Trial Outcomes & Findings for A Study of Tobramycin Inhalation Powder From a Modified Manufacturing Process Versus Placebo (NCT NCT00918957)
NCT ID: NCT00918957
Last Updated: 2012-10-03
Results Overview
Relative change in percentage predicted FEV1 in the Intent-to-treat (ITT), modified ITT (mITT) and Observed cases in the ITT populations were calculated from an adjusted analysis ANOVA model. ITT Patients with missing or unacceptable Day 29 spirometry measurements had their primary endpoint data imputed with zero. BSL = Baseline, defined as the latest measurement prior to the first dosing of study medication \- Relative change = 100 \* (value - baseline) / baseline There were 3 patients who had no screening nor baseline values (due to inadequate spirometry) and so were excluded from all change from baseline analyses.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
62 participants
Primary outcome timeframe
Baseline, Day 29
Results posted on
2012-10-03
Participant Flow
Although 32 patients were randomized to the TIP group and 30 to the Placebo group, the ITT population included 2 patients allocated to the TIP group but received placebo due to Investigator error during the drug dispensation process. The safety population contained 30 patients who were treated with TIP and 32 patients who were treated with placebo.
Participant milestones
| Measure |
TIP (Tobramycin Inhalation Powder)
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Overall Study
STARTED
|
32
|
30
|
|
Overall Study
COMPLETED
|
29
|
30
|
|
Overall Study
NOT COMPLETED
|
3
|
0
|
Reasons for withdrawal
| Measure |
TIP (Tobramycin Inhalation Powder)
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
A Study of Tobramycin Inhalation Powder From a Modified Manufacturing Process Versus Placebo
Baseline characteristics by cohort
| Measure |
TIP (Tobramycin Inhalation Powder)
n=30 Participants
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=32 Participants
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
12.9 years
STANDARD_DEVIATION 4.25 • n=5 Participants
|
12.9 years
STANDARD_DEVIATION 4.68 • n=7 Participants
|
12.9 years
STANDARD_DEVIATION 4.44 • n=5 Participants
|
|
Age, Customized
<13 years
|
15 participants
n=5 Participants
|
15 participants
n=7 Participants
|
30 participants
n=5 Participants
|
|
Age, Customized
>= 13 years
|
15 participants
n=5 Participants
|
17 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Baseline Forced Expiratory Volume in one second (FEV1) percentage predicted
|
59.1 Percentage
STANDARD_DEVIATION 18.18 • n=5 Participants
|
59.3 Percentage
STANDARD_DEVIATION 16.61 • n=7 Participants
|
59.2 Percentage
STANDARD_DEVIATION 17.25 • n=5 Participants
|
|
Baseline P. aeruginosa sputum density
|
7.4 Log10 CFU (colony forming unit)
STANDARD_DEVIATION 1.53 • n=5 Participants
|
7.4 Log10 CFU (colony forming unit)
STANDARD_DEVIATION 1.55 • n=7 Participants
|
7.4 Log10 CFU (colony forming unit)
STANDARD_DEVIATION 1.52 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 29Population: ITT: All randomized patients (pts) received at least one dose of study drug. Missing or unacceptable Day 29 spirometry test -change from baseline FEV1 % predicted imputed using last available post-baseline value or 0. mITT: Pts with unacceptable FEV1 measurements excluded. Observed cases: Pts with missing or unacceptable FEV1 measurements excluded.
Relative change in percentage predicted FEV1 in the Intent-to-treat (ITT), modified ITT (mITT) and Observed cases in the ITT populations were calculated from an adjusted analysis ANOVA model. ITT Patients with missing or unacceptable Day 29 spirometry measurements had their primary endpoint data imputed with zero. BSL = Baseline, defined as the latest measurement prior to the first dosing of study medication \- Relative change = 100 \* (value - baseline) / baseline There were 3 patients who had no screening nor baseline values (due to inadequate spirometry) and so were excluded from all change from baseline analyses.
