Second Open Label Extension to Bridging Study CTBM100C2303

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01069705
• Collaborator: (none)
• Enrollment: 49
• Locations: 17
• Arm: 1
• Actual Duration (Months): 25.2
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was an open-label, single arm (uncontrolled) study in participants suffering from cystic fibrosis, who have completed their study participation in CTBM100C2303 and extension study one CTBM100C2303E1 (all visits), who were proven infected with Pseudomonas aeruginosa at enrollment into CTBM100C2303.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Infections; Pseudomonas Aeruginosa	Drug: Tobramycin inhalation powder	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Open-Label Extension Study to Assess the Safety and Efficacy of Tobramycin Inhalation Powder After Manufacturing Process Modifications (TIPnew) in Cystic Fibrosis (CF) Patients Who Successfully Completed Participation in Study CTBM100C2303E1
• Actual Study Start Date: Feb 12, 2010
• Actual Primary Completion Date: Mar 19, 2012
• Actual Study Completion Date: Mar 19, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tobramycin Inhalation Powder (TIPnew) Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.	Drug: Tobramycin inhalation powder; Tobramycin dry powder for inhalation in capsules administered by the T-326 inhaler.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs) [From time of first administration of study drug until study completion (up to 169 days)]

   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.

2. Number of Participants With Serious Adverse Events (SAEs) [From time of consent to 4 weeks after study completion (up to 199 days)]

   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.

3. Percentage of Participants With a Decrease of ≥20% in Forced Expiratory Value in One Second (FEV1) Percent (%) Predicted From Pre-dose to 30-minute Post-dose [Pre-dose and post-dose of Day 1 and Day 29 of every Cycle (5, 6, 7)]

   Airway Reactivity >= 20% relative decrease in FEV1% predicted from pre-dose to 30 minutes post-dose. Relative Change = 100 * (30 minutes Post-dose - Pre-dose)/Pre-dose assessed by the number and percentage of participants with a decrease of ≥ 20% in FEV1 % predicted from pre-dose to 30 minutes post-dose.

4. Percentage of Participants With Frequency Decrease From Baseline in the Post-baseline Audiology Tests [Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)]

   Auditory acuity of participants was measured using a standard dual-channel audiometer at frequencies from 250 to 8000 Hertz, and an audiogram (pure-tone air conduction) and tympanogram were performed by an audiologist. The categories reported includes >= 10dB decrease in 3 consecutive frequencies in either ear, >= 15dB decrease in 2 consecutive frequencies in either ear, and >= 20dB decrease in at least one frequency in either ear

Secondary Outcome Measures

1. Relative Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent Predicted to Each Post-baseline Visit [Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)]

   Forced expiratory volume in one second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 % predicted was a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. Relative change in FEV1 % predicted from baseline to pre-dose day X = ((pre-dose day X FEV1 % predicted - baseline FEV1 % predicted) / baseline FEV1 % predicted) x 100.

2. Relative Change From Baseline of Forced Vital Capacity (FVC) Percent Predicted to Each Post-baseline Visit [Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)]

   Percent Predicted Forced Vital Capacity (FVC%) is the maximal exhaled breath volume following a maximal inhaled breath. Overall change in percent predicted FVC = (observed value)/(predicted value) * 100%. A higher value indicates a greater response.

3. Relative Change From Baseline of Forced Expiratory Flow Rate Over 25 and 75 Percent (FEF25-75%) Predicted to Each Post-baseline Visit [Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)]

   Forced Expiratory Flow Rate Over 25 and 75 Percent (FEF25-75%) is the forced expiratory flow from 25% to 75% of the Forced Vital Capacity (FVC). Relative change in FEF25-75% from baseline to pre-dose day X = (pre-dose day X FEF25-75 - baseline FEF25-75) / baseline FEF25-75) • 100.

4. Change From Baseline in Pseudomonas Aeruginosa Sputum Density to Each Post-baseline Visit [Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)]

   Pseudomonas Aeruginosa Density refers to overall density, defined as the sum of Biotypes (mucoid, dry and small colony variant). Absolute change was determined using the formula; Change = Post-baseline value- baseline value. Absolute Change in Pseudomonas Aeruginosa Sputum density is measured in log 10 Colony Forming Units per gram (Log 10 CFU/g).

5. Change From Baseline in Tobramycin Minimum Inhibitory Concentration (MIC) Values for Pseudomonas Aeruginosa to Each Post-baseline Visit [Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)]

   Minimum Inhibitory Concentration (MIC) is defined as the lowest concentration of an antimicrobial agent required to inhibit the visible growth of a microorganism after overnight incubation.

6. Number of Participants Who Used New Antipseudomonal Antibiotic During Treatment Period [Baseline, Cycles 5, 6, 7 (Days 1, 29)]

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

7. Percentage of Participants With Hospitalization Due to Respiratory Serious Adverse Events (SAEs) [From time of consent to 4 weeks after study completion (up to 199 days)]

   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.

8. Number of Days of Hospitalization Due to Respiratory Serious Adverse Events (SAEs) [From time of consent to 4 weeks after study completion (up to 199 days)]

   The average number of days patients were hospitalized due to respiratory events during the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Completed all visits in study CTBM100C2303 and CTBM100C2303E1, and visit 11 of study CTBM100C2303E1 took place not more than 5 days before enrollment into this study.

• Confirmed diagnosis of cystic fibrosis participants with P. aeruginosa infection.

• Forced Expiratory Volume in one second (FEV1) at screening (at start of study CTBM100C2303) must be between 25% and 80% of normal predicted values.

Exclusion Criteria:

• Any use of inhaled anti-pseudomonal antibiotics between the termination of the trial CTMB100C2303E1 and the enrollment into this study.

• Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Pleven		Bulgaria
2	Novartis Investigative Site	Plovdiv		Bulgaria
3	Novartis Investigative Site	Sofia		Bulgaria
4	Novartis Investigative Site	Varna		Bulgaria
5	Novartis Investigative Site	Tallin		Estonia
6	Novartis Investigative Site	Tartu		Estonia
7	Novartis Investigative Site	Riga		Latvia
8	Novartis Investigative Site	Kaunas		Lithuania
9	Novartis Investigative Site	Vilnius		Lithuania
10	Novartis Investigative Site	Bucharest		Romania
11	Novartis Investigative Site	Timisoara		Romania
12	Novartis Investigative Site	Kazan		Russian Federation
13	Novartis Investigative Site	Moscow		Russian Federation
14	Novartis Investigative Site	Saint Petersburg		Russian Federation
15	Novartis Investigative Site	Samara		Russian Federation
16	Novartis Investigative Site	Yaroslavl		Russian Federation
17	Novartis Investigative Site	Durban		South Africa

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01069705
• Other Study ID Numbers: CTBM100C2303E2
• First Posted: Feb 17, 2010
• Last Update Posted: Jun 2, 2021
• Last Verified: May 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Tobramycin Inhalation Powder; Cystic fibrosis; Lung diseases; Anti-Bacterial Agents; Treatment of pulmonary infections with P. aeruginosa in cystic fibrosis participants
• Additional relevant MeSH terms: Cystic Fibrosis; Tobramycin

Study Results

Participant Flow

Recruitment Details	The study was conducted at 14 centres in 8 countries from 12 February 2010 to 19 March 2012.
Pre-assignment Detail	This study enrolled 49 Participants with Cystic Fibrosis who completed participation in the study CTBM100C2303E1 (NCT00982930).

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Period Title: Overall Study
STARTED	49
COMPLETED	46
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Overall Participants	49
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.3 (4.31)
Sex: Female, Male (Count of Participants)
Female	32 65.3%
Male	17 34.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	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.
Time Frame	From time of first administration of study drug until study completion (up to 169 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed their participation in C2303E1, who gave their consent to enter the extension 2 study and who received at least one dose of study drug in the extension 2 study.

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Measure Participants	49
Count of Participants [Participants]	23 46.9%

2. Primary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs)
Description	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.
Time Frame	From time of consent to 4 weeks after study completion (up to 199 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed their participation in C2303E1, who gave their consent to enter the extension 2 study and who received at least one dose of study drug in the extension 2 study.

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Measure Participants	49
Count of Participants [Participants]	2 4.1%

3. Primary Outcome

Title	Percentage of Participants With a Decrease of ≥20% in Forced Expiratory Value in One Second (FEV1) Percent (%) Predicted From Pre-dose to 30-minute Post-dose
Description	Airway Reactivity >= 20% relative decrease in FEV1% predicted from pre-dose to 30 minutes post-dose. Relative Change = 100 * (30 minutes Post-dose - Pre-dose)/Pre-dose assessed by the number and percentage of participants with a decrease of ≥ 20% in FEV1 % predicted from pre-dose to 30 minutes post-dose.
Time Frame	Pre-dose and post-dose of Day 1 and Day 29 of every Cycle (5, 6, 7)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed their participation in C2303E1, who gave their consent to enter the extension 2 study and who received at least one dose of study drug in the extension 2 study. Number analyzed is the number of participants with data available at the given timepoint.

