Long-term Safety of TIP
Conditions
Keywords
CF, Open-label, TIP, phase IV, extension study
Brief summary
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.
Interventions
DRUGTBM100
Tobramycin inhalation powder (TIP) 112mg/b.i.d
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline (start of study treatment in core study) to Day 673 (end of the 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Baseline (start of study treatment in core study), Day 29, Day 85, Day 141, Day 197, Day 253, Day 309, Day 337, Day | 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. |
| Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | 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) | 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). |
| Percentage of Participants Who Used New Anti-pseudomonal Antibiotics Over 12 Treatment Cycles | Baseline of core study, Day 673 (end of the extension study) | The rate of anti-pseudomonal antibiotics use were determined from the collection of concomitant medication during the study. |
| Total Number of Days of New Anti-pseudomonal Antibiotics Use Over 12 Treatment Cycles | Baseline of core study, Day 673 (end of the extension study) | The total number of days with usage of new anti-pseudomonal antibiotic were determined. |
| Time to Use of New Anti-pseudomonal Antibiotics Over 12 Treatment Cycles | Baseline of core study, Day 673 (end of the 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. |
| 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) | The percentage of the participants hospitalized due to serious respiratory-related AEs were determined during the study. |
| Number of Hospitalization Days Due to Respiratory Related Serious Adverse Events (SAEs) Over 12 Treatment Cycles | Baseline of core study, Day 673 (end of the extension study) | The total number of hospitalization days due to serious respiratory-related adverse events was analyzed using Kaplan-Meier estimate. |
| Time to First Hospitalization Due to Respiratory Related Serious Adverse Events (SAEs) Over 12 Treatment Cycles | Baseline of core study, Day 673 (end of the extension study) | The day of first hospitalization due to serious respiratory-related adverse events was analysed using Kaplan Meier estimate. |
| 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 | 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) | 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. |
| Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | 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) | 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. |
| Absolute Change From Baseline in Pseudomonas Aeruginosa Density Over 6 Treatment Cycles in Extension Study | 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) | 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). |
| Percentage of Participants Who Used New Anti-pseudomonal Antibiotics in Extension Study | Baseline of extension study, Day 673 (end of extension study) | The rate of anti-pseudomonal antibiotics use were determined from the collection of concomitant medication during the study. |
| Total Number of Days of New Anti-pseudomonal Antibiotics Use in Extension Study | Baseline of extension study, Day 673 (end of extension study) | The total number of days with usage of new anti-pseudomonal antibiotic were determined. |
| Time to Use of New Anti-pseudomonal Antibiotics in Extension Study | Baseline of extension study, Day 673 (end of 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. |
| Percentage of Participants Hospitalized Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study | Baseline of extension study, Day 673 (end of the extension study) | The percentage of the participants hospitalized due to serious respiratory-related AEs were determined during the extension study. |
| Number of Hospitalization Days Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study | Baseline of extension study, Day 673 (end of extension study) | The total number of hospitalisation days due to serious respiratory-related adverse events was analysed using Kaplan-Meier estimate. |
| Time to First Hospitalization Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study | Baseline of extension study, Day 673 (end of extension study) | The day of first hospitalization due to serious respiratory related adverse events was analysed using Kaplan Meier estimate. |
| 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 | Baseline (start of study treatment in extension study) to Day 673 (end of the 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. |
| Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 6 Treatment Cycles in Extension Study | 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) | 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. |
Countries
Argentina, Australia, Canada, Germany, Hungary, Italy, Mexico, Spain, United States
Participant flow
Recruitment details
The study was conducted at 22 centers in 9 countries.
Pre-assignment details
Of 96 participants who completed the core study (CTBM100C2401), NCT01519661; 45 participants were enrolled in the extension study.