Outcome measures
| Measure |
TIP (Tobramycin Inhalation Powder)
n=31 Participants
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=28 Participants
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Relative Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent Predicted to End of Dosing (Day 29)
Participants analyzed: ITT Population (31, 28)
|
8.2 change in percentage
Standard Error 2.93 • Interval 2.3 to 14.1
|
2.3 change in percentage
Standard Error 3.13 • Interval -4.0 to 8.6
|
|
Relative Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent Predicted to End of Dosing (Day 29)
Parts. analyzed: Modified ITT Pop (27, 27)
|
9.7 change in percentage
Standard Error 3.30 • Interval 3.1 to 16.3
|
2.5 change in percentage
Standard Error 3.30 • Interval -4.1 to 9.2
|
|
Relative Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent Predicted to End of Dosing (Day 29)
Parts analyzed: Observed Cases in ITT Pop (25, 27)
|
10.3 change in percentage
Standard Error 3.42 • Interval 3.4 to 17.2
|
2.4 change in percentage
Standard Error 3.35 • Interval -4.3 to 9.2
|
PRIMARY outcome
Timeframe: Baseline, Day 29Population: ITT: All randomized patients (pts) received at least one dose of study drug. Missing or unacceptable Day 29 spirometry test -change from baseline FEV1 % predicted imputed using last available post-baseline value or 0. mITT: Pts with unacceptable FEV1 measurements excluded. Observed cases: Pts with missing or unacceptable FEV1 measurements excluded.
Absolute change in percentage predicted FEV1 in the Intent-to-treat (ITT), modified ITT (mITT) and Observed cases in the ITT populations were calculated from an adjusted analysis ANOVA model. In the adjusted analysis model: response = treatment + screening FEV1 % predicted (\<50 and \>=50) + age (\<13 and \>=13) + error. Significance for the FEV1 % predicted is reached for p-values \<= 0.05. There were 3 patients who had no screening nor baseline values (due to inadequate spirometry) and so were excluded from all change from baseline analyses.
Outcome measures
| Measure |
TIP (Tobramycin Inhalation Powder)
n=31 Participants
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=28 Participants
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Pre-planned Sensitivity Analysis: Absolute Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent (%) Predicted to End of Dosing (Day 29)
Participants analyzed: ITT Population (31, 28)
|
4.9 change in percentage
Standard Error 1.59
|
0.5 change in percentage
Standard Error 1.70
|
|
Pre-planned Sensitivity Analysis: Absolute Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent (%) Predicted to End of Dosing (Day 29)
Parts. analyzed: Modified ITT Pop (25, 27)
|
5.7 change in percentage
Standard Error 1.78
|
0.6 change in percentage
Standard Error 1.79
|
|
Pre-planned Sensitivity Analysis: Absolute Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent (%) Predicted to End of Dosing (Day 29)
Parts. analyzed: Observed Cases, ITT Pop (27, 27)
|
6.1 change in percentage
Standard Error 1.84
|
0.5 change in percentage
Standard Error 1.80
|
PRIMARY outcome
Timeframe: Baseline, Day 29Population: ITT: All randomized patients (pts) received at least one dose of study drug. Missing or unacceptable Day 29 spirometry test -change from baseline FEV1 % predicted imputed using last available post-baseline value or 0. mITT: Pts with unacceptable FEV1 measurements excluded. Observed cases: Pts with missing or unacceptable FEV1 measurements excluded.
Relative change in percentage predicted FEV1 without outlier (outliers with respect to FEV1 values and PK data), in the Intent-to-treat (ITT), modified ITT (mITT) and Observed cases in the ITT populations were calculated from an adjusted analysis ANOVA model.
