Trial Outcomes & Findings for Ext. Long-term Safety Study in CF Patients: Single Arm TIP (NCT NCT01775137)

Last Updated: 2015-11-06

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

45 participants

Primary outcome timeframe

Baseline (start of study treatment in core study) to Day 673 (end of the extension study)

Results posted on

2015-11-06

Participant Flow

The study was conducted at 22 centers in 9 countries.

Of 96 participants who completed the core study (CTBM100C2401), NCT01519661; 45 participants were enrolled in the extension study.

Participant milestones

Participant milestones
Measure	Tobramycin Inhalation Powder Participants inhaled four capsules of tobramycin inhalation powder (28 mg) twice daily (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.
Overall Study STARTED	45
Overall Study COMPLETED	34
Overall Study NOT COMPLETED	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Tobramycin Inhalation Powder Participants inhaled four capsules of tobramycin inhalation powder (28 mg) twice daily (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.
Overall Study Death	1
Overall Study Protocol deviation	2
Overall Study Unsatisfactory therapeutic effect	2
Overall Study Adverse Event	1
Overall Study Withdrawal by participants	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
Age, Categorical <=18 years	12 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	33 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	24.5 years STANDARD_DEVIATION 10.79 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants
Region of Enrollment Canada	1 participants n=5 Participants
Region of Enrollment Argentina	9 participants n=5 Participants
Region of Enrollment Hungary	1 participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants
Region of Enrollment Italy	7 participants n=5 Participants
Region of Enrollment Mexico	5 participants n=5 Participants
Region of Enrollment Australia	5 participants n=5 Participants
Region of Enrollment Germany	5 participants n=5 Participants
Region of Enrollment Spain	6 participants n=5 Participants
Pseudomonas aeruginosa tobramycin minimal inhibitory concentration (MIC) > 8 microgram/milliliter(ug/mL)	12 Participants n=5 Participants
Pseudomonas aeruginosa tobramycin minimal inhibitory concentration (MIC) <= 8 ug/mL	33 Participants n=5 Participants
Forced expiratory volume in one second (FEV1) percent (%) predicted	52.2 Percent predicted STANDARD_DEVIATION 15.01 • n=5 Participants
Forced vital capacity (FVC) % predicted	73.2 Percent predicted STANDARD_DEVIATION 17.49 • n=5 Participants
Forced expiratory flow from 25 to 75 % (FEF2575%) % predicted	24.7 Percent predicted STANDARD_DEVIATION 14.86 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
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
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
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
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
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
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
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
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
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 1.60
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 2.00
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 1.80
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
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
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
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
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
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 2.20
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
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
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
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
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 2.70

SECONDARY outcome

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.

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).

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 outcome

Timeframe: Baseline of core study, Day 673 (end of the extension study)

Population: The analysis was performed in extension safety population.

The rate of anti-pseudomonal antibiotics use were determined from the collection of concomitant medication during the study.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
Percentage of Participants Who Used New Anti-pseudomonal Antibiotics Over 12 Treatment Cycles	77.8 Percentage of participants

SECONDARY outcome

Timeframe: 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.

The total number of days with usage of new anti-pseudomonal antibiotic were determined.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
Total Number of Days of New Anti-pseudomonal Antibiotics Use Over 12 Treatment Cycles Overall route (n=35)	59.0 Days Interval 15.0 to 252.0
Total Number of Days of New Anti-pseudomonal Antibiotics Use Over 12 Treatment Cycles Oral use (n=31)	42.0 Days Interval 11.0 to 175.0
Total Number of Days of New Anti-pseudomonal Antibiotics Use Over 12 Treatment Cycles i.v use (n=25)	32.0 Days Interval 7.0 to 252.0
Total Number of Days of New Anti-pseudomonal Antibiotics Use Over 12 Treatment Cycles Inhaled use (n=1)	9.0 Days Interval 9.0 to 9.0

SECONDARY outcome

Timeframe: Baseline of core study, Day 673 (end of the extension study)

Population: The analysis was performed in extension safety population.

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.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
Time to Use of New Anti-pseudomonal Antibiotics Over 12 Treatment Cycles	202.0 Days Interval 89.0 to 336.0

SECONDARY outcome

Timeframe: Baseline of core study, Day 673 (end of the extension study)

Population: The analysis was performed in extension safety population.

The percentage of the participants hospitalized due to serious respiratory-related AEs were determined during the study.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
The Percentage of the Participants Hospitalized Due to Serious Respiratory-related AEs Were Determined During the Study.	40.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline of core study, Day 673 (end of the extension study)

Population: The analysis was performed in extension safety population.

The total number of hospitalization days due to serious respiratory-related adverse events was analyzed using Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
Number of Hospitalization Days Due to Respiratory Related Serious Adverse Events (SAEs) Over 12 Treatment Cycles	17.0 Days Interval 4.0 to 129.0

SECONDARY outcome

Timeframe: Baseline of core study, Day 673 (end of the extension study)

Population: The analysis was performed in extension safety population.

The day of first hospitalization due to serious respiratory-related adverse events was analysed using Kaplan Meier estimate.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
Time to First Hospitalization Due to Respiratory Related Serious Adverse Events (SAEs) Over 12 Treatment Cycles	NA Days Here, value is not applicable due to insufficient number of events.

SECONDARY outcome

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.

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.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
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
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
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
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
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
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
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
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
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 5.10
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
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
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
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 outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
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
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
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
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
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
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
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 outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
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
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 2.60
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
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
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
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
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 outcome

Timeframe: Baseline of extension study, Day 673 (end of extension study)

Population: The analysis was performed in extension safety population.

The rate of anti-pseudomonal antibiotics use were determined from the collection of concomitant medication during the study.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
Percentage of Participants Who Used New Anti-pseudomonal Antibiotics in Extension Study	68.9 Percentage of participants

SECONDARY outcome

Timeframe: 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

The total number of days with usage of new anti-pseudomonal antibiotic were determined.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
Total Number of Days of New Anti-pseudomonal Antibiotics Use in Extension Study i.v use (n=20)	16.0 Days Interval 7.0 to 252.0
Total Number of Days of New Anti-pseudomonal Antibiotics Use in Extension Study Inhaled use (n=1)	9.0 Days Interval 9.0 to 9.0
Total Number of Days of New Anti-pseudomonal Antibiotics Use in Extension Study Overall route (n=31)	33.0 Days Interval 1.0 to 252.0
Total Number of Days of New Anti-pseudomonal Antibiotics Use in Extension Study Oral use (n=23)	28.0 Days Interval 1.0 to 44.0

SECONDARY outcome

Timeframe: Baseline of extension study, Day 673 (end of extension study)

Population: The analysis was performed in extension safety population.

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.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
Time to Use of New Anti-pseudomonal Antibiotics in Extension Study	139 Days Interval 86.0 to 271.0

SECONDARY outcome

Timeframe: Baseline of extension study, Day 673 (end of the extension study)

Population: The analysis was performed in extension safety population.

The percentage of the participants hospitalized due to serious respiratory-related AEs were determined during the extension study.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
Percentage of Participants Hospitalized Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study	35.6 Percentage of participants

SECONDARY outcome

Timeframe: Baseline of extension study, Day 673 (end of extension study)

Population: The analysis was performed in extension safety population.

The total number of hospitalisation days due to serious respiratory-related adverse events was analysed using Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
Number of Hospitalization Days Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study	16.0 Days Interval 5.0 to 64.0

SECONDARY outcome

Timeframe: Baseline of extension study, Day 673 (end of extension study)

Population: The analysis was performed in extension safety population.

The day of first hospitalization due to serious respiratory related adverse events was analysed using Kaplan Meier estimate.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
Time to First Hospitalization Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study	NA Days Here, value is not applicable due to insufficient number of events.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tobramycin Inhalation Powder n=45 Participants 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.
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
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
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
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
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

Adverse Events

Core

Serious events: 12 serious events

Other events: 33 other events

Deaths: 0 deaths

Extension

Serious events: 16 serious events

Other events: 32 other events

Deaths: 0 deaths

Overall

Serious events: 19 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single site are postponed until the publication of the pooled data (i.e, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Core n=45 participants at risk Eligible participants were assigned to four capsules of TIP at 28 mg 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 112 mg tobramycin (4 capsules of 28 mg each) with the total daily dose = 224 mg tobramycin (112 mg b.i.d.). These 56 days represented 1 cycle of therapy during core study.	Extension n=45 participants at risk Participants inhaled four capsules of tobramycin inhalation powder (28 mg) bid via the T-326 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.	Overall n=45 participants at risk All participants who inhaled tobramycin inhalation powder during both core and extension study.
Cardiac disorders Cardiac failure	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Cardiac disorders Cardiogenic shock	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Gastrointestinal disorders Distal intestinal obstruction syndrome	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Infections and infestations Bronchopneumonia	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	24.4% 11/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	31.1% 14/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	37.8% 17/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Infections and infestations Influenza	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Infections and infestations Pneumonia	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Investigations Forced expiratory volume decreased	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Metabolism and nutrition disorders Hyperamylasaemia	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Nervous system disorders Syncope	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Reproductive system and breast disorders Ovarian cyst	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Reproductive system and breast disorders Prostatitis	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Respiratory, thoracic and mediastinal disorders Respiratory acidosis	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Vascular disorders Haemodynamic instability	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)

Measure	Core n=45 participants at risk Eligible participants were assigned to four capsules of TIP at 28 mg 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 112 mg tobramycin (4 capsules of 28 mg each) with the total daily dose = 224 mg tobramycin (112 mg b.i.d.). These 56 days represented 1 cycle of therapy during core study.	Extension n=45 participants at risk Participants inhaled four capsules of tobramycin inhalation powder (28 mg) bid via the T-326 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.	Overall n=45 participants at risk All participants who inhaled tobramycin inhalation powder during both core and extension study.
Gastrointestinal disorders Abdominal pain	8.9% 4/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	8.9% 4/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	15.6% 7/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Gastrointestinal disorders Constipation	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	6.7% 3/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	6.7% 3/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Gastrointestinal disorders Diarrhoea	11.1% 5/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	11.1% 5/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	17.8% 8/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Gastrointestinal disorders Dyspepsia	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Gastrointestinal disorders Nausea	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Gastrointestinal disorders Vomiting	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	6.7% 3/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
General disorders Chest discomfort	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
General disorders Fatigue	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	6.7% 3/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	8.9% 4/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
General disorders Pyrexia	6.7% 3/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	8.9% 4/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Infections and infestations Bacterial disease carrier	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	6.7% 3/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	6.7% 3/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Infections and infestations Ear infection	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	40.0% 18/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	35.6% 16/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	55.6% 25/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Infections and infestations Nasopharyngitis	20.0% 9/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	20.0% 9/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	28.9% 13/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Infections and infestations Pharyngitis	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Infections and infestations Rhinitis	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Infections and infestations Sinusitis	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	6.7% 3/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	8.9% 4/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Infections and infestations Upper respiratory tract infection	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	8.9% 4/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Infections and infestations Urinary tract infection	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Investigations Forced expiratory volume decreased	8.9% 4/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	11.1% 5/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	17.8% 8/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Investigations Pulmonary function test decreased	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Investigations Staphylococcus test positive	6.7% 3/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	6.7% 3/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Musculoskeletal and connective tissue disorders Back pain	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Nervous system disorders Headache	8.9% 4/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	8.9% 4/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	13.3% 6/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Reproductive system and breast disorders Dysmenorrhoea	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Respiratory, thoracic and mediastinal disorders Cough	17.8% 8/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	17.8% 8/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	24.4% 11/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Respiratory, thoracic and mediastinal disorders Dysphonia	8.9% 4/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	8.9% 4/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Respiratory, thoracic and mediastinal disorders Haemoptysis	17.8% 8/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	22.2% 10/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	26.7% 12/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	13.3% 6/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	6.7% 3/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	20.0% 9/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Respiratory, thoracic and mediastinal disorders Productive cough	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	6.7% 3/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	6.7% 3/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Respiratory, thoracic and mediastinal disorders Sputum increased	15.6% 7/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	11.1% 5/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	22.2% 10/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Respiratory, thoracic and mediastinal disorders Wheezing	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	2.2% 1/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)
Vascular disorders Hypertension	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	0.00% 0/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)	4.4% 2/45 • Baseline (start of study treatment in extension study) to Day 673 (end of the extension study)