Trial Outcomes & Findings for Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI) (NCT NCT01844778)
NCT ID: NCT01844778
Last Updated: 2016-07-27
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
60 participants
Primary outcome timeframe
days 22 through 28 (cycle 1), days 78 through 84 (cycle 2)
Results posted on
2016-07-27
Participant Flow
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.
Participant milestones
| Measure |
TIS/TIP
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.
|
COLI/TIP
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.
|
TIP/TIP
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 Study
STARTED
|
14
|
28
|
18
|
|
Overall Study
Safety Set 1 (at Least 1 Dose, Cycle 1)
|
14
|
28
|
18
|
|
Overall Study
Safety Set 2 (at Least 1 Dose, Cycle 2)
|
12
|
25
|
15
|
|
Overall Study
COMPLETED
|
12
|
25
|
14
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
4
|
Reasons for withdrawal
| Measure |
TIS/TIP
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.
|
COLI/TIP
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.
|
TIP/TIP
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 Study
Protocol deviation
|
0
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
0
|
|
Overall Study
Adverse Event
|
0
|
2
|
2
|
Baseline Characteristics
Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
Baseline characteristics by cohort
| Measure |
TIS/TIP
n=14 Participants
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.
|
COLI/TIP
n=28 Participants
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.
|
TIP/TIP
n=18 Participants
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
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
27.4 Years
STANDARD_DEVIATION 6.82 • n=5 Participants
|
28.4 Years
STANDARD_DEVIATION 9.86 • n=7 Participants
|
26.6 Years
STANDARD_DEVIATION 7.25 • n=5 Participants
|
27.6 Years
STANDARD_DEVIATION 8.40 • n=4 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
39 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: days 22 through 28 (cycle 1), days 78 through 84 (cycle 2)Population: 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.
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.
Outcome measures
| Measure |
TIS/TIP
n=14 Participants
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.
|
COLI/TIP
n=28 Participants
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.
|
TIP/TIP
n=18 Participants
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.
|
|---|---|---|---|
|
Mean Total Administration Time
Cycle 1 (n=8,17,14)
|
37.0 minutes
Standard Deviation 22.06
|
16.4 minutes
Standard Deviation 9.54
|
4.2 minutes
Standard Deviation 2.02
|
|
Mean Total Administration Time
Cycle 2 (n=10,16,11)
|
5.0 minutes
Standard Deviation 2.04
|
3.8 minutes
Standard Deviation 1.70
|
3.4 minutes
Standard Deviation 2.06
|
SECONDARY outcome
Timeframe: days 1, 28 (cycle 1); 57, 84, 112 (cycle 2)Population: 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.
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.
Outcome measures
| Measure |
TIS/TIP
n=14 Participants
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.
|
COLI/TIP
n=28 Participants
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.
|
TIP/TIP
n=18 Participants
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.
|
|---|---|---|---|
|
Change in P. Aeruginosa Sputum Density
Cycle 1, on-treatment change (n=11,22,9)
|
-1.4 log10 CFU/mL
Standard Deviation 1.85
|
-0.6 log10 CFU/mL
Standard Deviation 1.88
|
-1.7 log10 CFU/mL
Standard Deviation 2.87
|
|
Change in P. Aeruginosa Sputum Density
Cycle 1, off-treatment change (n=10,20,8)
|
0.2 log10 CFU/mL
Standard Deviation 1.98
|
-0.6 log10 CFU/mL
Standard Deviation 2.36
|
-0.2 log10 CFU/mL
Standard Deviation 1.56
|
|
Change in P. Aeruginosa Sputum Density
Cycle 2, on-treatment (n=9,16,5)
|
-0.9 log10 CFU/mL
Standard Deviation 1.66
|
-0.5 log10 CFU/mL
Standard Deviation 1.65
|
-1.6 log10 CFU/mL
Standard Deviation 1.53
|
|
Change in P. Aeruginosa Sputum Density
Cycle 2, off-treatment (n=9,18,5)
|
0.0 log10 CFU/mL
Standard Deviation 0.95
|
0.5 log10 CFU/mL
Standard Deviation 2.55
|
0.0 log10 CFU/mL
Standard Deviation 0.91
|
SECONDARY outcome
Timeframe: days (d) 1, 28, 57, 84Population: 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.
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.
Outcome measures
| Measure |
TIS/TIP
n=14 Participants
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.
|
COLI/TIP
n=28 Participants
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.
|
TIP/TIP
n=18 Participants
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.
|
|---|---|---|---|
|
Number of Participants With Any Contaminated Delivery Device
P. a biotype 2 - dry,d1,neb, moderate,(n=0,0,1)
|
NA Participants
no contamination
|
NA Participants
no contamination
|
1 Participants
|
|
Number of Participants With Any Contaminated Delivery Device
A. baumannii,d1,neb,heavy,n=0,7,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
A. junii,d1,neb,moderate,n=0,7,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
A.lwoffi,d1,neb,light,n=0,7,0
|
NA Participants
no contamination
|
2 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
H. parainfluenza,d1,neb,light,n=0,7,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
O. anthropic,d1,neb,heavy,n=0,7,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
P. fluorescens,d1,neb,light,n=0,7,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
P. putida,d1,neb,light,n=0,7,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
P. stutzeri,d1,neb,moderate,n=0,7,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
S.liquefaciens,d1,neb,light,n=0,7,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
S. multivorum,d1,neb,light,n=0,7,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
S. maltophilia,d1,neb,light,n=0,7,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
Acinetobacter species,d28,neb,light,n=0,6,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
C. indologenes,d28,neb,moderate,n=0,6,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
D. acidovorans,d 28,neb,light,n=0,6,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
P. fluorescens,d28,neb,light,n=0,6,0
|
NA Participants
no contamination
|
2 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
S. paucimobilis,d28,neb,heavy,n=0,6,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
S. aureus,d28,neb,light,n=0,6,0
|
NA Participants
no contamination
|
1 Participants
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
P. a biotype 2 - dry,d57,neb,light,n=1,0,0
|
1 Participants
|
NA Participants
no contamination
|
NA Participants
no contamination
|
|
Number of Participants With Any Contaminated Delivery Device
S. aureus,d84,T-326,light,n=1,0,0
|
1 Participants
|
NA Participants
no contamination
|
NA Participants
no contamination
|
SECONDARY outcome
Timeframe: days 1, 28, 57, 84, 112Population: 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.
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.
Outcome measures
| Measure |
TIS/TIP
n=14 Participants
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.
|
COLI/TIP
n=28 Participants
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.
|
TIP/TIP
n=18 Participants
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.
|
|---|---|---|---|
|
Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values
MIC50: Day 57, n=11,19,15; m=23,34,24
|
4 ug/mL
|
4 ug/mL
|
2 ug/mL
|
|
Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values
MIC50: Day 1, n=14,27,18; m=27,51,29
|
2 ug/mL
|
2 ug/mL
|
2 ug/mL
|
|
Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values
MIC50: Day 28, n=13,23,13; m=25,46,21
|
2 ug/mL
|
2 ug/mL
|
2 ug/mL
|
|
Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values
MIC50: Day 84, n=12,17,11; m=25,29,18
|
4 ug/mL
|
4 ug/mL
|
2 ug/mL
|
|
Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values
MIC50: Day 112, n=12,19,12; m=24,33,19
|
2 ug/mL
|
2 ug/mL
|
1 ug/mL
|
|
Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values
MIC90: Day 1, n=14,27,18; m=27,51,29
|
256 ug/mL
|
16 ug/mL
|
64 ug/mL
|
|
Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values
MIC90: Day 28, n=13,23,13; m=25,46,21
|
256 ug/mL
|
16 ug/mL
|
64 ug/mL
|
|
Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values
MIC90: Day 57, n=11,19,15; m=23,34,24
|
64 ug/mL
|
16 ug/mL
|
64 ug/mL
|
|
Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values
MIC90: Day 84, n=12,17,11; m=25,29,18
|
512 ug/mL
|
32 ug/mL
|
64 ug/mL
|
|
Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values
MIC90: Day 112, n=12,19,12; m=24,33,19
|
32 ug/mL
|
32 ug/mL
|
32 ug/mL
|
SECONDARY outcome
Timeframe: days 1, 28, 57, 84Population: 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.
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.
Outcome measures
| Measure |
TIS/TIP
n=14 Participants
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.
|
COLI/TIP
n=28 Participants
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.
|
TIP/TIP
n=18 Participants
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.
|
|---|---|---|---|
|
Number of Participants With Post-inhalation Bronchospasm
Day 1, n=8,17,14
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Post-inhalation Bronchospasm
Day 28, n=6,19,14
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Post-inhalation Bronchospasm
Day 57, n=10,22,13
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Post-inhalation Bronchospasm
Day 84, n=8,14,10
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
TIS/TIP - Cycle 1
Serious events: 3 serious events
Other events: 5 other events
Deaths: 0 deaths
TIS/TIP - Cycle 2
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
COLI/TIP - Cycle 1
Serious events: 9 serious events
Other events: 13 other events
Deaths: 0 deaths
COLI/TIP - Cycle 2
Serious events: 3 serious events
Other events: 12 other events
Deaths: 0 deaths
TIP/TIP - Cycle 1
Serious events: 3 serious events
Other events: 10 other events
Deaths: 0 deaths
TIP/TIP - Cycle 2
Serious events: 2 serious events
Other events: 10 other events
Deaths: 0 deaths
Overall TIP Cycle 2
Serious events: 8 serious events
Other events: 28 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TIS/TIP - Cycle 1
n=14 participants at risk
During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment.
|
TIS/TIP - Cycle 2
n=12 participants at risk
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.
|
COLI/TIP - Cycle 1
n=28 participants at risk
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.
|
COLI/TIP - Cycle 2
n=25 participants at risk
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.
|
TIP/TIP - Cycle 1
n=18 participants at risk
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.
|
TIP/TIP - Cycle 2
n=15 participants at risk
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 TIP Cycle 2
n=52 participants at risk
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.
|
|---|---|---|---|---|---|---|---|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Gastrointestinal disorders
Faecaloma
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
General disorders
Pyrexia
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Hepatobiliary disorders
Bile duct stenosis
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Hepatobiliary disorders
Biliary tract disorder
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Infections and infestations
Fungal infection
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
21.4%
3/14
|
25.0%
3/12
|
21.4%
6/28
|
12.0%
3/25
|
11.1%
2/18
|
0.00%
0/15
|
11.5%
6/52
|
|
Infections and infestations
Influenza
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Infections and infestations
Sinusitis
|
0.00%
0/14
|
8.3%
1/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Investigations
Acoustic stimulation tests abnormal
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Investigations
Forced expiratory volume decreased
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Investigations
Pulmonary function test decreased
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
Other adverse events
| Measure |
TIS/TIP - Cycle 1
n=14 participants at risk
During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment.
|
TIS/TIP - Cycle 2
n=12 participants at risk
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.
|
COLI/TIP - Cycle 1
n=28 participants at risk
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.
|
COLI/TIP - Cycle 2
n=25 participants at risk
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.
|
TIP/TIP - Cycle 1
n=18 participants at risk
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.
|
TIP/TIP - Cycle 2
n=15 participants at risk
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 TIP Cycle 2
n=52 participants at risk
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.
|
|---|---|---|---|---|---|---|---|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/14
|
8.3%
1/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
3.8%
2/52
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Gastrointestinal disorders
Distal intestinal obstruction syndrome
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Gastrointestinal disorders
Odynophagia
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
General disorders
Fatigue
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
|
General disorders
Influenza like illness
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
General disorders
Malaise
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/14
|
8.3%
1/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
3.8%
2/52
|
|
General disorders
Pyrexia
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Hepatobiliary disorders
Bile duct stone
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Infections and infestations
Cystitis
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
14.3%
2/14
|
8.3%
1/12
|
17.9%
5/28
|
24.0%
6/25
|
0.00%
0/18
|
6.7%
1/15
|
15.4%
8/52
|
|
Infections and infestations
Influenza
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/14
|
0.00%
0/12
|
10.7%
3/28
|
0.00%
0/25
|
11.1%
2/18
|
20.0%
3/15
|
5.8%
3/52
|
|
Infections and infestations
Oral candidiasis
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Infections and infestations
Oral herpes
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Infections and infestations
Sinusitis
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Infections and infestations
Tongue fungal infection
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Infections and infestations
Tracheobronchitis
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Infections and infestations
Vulvovaginal candidiasis
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
5.6%
1/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Investigations
Forced expiratory volume decreased
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Investigations
Glucose urine present
|
0.00%
0/14
|
8.3%
1/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Investigations
Liver function test abnormal
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/14
|
8.3%
1/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Nervous system disorders
Aphonia
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
5.6%
1/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Nervous system disorders
Burning sensation
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Nervous system disorders
Dizziness
|
7.1%
1/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Nervous system disorders
Headache
|
7.1%
1/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
16.7%
3/18
|
20.0%
3/15
|
5.8%
3/52
|
|
Nervous system disorders
Lethargy
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.3%
2/14
|
8.3%
1/12
|
7.1%
2/28
|
0.00%
0/25
|
11.1%
2/18
|
13.3%
2/15
|
5.8%
3/52
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
1.9%
1/52
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/14
|
8.3%
1/12
|
0.00%
0/28
|
8.0%
2/25
|
11.1%
2/18
|
0.00%
0/15
|
5.8%
3/52
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Respiratory, thoracic and mediastinal disorders
Prolonged expiration
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
5.6%
1/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
7.1%
1/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
7.1%
1/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
16.7%
3/18
|
13.3%
2/15
|
3.8%
2/52
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
7.1%
1/14
|
8.3%
1/12
|
0.00%
0/28
|
4.0%
1/25
|
0.00%
0/18
|
0.00%
0/15
|
3.8%
2/52
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/14
|
0.00%
0/12
|
3.6%
1/28
|
0.00%
0/25
|
0.00%
0/18
|
0.00%
0/15
|
0.00%
0/52
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.00%
0/14
|
0.00%
0/12
|
0.00%
0/28
|
0.00%
0/25
|
0.00%
0/18
|
6.7%
1/15
|
1.9%
1/52
|
Additional Information
Study Director
Novartis
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 or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER