either ear, >= 15dB decrease in 2 consecutive frequencies in either ear, and >= 20dB decrease in at least one frequency in either ear | Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent Predicted to Each Post-baseline Visit | 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 % predicted was a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. Relative change in FEV1 % predicted from baseline to pre-dose day X = ((pre-dose day X FEV1 % predicted - baseline FEV1 % predicted) / baseline FEV1 % predicted) x 100. | Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57) | 
| Relative Change From Baseline of Forced Vital Capacity (FVC) Percent Predicted to Each Post-baseline Visit | Percent Predicted Forced Vital Capacity (FVC%) is the maximal exhaled breath volume following a maximal inhaled breath. Overall change in percent predicted FVC = (observed value)/(predicted value) * 100%. A higher value indicates a greater response. | Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57) | 
| Relative Change From Baseline of Forced Expiratory Flow Rate Over 25 and 75 Percent (FEF25-75%) Predicted to Each Post-baseline Visit | Forced Expiratory Flow Rate Over 25 and 75 Percent (FEF25-75%) is the forced expiratory flow from 25% to 75% of the Forced Vital Capacity (FVC). Relative change in FEF25-75% from baseline to pre-dose day X = (pre-dose day X FEF25-75 - baseline FEF25-75) / baseline FEF25-75) • 100. | Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57) | 
| Change From Baseline in Pseudomonas Aeruginosa Sputum Density to Each Post-baseline Visit | Pseudomonas Aeruginosa Density refers to overall density, defined as the sum of Biotypes (mucoid, dry and small colony variant). Absolute change was determined using the formula; Change = Post-baseline value- baseline value. Absolute Change in Pseudomonas Aeruginosa Sputum density is measured in log 10 Colony Forming Units per gram (Log 10 CFU/g). | Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57) | 
| Change From Baseline in Tobramycin Minimum Inhibitory Concentration (MIC) Values for Pseudomonas Aeruginosa to Each Post-baseline Visit | Minimum Inhibitory Concentration (MIC) is defined as the lowest concentration of an antimicrobial agent required to inhibit the visible growth of a microorganism after overnight incubation. | Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57) | 
| Number of Participants Who Used New Antipseudomonal Antibiotic During Treatment Period | The rate of anti-pseudomonal antibiotics use were determined from the collection of concomitant medication during the study Treatment period. | Baseline, Cycles 5, 6, 7 (Days 1, 29) | 
| Percentage of Participants With Hospitalization Due to Respiratory Serious Adverse Events (SAEs) | A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the participant or require medical or surgical intervention to prevent one of the aforementioned outcomes. | From time of consent to 4 weeks after study completion (up to 199 days) | 
| Number of Days of Hospitalization Due to Respiratory Serious Adverse Events (SAEs) | The average number of days patients were hospitalized due to respiratory events during the study. | From time of consent to 4 weeks after study completion (up to 199 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tobramycin Inhalation Powder, Cystic fibrosis, Lung diseases, Anti-Bacterial Agents, Treatment of pulmonary infections with P. aeruginosa in cystic fibrosis participants