Trial Outcomes & Findings for A Study Comparing the Efficacy and Tolerability of Tobrineb®/Actitob®/Bramitob® Versus TOBI® (NCT NCT00885365)
NCT ID: NCT00885365
Last Updated: 2018-06-27
Results Overview
Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEV1 values for children were different than the reference normal values used with adult participants. Three measurements were collected and the greatest FEV1 value was recorded.
COMPLETED
PHASE3
324 participants
Day 0 (baseline), Week 4
2018-06-27
Participant Flow
406 participants screened, 324 participants randomized
Participant milestones
| Measure |
Bramitob
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
4 Weeks ON Treatment
STARTED
|
159
|
165
|
|
4 Weeks ON Treatment
Intent-to-Treat Population
|
158
|
163
|
|
4 Weeks ON Treatment
Safety Population
|
156
|
168
|
|
4 Weeks ON Treatment
COMPLETED
|
155
|
159
|
|
4 Weeks ON Treatment
NOT COMPLETED
|
4
|
6
|
|
4 Weeks OFF Treatment
STARTED
|
155
|
159
|
|
4 Weeks OFF Treatment
COMPLETED
|
155
|
159
|
|
4 Weeks OFF Treatment
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Bramitob
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
4 Weeks ON Treatment
Adverse Event
|
2
|
4
|
|
4 Weeks ON Treatment
Protocol Violation
|
1
|
2
|
|
4 Weeks ON Treatment
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
A Study Comparing the Efficacy and Tolerability of Tobrineb®/Actitob®/Bramitob® Versus TOBI®
Baseline characteristics by cohort
| Measure |
Bramitob
n=156 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=168 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
Total
n=324 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
15.95 years
STANDARD_DEVIATION 6.74 • n=93 Participants
|
15.74 years
STANDARD_DEVIATION 7.24 • n=4 Participants
|
15.84 years
STANDARD_DEVIATION 6.99 • n=27 Participants
|
|
Age, Customized
6-12 years
|
49 participants
n=93 Participants
|
54 participants
n=4 Participants
|
103 participants
n=27 Participants
|
|
Age, Customized
13-17 years
|
50 participants
n=93 Participants
|
62 participants
n=4 Participants
|
112 participants
n=27 Participants
|
|
Age, Customized
> 17 years
|
57 participants
n=93 Participants
|
52 participants
n=4 Participants
|
109 participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
84 Participants
n=93 Participants
|
83 Participants
n=4 Participants
|
167 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
72 Participants
n=93 Participants
|
85 Participants
n=4 Participants
|
157 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White
|
156 participants
n=93 Participants
|
168 participants
n=4 Participants
|
324 participants
n=27 Participants
|
|
Height
|
153.05 centimeters
STANDARD_DEVIATION 17.31 • n=93 Participants
|
153.41 centimeters
STANDARD_DEVIATION 19.88 • n=4 Participants
|
153.24 centimeters
STANDARD_DEVIATION 18.66 • n=27 Participants
|
|
Weight
|
42.64 kilograms
STANDARD_DEVIATION 14.92 • n=93 Participants
|
43.81 kilograms
STANDARD_DEVIATION 16.39 • n=4 Participants
|
43.25 kilograms
STANDARD_DEVIATION 15.69 • n=27 Participants
|
|
Body Mass Index
|
17.55 kilograms/meters^2
STANDARD_DEVIATION 3.12 • n=93 Participants
|
17.79 kilograms/meters^2
STANDARD_DEVIATION 3.32 • n=4 Participants
|
17.68 kilograms/meters^2
STANDARD_DEVIATION 3.22 • n=27 Participants
|
|
Time from diagnosis of chronic colonization of P. aeruginosa
|
2.27 years
STANDARD_DEVIATION 4.22 • n=93 Participants
|
2.36 years
STANDARD_DEVIATION 4.23 • n=4 Participants
|
2.31 years
STANDARD_DEVIATION 4.22 • n=27 Participants
|
|
Time from first Cystic Fibrosis diagnosis
|
12.16 years
STANDARD_DEVIATION 6.13 • n=93 Participants
|
11.74 years
STANDARD_DEVIATION 6.55 • n=4 Participants
|
11.94 years
STANDARD_DEVIATION 6.34 • n=27 Participants
|
|
Tobramycin Minimal Inhibitory Concentration (MIC) value
<16 mcg/mL
|
143 participants
n=93 Participants
|
159 participants
n=4 Participants
|
302 participants
n=27 Participants
|
|
Tobramycin Minimal Inhibitory Concentration (MIC) value
>=16 mcg/mL
|
13 participants
n=93 Participants
|
8 participants
n=4 Participants
|
21 participants
n=27 Participants
|
|
Tobramycin Minimal Inhibitory Concentration (MIC) value
Missing
|
0 participants
n=93 Participants
|
1 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Forced Expiratory Volume in 1 second (FEV1)
<50 % predicted
|
37 participants
n=93 Participants
|
38 participants
n=4 Participants
|
75 participants
n=27 Participants
|
|
Forced Expiratory Volume in 1 second (FEV1)
>=50 % predicted
|
119 participants
n=93 Participants
|
130 participants
n=4 Participants
|
249 participants
n=27 Participants
|
|
Use of rhDNase
Yes
|
110 participants
n=93 Participants
|
119 participants
n=4 Participants
|
229 participants
n=27 Participants
|
|
Use of rhDNase
No
|
46 participants
n=93 Participants
|
49 participants
n=4 Participants
|
95 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Day 0 (baseline), Week 4Population: Intent-to-Treat (ITT) Population, Last Observation Carried Forward (LOCF)
Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEV1 values for children were different than the reference normal values used with adult participants. Three measurements were collected and the greatest FEV1 value was recorded.
Outcome measures
| Measure |
Bramitob
n=158 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=163 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Change From Baseline to End of the Treatment Period of Forced Expiratory Volume in 1 Second (FEV1), Expressed as Percentage of Predicted Normal
|
6.99 percentage predicted FEV1
Standard Deviation 9.52
|
7.51 percentage predicted FEV1
Standard Deviation 9.63
|
SECONDARY outcome
Timeframe: Day 0 (baseline), Week 2, Week 4, Week 8Population: Intent-to-Treat (ITT) Population, observed values. Differences in number of participants analyzed to the ITT population represent participants who missed visits, or failed to take the FEV1 test.
Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEV1 values for children were different than the reference normal values used with adult participants. Three measurements were collected and the greatest FEV1 value was recorded. Observed values are summarized (without last observation carry forward).
Outcome measures
| Measure |
Bramitob
n=158 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=163 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Volume in 1 Second (FEV1), Expressed as Percentage of Predicted Normal
Week 2 [n=158, 163]
|
6.70 percentage predicted FEV1
Standard Deviation 9.99
|
6.93 percentage predicted FEV1
Standard Deviation 9.40
|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Volume in 1 Second (FEV1), Expressed as Percentage of Predicted Normal
Week 4 [N=155, 161]
|
7.10 percentage predicted FEV1
Standard Deviation 9.57
|
7.63 percentage predicted FEV1
Standard Deviation 9.61
|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Volume in 1 Second (FEV1), Expressed as Percentage of Predicted Normal
Week 8 [n=155, 159]
|
5.47 percentage predicted FEV1
Standard Deviation 11.88
|
5.37 percentage predicted FEV1
Standard Deviation 11.11
|
SECONDARY outcome
Timeframe: Day 0 (baseline), Week 2, Week 4, Week 8Population: Intent-to-Treat (ITT) Population, observed values. Differences in number of participants analyzed to the ITT population represent participants who missed visits, or failed to take the FEV1 test.
Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Three measurements were collected and the greatest FEV1 value was recorded. Observed values are summarized (without last observation carry forward).
Outcome measures
| Measure |
Bramitob
n=158 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=163 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Absolute Forced Expiratory Volume in 1 Second (FEV1)
Week 2 [n=158, 163]
|
0.18 liters
Standard Deviation 0.27
|
0.19 liters
Standard Deviation 0.27
|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Absolute Forced Expiratory Volume in 1 Second (FEV1)
Week 4 [n=155, 161]
|
0.20 liters
Standard Deviation 0.29
|
0.22 liters
Standard Deviation 0.28
|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Absolute Forced Expiratory Volume in 1 Second (FEV1)
Week 8 [n=155,159]
|
0.16 liters
Standard Deviation 0.33
|
0.16 liters
Standard Deviation 0.32
|
SECONDARY outcome
Timeframe: Day 0 (baseline), Week 2, Week 4, Week 8Population: Intent-to-Treat (ITT) Population, observed values. Differences in number of participants analyzed to the ITT population represent participants who missed visits, or failed to take the FVC test.
FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. It is measured via spirometry. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FVC values for children were different than the reference normal values used with adult participants.