Participants by arm
| Arm | Count |
|---|---|
| Tobramycin Inhalation Powder Participants inhaled four capsules of tobramycin inhalation powder (28 mg) bid via the T326 inhaler device, for 28 days (treatment phase in each cycle). Each treatment phase therefore consisted of 112 mg tobramycin (4 capsules of 28 mg each) with the total daily dose of 224 mg tobramycin (112 mg bid).The treatment phase was followed by 28 days of no study treatment (off treatment in each cycle). These 56 days represented 1 cycle of therapy. | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Protocol deviation | 2 |
| Overall Study | Unsatisfactory therapeutic effect | 2 |
| Overall Study | Withdrawal by participants | 5 |
Baseline characteristics
| Characteristic | Tobramycin Inhalation Powder |
|---|---|
| Age, Categorical <=18 years | 12 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 33 Participants |
| Age, Continuous | 24.5 years STANDARD_DEVIATION 10.79 |
| Forced expiratory flow from 25 to 75 % (FEF2575%) % predicted | 24.7 Percent predicted STANDARD_DEVIATION 14.86 |
| Forced expiratory volume in one second (FEV1) percent (%) predicted | 52.2 Percent predicted STANDARD_DEVIATION 15.01 |
| Forced vital capacity (FVC) % predicted | 73.2 Percent predicted STANDARD_DEVIATION 17.49 |
| Pseudomonas aeruginosa tobramycin minimal inhibitory concentration (MIC) > 8 microgram/milliliter(ug/mL) | 12 Participants |
| Pseudomonas aeruginosa tobramycin minimal inhibitory concentration (MIC) <= 8 ug/mL | 33 Participants |
| Region of Enrollment Argentina | 9 participants |
| Region of Enrollment Australia | 5 participants |
| Region of Enrollment Canada | 1 participants |
| Region of Enrollment Germany | 5 participants |
| Region of Enrollment Hungary | 1 participants |
| Region of Enrollment Italy | 7 participants |
| Region of Enrollment Mexico | 5 participants |
| Region of Enrollment Spain | 6 participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 45 | 32 / 45 | 36 / 45 |
| serious Total, serious adverse events | 12 / 45 | 16 / 45 | 19 / 45 |
Outcome results
Primary
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.
Time frame: Baseline (start of study treatment in core study) to Day 673 (end of the extension study)
Population: The analysis was performed in extension safety population, defined as all the participants who entered the extension study and received at least one dose of study drug within the extension.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tobramycin Inhalation Powder | 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 | AEs | 39 Participants |
| Tobramycin Inhalation Powder | 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 | Mild AEs | 10 Participants |
| Tobramycin Inhalation Powder | 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 | Moderate AEs | 18 Participants |
| Tobramycin Inhalation Powder | 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 | Severe AEs | 11 Participants |
| Tobramycin Inhalation Powder | 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 | SAEs | 19 Participants |
| Tobramycin Inhalation Powder | 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 | Discontinued study drug due to AEs | 2 Participants |
| Tobramycin Inhalation Powder | 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 | Discontinued study drug due to SAEs | 1 Participants |
| Tobramycin Inhalation Powder | 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 | Deaths | 1 Participants |
Secondary
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).
Time frame: 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)
Population: The analysis was performed in extension safety population, who had microbiological data at specified time points. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Density Over 6 Treatment Cycles in Extension Study | Extension Cycle 7, day 365(n=38) | -0.7 log10 CFU | Standard Deviation 2.77 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Density Over 6 Treatment Cycles in Extension Study | Extension Cycle 8, day 421(n=39) | -0.2 log10 CFU | Standard Deviation 2.6 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Density Over 6 Treatment Cycles in Extension Study | Extension Cycle 9, day 477(n=39) | -0.2 log10 CFU | Standard Deviation 2.51 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Density Over 6 Treatment Cycles in Extension Study | Extension Cycle 10, day 533(n=35) | 0.2 log10 CFU | Standard Deviation 2.89 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Density Over 6 Treatment Cycles in Extension Study | Extension Cycle 11, day 589(n=36) | 0.0 log10 CFU | Standard Deviation 2.49 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Density Over 6 Treatment Cycles in Extension Study | Extension Cycle 12, day 645(n=32) | 0.4 log10 CFU | Standard Deviation 2.75 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Density Over 6 Treatment Cycles in Extension Study | Extension completion, (n=29) | 0.3 log10 CFU | Standard Deviation 2.48 |
Secondary
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.