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Measure Participants	49
Acute Change from Pre-dose to 30 mins Post-dose Cycle 5 (Day 1)	2.3 4.7%
Acute Change from Pre-dose to 30 mins Post-dose Cycle 5 (Day 29)	0.0 0%
Acute Change from Pre-dose to 30 mins Post-dose Cycle 6 (Day 1)	2.5 5.1%
Acute Change from Pre-dose to 30 mins Post-dose Cycle 6 (Day 29)	4.3 8.8%
Acute Change from Pre-dose to 30 mins Post-dose Cycle 7 (Day 1)	6.7 13.7%
Acute Change from Pre-dose to 30 mins Post-dose Cycle 7 (Day 29)	0.0 0%

4. Primary Outcome

Title	Percentage of Participants With Frequency Decrease From Baseline in the Post-baseline Audiology Tests
Description	Auditory acuity of participants was measured using a standard dual-channel audiometer at frequencies from 250 to 8000 Hertz, and an audiogram (pure-tone air conduction) and tympanogram were performed by an audiologist. The categories reported includes >= 10dB decrease in 3 consecutive frequencies in either ear, >= 15dB decrease in 2 consecutive frequencies in either ear, and >= 20dB decrease in at least one frequency in either ear
Time Frame	Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)

Outcome Measure Data

Analysis Population Description

All participants included in the safety population with at least one audiology testing. Number analyzed is the number of participants with data available at the given timepoint.

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Measure Participants	19
Cycle 5: Day 1; >= 10 dB Decrease in 3 Consecutive Frequencies in Either Ear	0.0 0%
Cycle 5: Day 1; >= 15 dB Decrease in 2 Consecutive Frequencies in Either Ear	0.0 0%
Cycle 5: Day 1; >= 20 dB Decrease in at least one Frequency in Either Ear	0.0 0%
Cycle 5: Day 29; >= 10 dB Decrease in 3 Consecutive Frequencies in Either Ear	0.0 0%
Cycle 5: Day 29; >= 15 dB Decrease in 2 Consecutive Frequencies in Either Ear	5.3 10.8%
Cycle 5: Day 29; >= 20 dB Decrease in at least one Frequency in Either Ear	0.0 0%
Cycle 6: Day 29; >= 10 dB Decrease in 3 Consecutive Frequencies in Either Ear	0.0 0%
Cycle 6: Day 29; >= 15 dB Decrease in 2 Consecutive Frequencies in Either Ear	5.3 10.8%
Cycle 6: Day 29; >= 20 dB Decrease in at least one Frequency in Either Ear	0.0 0%
Cycle 7: Day 29; ˃= 10 dB Decrease in 3 Consecutive Frequencies in Either Ear	10.5 21.4%
Cycle 7: Day 29; >= 15 dB Decrease In 2 Consecutive Frequencies in Either Ear	5.3 10.8%
Cycle 7: Day 29; >= 20 dB Decrease in at Least One Frequency in Either Ear	5.3 10.8%
Follow Up: Week 57/Day 57; ˃= 10 dB Decrease in 3 Consecutive Frequencies in Either Ear	20.0 40.8%
Follow Up: Week 57/Day 57; >= 15 dB Decrease In 2 Consecutive Frequencies in Either Ear	0.0 0%
Follow Up: Week 57/Day 57; >= 20 dB Decrease in at Least One Frequency in Either Ear	0.0 0%

5. Secondary Outcome

Title	Relative Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent Predicted to Each Post-baseline Visit
Description	Forced expiratory volume in one second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 % predicted was a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. Relative change in FEV1 % predicted from baseline to pre-dose day X = ((pre-dose day X FEV1 % predicted - baseline FEV1 % predicted) / baseline FEV1 % predicted) x 100.
Time Frame	Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed their participation in C2303E1, who gave their consent to enter the extension 2 study and who received at least one dose of study drug in the extension 2 study. Number analyzed is the number of participants with data available at the given timepoint.