Outcome measures
| Measure |
Bramitob
n=156 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=163 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Change From Baseline at End of Weeks 2, 4, and 8 of Forced Vital Capacity (FVC) Expressed as Percentage of Predicted Normal
Week 8 [n=153,159]
|
2.70 percentage predicted FVC
Standard Deviation 12.30
|
5.04 percentage predicted FVC
Standard Deviation 12.21
|
|
Change From Baseline at End of Weeks 2, 4, and 8 of Forced Vital Capacity (FVC) Expressed as Percentage of Predicted Normal
Week 2 [n=156, 163]
|
4.36 percentage predicted FVC
Standard Deviation 10.81
|
5.36 percentage predicted FVC
Standard Deviation 10.03
|
|
Change From Baseline at End of Weeks 2, 4, and 8 of Forced Vital Capacity (FVC) Expressed as Percentage of Predicted Normal
Week 4 [n=153, 161]
|
4.83 percentage predicted FVC
Standard Deviation 10.05
|
5.58 percentage predicted FVC
Standard Deviation 10.86
|
SECONDARY outcome
Timeframe: Day 0 (baseline), Week 2, Week 4, Week 8Population: Intent-to-Treat (ITT) Population, observed values. Differences in number of participants analyzed to the ITT population represent participants who missed visits, or failed to take the FVC test.
FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. It is measured via spirometry.
Outcome measures
| Measure |
Bramitob
n=156 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=163 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Absolute Forced Vital Capacity (FVC)
Week 2 [n=156, 163]
|
0.14 liters
Standard Deviation 0.34
|
0.16 liters
Standard Deviation 0.32
|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Absolute Forced Vital Capacity (FVC)
Week 4 [n=153, 161]
|
0.16 liters
Standard Deviation 0.34
|
0.18 liters
Standard Deviation 0.36
|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Absolute Forced Vital Capacity (FVC)
Week 8 [n=153,159]
|
0.10 liters
Standard Deviation 0.38
|
0.16 liters
Standard Deviation 0.39
|
SECONDARY outcome
Timeframe: Day 0 (baseline), Week 2, Week 4, Week 8Population: Intent-to-Treat (ITT) Population, observed values. Differences in number of participants analyzed to the ITT population represent participants who missed visits, or failed to take the FEF 25-75% test.
Difference in the forced expiratory flow rate in mid-exhalation as a percent of predicted to standard values measured from baseline to weeks 2 (treated), 4 (treated), and 8 (untreated). Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEF 25-75% values for children were different than the reference normal values used with adult participants.
Outcome measures
| Measure |
Bramitob
n=156 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=162 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Flow at 25-75% of Vital Capacity (FEF 25-75%), Expressed as Percentage of Predicted Normal
Week 2 [n=156, 162]
|
10.30 percentage predicted FEF 25-75%
Standard Deviation 17.07
|
8.57 percentage predicted FEF 25-75%
Standard Deviation 19.00
|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Flow at 25-75% of Vital Capacity (FEF 25-75%), Expressed as Percentage of Predicted Normal
Week 4 [n=154, 159]
|
10.44 percentage predicted FEF 25-75%
Standard Deviation 15.17
|
9.32 percentage predicted FEF 25-75%
Standard Deviation 17.99
|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Flow at 25-75% of Vital Capacity (FEF 25-75%), Expressed as Percentage of Predicted Normal
Week 8 [n=154,158]
|
9.05 percentage predicted FEF 25-75%
Standard Deviation 19.59
|
6.41 percentage predicted FEF 25-75%
Standard Deviation 20.46
|
SECONDARY outcome
Timeframe: Day 0 (baseline), Week 2, Week 4, Week 8Population: Intent-to-Treat (ITT) Population, observed values. Differences in number of participants analyzed to the ITT population represent participants who missed visits, or failed to take the FEF 25-75% test.
Difference in the forced expiratory flow rate in mid-exhalation measured from baseline to weeks 2 (treated), 4 (treated), and 8 (untreated).
Outcome measures
| Measure |
Bramitob
n=156 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=162 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Flow at 25-75% of Vital Capacity (FEF 25-75%)
Week 2 [n=156, 162]
|
0.32 liters/second
Standard Deviation 0.50
|
0.28 liters/second
Standard Deviation 0.56
|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Flow at 25-75% of Vital Capacity (FEF 25-75%)
Week 4 [n=154, 159]
|
0.34 liters/second
Standard Deviation 0.48
|
0.29 liters/second
Standard Deviation 0.57
|
|
Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Flow at 25-75% of Vital Capacity (FEF 25-75%)
Week 8 [n=154,158]
|
0.28 liters/second
Standard Deviation 0.57
|
0.21 liters/second
Standard Deviation 0.67
|
SECONDARY outcome
Timeframe: Day -10 to -1 (baseline), Week 4, Week 8Population: Intent-to-Treat (ITT) Population; At Week 4, six Bramitob patients and seven TOBI patients were missing sputum samples. At Week 8, 11 Bramitob patients and 16 TOBI patients were missing sputum samples.
If a participant had more than one Pseudomonas aeruginosa (PA) morphotype at a given visit, and therefore more than one bacterial load value, then the bacterial load value corresponding to the highest tobramycin minimal inhibitory concentration (MIC) value regardless of the PA morphotype was used. If the tobramycin MIC value was the same for different PA morphotypes, then the bacterial load value corresponding to morphotype 1 (mucoid colony) was used. If morphotype 1 was not available, bacterial load value corresponding to morphotype 2 (dry colony) was used.
Outcome measures
| Measure |
Bramitob
n=158 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=163 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Change From Baseline to End of Weeks 4 and 8 in Pseudomonas Aeruginosa Log10 Bacterial Load in Sputum
Week 4 [n=152, 156]
|
-2.14 colony forming units/gram
Standard Deviation 2.41
|
-2.07 colony forming units/gram
Standard Deviation 2.20
|
|
Change From Baseline to End of Weeks 4 and 8 in Pseudomonas Aeruginosa Log10 Bacterial Load in Sputum
Week 8 [n=147, 147]
|
-0.72 colony forming units/gram
Standard Deviation 2.17
|
-0.87 colony forming units/gram
Standard Deviation 2.23
|
SECONDARY outcome
Timeframe: Week 4, Week 8Population: Intent-to-Treat (ITT) Population
MIC50 is the concentration of tobramycin required to inhibit 50% of Pseudomonas aeruginosa. MIC values were calculated for three different Pseudomonas aeruginosa (PA) strains: * Morphotype 1: mucoid * Morphotype 2: dry * Morphotype 3: variant Overall MIC50 values are reported. If a participant has more than one PA morphotype at a given visit, then the highest tobramycin MIC value was used, regardless of PA morphotype. If a participant has more than one available result for each morphotype then the highest tobramycin MIC value was used. If the tobramycin MIC values are equal then the MIC value for the isolate with the highest bacterial load value was used.
Outcome measures
| Measure |
Bramitob
n=158 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=163 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Minimal Inhibitory Concentration Inhibiting Growth of 50% (MIC50) of Pseudomonas Aeruginosa
Week 4 [n=126, 134]
|
1 micrograms/milliliters
|
0.5 micrograms/milliliters
|
|
Minimal Inhibitory Concentration Inhibiting Growth of 50% (MIC50) of Pseudomonas Aeruginosa
Week 8 [n=129, 128]
|
1 micrograms/milliliters
|
1 micrograms/milliliters
|
SECONDARY outcome
Timeframe: Week 4, Week 8Population: Intent-to-Treat (ITT) Population
MIC90 is the concentration of tobramycin required to inhibit 90% of Pseudomonas aeruginosa. MIC values were calculated for three different Pseudomonas aeruginosa (PA) strains: * Morphotype 1: mucoid * Morphotype 2: dry * Morphotype 3: variant Overall MIC90 values are reported. If a participant has more than one PA morphotype at a given visit, then the highest tobramycin MIC value was used, regardless of PA morphotype. If a participant has more than one available result for each morphotype then the highest tobramycin MIC value was used. If the tobramycin MIC values are equal then the MIC value for the isolate with the highest bacterial load value was used.
Outcome measures
| Measure |
Bramitob
n=158 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=163 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Minimal Inhibitory Concentration Inhibiting Growth of 90% (MIC90) of Pseudomonas Aeruginosa
Week 4 [n=126, 134]
|
32 micrograms/milliliters
|
32 micrograms/milliliters
|
|
Minimal Inhibitory Concentration Inhibiting Growth of 90% (MIC90) of Pseudomonas Aeruginosa
Week 8 [n=129, 128]
|
32 micrograms/milliliters
|
32 micrograms/milliliters
|
SECONDARY outcome
Timeframe: Day -10 to -1 (screening), Weeks 4 and 8Population: Intent-to-Treat Population.
Microbiological outcomes are derived considering all P. aeruginosa (PA) morphotypes together. Week 4 and Week 8 microbiological outcomes: * Eradication = elimination of PA * Persistence = persistence of PA detected at previous visit * Superinfection = appearance of a pathogen (other than PA) not detected at previous visit * Re-infection (week 8 only) = re-appearance of PA detected at Screening and eradicated at Week 4 Superinfection supersedes eradication. Persistence for P. aeruginosa supersedes superinfection. Re-infection for P. aeruginosa supersedes superinfection.
Outcome measures
| Measure |
Bramitob
n=158 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=163 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Microbiological Outcome Summary by Visit
Screening: Presence of P aeruginosa
|
100 percentage of participants
|
100 percentage of participants
|
|
Microbiological Outcome Summary by Visit
Week 4: Eradication
|
9.2 percentage of participants
|
7.1 percentage of participants
|
|
Microbiological Outcome Summary by Visit
Week 4: Persistence
|
82.9 percentage of participants
|
85.3 percentage of participants
|
|
Microbiological Outcome Summary by Visit
Week 4: Superinfection
|
7.9 percentage of participants
|
7.7 percentage of participants
|
|
Microbiological Outcome Summary by Visit
Week 8: Eradication
|
2.7 percentage of participants
|
3.4 percentage of participants
|
|
Microbiological Outcome Summary by Visit
Week 8: Persistence
|
78.9 percentage of participants
|
83.0 percentage of participants
|
|
Microbiological Outcome Summary by Visit
Week 8: Superinfection
|
9.5 percentage of participants
|
9.5 percentage of participants
|
|
Microbiological Outcome Summary by Visit
Week 8: Re-infection
|
8.8 percentage of participants
|
4.1 percentage of participants
|
SECONDARY outcome
Timeframe: Day 0 (baseline), Weeks 2, 4 and 8Population: Intent-to-Treat (ITT) Population, observed values. Two participants from both treatment arms were missing data at Week 4. Three participants from Bramitob and 4 participants from TOBI were missing data at Week 8.
Body weight was measured at all study visits as part of the physical examination.
Outcome measures
| Measure |
Bramitob
n=158 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=163 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Change From Baseline to End of Weeks 2, 4 and 8 in Body Weight
Week 2 [n=158, 163]
|
0.24 kilograms
Standard Deviation 0.68
|
0.22 kilograms
Standard Deviation 0.72
|
|
Change From Baseline to End of Weeks 2, 4 and 8 in Body Weight
Week 4 [n=156, 161]
|
0.39 kilograms
Standard Deviation 0.90
|
0.42 kilograms
Standard Deviation 0.97
|
|
Change From Baseline to End of Weeks 2, 4 and 8 in Body Weight
Week 8 [n=155,159]
|
0.60 kilograms
Standard Deviation 1.14
|
0.53 kilograms
Standard Deviation 1.27
|
SECONDARY outcome
Timeframe: Day 0 (baseline), Weeks 2, 4 and 8Population: Intent-to-Treat (ITT) Population, observed values. Two participants from both treatment arms were missing data at Week 4. Three participants from Bramitob and 4 participants from TOBI were missing data at Week 8.
Outcome measures
| Measure |
Bramitob
n=158 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=163 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Change From Baseline to End of Weeks 2, 4 and 8 in Body Mass Index (BMI)
Week 2 [n=158, 163]
|
0.10 kilograms/meters^2
Standard Deviation 0.28
|
0.10 kilograms/meters^2
Standard Deviation 0.29
|
|
Change From Baseline to End of Weeks 2, 4 and 8 in Body Mass Index (BMI)
Week 4 [n=156, 161]
|
0.12 kilograms/meters^2
Standard Deviation 0.37
|
0.13 kilograms/meters^2
Standard Deviation 0.38
|
|
Change From Baseline to End of Weeks 2, 4 and 8 in Body Mass Index (BMI)
Week 8 [n=155,159]
|
0.16 kilograms/meters^2
Standard Deviation 0.48
|
0.14 kilograms/meters^2
Standard Deviation 0.49
|
SECONDARY outcome
Timeframe: Day 0 to Week 8Population: Safety population: all randomised patients who took at least one dose of study medication
Treatment-Emergent Adverse Events defined as adverse events occurring after the first intake of study treatment (or the same day). The investigator assessed relation to study treatment as a binary question: Reasonable possibility of relatedness or no reasonable possibility of relatedness. The expression "reasonable possibility of relatedness" is meant to convey in general that there are facts (evidence) or arguments meant to suggest a causal relationship. A serious AE results in death, is life-threatening, requires hospitalization or prolongation of existing inpatient hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or an important medical event. The investigator rates the severity of the AE based on a three point scale: mild, moderate or severe. A severe event prevents any usual routine activity of the participant and causes severe discomfort.
Outcome measures
| Measure |
Bramitob
n=156 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=168 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Count of Participants With Treatment-Emergent Adverse Events (TEAEs)
Severe TEAE
|
1.9 percentage of participants
|
1.2 percentage of participants
|
|
Count of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE
|
31.4 percentage of participants
|
28.0 percentage of participants
|
|
Count of Participants With Treatment-Emergent Adverse Events (TEAEs)
Related TEAE
|
6.4 percentage of participants
|
6.0 percentage of participants
|
|
Count of Participants With Treatment-Emergent Adverse Events (TEAEs)
Serious TEAE
|
3.8 percentage of participants
|
1.2 percentage of participants
|
|
Count of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE leading to withdrawal
|
0.6 percentage of participants
|
3.0 percentage of participants
|
SECONDARY outcome
Timeframe: Day -10 to -1 (screening), Weeks 4 and 8Population: Safety population
The potential ototoxic effects (hearing loss) of tobramycin were investigated by performing audiometric tests. Participants with a loss of auditory acuity greater than the 20 decibels auditory threshold are reported.
Outcome measures
| Measure |
Bramitob
n=156 Participants
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=168 Participants
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Participants With a Hearing Threshold >20 Decibel in at Least One Ear
Screening
|
0 percentage of participants
|
0 percentage of participants
|
|
Participants With a Hearing Threshold >20 Decibel in at Least One Ear
Week 4
|
1.9 percentage of participants
|
1.2 percentage of participants
|
|
Participants With a Hearing Threshold >20 Decibel in at Least One Ear
Week 8
|
1.3 percentage of participants
|
1.2 percentage of participants
|
Adverse Events
Bramitob
TOBI
Serious adverse events
| Measure |
Bramitob
n=156 participants at risk
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=168 participants at risk
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Infections and infestations
Appendicitis
|
0.64%
1/156 • Number of events 1 • Day 0 to Week 8
|
0.00%
0/168 • Day 0 to Week 8
|
|
Infections and infestations
Bronchitis
|
0.64%
1/156 • Number of events 1 • Day 0 to Week 8
|
0.60%
1/168 • Number of events 1 • Day 0 to Week 8
|
|
Infections and infestations
Laryngitis
|
0.64%
1/156 • Number of events 1 • Day 0 to Week 8
|
0.00%
0/168 • Day 0 to Week 8
|
|
Infections and infestations
Lung infection
|
0.64%
1/156 • Number of events 1 • Day 0 to Week 8
|
0.00%
0/168 • Day 0 to Week 8
|
|
Congenital, familial and genetic disorders
Cystic fibrosis lung
|
0.64%
1/156 • Number of events 1 • Day 0 to Week 8
|
0.60%
1/168 • Number of events 1 • Day 0 to Week 8
|
|
Injury, poisoning and procedural complications
Head injury
|
0.64%
1/156 • Number of events 1 • Day 0 to Week 8
|
0.00%
0/168 • Day 0 to Week 8
|
|
Nervous system disorders
Syncope
|
0.64%
1/156 • Number of events 1 • Day 0 to Week 8
|
0.00%
0/168 • Day 0 to Week 8
|
Other adverse events
| Measure |
Bramitob
n=156 participants at risk
tobramycin / Bramitob administered 300mg twice a day for 4 weeks
|
TOBI
n=168 participants at risk
tobramycin / TOBI administered 300mg twice a day for 4 weeks
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.4%
10/156 • Number of events 12 • Day 0 to Week 8
|
6.0%
10/168 • Number of events 11 • Day 0 to Week 8
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Upon PI submission of publication to Sponsor, Sponsor will complete its review within 90 days after receipt. At Sponsor's request, publication may be delayed up to 120 additional days for Sponsor to file necessary patent applications. In multicenter trials, PIs will postpone single center publications until after multicenter data publication. If no multicenter publication occurs within 12 months of trial completion, PI may publish single center results, subject to review timelines listed above.
- Publication restrictions are in place
Restriction type: OTHER