Time frame: Baseline (start of study treatment in core study), Day 29, Day 85, Day 141, Day 197, Day 253, Day 309, Day 337, Day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Core cycle 6, day 309 (n=39) | -1.4 log 10 CFU/g | Standard Deviation 2.02 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Core cycle 5, day 253 (n=40) | -2.2 log 10 CFU/g | Standard Deviation 2.26 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Core cycle 1, day 29 (n=42) | -1.9 log 10 CFU/g | Standard Deviation 2.83 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Core cycle 2, day 85 (n=43) | -1.5 log 10 CFU/g | Standard Deviation 1.6 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Core cycle 3, day 141 (n=44) | -1.4 log 10 CFU/g | Standard Deviation 2 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Core cycle 4, day 197 (n=41) | -1.2 log 10 CFU/g | Standard Deviation 1.8 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Core study completion, day 337 (n=42) | -0.7 log 10 CFU/g | Standard Deviation 2.38 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Extension cycle 7, day 337 (n=40) | -0.7 log 10 CFU/g | Standard Deviation 2.46 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Extension cycle 7, day 365 (n=41) | -1.4 log 10 CFU/g | Standard Deviation 2.18 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Extension cycle 8, day 421 (n=41) | -1.1 log 10 CFU/g | Standard Deviation 2.2 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Extension cycle 9, day 477 (n=39) | -1.1 log 10 CFU/g | Standard Deviation 2.33 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Extension cycle 10, day 533 (n=35) | -0.8 log 10 CFU/g | Standard Deviation 1.97 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Extension cycle 11, day 589 (n=36) | -1.0 log 10 CFU/g | Standard Deviation 2.38 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Extension cycle 12, day 645 (n=31) | -0.6 log 10 CFU/g | Standard Deviation 1.96 |
| Tobramycin Inhalation Powder | Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles | Extension completion, day 673 (n=29) | -1.0 log 10 CFU/g | Standard Deviation 2.7 |
Secondary
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.
Time frame: 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)
Population: The analysis was performed in extension safety population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder | 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 | Core cycle 1, day 1 (n=44) | -4.9 Percent change in FEV1 % predicted | Standard Deviation 6.72 |
| Tobramycin Inhalation Powder | 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 | Core cycle 1, day 29 (n=41) | -3.5 Percent change in FEV1 % predicted | Standard Deviation 4.25 |
| Tobramycin Inhalation Powder | 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 | Core cycle 2, day 85 (n=39) | -3.5 Percent change in FEV1 % predicted | Standard Deviation 6.19 |
| Tobramycin Inhalation Powder | 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 | Core cycle 3, day 141 (n=42) | -2.6 Percent change in FEV1 % predicted | Standard Deviation 6.06 |
| Tobramycin Inhalation Powder | 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 | Core cycle 4, day 197 (n=40) | -3.2 Percent change in FEV1 % predicted | Standard Deviation 5.41 |
| Tobramycin Inhalation Powder | 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 | Core cycle 5, day 253 (n=41) | -3.8 Percent change in FEV1 % predicted | Standard Deviation 5.47 |
| Tobramycin Inhalation Powder | 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 | Core cycle 6, day 309 (n=39) | -2.5 Percent change in FEV1 % predicted | Standard Deviation 5.94 |
| Tobramycin Inhalation Powder | 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 | Extension cycle 7, day 365(n=37) | -0.1 Percent change in FEV1 % predicted | Standard Deviation 7.79 |
| Tobramycin Inhalation Powder | 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 | Extension cycle 8, day 421(n=36) | -3.7 Percent change in FEV1 % predicted | Standard Deviation 5.1 |
| Tobramycin Inhalation Powder | 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 | Extension cycle 9, day 477(n=37) | -3.5 Percent change in FEV1 % predicted | Standard Deviation 4.78 |
| Tobramycin Inhalation Powder | 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 | Extension cycle 10, day 533(n=36) | -1.0 Percent change in FEV1 % predicted | Standard Deviation 12.54 |
| Tobramycin Inhalation Powder | 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 | Extension cycle 11, day 589(n=35) | -3.3 Percent change in FEV1 % predicted | Standard Deviation 6.73 |
| Tobramycin Inhalation Powder | 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 | Extension cycle 12, day 645(n=30) | -3.1 Percent change in FEV1 % predicted | Standard Deviation 4.01 |
Secondary
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.