Outcome measures
| Measure |
TIP (Tobramycin Inhalation Powder)
n=31 Participants
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=28 Participants
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Post-hoc: Relative Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent Predicted to End of Dosing (Day 29) Without Outlier
Participants analyzed: ITT Population (30, 28)
|
10.4 change in percentage
Standard Error 2.81
|
3.1 change in percentage
Standard Error 2.92
|
|
Post-hoc: Relative Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent Predicted to End of Dosing (Day 29) Without Outlier
Parts. analyzed: Modified ITT Pop (24, 27)
|
12.4 change in percentage
Standard Error 3.14
|
3.5 change in percentage
Standard Error 3.05
|
|
Post-hoc: Relative Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent Predicted to End of Dosing (Day 29) Without Outlier
Parts. analyzed: Observed Cases, ITT Pop (26, 27)
|
13.1 change in percentage
Standard Error 3.25
|
3.4 change in percentage
Standard Error 3.08
|
SECONDARY outcome
Timeframe: Baseline, Day 29, Day 57Population: Intent-to-treat (ITT) population: All randomized patients who received at least one dose of study drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.
Results of statistical analysis were calculated from an ANOVA model. Baseline is defined as the latest measurement prior to the first dosing of study medication. Response (percentage change) = treatment + Screening FEV1 percentage predicted (\<50 and \>=50) + age (\<13 and \>=13) + error
Outcome measures
| Measure |
TIP (Tobramycin Inhalation Powder)
n=31 Participants
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=28 Participants
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Change From Baseline of Forced Vital Capacity (FVC) Percent Predicted to End of Dosing (Day 29) and to the End of Off-cycle Period (Day 57)
Number of participants analyzed (31, 28): Baseline
|
73.3 percentage change
Standard Error 19.19
|
76.9 percentage change
Standard Error 15.16
|
|
Change From Baseline of Forced Vital Capacity (FVC) Percent Predicted to End of Dosing (Day 29) and to the End of Off-cycle Period (Day 57)
Number of participants analyzed (25, 27): Day 29
|
7.2 percentage change
Standard Error 9.94 • Interval 1.1 to 10.4
|
1.6 percentage change
Standard Error 14.74 • Interval -3.4 to 6.6
|
|
Change From Baseline of Forced Vital Capacity (FVC) Percent Predicted to End of Dosing (Day 29) and to the End of Off-cycle Period (Day 57)
Number of participants analyzed (28, 23): Day 57
|
5.2 percentage change
Standard Error 16.99
|
3.1 percentage change
Standard Error 15.05
|
SECONDARY outcome
Timeframe: Baseline, Day 29, Day 57Population: Intent-to-treat (ITT) population: All randomized patients who received at least one dose of study drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.
FEF25-75: Forced expiratory flow rate over 25% to 75% of vital capacity For FEF25-75 percentage predicted the relative change is analyzed. If screening FEV1 percentage predicted is missing, it will be imputed by the baseline value.
Outcome measures
| Measure |
TIP (Tobramycin Inhalation Powder)
n=31 Participants
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=28 Participants
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Change From Baseline of Forced Expiratory Flow Rate Over 25 and 75 Percent. (FEF25-75%) Predicted to End of Dosing (Day 29) and End of Off-cycle Period (Day 57)
Number of participants analyzed (31, 28): Baseline
|
36.2 percentage change
Standard Error 20.15
|
35.9 percentage change
Standard Error 20.67
|
|
Change From Baseline of Forced Expiratory Flow Rate Over 25 and 75 Percent. (FEF25-75%) Predicted to End of Dosing (Day 29) and End of Off-cycle Period (Day 57)
Number of participants analyzed (25, 27): Day 29
|
21.00 percentage change
Standard Error 36.55 • Interval 4.7 to 28.3
|
7.8 percentage change
Standard Error 29.65 • Interval -5.9 to 19.3
|
|
Change From Baseline of Forced Expiratory Flow Rate Over 25 and 75 Percent. (FEF25-75%) Predicted to End of Dosing (Day 29) and End of Off-cycle Period (Day 57)
Number of participants analyzed (28, 23): Day 57
|
23.9 percentage change
Standard Error 35.57
|
17.7 percentage change
Standard Error 37.40
|
SECONDARY outcome
Timeframe: Baseline, Day 29, Day 57Population: Intent-to-treat (ITT) population: All randomized patients who received at least one dose of study drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.
