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Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)

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ClinicalTrials.gov Identifier: NCT01844778
Recruitment Status : Completed
First Posted : May 1, 2013
Results First Posted : May 24, 2016
Last Update Posted : July 27, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Drug: Tobramycin Inhalation Powder
Drug: Tobramycin inhalation solution
Drug: Colistimethate
Enrollment 60
Recruitment Details  
Pre-assignment Details Each participant was assigned to 1 of 3 treatment arms, TIS/TIP, COLI/TIP, or TIP/TIP with the first treatment cycle based on the participant's usual antibiotic treatment. Then all participants were crossed-over to receive TIP for the second cycle of treatment.
Arm/Group Title TIS/TIP COLI/TIP TIP/TIP
Hide Arm/Group Description During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment. During the first cycle, participants received nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant's usual dose and regimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off-treatment (cycling regimen), depending on local treatment guidelines. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment. During the first and second cycles, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
Period Title: Overall Study
Started 14 28 18
Safety Set 1 (at Least 1 Dose, Cycle 1) 14 28 18
Safety Set 2 (at Least 1 Dose, Cycle 2) 12 25 15
Completed 12 25 14
Not Completed 2 3 4
Reason Not Completed
Protocol deviation             0             1             2
Withdrawal by Subject             2             0             0
Adverse Event             0             2             2
Arm/Group Title TIS/TIP COLI/TIP TIP/TIP Total
Hide Arm/Group Description During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment. During the first cycle, participants received nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant's usual dose and regimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off-treatment (cycling regimen), depending on local treatment guidelines. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment. During the first and second cycles, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment. Total of all reporting groups
Overall Number of Baseline Participants 14 28 18 60
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 28 participants 18 participants 60 participants
27.4  (6.82) 28.4  (9.86) 26.6  (7.25) 27.6  (8.40)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 28 participants 18 participants 60 participants
Female
4
  28.6%
10
  35.7%
7
  38.9%
21
  35.0%
Male
10
  71.4%
18
  64.3%
11
  61.1%
39
  65.0%
1.Primary Outcome
Title Mean Total Administration Time
Hide Description The mean total time for administration of TIP via T-326 inhaler versus the total time for administration of COLI or TIS was assessed from information entered by participants into an ediary during the last 7 days prior to the last dose of a cycle. The total time included the setup, preparation, administration and cleaning/disinfection time.
Time Frame days 22 through 28 (cycle 1), days 78 through 84 (cycle 2)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) was considered for this analysis. The FAS included participants who received at least 1 dose of treatment. Only participants (n), with non-missing mean total administration time of initial and second cycles, were analyzed.
Arm/Group Title TIS/TIP COLI/TIP TIP/TIP
Hide Arm/Group Description:
During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
During the first cycle, participants received nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant's usual dose and regimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off-treatment (cycling regimen), depending on local treatment guidelines. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
During the first and second cycles, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
Overall Number of Participants Analyzed 14 28 18
Mean (Standard Deviation)
Unit of Measure: minutes
Cycle 1 (n=8,17,14) 37.0  (22.06) 16.4  (9.54) 4.2  (2.02)
Cycle 2 (n=10,16,11) 5.0  (2.04) 3.8  (1.70) 3.4  (2.06)
2.Secondary Outcome
Title Change in P. Aeruginosa Sputum Density
Hide Description Sputum samples were sent to a central laboratory at the start and end of 2 treatment periods. The absolute change in the number of colony forming units (CFU) of Pseudomonas aeruginosa in sputum = the value of end of on/off treatment period of the cycle minus the pre-dose value at the start of that cycle. A negative change from baseline indicates improvement.
Time Frame days 1, 28 (cycle 1); 57, 84, 112 (cycle 2)
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS was considered and included participants who received at least 1 dose of treatment. Only participants (n), with values at the start and end of an on-treatment period ("on-treatment" change), and/or with values at the start of an on-treatment period and end of an off-treatment period ("off-treatment" change), were analyzed.
Arm/Group Title TIS/TIP COLI/TIP TIP/TIP
Hide Arm/Group Description:
During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
During the first cycle, participants received nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant's usual dose and regimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off-treatment (cycling regimen), depending on local treatment guidelines. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
During the first and second cycles, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
Overall Number of Participants Analyzed 14 28 18
Mean (Standard Deviation)
Unit of Measure: log10 CFU/mL
Cycle 1, on-treatment change (n=11,22,9) -1.4  (1.85) -0.6  (1.88) -1.7  (2.87)
Cycle 1, off-treatment change (n=10,20,8) 0.2  (1.98) -0.6  (2.36) -0.2  (1.56)
Cycle 2, on-treatment (n=9,16,5) -0.9  (1.66) -0.5  (1.65) -1.6  (1.53)
Cycle 2, off-treatment (n=9,18,5) 0.0  (0.95) 0.5  (2.55) 0.0  (0.91)
3.Secondary Outcome
Title Number of Participants With Any Contaminated Delivery Device
Hide Description Devices used to administer the drugs (the T-326 inhaler and nebulisers) were swabbed for contamination testing at the start and end of each treatment cycle (or discontinuation visit if the participant withdrew). No assessments were required from the T-326 inhaler when participants started the treatment period (days 1 and 57). Microbial contamination was measured according to device type and the frequency of organism growth (light/ moderate/ heavy). All nebulisers (neb) used by the participants were analyzed, including those for inhaling other medications, like mucolytics.
Time Frame days (d) 1, 28, 57, 84
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS was considered for the analysis and included participants who had at least one dose of study treatment. Only participants (n), with an available culture from the delivery device, were analyzed.
Arm/Group Title TIS/TIP COLI/TIP TIP/TIP
Hide Arm/Group Description:
During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
During the first cycle, participants received nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant's usual dose and regimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off-treatment (cycling regimen), depending on local treatment guidelines. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
During the first and second cycles, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
Overall Number of Participants Analyzed 14 28 18
Measure Type: Number
Unit of Measure: Participants
P. a biotype 2 - dry,d1,neb, moderate,(n=0,0,1) NA [1]  NA [1]  1
A. baumannii,d1,neb,heavy,n=0,7,0 NA [1]  1 NA [1] 
A. junii,d1,neb,moderate,n=0,7,0 NA [1]  1 NA [1] 
A.lwoffi,d1,neb,light,n=0,7,0 NA [1]  2 NA [1] 
H. parainfluenza,d1,neb,light,n=0,7,0 NA [1]  1 NA [1] 
O. anthropic,d1,neb,heavy,n=0,7,0 NA [1]  1 NA [1] 
P. fluorescens,d1,neb,light,n=0,7,0 NA [1]  1 NA [1] 
P. putida,d1,neb,light,n=0,7,0 NA [1]  1 NA [1] 
P. stutzeri,d1,neb,moderate,n=0,7,0 NA [1]  1 NA [1] 
S.liquefaciens,d1,neb,light,n=0,7,0 NA [1]  1 NA [1] 
S. multivorum,d1,neb,light,n=0,7,0 NA [1]  1 NA [1] 
S. maltophilia,d1,neb,light,n=0,7,0 NA [1]  1 NA [1] 
Acinetobacter species,d28,neb,light,n=0,6,0 NA [1]  1 NA [1] 
C. indologenes,d28,neb,moderate,n=0,6,0 NA [1]  1 NA [1] 
D. acidovorans,d 28,neb,light,n=0,6,0 NA [1]  1 NA [1] 
P. fluorescens,d28,neb,light,n=0,6,0 NA [1]  2 NA [1] 
S. paucimobilis,d28,neb,heavy,n=0,6,0 NA [1]  1 NA [1] 
S. aureus,d28,neb,light,n=0,6,0 NA [1]  1 NA [1] 
P. a biotype 2 - dry,d57,neb,light,n=1,0,0 1 NA [1]  NA [1] 
S. aureus,d84,T-326,light,n=1,0,0 1 NA [1]  NA [1] 
[1]
no contamination
4.Secondary Outcome
Title Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values
Hide Description MIC50/90 is the lowest concentration required to inhibit 50%/90% of the isolates tested. The MIC50/90 of a range of antibiotics for P.aeruginosa was determined at the start and end of each treatment cycle, and at the end of the off-treatment period of the second cycle.
Time Frame days 1, 28, 57, 84, 112
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS was considered for the analysis and included participants who had at least one dose of study treatment. Only participants (n), with values on a given day, were analyzed for that day. The number of isolates tested = m.
Arm/Group Title TIS/TIP COLI/TIP TIP/TIP
Hide Arm/Group Description:
During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
During the first cycle, participants received nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant's usual dose and regimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off-treatment (cycling regimen), depending on local treatment guidelines. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
During the first and second cycles, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
Overall Number of Participants Analyzed 14 28 18
Measure Type: Number
Unit of Measure: ug/mL
MIC50: Day 1, n=14,27,18; m=27,51,29 2 2 2
MIC50: Day 28, n=13,23,13; m=25,46,21 2 2 2
MIC50: Day 57, n=11,19,15; m=23,34,24 4 4 2
MIC50: Day 84, n=12,17,11; m=25,29,18 4 4 2
MIC50: Day 112, n=12,19,12; m=24,33,19 2 2 1
MIC90: Day 1, n=14,27,18; m=27,51,29 256 16 64
MIC90: Day 28, n=13,23,13; m=25,46,21 256 16 64
MIC90: Day 57, n=11,19,15; m=23,34,24 64 16 64
MIC90: Day 84, n=12,17,11; m=25,29,18 512 32 64
MIC90: Day 112, n=12,19,12; m=24,33,19 32 32 32
5.Secondary Outcome
Title Number of Participants With Post-inhalation Bronchospasm
Hide Description Bronchospasm was defined as the relative decrease of 20% or more in forced expiratory volume in 1 second (FEV1) percent predicted from pre-dose to 15 to 45 minutes post-dose.
Time Frame days 1, 28, 57, 84
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS was considered for the analysis and included participants who had at least one dose of study treatment. Only participants (n), with values on a given day, were analyzed for that day.
Arm/Group Title TIS/TIP COLI/TIP TIP/TIP
Hide Arm/Group Description:
During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
During the first cycle, participants received nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant's usual dose and regimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off-treatment (cycling regimen), depending on local treatment guidelines. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
During the first and second cycles, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
Overall Number of Participants Analyzed 14 28 18
Measure Type: Number
Unit of Measure: Participants
Day 1, n=8,17,14 0 1 0
Day 28, n=6,19,14 0 1 0
Day 57, n=10,22,13 0 0 1
Day 84, n=8,14,10 0 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title TIS/TIP - Cycle 1 TIS/TIP - Cycle 2 COLI/TIP - Cycle 1 COLI/TIP - Cycle 2 TIP/TIP - Cycle 1 TIP/TIP - Cycle 2 Overall TIP Cycle 2
Hide Arm/Group Description During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment. During the first cycle, participants received nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant's usual dose and regimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off-treatment (cycling regimen), depending on local treatment guidelines. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment. During the first and second cycles, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment. During the first and second cycles, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment. During the second cycle, each treatment group received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.
All-Cause Mortality
TIS/TIP - Cycle 1 TIS/TIP - Cycle 2 COLI/TIP - Cycle 1 COLI/TIP - Cycle 2 TIP/TIP - Cycle 1 TIP/TIP - Cycle 2 Overall TIP Cycle 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
TIS/TIP - Cycle 1 TIS/TIP - Cycle 2 COLI/TIP - Cycle 1 COLI/TIP - Cycle 2 TIP/TIP - Cycle 1 TIP/TIP - Cycle 2 Overall TIP Cycle 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/14 (21.43%)   3/12 (25.00%)   9/28 (32.14%)   3/25 (12.00%)   3/18 (16.67%)   2/15 (13.33%)   8/52 (15.38%) 
Ear and labyrinth disorders               
Tinnitus  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Gastrointestinal disorders               
Faecaloma  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
General disorders               
Pyrexia  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0/52 (0.00%) 
Hepatobiliary disorders               
Bile duct stenosis  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Biliary tract disorder  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Cholelithiasis  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Infections and infestations               
Fungal infection  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Infective pulmonary exacerbation of cystic fibrosis  1  3/14 (21.43%)  3/12 (25.00%)  6/28 (21.43%)  3/25 (12.00%)  2/18 (11.11%)  0/15 (0.00%)  6/52 (11.54%) 
Influenza  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Respiratory tract infection  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Sinusitis  1  0/14 (0.00%)  1/12 (8.33%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Upper respiratory tract infection  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Investigations               
Acoustic stimulation tests abnormal  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Forced expiratory volume decreased  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Pulmonary function test decreased  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0/52 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Haemoptysis  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0/52 (0.00%) 
Sputum increased  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
TIS/TIP - Cycle 1 TIS/TIP - Cycle 2 COLI/TIP - Cycle 1 COLI/TIP - Cycle 2 TIP/TIP - Cycle 1 TIP/TIP - Cycle 2 Overall TIP Cycle 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/14 (35.71%)   6/12 (50.00%)   13/28 (46.43%)   12/25 (48.00%)   10/18 (55.56%)   10/15 (66.67%)   28/52 (53.85%) 
Ear and labyrinth disorders               
Tinnitus  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Gastrointestinal disorders               
Abdominal pain upper  1  0/14 (0.00%)  1/12 (8.33%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  2/52 (3.85%) 
Diarrhoea  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Distal intestinal obstruction syndrome  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Odynophagia  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Vomiting  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
General disorders               
Fatigue  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Influenza like illness  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Malaise  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Non-cardiac chest pain  1  0/14 (0.00%)  1/12 (8.33%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  2/52 (3.85%) 
Pyrexia  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  1/15 (6.67%)  1/52 (1.92%) 
Hepatobiliary disorders               
Bile duct stone  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Hepatic function abnormal  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Immune system disorders               
Anaphylactic reaction  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Hypersensitivity  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Seasonal allergy  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0/52 (0.00%) 
Infections and infestations               
Cystitis  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0/52 (0.00%) 
Infective pulmonary exacerbation of cystic fibrosis  1  2/14 (14.29%)  1/12 (8.33%)  5/28 (17.86%)  6/25 (24.00%)  0/18 (0.00%)  1/15 (6.67%)  8/52 (15.38%) 
Influenza  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Nasopharyngitis  1  0/14 (0.00%)  0/12 (0.00%)  3/28 (10.71%)  0/25 (0.00%)  2/18 (11.11%)  3/15 (20.00%)  3/52 (5.77%) 
Oral candidiasis  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Oral herpes  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Sinusitis  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Tongue fungal infection  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  1/15 (6.67%)  1/52 (1.92%) 
Tracheobronchitis  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Upper respiratory tract infection  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Urinary tract infection  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0/52 (0.00%) 
Vulvovaginal candidiasis  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  1/18 (5.56%)  0/15 (0.00%)  1/52 (1.92%) 
Vulvovaginal mycotic infection  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0/52 (0.00%) 
Injury, poisoning and procedural complications               
Muscle strain  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Investigations               
Alanine aminotransferase increased  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Aspartate aminotransferase increased  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Forced expiratory volume decreased  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0/52 (0.00%) 
Gamma-glutamyltransferase increased  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Glucose urine present  1  0/14 (0.00%)  1/12 (8.33%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Liver function test abnormal  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Metabolism and nutrition disorders               
Hyperglycaemia  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Hypokalaemia  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Musculoskeletal and connective tissue disorders               
Back pain  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0/52 (0.00%) 
Musculoskeletal pain  1  0/14 (0.00%)  1/12 (8.33%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  1/52 (1.92%) 
Nervous system disorders               
Aphonia  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  1/18 (5.56%)  0/15 (0.00%)  1/52 (1.92%) 
Burning sensation  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Dizziness  1  1/14 (7.14%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Headache  1  1/14 (7.14%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  3/18 (16.67%)  3/15 (20.00%)  3/52 (5.77%) 
Lethargy  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Psychiatric disorders               
Insomnia  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0/52 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Cough  1  2/14 (14.29%)  1/12 (8.33%)  2/28 (7.14%)  0/25 (0.00%)  2/18 (11.11%)  2/15 (13.33%)  3/52 (5.77%) 
Dysphonia  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Dyspnoea  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  1/52 (1.92%) 
Epistaxis  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0/52 (0.00%) 
Haemoptysis  1  0/14 (0.00%)  1/12 (8.33%)  0/28 (0.00%)  2/25 (8.00%)  2/18 (11.11%)  0/15 (0.00%)  3/52 (5.77%) 
Oropharyngeal pain  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Prolonged expiration  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0/52 (0.00%) 
Rales  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  1/18 (5.56%)  0/15 (0.00%)  0/52 (0.00%) 
Respiratory arrest  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Respiratory tract congestion  1  1/14 (7.14%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Sputum increased  1  1/14 (7.14%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  3/18 (16.67%)  2/15 (13.33%)  2/52 (3.85%) 
Wheezing  1  1/14 (7.14%)  1/12 (8.33%)  0/28 (0.00%)  1/25 (4.00%)  0/18 (0.00%)  0/15 (0.00%)  2/52 (3.85%) 
Skin and subcutaneous tissue disorders               
Dermatitis allergic  1  0/14 (0.00%)  0/12 (0.00%)  1/28 (3.57%)  0/25 (0.00%)  0/18 (0.00%)  0/15 (0.00%)  0/52 (0.00%) 
Night sweats  1  0/14 (0.00%)  0/12 (0.00%)  0/28 (0.00%)  0/25 (0.00%)  0/18 (0.00%)  1/15 (6.67%)  1/52 (1.92%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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 or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01844778    
Other Study ID Numbers: CTBM100C2403
2012-001565-33 ( EudraCT Number )
First Submitted: April 29, 2013
First Posted: May 1, 2013
Results First Submitted: April 15, 2016
Results First Posted: May 24, 2016
Last Update Posted: July 27, 2016