Time frame: Baseline of extension study, Day 673 (end of extension study)
Population: The analysis was performed in extension safety population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tobramycin Inhalation Powder | Number of Hospitalization Days Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study | 16.0 Days |
Secondary
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.
Time frame: Baseline of core study, Day 673 (end of the extension study)
Population: The analysis was performed in extension safety population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tobramycin Inhalation Powder | Number of Hospitalization Days Due to Respiratory Related Serious Adverse Events (SAEs) Over 12 Treatment Cycles | 17.0 Days |
Secondary
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.
Time frame: Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Population: The analysis was performed in extension safety population, defined as all the participants who entered the extension study and received at least one dose of study drug within the extension.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tobramycin Inhalation Powder | 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 | AEs | 36 Number of participants |
| Tobramycin Inhalation Powder | 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 | SAEs | 16 Number of participants |
| Tobramycin Inhalation Powder | 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 | Discontinued study drug due to AEs | 1 Number of participants |
| Tobramycin Inhalation Powder | 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 | Discontinued study drug due to SAEs | 0 Number of participants |
| Tobramycin Inhalation Powder | 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 | Deaths | 1 Number of participants |
Secondary
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.
Time frame: Baseline of extension study, Day 673 (end of the extension study)
Population: The analysis was performed in extension safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tobramycin Inhalation Powder | Percentage of Participants Hospitalized Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study | 35.6 Percentage of participants |
Secondary
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.
Time frame: Baseline of extension study, Day 673 (end of extension study)
Population: The analysis was performed in extension safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tobramycin Inhalation Powder | Percentage of Participants Who Used New Anti-pseudomonal Antibiotics in Extension Study | 68.9 Percentage of participants |
Secondary
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.
Time frame: Baseline of core study, Day 673 (end of the extension study)
Population: The analysis was performed in extension safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tobramycin Inhalation Powder | Percentage of Participants Who Used New Anti-pseudomonal Antibiotics Over 12 Treatment Cycles | 77.8 Percentage of participants |
Secondary
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.