P. aeruginosa sputum density refers to overall density, defined as the sum of biotypes (mucoid, dry and small colony variant). If sub-isolates exist for CFU biotype mucoid or dry, then the sum of sub-isolates is analyzed.
Outcome measures
| Measure |
TIP (Tobramycin Inhalation Powder)
n=31 Participants
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=28 Participants
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Absolute Change From Baseline to End of Dosing (Day 29) and End of Off-cycle Period (Day 57) in Sputum Pseudomonas Aeruginosa Density (log10 Colony Forming Units(CFU) Per Gram Sputum)
Number of participants analyzed (29, 28): Baseline
|
7.5 Log10 CFU (colony forming unit)
Standard Error 1.49
|
7.3 Log10 CFU (colony forming unit)
Standard Error 1.58
|
|
Absolute Change From Baseline to End of Dosing (Day 29) and End of Off-cycle Period (Day 57) in Sputum Pseudomonas Aeruginosa Density (log10 Colony Forming Units(CFU) Per Gram Sputum)
Number of participants analyzed (14, 27): Day 29
|
-2.4 Log10 CFU (colony forming unit)
Standard Error 1.54 • Interval -1.7 to -0.7
|
0.0 Log10 CFU (colony forming unit)
Standard Error 0.89 • Interval -0.6 to 0.5
|
|
Absolute Change From Baseline to End of Dosing (Day 29) and End of Off-cycle Period (Day 57) in Sputum Pseudomonas Aeruginosa Density (log10 Colony Forming Units(CFU) Per Gram Sputum)
Number of participants analyzed (19, 24): Day 57
|
-0.9 Log10 CFU (colony forming unit)
Standard Error 2.09
|
-0.2 Log10 CFU (colony forming unit)
Standard Error 1.20
|
SECONDARY outcome
Timeframe: Baseline, Day 29, Day 57Population: Intent-to-treat (ITT) population: All randomized patients who received at least one dose of study drug. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.
Maximum MIC values from all biotypes were used. Absolute values and changes in tobramycin MIC for P. aeruginosa from baseline are summarized by biotype. Overall, a high variability of MIC was observed within each treatment group. For the maximum of all biotypes, large differences in mean changes from baseline at Day 29 were observed between the TIP group and the placebo group.
Outcome measures
| Measure |
TIP (Tobramycin Inhalation Powder)
n=31 Participants
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=28 Participants
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Change From Baseline to End of Dosing (Day 29) and End of Off-cycle Period (Day 57) of Pseudomonas Aeruginosa Minimum Inhibitory Concentration (MIC)
Number of participants analyzed (28, 29):Baseline
|
0.8 μg/mL
Standard Deviation 1.49
|
2.7 μg/mL
Standard Deviation 11.81
|
|
Change From Baseline to End of Dosing (Day 29) and End of Off-cycle Period (Day 57) of Pseudomonas Aeruginosa Minimum Inhibitory Concentration (MIC)
Number of participants analyzed (13, 27): Day 29
|
0.1 μg/mL
Standard Deviation 0.73
|
10.0 μg/mL
Standard Deviation 38.32
|
|
Change From Baseline to End of Dosing (Day 29) and End of Off-cycle Period (Day 57) of Pseudomonas Aeruginosa Minimum Inhibitory Concentration (MIC)
Number of participants analyzed (19, 24): Day 57
|
0.5 μg/mL
Standard Deviation 1.49
|
1.4 μg/mL
Standard Deviation 6.58
|
SECONDARY outcome
Timeframe: Baseline, Study completionPopulation: Safety population: All randomized patients who received at least one dose of study drug. In all safety analyses patients were analyzed according to the treatment received.
Hematology values shift from baseline to above upper/below lower limit of normal at any time post-baseline. Biochemistry values shift from baseline to above upper/below lower limit of normal at any time post-baseline.
Outcome measures
| Measure |
TIP (Tobramycin Inhalation Powder)
n=30 Participants
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=32 Participants
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hematology (Hem): Absolute Basophilis- low - low
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Absolute Eosinophils - low
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Absolute Monocytes - low
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Monocytes - high
|
27.8 percentage of participants at risk
|
24.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Alkaline phosphatase, serum - low
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Creatinine - high
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Potassioum - high
|
7.1 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Absolute Basophilis - high
|
8.3 percentage of participants at risk
|
10.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Absolute Eosinophils - high
|
14.3 percentage of participants at risk
|
7.4 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Absolute Lymphocytes - low
|
4.2 percentage of participants at risk
|
3.7 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Absolute Lymphocytes - high
|
11.1 percentage of participants at risk
|
9.5 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Absolute Monocytes - high
|
9.5 percentage of participants at risk
|
19.2 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Absolute Neutrophils (Seg. + Bands) - low
|
9.5 percentage of participants at risk
|
10.3 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Absolute Neutrophils (Seg. + Bands) - high
|
11.1 percentage of participants at risk
|
25.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Basophils - low
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Basophils - high
|
60.0 percentage of participants at risk
|
40.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Eosinophils - low
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Eosinophils - high
|
28.6 percentage of participants at risk
|
14.8 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Lymphocytes -low
|
4.3 percentage of participants at risk
|
14.3 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Lymphocytes - high
|
14.3 percentage of participants at risk
|
7.7 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Monocytes - low
|
8.3 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Neutrophils (Seg. + Bands) - low
|
13.6 percentage of participants at risk
|
11.1 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Neutrophils (Seg. + Bands) - high
|
4.3 percentage of participants at risk
|
6.9 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Platelet count (direct) - low
|
4.5 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Platelet count (direct) - high
|
7.7 percentage of participants at risk
|
13.3 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: RBC- low
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: RBC- high
|
16.7 percentage of participants at risk
|
9.1 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: WBC (total)- low
|
9.5 percentage of participants at risk
|
3.7 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: WBC (total) - high
|
5.3 percentage of participants at risk
|
26.1 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Hematocrit - low
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Hematocrit - high
|
14.3 percentage of participants at risk
|
14.8 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Hemoglobin - low
|
3.8 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Hem: Hemoglobin - high
|
4.2 percentage of participants at risk
|
3.3 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Biochemistry (Bio): Album - low
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Album - high
|
20.0 percentage of participants at risk
|
10.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Alkaline phosphatase, serum - high
|
14.3 percentage of participants at risk
|
4.3 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Bilirubin (direct/conjugated) -low
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Bilirubin (direct/conjugated) -high
|
7.7 percentage of participants at risk
|
7.1 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Bilirubin (total) - low
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Bilirubin (total) - high
|
3.4 percentage of participants at risk
|
3.3 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Blood Urea Nitrogen (BUN) - low
|
0.0 percentage of participants at risk
|
13.8 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Blood Urea Nitrogen (BUN) - high
|
3.4 percentage of participants at risk
|
3.2 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Calcium -low
|
0.0 percentage of participants at risk
|
12.9 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Calcium -high
|
6.9 percentage of participants at risk
|
6.7 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Chloride - low
|
0.0 percentage of participants at risk
|
6.5 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Chloride - high
|
10.3 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Creatinine - low
|
0.0 percentage of participants at risk
|
50.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Gamma Glutamyltransferase - low
|
0.0 percentage of participants at risk
|
3.2 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Gamma Glutamyltransferase - high
|
4.2 percentage of participants at risk
|
3.8 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Glucose - low
|
12.0 percentage of participants at risk
|
20.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Glucose - high
|
11.1 percentage of participants at risk
|
6.7 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Phosphate (Inorganic Phosphorus) - low
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Phosphate (Inorganic Phosphorus) - high
|
19.2 percentage of participants at risk
|
13.8 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Potassioum - low
|
0.0 percentage of participants at risk
|
3.2 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: SGOT (AST) - low
|
0.0 percentage of participants at risk
|
3.2 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: SGOT (AST) - high
|
12.5 percentage of participants at risk
|
12.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: SGPT (ALT) - low
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: SGPT (ALT) - high
|
9.5 percentage of participants at risk
|
13.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Serum bicarbonate - low
|
47.6 percentage of participants at risk
|
23.8 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Serum bicarbonate - high
|
0.0 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Sodium - low
|
0.0 percentage of participants at risk
|
6.5 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Sodium - high
|
10.3 percentage of participants at risk
|
0.0 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Total Protein (Serum) - low
|
0.0 percentage of participants at risk
|
3.2 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Total Protein (Serum) - high
|
4.2 percentage of participants at risk
|
29.2 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Uric Acid - low
|
3.6 percentage of participants at risk
|
3.2 percentage of participants at risk
|
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Bio: Uric Acid - high
|
10.7 percentage of participants at risk
|
19.2 percentage of participants at risk
|
SECONDARY outcome
Timeframe: First administration of study drug, study completionPopulation: Safety population: All randomized patients who received at least one dose of study drug.In all safety analyses patients were analyzed according to the treatment received
Adverse Events (AEs) (on and off treatment) regardless of study relationship by primary system organ and treatment group. Primary system organ classes are sorted in descending order of frequency in the TIP treatment group. A patient with more than one AE within a primary system organ class is counted only once for that class.
Outcome measures
| Measure |
TIP (Tobramycin Inhalation Powder)
n=30 Participants
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=32 Participants
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Percentage of Participants With Adverse Events (AEs)
Respiratory, thoracic & mediastinal disorders
|
13.3 Percentage of participants
|
3.1 Percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
Ear and labyrinth disorders
|
10.0 Percentage of participants
|
6.3 Percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
Infections and infestations
|
10.0 Percentage of participants
|
25.0 Percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
Gastrointestinal disorders
|
3.3 Percentage of participants
|
3.1 Percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
Metabolism and nutrition disorders
|
3.3 Percentage of participants
|
3.1 Percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
Nervous system disorders
|
3.3 Percentage of participants
|
0.0 Percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
Renal and urinary disorders
|
3.3 Percentage of participants
|
0.0 Percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
Skin and subcutaneous tissue disorder
|
3.3 Percentage of participants
|
0.0 Percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
Blood and lymphatic system disorder
|
0.0 Percentage of participants
|
3.1 Percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
Injury, poisoning and procedural complications
|
0.0 Percentage of participants
|
3.1 Percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
Investigation
|
0.0 Percentage of participants
|
3.1 Percentage of participants
|
SECONDARY outcome
Timeframe: Time of consent, 4 weeks after study completionPopulation: Safety population: All randomized patients who received at least one dose of study drug. In all safety analyses patients were analyzed according to the treatment received.
Serious Adverse Events (on and off treatment) by preferred term and treatment group. Preferred terms are sorted in descending order of frequency in the TIP treatment group. A patient with multiple occurrences of the same preferred term is counted only once in the preferred term.
Outcome measures
| Measure |
TIP (Tobramycin Inhalation Powder)
n=30 Participants
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=32 Participants
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Percentage of Participants With Serious Adverse Events (SAEs)
Lower limb fracture
|
0.0 percentage of participants
|
3.1 percentage of participants
|
|
Percentage of Participants With Serious Adverse Events (SAEs)
Pneumonia
|
0.0 percentage of participants
|
3.1 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1, Day 29Population: Safety population: All randomized patients who received at least one dose of study drug.In all safety analyses patients were analyzed according to the treatment received.