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Measure Participants	49
Baseline	59.5 (16.51)
Relative Change from Baseline to Cycle 5 (Day 1)	11.4 (21.79)
Relative Change from Baseline to Cycle 5 (Day 29)	12.6 (24.49)
Relative Change from Baseline to Cycle 6 (Day 1)	8.6 (19.73)
Relative Change from Baseline to Cycle 6 (Day 29)	11.9 (24.23)
Relative Change from Baseline to Cycle 7 (Day 1)	9.0 (22.44)
Relative Change from Baseline to Cycle 7 (Day 29)	10.1 (26.37)
Relative Change from Baseline to Follow -Up (Week 57/Day 57)	8.1 (25.79)

6. Secondary Outcome

Title	Relative Change From Baseline of Forced Vital Capacity (FVC) Percent Predicted to Each Post-baseline Visit
Description	Percent Predicted Forced Vital Capacity (FVC%) is the maximal exhaled breath volume following a maximal inhaled breath. Overall change in percent predicted FVC = (observed value)/(predicted value) * 100%. A higher value indicates a greater response.
Time Frame	Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed their participation in C2303E1, who gave their consent to enter the extension 2 study and who received at least one dose of study drug in the extension 2 study. Number analyzed is the number of participants with data available at the given timepoint.

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Measure Participants	49
Baseline	75.0 (17.63)
Relative Change from Baseline to Cycle 5 (Day 1)	5.1 (15.60)
Relative Change from Baseline to Cycle 5 (Day 29)	5.2 (17.87)
Relative Change from Baseline to Cycle 6 (Day 1)	2.6 (16.36)
Relative Change from Baseline to Cycle 6 (Day 29)	6.2 (20.01)
Relative Change from Baseline to Cycle 7 (Day 1)	2.3 (19.20)
Relative Change from Baseline to Cycle 7 (Day 29)	2.9 (20.40)
Relative Change from Baseline to Follow-up (Week 57/Day 57)	4.0 (20.37)

7. Secondary Outcome

Title	Relative Change From Baseline of Forced Expiratory Flow Rate Over 25 and 75 Percent (FEF25-75%) Predicted to Each Post-baseline Visit
Description	Forced Expiratory Flow Rate Over 25 and 75 Percent (FEF25-75%) is the forced expiratory flow from 25% to 75% of the Forced Vital Capacity (FVC). Relative change in FEF25-75% from baseline to pre-dose day X = (pre-dose day X FEF25-75 - baseline FEF25-75) / baseline FEF25-75) • 100.
Time Frame	Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed their participation in C2303E1, who gave their consent to enter the extension 2 study and who received at least one dose of study drug in the extension 2 study. Number analyzed is the number of participants with data available at the given timepoint.

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Measure Participants	49
Baseline	36.8 (20.30)
Relative Change from Baseline to Cycle 5 (Day 1)	37.7 (57.39)
Relative Change from Baseline to Cycle 5 (Day 29)	43.2 (67.51)
Relative Change from Baseline to Cycle 6 (Day 1)	35.1 (66.39)
Relative Change from Baseline to Cycle 6 (Day 29)	34.3 (63.53)
Relative Change from Baseline to Cycle 7 (Day 1)	44.4 (80.91)
Relative Change from Baseline to Cycle 7 (Day 29)	36.1 (61.75)
Relative Change from Baseline to Follow-up (Week 57/Day 57)	35.6 (77.34)

8. Secondary Outcome

Title	Change From Baseline in Pseudomonas Aeruginosa Sputum Density to Each Post-baseline Visit
Description	Pseudomonas Aeruginosa Density refers to overall density, defined as the sum of Biotypes (mucoid, dry and small colony variant). Absolute change was determined using the formula; Change = Post-baseline value- baseline value. Absolute Change in Pseudomonas Aeruginosa Sputum density is measured in log 10 Colony Forming Units per gram (Log 10 CFU/g).
Time Frame	Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed their participation in C2303E1, who gave their consent to enter the extension 2 study and who received at least one dose of study drug in the extension 2 study. Number analyzed is the number of participants with data available at the given timepoint.

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Measure Participants	49
Baseline	7.4 (1.50)
Change from Baseline to Cycle 5 (Day 1)	-1.1 (2.82)
Change from Baseline to Cycle 5 (Day 29)	-3.7 (2.95)
Change from Baseline to Cycle 6 (Day 1)	-1.6 (2.95)
Change from Baseline to Cycle 6 (Day 29)	-3.6 (2.73)
Change from Baseline to Cycle 7 (Day 1)	-1.5 (3.40)
Change from Baseline to Cycle 7 (Day 29)	-2.6 (2.92)
Change from Baseline to Follow-up (Week 57/Day 57)	-1.8 (3.62)

9. Secondary Outcome

Title	Change From Baseline in Tobramycin Minimum Inhibitory Concentration (MIC) Values for Pseudomonas Aeruginosa to Each Post-baseline Visit
Description	Minimum Inhibitory Concentration (MIC) is defined as the lowest concentration of an antimicrobial agent required to inhibit the visible growth of a microorganism after overnight incubation.
Time Frame	Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed their participation in C2303E1, who gave their consent to enter the extension 2 study and who received at least one dose of study drug in the extension 2 study. Number analyzed is the number of participants with data available at the given timepoint.

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Measure Participants	49
Baseline	2.2 (9.11)
Change from Baseline in Cycle 5 (Day 1)	31.4 (117.6)
Change from Baseline in Cycle 5 (Day 29)	21.6 (92.35)
Change from Baseline in Cycle 6 (Day 1)	39.3 (138.37)
Change from Baseline in Cycle 6 (Day 29)	25.5 (94.74)
Change from Baseline in Cycle 7 (Day 1)	3.7 (22.94)
Change from Baseline in Cycle 7 (Day 29)	31.7 (115.97)
Change from Baseline to Follow-up (Week 57/Day 57)	1.7 (11.14)

10. Secondary Outcome

Title	Number of Participants Who Used New Antipseudomonal Antibiotic During Treatment Period
Description	The rate of anti-pseudomonal antibiotics use were determined from the collection of concomitant medication during the study Treatment period.
Time Frame	Baseline, Cycles 5, 6, 7 (Days 1, 29)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed their participation in C2303E1, who gave their consent to enter the extension 2 study and who received at least one dose of study drug in the extension 2 study.

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Measure Participants	49
Count of Participants [Participants]	7 14.3%

11. Secondary Outcome

Title	Percentage of Participants With Hospitalization Due to Respiratory Serious Adverse Events (SAEs)
Description	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.
Time Frame	From time of consent to 4 weeks after study completion (up to 199 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed their participation in C2303E1, who gave their consent to enter the extension 2 study and who received at least one dose of study drug in the extension 2 study. Number analyzed is the number of participants with data available at the given timepoint.

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Measure Participants	49
Number [percentage of participants]	4.1 8.4%

12. Secondary Outcome

Title	Number of Days of Hospitalization Due to Respiratory Serious Adverse Events (SAEs)
Description	The average number of days patients were hospitalized due to respiratory events during the study.
Time Frame	From time of consent to 4 weeks after study completion (up to 199 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who completed their participation in C2303E1, who gave their consent to enter the extension 2 study and who received at least one dose of study drug in the extension 2 study. Number analyzed is the number of participants with data available at the given timepoint.

Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
Measure Participants	49
Mean (Standard Deviation) [days]	16.5 (2.12)

Adverse Events

Time Frame	From the time of first administration of study drug until study completion (up to 169 days)
Adverse Event Reporting Description	AEs were deemed treatment-emergent if the onset date was on or after the date of the first study drug of extension 2 and until study completion of the extension 2.
Arm/Group Title	Tobramycin Inhalation Powder (TIPnew)
Arm/Group Description	Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles.
All Cause Mortality
	Tobramycin Inhalation Powder (TIPnew)
	Affected / at Risk (%)	# Events
Total	0/49 (0%)
Serious Adverse Events
	Tobramycin Inhalation Powder (TIPnew)
	Affected / at Risk (%)	# Events
Total	2/49 (4.1%)
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis	1/49 (2%)
Pneumonia	1/49 (2%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/49 (2%)
Other (Not Including Serious) Adverse Events
	Tobramycin Inhalation Powder (TIPnew)
	Affected / at Risk (%)	# Events
Total	22/49 (44.9%)
Ear and labyrinth disorders
Hypoacusis	2/49 (4.1%)
Gastrointestinal disorders
Constipation	1/49 (2%)
Diarrhoea	1/49 (2%)
General disorders
Asthenia	1/49 (2%)
Non-cardiac chest pain	2/49 (4.1%)
Pyrexia	1/49 (2%)
Infections and infestations
Acute sinusitis	2/49 (4.1%)
Alcaligenes infection	1/49 (2%)
Bronchitis	3/49 (6.1%)
Burkholderia cepacia complex infection	1/49 (2%)
Infective pulmonary exacerbation of cystic fibrosis	2/49 (4.1%)
Influenza	1/49 (2%)
Nasopharyngitis	1/49 (2%)
Respiratory tract infection	5/49 (10.2%)
Respiratory tract infection viral	4/49 (8.2%)
Investigations
Antibiotic resistant Staphylococcus test positive	1/49 (2%)
Protein urine present	1/49 (2%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/49 (2%)
Cough	3/49 (6.1%)
Dysphonia	2/49 (4.1%)
Productive cough	1/49 (2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.