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 had completed their study participation in CTBM100C2303 (all visits) and who were proven infected with Pseudomonas aeruginosa (P. 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) Subjects Who Completed Participation in Study CTBM100C2303.

Conditions
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Pseudomonas Aeruginosa, Cystic Fibrosis

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 visit 4 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 (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 core trial CTMB100C2303 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 (TIP)<br>Participants received 112 mg (four 28 mg capsules) of TIP administered by the T-326 Inhaler, twice a day (b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment (one cycle = 56 days) for up to 3 cycles. | Drug: Tobramycin inhalation powder<br>* Tobramycin inhalation powder, 112 mg (4 capsules of 28 mg), inhalation capsules, b.i.d.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events (AEs) | AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal product. | From first administration of study drug to study completion (up to approximately 25 weeks) | 
| Percentage of Participants With Serious Adverse Events (SAEs) | SAEs included adverse events that resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. | From time of consent to 4 weeks after study completion (up to approximately 29 weeks) | 
| Percentage of Death Cases |  | From time of consent to 4 weeks after study completion (up to approximately 29 weeks) | 
| Percentage of Participants With Adverse Events and Serious Adverse Events Leading to Permanent Study Discontinuation | AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal product. SAEs included adverse events that resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. | From first administration of study drug to study completion (up to approximately 25 weeks) | 
| Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal | Shift from baseline in hematology and biochemistry values to above upper/below lower limit of normal at any time post-baseline were reported. Baseline for safety analyses was defined as the last measurement prior to first dose of study drug in the core study CTBM100C2303. Change to low referred to number of participants with normal or high values at baseline. Change to high referred to number of participants with normal or low values at baseline. | From baseline to study completion (up to approximately 25 weeks) | 
| Acute Relative Change in Airways Reactivity [Forced Expiratory Value in One Second (FEV1) Percent (%) Predicted] From Pre-dose to 30 Minutes After Completion of First Dose of Study Drug | Airway Reactivity was defined as ≥20% FEV1 relative decrease in percent predicted from pre dose to 30 minutes post dose. FEV1 was defined as the volume of air expired in 1 second. 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 = 100* (30 minutes post dose - pre dose) / pre dose assessed by number and percentage of participants with a decrease in ≥20% FEV1 percent predicted from pre dose to 30 minutes post dose. Baseline for was defined as the last measurement prior to first dose of study drug in the core study CTBM100C2303. | Pre-dose and 30 minutes Post-dose on Day 1 and Day 29 of every Cycle (2, 3, 4) | 
| 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. | From first dose of study drug to study completion (up to approximately 25 weeks) | 
| Number of Participants With Adverse Events (AEs) Associated With the Use of New Antipseudomonal Antibiotic | AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal product. SAEs included adverse events that resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. | From first administration of study drug to study completion (up to approximately 25 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted to End of Dosing at Each Cycle and Study Completion | FEV1 was defined as the volume of air expired in 1 second. 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 = 100* (30 minutes post dose - pre dose) / pre dose assessed by number and percentage of participants with a decrease in ≥20% FEV1 percent predicted from pre dose to 30 minutes post dose. Baseline for was defined as the last measurement prior to first dose of study drug in the core study CTBM100C2303. Termination referred to the last available pre dose post-baseline measurement. | Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion) | 
| Change From Baseline in Forced Vital Capacity (FVC) Percent (%) Predicted to End of Dosing at Each Cycle and Study Completion | Relative change from baseline in FVC % predicted to end of dosing in each cycle and study completion were reported. Relative change from baseline was defined as: Relative change = 100* (Post baseline- baseline) / baseline. Baseline was defined as last measurement prior to first dose of study drug in the core study CTBM100C2303. Termination referred to the last available pre dose post-baseline measurement. | Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion) | 
| Change From Baseline in Forced Expiratory Flow Rate Over 25 Percent and 75 Percent (FEF25-75%) Predicted to End of Dosing at Each Cycle and Study Completion | Relative change from baseline in FEF25-75% predicted to end of dosing in each cycle and study completion were reported. Relative change from baseline was defined as: Relative change = 100* (Post baseline- baseline) / baseline. Baseline was defined as last measurement prior to first dose of study drug in the core study CTBM100C2303. Termination referred to the last available pre dose post-baseline measurement. | Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion) | 
| Absolute Change From Baseline in Sputum Pseudomonas Aeruginosa Density [log10 Colony Forming Units (CFU) Per Gram Sputum] to End of Dosing at Each Cycle and Study Completion | P. aeruginosa sputum density referred to overall density, defined as the sum of biotypes (mucoid, dry and small colony variant). If sub-isolates existed for CFU biotype mucoid or dry, then the sum of sub-isolates was analyzed. Absolute change from baseline was defined as: Absolute change = Post Baseline - Baseline. Baseline was defined as last measurement prior to first dose of study drug in the core study CTBM100C2303. Termination referred to the last available pre dose post-baseline measurement. | Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion) | 
| Change From Baseline in Pseudomonas Aeruginosa Minimum Inhibitory Concentration (MIC) to End of Dosing at Each Cycle and Study Completion | Change in tobramycin MIC values for P. aeruginosa were reported for specimens and were used to assess the change in pathogen susceptibility to tobramycin before (baseline) and after (post-baseline) the treatment. Maximum MIC values from all biotypes were used. Change from baseline was defined as: Change = Post-baseline - Baseline. Baseline was defined as last measurement prior to first dose of study drug in the core studyCTBM100C2303.Termination referred to the last available pre dose post-baseline measurement. | Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion) | 
| Percentage of Participants With Anti-Pseudomonal Antibiotic Use During The Treatment Period |  | From first administration of study drug to study completion (up to approximately 25 weeks) | 
| Number of Days of Hospitalization Due to Respiratory Serious Adverse Events | SAEs included adverse events that resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. For calculation of days in hospitalization due to respiratory events, the end date was defined as the discharge date (if provided and even if after the end of the extension study), and otherwise as the date of last visit. | From first administration of study drug to study completion (up to approximately 25 weeks) | 

 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