Time frame: 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)
Population: Extension safety population, defined as all the participants who entered the extension study and received at least one dose of study drug within the extension and had FEV1% values at both baseline and the post baseline time points. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Core cycle 1, Day 29 (n=44) | 5.0 Percent change in FEV1 % predicted | Standard Deviation 20.36 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Core cycle 2, day 85 (n=45) | 0.8 Percent change in FEV1 % predicted | Standard Deviation 19.51 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Core cycle 3, day 141 (n=45) | 1.3 Percent change in FEV1 % predicted | Standard Deviation 15.32 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Core cycle 4, day 197 (n=44) | 0.0 Percent change in FEV1 % predicted | Standard Deviation 17.34 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Core cycle 5, day 253 (n=43) | -0.5 Percent change in FEV1 % predicted | Standard Deviation 17.91 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Core cycle 6, day 309 (n=45) | -1.6 Percent change in FEV1 % predicted | Standard Deviation 14.19 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Core study completion, (n=43) | -3.1 Percent change in FEV1 % predicted | Standard Deviation 19.72 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Extension Cycle 7, day 337(n=44) | -5.2 Percent change in FEV1 % predicted | Standard Deviation 14.29 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Extension Cycle 7, day 365(n=44) | -3.7 Percent change in FEV1 % predicted | Standard Deviation 14.84 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Extension Cycle 8, day 421(n=41) | -6.1 Percent change in FEV1 % predicted | Standard Deviation 14.55 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Extension Cycle 9, day 477(n=42) | -4.8 Percent change in FEV1 % predicted | Standard Deviation 14.03 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Extension Cycle 10, day 533(n=39) | -7.5 Percent change in FEV1 % predicted | Standard Deviation 13.97 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Extension Cycle 11, day 589(n=38) | -5.4 Percent change in FEV1 % predicted | Standard Deviation 19.49 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Extension Cycle 12, day 645(n=35) | -7.5 Percent change in FEV1 % predicted | Standard Deviation 14.15 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles | Extension completion, (n=33) | -9.3 Percent change in FEV1 % predicted | Standard Deviation 12.76 |
Secondary
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.
Time frame: 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)
Population: Extension safety population, defined as all the participants who entered the extension study and received at least one dose of study drug within the extension and had FEV1% values at both baseline and the post baseline time points. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 6 Treatment Cycles in Extension Study | Extension Cycle 7, day 365(n=44) | 4.0 Percent change in FEV1 % predicted | Standard Deviation 16.93 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 6 Treatment Cycles in Extension Study | Extension Cycle 8, day 421(n=41) | 2.4 Percent change in FEV1 % predicted | Standard Deviation 13.71 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 6 Treatment Cycles in Extension Study | Extension Cycle 9, day 477(n=42) | 2.4 Percent change in FEV1 % predicted | Standard Deviation 16.18 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 6 Treatment Cycles in Extension Study | Extension Cycle 10, day 533(n=39) | -1.4 Percent change in FEV1 % predicted | Standard Deviation 13.75 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 6 Treatment Cycles in Extension Study | Extension Cycle 11, day 589(n=38) | 0.3 Percent change in FEV1 % predicted | Standard Deviation 14.76 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 6 Treatment Cycles in Extension Study | Extension Cycle 12, day 645(n=35) | -0.6 Percent change in FEV1 % predicted | Standard Deviation 13.95 |
| Tobramycin Inhalation Powder | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 6 Treatment Cycles in Extension Study | Extension completion, (n=33) | -3.5 Percent change in FEV1 % predicted | Standard Deviation 10.74 |
Secondary
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.
Time frame: Baseline of core study, Day 673 (end of the extension study)
Population: The analysis was performed in extension safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tobramycin Inhalation Powder | The Percentage of the Participants Hospitalized Due to Serious Respiratory-related AEs Were Determined During the Study. | 40.0 Percentage of participants |
Secondary
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.
Time frame: Baseline of extension study, Day 673 (end of extension study)
Population: The analysis was performed in extension safety population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tobramycin Inhalation Powder | Time to First Hospitalization Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study | NA Days |
Secondary
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.
Time frame: Baseline of core study, Day 673 (end of the extension study)
Population: The analysis was performed in extension safety population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tobramycin Inhalation Powder | Time to First Hospitalization Due to Respiratory Related Serious Adverse Events (SAEs) Over 12 Treatment Cycles | NA Days |
Secondary
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.
Time frame: Baseline of extension study, Day 673 (end of extension study)
Population: The analysis was performed in extension safety population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tobramycin Inhalation Powder | Time to Use of New Anti-pseudomonal Antibiotics in Extension Study | 139 Days |
Secondary
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.
Time frame: Baseline of core study, Day 673 (end of the extension study)
Population: The analysis was performed in extension safety population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tobramycin Inhalation Powder | Time to Use of New Anti-pseudomonal Antibiotics Over 12 Treatment Cycles | 202.0 Days |
Secondary
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).