Relative change = 100 \* (30-m-post-dose - pre-dose)/pre-dose assessed by the number and percentage of patients with a decrease of ≥20 % in FEV1 % predicted from pre dose to 30 minutes post dose. Day 1 is the scheduled visit of first study drug administration.
Outcome measures
| Measure |
TIP (Tobramycin Inhalation Powder)
n=30 Participants
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=32 Participants
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Acute Change in Airways Reactivity (FEV1 Percent Predicted) From Pre-dose to 30 Minutes After Completion of First Dose of Study Drug
Day 1
|
4.8 Percentage of participants
|
0.0 Percentage of participants
|
|
Acute Change in Airways Reactivity (FEV1 Percent Predicted) From Pre-dose to 30 Minutes After Completion of First Dose of Study Drug
Day 29
|
0.0 Percentage of participants
|
8.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Pre-dose, 0 - 1 hour post-dose, 1 -2 hours post-dose, 2 - 6 hours post-dosePopulation: Safety population: All randomized patients who received at least one dose of study drug. In all safety analyses patients were analyzed according to the treatment received. This measures the concentration of active substance in the body at different time-point to evaluate there is abnormal accumulation of active substance. Not for Placebo Patients.
Descriptive statistics of serum and sputum concentrations per scheduled sampling time. Detectable concentration values at pre-dose on Day 1 were excluded from the analysis.
Outcome measures
| Measure |
TIP (Tobramycin Inhalation Powder)
n=30 Participants
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Tobramycin Serum Concentration
Day 29: Pre-dose (27, 0)
|
0.41 μg/mL
Standard Deviation 0.51
|
—
|
|
Tobramycin Serum Concentration
Day 29: 0 -1 hr post dose (28, 0)
|
1.48 μg/mL
Standard Deviation 0.69
|
—
|
|
Tobramycin Serum Concentration
Day1: 0 -1 hour (hr) post dose (28, 0)
|
0.83 μg/mL
Standard Deviation 0.40
|
—
|
|
Tobramycin Serum Concentration
Day 1: 1 -2 hours (hr) post dose (28, 0)
|
0.93 μg/mL
Standard Deviation 0.44
|
—
|
|
Tobramycin Serum Concentration
Day 1: 2 -6 hours (hr) post dose (29, 0)
|
0.73 μg/mL
Standard Deviation 0.39
|
—
|
|
Tobramycin Serum Concentration
Day 29: 1 -2 hrs post dose (29, 0)
|
1.37 μg/mL
Standard Deviation 0.64
|
—
|
|
Tobramycin Serum Concentration
Day 29: 2 -6 hrs post dose (27, 0)
|
1.14 μg/mL
Standard Deviation 0.65
|
—
|
Adverse Events
TIP (Tobramycin Inhalation Powder)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TIP (Tobramycin Inhalation Powder)
n=30 participants at risk
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=32 participants at risk
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.00%
0/30
|
3.1%
1/32
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/30
|
3.1%
1/32
|
Other adverse events
| Measure |
TIP (Tobramycin Inhalation Powder)
n=30 participants at risk
Tobramycin 28 mg powder. The TIP dose of 112 mg twice a day (bis in diem = b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment.
|
Placebo
n=32 participants at risk
Placebo 20 mg powder capsules. The dose regimen for the reference product was inhaling the contents of four capsules twice a day (bis in diem = b.i.d.) in the morning and in the evening for 28 days (on treatment), followed by 28 days of no study treatment (off treatment).
|
|---|---|---|
|
Ear and labyrinth disorders
Hypoacusis
|
10.0%
3/30
|
6.2%
2/32
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/30
|
6.2%
2/32
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/30
|
9.4%
3/32
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
3/30
|
0.00%
0/32
|
Additional Information
Clinical Disclosure Office
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER