Pseudomonas Aeruginosa in Cystic Fibrosis, Pulmonary Infections
Conditions
Keywords
Tobramycin Inhalation powder, Cystic fibrosis, Lung disease, Anti-bacterial agents
Brief summary
This study assessed the long term safety data for the use of tobramycin inhalation powder in patients suffering from cystic fibrosis who have a chronic pulmonary infection with Pseudomonas aeruginosa.
Interventions
DRUGTBM100
Tobramycin inhalation powder was assigned as four capsules at 28mg dosage strength. It was inhaled b.i.d in the morning and in the evening via the T-326 Inhaler.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of Cystic Fibrosis * FEV1 at screening must be between 25 and 75 percent of normal predicted values for age, sex and height based on the Knudson equation * Pseudomonas aeruginosa must be present in a sputum / deep cough throat swab culture or bronchoalveolar lavage within 6 months prior to screening and in the sputum/deep-throat cough swab culture at screening
Exclusion criteria
* History of sputum culture or deep cough throat swab culture yielding Burkholderia cenocepacia complex within 2 years prior to screening and /or sputum culture yielding Burkholderia cenocepacia at screening * Hemoptysis more than 60mL at any time within 30 days prior to study drug administration * History of hearing loss or chronic tinnitus deemed clinically significant * Serum creatinine 2mg/dl or more, BUN 40mg/dl or more, or an abnormal urinalysis defined as 2+ or greater proteinuria at screening * Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics * Patients who are regularly receiving more than 1 class of inhaled anti-pseudomonal antibiotic * Any use of inhaled or systemic anti-pseudomonal antibiotic within 28 days prior to study drug administration * Use of loop diuretics within 7 days prior to study drug administration Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment Emergent Adverse Events, Serious Adverse Events (SAEs) and Deaths | 337 days | Adverse events were deemed treatment-emergent if the onset date/time was on or after the date and time of first study drug. All adverse events were included after this time during both on and off-treatment periods. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted | Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period. | Spirometry was performed at each visit. FEV1, FVC, and FEF25-75 were recorded at all visits according to American Thoracic Society (ATS) guidelines. FEV1 = the volume of air expired in 1 second. FEV1 % predicted is a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. FVC (forced vital capacity) = the maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration. FEF25-75 = forced expiratory flow from 25% to 75% of the FVC. Relative change in FEV1 % predicted from baseline to pre-dose day X = ((pre-dose day X FEV1 % predicted - baseline FEV1 % predicted) / baseline FEV1 % predicted) • 100. |
| Relative Change From Baseline in FVC Percent Predicted | Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period. | Spirometry was performed at each visit. FEV1, FVC, and FEF25-75 were recorded at all visits according to American Thoracic Society (ATS) guidelines. FEV1 = the volume of air expired in 1 second. FEV1 % predicted is a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. FVC (forced vital capacity) = the maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration. FEF25-75 = forced expiratory flow from 25% to 75% of the FVC. Relative change in FVC % predicted from baseline to pre-dose day X = ((pre-dose day X FVC % predicted - baseline FVC % predicted) / baseline FVC % predicted) • 100. |
| Relative Change From Baseline in FEF Rate Over 25 to 75 Percent of Vital Capacity Predicted | Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period. | Spirometry was performed at each visit. FEV1, FVC, and FEF25-75 were recored at all visits according to American Thoracic Society (ATS) guidelines. FEV1 = the volume of air expired in 1 second. FEV1 % predicted is a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. FVC (forced vital capacity) = the maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration. FEF25-75 = forced expiratory flow from 25% to 75% of the FVC. Relative change in FEEF25-75 from baseline to pre-dose day X = ((pre-dose day X FEF25-75 - baseline FEF25-75) / baseline FEF25-75) • 100. |
| Change From Baseline in Pseudomonas Aeruginosa Colony Forming Units in Sputum | Baseline, day 1, day 29, day 85, day 141, day 197, day 253, day 309, day 337 | Sputum was collected in sterile containers and cultured for Pseudomonas aeruginosa (Pa.) (quantitative test) and other typical Cystic Fibrosis respiratory pathogens. The Pa. biotypes measured were mucoid, dry and small colony variant. Results are presented for the sum of all biotypes of Pa, with data transformed using a base 10 logarithm. |
| Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337 | 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. |
| Time to Use of New Anti-pseudomonal Antibiotic | Day 337 | Time to first use of new anti-pseudomonal antibiotic was analyzed. |
| Number of Hospitalization Days Due to Serious Respiratory-related Adverse Events | Day 337 | The total number of hospitalization days due to serious respiratory-related adverse events was analyzed. |
| Time to First Hospitalization Due to Serious Respiratory-related Adverse Events | Day 337 | The day of first hospitalization due to serious respiratory-related adverse events was analyzed. |
| Percentage of Participants Who Used New Anti-pseudomonal Antibiotics | Day 337 | — |
| Number of Days of New Anti-pseudomonal Antibiotic Use | Day 337 | The total number of days of new anti-pseudomonal antibiotic use was analyzed. |
| Percentage of Participants Hospitalized Due to Serious Respiratory-related Adverse Events | Day 337 | — |
Countries
Argentina, Australia, Canada, France, Germany, Hungary, Italy, Mexico, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tobramycin Inhalation Powder (TIP) Eligible patients were assigned to four capsules of TIP at 28mg dosage strength, inhaled b.i.d. in the morning and in the evening via the T-326 inhaler, for 28 days (on treatment), followed by 28 days of no study treatment (off treatment). Each treatment therefore consisted of 112mg tobramycin (4 capsules of 28mg each) with the total daily dose = 224mg tobramycin (112mg b.i.d.). These 56 days represented 1 cycle of therapy. | 157 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 29 |
| Overall Study | Lack of Efficacy | 6 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Protocol deviation | 6 |
| Overall Study | Withdrawal by Subject | 17 |
Baseline characteristics
| Characteristic | Tobramycin Inhalation Powder (TIP) |
|---|---|
| Age, Continuous | 27.8 Years STANDARD_DEVIATION 10.82 |
| Body Mass Index | 20.5 kg/m^2 STANDARD_DEVIATION 3.35 |
| FEF25-75 % predicted | 21.8 percent STANDARD_DEVIATION 12.75 |
| FEV1 % predicted | 50.2 percent STANDARD_DEVIATION 13.95 |
| FVC % predicted | 73.9 percent STANDARD_DEVIATION 15.88 |
| P. aeruginosa tobramycin minimal inhibitory concentration (MIC) <= 8 ug/mL | 73.2 percentage of participants |
| P. aeruginosa tobramycin minimal inhibitory concentration (MIC) > 8 ug/mL | 26.1 percentage of participants |
| P. aeruginosa tobramycin minimal inhibitory concentration (MIC) Missing | 0.6 percentage of participants |
| Sex: Female, Male Female | 60 Participants |
| Sex: Female, Male Male | 97 Participants |
| Sputum density of P. aeruginosa - sum of all biotypes | 7.6 log10 Colony Forming Units (CFU) STANDARD_DEVIATION 1.65 |
| Weight | 57.4 kilograms (kg) STANDARD_DEVIATION 13.52 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 121 / 157 |
| serious Total, serious adverse events | 49 / 157 |
Outcome results
Primary
Percentage of Participants With Treatment Emergent Adverse Events, Serious Adverse Events (SAEs) and Deaths
Adverse events were deemed treatment-emergent if the onset date/time was on or after the date and time of first study drug. All adverse events were included after this time during both on and off-treatment periods.
Time frame: 337 days
Population: Safety set: The safety set included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Percentage of Participants With Treatment Emergent Adverse Events, Serious Adverse Events (SAEs) and Deaths | Adverse events (serious and non-serious) | 85.4 Percentage of participants |
| Tobramycin Inhalation Powder (TIP) | Percentage of Participants With Treatment Emergent Adverse Events, Serious Adverse Events (SAEs) and Deaths | Serious adverse events | 31.2 Percentage of participants |
| Tobramycin Inhalation Powder (TIP) | Percentage of Participants With Treatment Emergent Adverse Events, Serious Adverse Events (SAEs) and Deaths | Deaths | 0.0 Percentage of participants |
Secondary
Change From Baseline in Pseudomonas Aeruginosa Colony Forming Units in Sputum
Sputum was collected in sterile containers and cultured for Pseudomonas aeruginosa (Pa.) (quantitative test) and other typical Cystic Fibrosis respiratory pathogens. The Pa. biotypes measured were mucoid, dry and small colony variant. Results are presented for the sum of all biotypes of Pa, with data transformed using a base 10 logarithm.
Time frame: Baseline, day 1, day 29, day 85, day 141, day 197, day 253, day 309, day 337
Population: Participants from the safety set who had Pa sputum density values at both baseline and the given time point were included in the analysis. The safety set included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Change From Baseline in Pseudomonas Aeruginosa Colony Forming Units in Sputum | Sum of all biotypes, Day 29, Cycle 1 (n=141) | -1.6 log10 Colony Forming Unit (CFU) | Standard Deviation 2.28 |
| Tobramycin Inhalation Powder (TIP) | Change From Baseline in Pseudomonas Aeruginosa Colony Forming Units in Sputum | Sum of all biotypes, Day 85, Cycle 2 (n=135) | -1.1 log10 Colony Forming Unit (CFU) | Standard Deviation 1.8 |
| Tobramycin Inhalation Powder (TIP) | Change From Baseline in Pseudomonas Aeruginosa Colony Forming Units in Sputum | Sum of all biotypes, Day 141, Cycle 3 (n=119) | -1.2 log10 Colony Forming Unit (CFU) | Standard Deviation 1.98 |
| Tobramycin Inhalation Powder (TIP) | Change From Baseline in Pseudomonas Aeruginosa Colony Forming Units in Sputum | Sum of all biotypes, Day 197, Cycle 4(n=107) | -1.1 log10 Colony Forming Unit (CFU) | Standard Deviation 2.11 |
| Tobramycin Inhalation Powder (TIP) | Change From Baseline in Pseudomonas Aeruginosa Colony Forming Units in Sputum | Sum of all biotypes. Day 253, Cycle 5 (n=98) | -1.3 log10 Colony Forming Unit (CFU) | Standard Deviation 2.23 |
| Tobramycin Inhalation Powder (TIP) | Change From Baseline in Pseudomonas Aeruginosa Colony Forming Units in Sputum | Sum of all biotypes, Day 309, Cycle 6 (n=89) | -1.2 log10 Colony Forming Unit (CFU) | Standard Deviation 2.09 |
| Tobramycin Inhalation Powder (TIP) | Change From Baseline in Pseudomonas Aeruginosa Colony Forming Units in Sputum | Sum of all biotypes, Day 337, Completion (n=85) | -0.4 log10 Colony Forming Unit (CFU) | Standard Deviation 2.08 |
Secondary
Number of Days of New Anti-pseudomonal Antibiotic Use
The total number of days of new anti-pseudomonal antibiotic use was analyzed.
Time frame: Day 337
Population: Safety set: The safety set included all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Number of Days of New Anti-pseudomonal Antibiotic Use | 33.1 Days | Standard Deviation 25.17 |
Secondary
Number of Hospitalization Days Due to Serious Respiratory-related Adverse Events
The total number of hospitalization days due to serious respiratory-related adverse events was analyzed.
Time frame: Day 337
Population: Safety set: The safety set included all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Number of Hospitalization Days Due to Serious Respiratory-related Adverse Events | 18.1 Days | Standard Deviation 17.14 |
Secondary
Percentage of Participants Hospitalized Due to Serious Respiratory-related Adverse Events
Time frame: Day 337
Population: Safety set: The safety set included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Percentage of Participants Hospitalized Due to Serious Respiratory-related Adverse Events | 26.8 Percentage of participants |
Secondary
Percentage of Participants Who Used New Anti-pseudomonal Antibiotics
Time frame: Day 337
Population: Safety set: The safety set included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Percentage of Participants Who Used New Anti-pseudomonal Antibiotics | 65.6 Percentage of participants |
Secondary
Relative Change From Baseline in FEF Rate Over 25 to 75 Percent of Vital Capacity Predicted
Spirometry was performed at each visit. FEV1, FVC, and FEF25-75 were recored at all visits according to American Thoracic Society (ATS) guidelines. FEV1 = the volume of air expired in 1 second. FEV1 % predicted is a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. FVC (forced vital capacity) = the maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration. FEF25-75 = forced expiratory flow from 25% to 75% of the FVC. Relative change in FEEF25-75 from baseline to pre-dose day X = ((pre-dose day X FEF25-75 - baseline FEF25-75) / baseline FEF25-75) • 100.
Time frame: Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period.
Population: Participants from the safety set who had values at both baseline and the given assessment day were included in the analysis for that assessment day. Therefore, the 'n' for each assessment day is different. The safety set included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FEF Rate Over 25 to 75 Percent of Vital Capacity Predicted | Day 29, Cycle 1 (n=149) | 10.3 Percent change | Standard Deviation 36.05 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FEF Rate Over 25 to 75 Percent of Vital Capacity Predicted | Day 85, Cycle 2 (n=146) | 9.4 Percent change | Standard Deviation 55.35 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FEF Rate Over 25 to 75 Percent of Vital Capacity Predicted | Day 141, Cycle 3 (n=128) | 5.5 Percent change | Standard Deviation 31.82 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FEF Rate Over 25 to 75 Percent of Vital Capacity Predicted | Day 197, Cycle 4 (n=116) | 6.0 Percent change | Standard Deviation 30.96 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FEF Rate Over 25 to 75 Percent of Vital Capacity Predicted | Day 253, Cycle 5 (n=105) | 2.9 Percent change | Standard Deviation 33.23 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FEF Rate Over 25 to 75 Percent of Vital Capacity Predicted | Day 309, Cycle 6 (n=100) | 4.3 Percent change | Standard Deviation 32.44 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FEF Rate Over 25 to 75 Percent of Vital Capacity Predicted | Day 337, Completion (n=93) | 0.7 Percent change | Standard Deviation 33.78 |
Secondary
Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted
Spirometry was performed at each visit. FEV1, FVC, and FEF25-75 were recorded at all visits according to American Thoracic Society (ATS) guidelines. FEV1 = the volume of air expired in 1 second. FEV1 % predicted is a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. FVC (forced vital capacity) = the maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration. FEF25-75 = forced expiratory flow from 25% to 75% of the FVC. Relative change in FEV1 % predicted from baseline to pre-dose day X = ((pre-dose day X FEV1 % predicted - baseline FEV1 % predicted) / baseline FEV1 % predicted) • 100.
Time frame: Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period.
Population: Participants from the safety set who had FEV1 percent predicted values at both baseline and the post baseline time points were analyzed at each given time point. The safety set included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted | Day 29, Cycle 1 (n=149) | 0.8 Percent change | Standard Deviation 17.17 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted | Day 85, Cycle 2 (n=146) | 0.0 Percent change | Standard Deviation 17.09 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted | Day 141, Cycle 3 (n=128) | 0.2 Percent change | Standard Deviation 15.13 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted | Day 197, Cycle 4 (n=116) | -0.2 Percent change | Standard Deviation 15.36 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted | Day 253, Cycle 5 (n=105) | -1.5 Percent change | Standard Deviation 17.19 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted | Day 309, Cycle 6 (n=100) | -1.9 Percent change | Standard Deviation 14.55 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted | Day 337, Completion (n=93) | -3.5 Percent change | Standard Deviation 16.81 |
Secondary
Relative Change From Baseline in FVC Percent Predicted
Spirometry was performed at each visit. FEV1, FVC, and FEF25-75 were recorded at all visits according to American Thoracic Society (ATS) guidelines. FEV1 = the volume of air expired in 1 second. FEV1 % predicted is a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. FVC (forced vital capacity) = the maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration. FEF25-75 = forced expiratory flow from 25% to 75% of the FVC. Relative change in FVC % predicted from baseline to pre-dose day X = ((pre-dose day X FVC % predicted - baseline FVC % predicted) / baseline FVC % predicted) • 100.
Time frame: Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period.
Population: Participants from the safety set who had values at both baseline and the given assessment day were included in the analysis for that assessment day. Therefore, the 'n' for each assessment day is different. The safety set included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FVC Percent Predicted | Day 29, Cycle 1 (n=149) | -2.5 Percent change | Standard Deviation 12.95 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FVC Percent Predicted | Day 85, Cycle 2 (n=146) | -2.8 Percent change | Standard Deviation 12.81 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FVC Percent Predicted | Day 141, Cycle 3 (n=128) | -2.1 Percent change | Standard Deviation 12.25 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FVC Percent Predicted | Day 197, Cycle 4 (n=116) | -1.8 Percent change | Standard Deviation 12.64 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FVC Percent Predicted | Day 253, Cycle 5 (n=105) | -3.5 Percent change | Standard Deviation 13.11 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FVC Percent Predicted | Day 309, Cycle 6 (n=100) | -3.1 Percent change | Standard Deviation 12.17 |
| Tobramycin Inhalation Powder (TIP) | Relative Change From Baseline in FVC Percent Predicted | Day 337, Completion (n=93) | -2.8 Percent change | Standard Deviation 13.5 |
Secondary
Time to First Hospitalization Due to Serious Respiratory-related Adverse Events
The day of first hospitalization due to serious respiratory-related adverse events was analyzed.
Time frame: Day 337
Population: Safety set The safety set included all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Time to First Hospitalization Due to Serious Respiratory-related Adverse Events | NA Days |
Secondary
Time to Use of New Anti-pseudomonal Antibiotic
Time to first use of new anti-pseudomonal antibiotic was analyzed.
Time frame: Day 337
Population: Safety set The safety set included all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Time to Use of New Anti-pseudomonal Antibiotic | 136 Days |
Secondary
Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa
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.
Time frame: Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337
Population: Participants from the safety set who had data at each time point/cycle were analyzed at each time point. The safety set included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Baseline - MIC 50 (n=156) | 2 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Cycle 1, day 29 - MIC 50 (n=144) | 2 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Cycle 2, day 85 - MIC 50 (n=137) | 2 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Cycle 3, day 141 - MIC 50 (n=124) | 2 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Cycle 4, day 197 - MIC 50 (n=108) | 2 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Cycle 5, day 253 - MIC 50 (n=98) | 2 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Cycle 6, day 309 - MIC 50 (n=90) | 4 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Completion, day 337 - MIC 50 (n=89) | 2 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Baseline - MIC 90 (n=156) | 128 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Cycle 1, day 29 - MIC 90 (n=144) | 256 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Cycle 2, day 85 - MIC 90 (n=137) | 256 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Cycle 3, day 141 - MIC 90 (n=124) | 256 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Cycle 4, day 197 - MIC 90 (n=108) | 128 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Cycle 5, day 253 - MIC 90 (n=98) | 256 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Cycle 6, day 309 - MIC 90 (n=90) | 256 ug/mL |
| Tobramycin Inhalation Powder (TIP) | Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa | Completion, day 337 - MIC 90 (n=89) | 512 ug/mL |