Ext. Long-term Safety Study in CF Patients: Single Arm TIP

Study Overview
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Brief Summary
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The purpose of this extension study is to collect additional 48 weeks of safety data from patients taking TIP who have completed the core study CTBM100C2401. The purpose of collecting second year safety data through this study is to obtain long-term (2 years) safety data of TIP.

Official Title
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A 48 Week Extension to CTBM100C2401, a Single Arm, Open-label, Multicenter, Phase IV Extension Trial to Assess Long Term Safety of Tobramycin Inhalation Powder (TIP) in Patients With Cystic Fibrosis Who Completed Participation in CTBM100C2401.

Conditions
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Long-term Safety of TIP

Intervention / Treatment
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* Drug: TBM100


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completion of the core study CTBM100C2401 and able to comply with all protocol requirements of the extension study Exclusion Criteria: Serum creatinine 2mg/dl, BUN 40mg/dl or proteinuria 2+ or more at the time of entry into the extension Use of loop diuretics within 7 days prior to entry into the extension study Pregnant or nursing women Women of child bearing potential unless using highly effective method of contraception as indicated in the protoco

Ages Eligible for Study
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Minimum Age: 6 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

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TBM100<br>TIP 112 mg/b.i.d | Drug: TBM100<br>* Tobramycin inhalation powder (TIP) 112mg/b.i.d<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), Serious Adverse Events (SAEs), AEs/SAEs Leading to Discontinuation of Study Drug and Deaths Over 12 Treatment Cycles | 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. 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. Based on the severity, AEs were categorised into 3 types as mild, moderate and severe. Death was a fatal event leading to permanent cessations of all vital functions of the body. | Baseline (start of study treatment in core study) to Day 673 (end of the extension study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | FEV1 was defined as the volume of air expired in 1 second. FEV1 was assessed as a pulmonary function by using spirometry tests in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) criteria. FEV1% predicted is 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*FEV1% predicted - baseline FEV1% predicted) / baseline FEV1 % predicted) x 100. | Baseline (start of study treatment in core study), Day 29, Day 85, Day 141, Day 197, Day 253, Day 309, Day 337, Day 365, Day 421, Day 477, Day 533, Day 589, Day 645, 673 (end of the extension study) | 
| Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Microbiological data was collected to understand the direct impact of the drug on the pathogens. Sputum samples were cultured for the presence of three Pseudomonas aeruginosa (P. aeruginosa) biotypes measured were mucoid, dry and small colony variant. Absolute change was determined using the formula = (Post-baseline value- baseline value). If no P. aeruginosa was isolated for a visit, log10 colony forming units (CFU) was imputed with log10 (19) for all biotypes. | Baseline (start of study treatment in core study), Day 29, Day 85, Day 141, Day 197, Day 253, Day 309, Day 337, Day | 
| Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | MIC was defined as the lowest concentration of an antimicrobial agent required to inhibit the visible growth of a microorganism after overnight incubation. Tobramycin MIC 50 and MIC 90 values were defined as the lowest concentration of tobramycin required to inhibit 50% and 90%, respectively, of the P. aeruginosa strains tested (mucoid,dry and small colony variant biotypes). | Baseline (start of study treatment in core study), Day 29, Day 85, Day 141, Day 197, Day 253, Day 309, Day 337, Day 365, Day 421, Day 477, Day 533, Day 589, Day 645, 673 (end of the extension study) | 
| Percentage of Participants Who Used New Anti-pseudomonal Antibiotics Over 12 Treatment Cycles | The rate of anti-pseudomonal antibiotics use were determined from the collection of concomitant medication during the study. | Baseline of core study, Day 673 (end of the extension study) | 
| Total Number of Days of New Anti-pseudomonal Antibiotics Use Over 12 Treatment Cycles | The total number of days with usage of new anti-pseudomonal antibiotic were determined. | Baseline of core study, Day 673 (end of the extension study) | 
| Time to Use of New Anti-pseudomonal Antibiotics Over 12 Treatment Cycles | Time to first usage of anti-pseudomonal antibiotic was determined using Kaplan Meier estimate. Participants without an event were censored at the date of the last available post-baseline measurement. | Baseline of core study, Day 673 (end of the extension study) | 
| The Percentage of the Participants Hospitalized Due to Serious Respiratory-related AEs Were Determined During the Study. | The percentage of the participants hospitalized due to serious respiratory-related AEs were determined during the study. | Baseline of core study, Day 673 (end of the extension study) | 
| Number of Hospitalization Days Due to Respiratory Related Serious Adverse Events (SAEs) Over 12 Treatment Cycles | The total number of hospitalization days due to serious respiratory-related adverse events was analyzed using Kaplan-Meier estimate. | Baseline of core study, Day 673 (end of the extension study) | 
| Time to First Hospitalization Due to Respiratory Related Serious Adverse Events (SAEs) Over 12 Treatment Cycles | The day of first hospitalization due to serious respiratory-related adverse events was analysed using Kaplan Meier estimate. | Baseline of core study, Day 673 (end of the extension study) | 
| Acute Relative Change From Pre-dose to 30-minute Post-dose in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | FEV1 was defined as the volume of air expired in 1 second. FEV1 was assessed as a pulmonary function by using spirometry tests in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) criteria. Relative change in FEV1 % predicted was calculated by using the formula = 100 *(30-min post-dose value - pre-dose value) / pre-dose value. | Baseline (start of study treatment in core study), Day 29, Day 85, Day 141, Day 197, Day 253, Day 309, Day 337, Day 365, Day 421, Day 477, Day 533, Day 589, Day 645, 673 (end of the extension study) | 
| Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 6 Treatment Cycles in Extension Study | FEV1 was defined as the volume of air expired in 1 second. FEV1 was assessed as a pulmonary function by using spirometry tests in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) criteria. FEV1% predicted is 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*FEV1% predicted - baseline FEV1% predicted) / baseline FEV1 % predicted) x 100. | Baseline (start of study treatment in extension study), Day 365, Day 421, Day 477, Day 533, Day 589, Day 645, 673 (end of the extension study) | 
| Absolute Change From Baseline in Pseudomonas Aeruginosa Density Over 6 Treatment Cycles in Extension Study | Microbiological data was collected to understand the direct impact of the drug on the pathogens. Sputum samples were cultured for the presence of three Pseudomonas aeruginosa (P. aeruginosa) biotypes measured were mucoid, dry and small colony variant. If no P. aeruginosa was isolated for a visit, log10 colony forming units (CFU) was imputed with log10 (19) for all biotypes. Absolute change was calculated by using the formula = (Value at actual time point - start of extension value). | Baseline (start of study treatment in extension study), Day 365, Day 421, Day 477, Day 533, Day 589, Day 645, 673 (end of the extension study) | 
| Percentage of Participants Who Used New Anti-pseudomonal Antibiotics in Extension Study | The rate of anti-pseudomonal antibiotics use were determined from the collection of concomitant medication during the study. | Baseline of extension study, Day 673 (end of extension study) | 
| Total Number of Days of New Anti-pseudomonal Antibiotics Use in Extension Study | The total number of days with usage of new anti-pseudomonal antibiotic were determined. | Baseline of extension study, Day 673 (end of extension study) | 
| Time to Use of New Anti-pseudomonal Antibiotics in Extension Study | Time to first usage of anti-pseudomonal antibiotic was determined using Kaplan Meier estimate. Participants without an event were censored at the date of the last available post-baseline measurement. | Baseline of extension study, Day 673 (end of extension study) | 
| Percentage of Participants Hospitalized Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study | The percentage of the participants hospitalized due to serious respiratory-related AEs were determined during the extension study. | Baseline of extension study, Day 673 (end of the extension study) | 
| Number of Hospitalization Days Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study | The total number of hospitalisation days due to serious respiratory-related adverse events was analysed using Kaplan-Meier estimate. | Baseline of extension study, Day 673 (end of extension study) | 
| Time to First Hospitalization Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study | The day of first hospitalization due to serious respiratory related adverse events was analysed using Kaplan Meier estimate. | Baseline of extension study, Day 673 (end of extension study) | 
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs/SAEs Leading to Discontinuation of Study Drug and Deaths Over 6 Treatment Cycles in Extension Study | 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. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalisation, 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. Death was a fatal event leading to permanent cessations of all vital functions of the body. | Baseline (start of study treatment in extension study) to Day 673 (end of the extension study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CF, Open-label, TIP, phase IV, extension study