Time frame: 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)
Population: The analysis was performed in extension safety population, who had microbiological data at specified time points. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle, Baseline- MIC 50 (n=45) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle 1, day 29- MIC 50 (n=41) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle 2, day 85- MIC 50 (n=40) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle 3, day 141- MIC 50 (n=43) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle 4, day 197- MIC 50 (n=40) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle 5, day 253- MIC 50 (n=36) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle 6, day 309- MIC 50 (n=37) | 4 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core study completion, Day 337- MIC 50 (n=40) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 7, day 337- MIC 50 (n=38) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 7, day 365- MIC 50 (n=38) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 8, day 421- MIC 50 (n=39) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 9, day 477- MIC 50 (n=39) | 4 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 10, day 533- MIC 50 (n=35) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 11, day 589- MIC 50 (n=36) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 12, day 645- MIC 50 (n=32) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension completion, Day 673 - MIC 50 (n=29) | 2 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle, Baseline- MIC 90 (n=45) | 32 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle 1, day 29- MIC 90 (n=41) | 256 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle 2, day 85- MIC 90 (n=40) | 256 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle 3, day 141- MIC 90 (n=43) | 512 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle 4, day 197- MIC 90 (n=40) | 128 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle 5, day 253- MIC 90 (n=36) | 256 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core cycle 6, day 309- MIC 90 (n=37) | 512 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Core study completion, Day 337- MIC 90 (n=40) | 512 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 7, day 337- MIC 90 (n=38) | 512 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 7, day 365- MIC 90 (n=38) | 128 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 8, day 421- MIC 90 (n=39) | 128 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 9, day 477- MIC 90 (n=39) | 512 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 10, day 533- MIC 90 (n=35) | 256 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 11, day 589- MIC 90 (n=36) | 512 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension cycle 12, day 645- MIC 90 (n=32) | 512 micrograms/milliliters |
| Tobramycin Inhalation Powder | Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles | Extension completion, Day 673 - MIC 90 (n=29) | 512 micrograms/milliliters |
Secondary
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.
Time frame: Baseline of extension study, Day 673 (end of extension study)
Population: The analysis was performed in extension safety population.The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tobramycin Inhalation Powder | Total Number of Days of New Anti-pseudomonal Antibiotics Use in Extension Study | Overall route (n=31) | 33.0 Days |
| Tobramycin Inhalation Powder | Total Number of Days of New Anti-pseudomonal Antibiotics Use in Extension Study | Oral use (n=23) | 28.0 Days |
| Tobramycin Inhalation Powder | Total Number of Days of New Anti-pseudomonal Antibiotics Use in Extension Study | i.v use (n=20) | 16.0 Days |
| Tobramycin Inhalation Powder | Total Number of Days of New Anti-pseudomonal Antibiotics Use in Extension Study | Inhaled use (n=1) | 9.0 Days |
Secondary
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.
Time frame: Baseline of core study, Day 673 (end of the extension study)
Population: The analysis was performed in extension safety population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tobramycin Inhalation Powder | Total Number of Days of New Anti-pseudomonal Antibiotics Use Over 12 Treatment Cycles | Overall route (n=35) | 59.0 Days |
| Tobramycin Inhalation Powder | Total Number of Days of New Anti-pseudomonal Antibiotics Use Over 12 Treatment Cycles | Oral use (n=31) | 42.0 Days |
| Tobramycin Inhalation Powder | Total Number of Days of New Anti-pseudomonal Antibiotics Use Over 12 Treatment Cycles | i.v use (n=25) | 32.0 Days |
| Tobramycin Inhalation Powder | Total Number of Days of New Anti-pseudomonal Antibiotics Use Over 12 Treatment Cycles | Inhaled use (n=1) | 9.0 Days |