Trial Outcomes & Findings for Safety of Tobramycin Inhalation Powder (TIP) vs Tobramycin Solution for Inhalation in Patients With Cystic Fibrosis (NCT NCT00388505)
NCT ID: NCT00388505
Last Updated: 2012-07-24
Results Overview
An adverse event (AE) is any untoward medical occurrence, including any unfavorable and unintended sign, symptom or disease temporally associated with the use of the study medication that does not necessarily have a causal relationship with study medication. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability, is a congenital anomaly or defect, or is a significant medical event that may jeopardize the patient or require intervention to prevent one of the outcomes listed above.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
517 participants
Primary outcome timeframe
25 weeks
Results posted on
2012-07-24
Participant Flow
Participant milestones
| Measure |
Tobramycin Inhalation Powder (TIP)
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
|---|---|---|
|
Overall Study
STARTED
|
308
|
209
|
|
Overall Study
COMPLETED
|
225
|
171
|
|
Overall Study
NOT COMPLETED
|
83
|
38
|
Reasons for withdrawal
| Measure |
Tobramycin Inhalation Powder (TIP)
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
|---|---|---|
|
Overall Study
Adverse Event or Death
|
43
|
17
|
|
Overall Study
Withdrawal by Subject
|
24
|
9
|
|
Overall Study
Lost to Follow-up
|
5
|
3
|
|
Overall Study
Inappropriate Enrollment
|
0
|
1
|
|
Overall Study
Administrative Reason
|
1
|
0
|
|
Overall Study
Protocol Violation
|
6
|
5
|
|
Overall Study
Unable to classify
|
4
|
3
|
Baseline Characteristics
Safety of Tobramycin Inhalation Powder (TIP) vs Tobramycin Solution for Inhalation in Patients With Cystic Fibrosis
Baseline characteristics by cohort
| Measure |
Tobramycin Inhalation Powder (TIP)
n=308 Participants
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
n=209 Participants
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Total
n=517 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
25.9 years
STANDARD_DEVIATION 11.36 • n=93 Participants
|
25.2 years
STANDARD_DEVIATION 10.20 • n=4 Participants
|
25.6 years
STANDARD_DEVIATION 10.90 • n=27 Participants
|
|
Age, Customized
≥6 to <13 years
|
28 participants
n=93 Participants
|
18 participants
n=4 Participants
|
46 participants
n=27 Participants
|
|
Age, Customized
≥13 to <20 years
|
66 participants
n=93 Participants
|
48 participants
n=4 Participants
|
114 participants
n=27 Participants
|
|
Age, Customized
≥20 years
|
214 participants
n=93 Participants
|
143 participants
n=4 Participants
|
357 participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
137 Participants
n=93 Participants
|
94 Participants
n=4 Participants
|
231 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
171 Participants
n=93 Participants
|
115 Participants
n=4 Participants
|
286 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 25 weeksPopulation: All Randomized Safety population.
An adverse event (AE) is any untoward medical occurrence, including any unfavorable and unintended sign, symptom or disease temporally associated with the use of the study medication that does not necessarily have a causal relationship with study medication. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability, is a congenital anomaly or defect, or is a significant medical event that may jeopardize the patient or require intervention to prevent one of the outcomes listed above.
Outcome measures
| Measure |
Tobramycin Inhalation Powder (TIP)
n=308 Participants
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
n=209 Participants
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events
Discontinued due to SAE(s)
|
14 participants
|
6 participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Any adverse event
|
278 participants
|
176 participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Serious adverse event
|
85 participants
|
61 participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Death
|
3 participants
|
0 participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Discontinued due to AE(s)
|
46 participants
|
17 participants
|
SECONDARY outcome
Timeframe: Weeks 1, 5, 17 and 21Population: Pharmacokinetic subpopulation
Serum tobramycin concentrations were measured in a subset of participants at Week 1 (start of cycle 1), Week 5 (End of Cycle 1), Week 17 (start of cycle 3) and Week 21 (end of cycle 3). Serum samples were collected at pre-dose and post-dose at specified intervals; one specimen between 0 to 2 hours; two additional specimens between 2 and 5 hours (sample times must have been a minimum of 2 hours apart).
Outcome measures
| Measure |
Tobramycin Inhalation Powder (TIP)
n=28 Participants
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
n=14 Participants
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
|---|---|---|
|
Serum Tobramycin Concentrations
Week 1: Predose [N=28, 14]
|
0.00 μg/mL
Standard Deviation 0.02
|
0.02 μg/mL
Standard Deviation 0.05
|
|
Serum Tobramycin Concentrations
Week 1: 0 to 2 hours [N=28, 14]
|
0.82 μg/mL
Standard Deviation 0.39
|
0.61 μg/mL
Standard Deviation 0.35
|
|
Serum Tobramycin Concentrations
Week 1: 2 to 5 hours (1st sample) [N=26, 14]
|
0.74 μg/mL
Standard Deviation 0.34
|
0.69 μg/mL
Standard Deviation 0.39
|
|
Serum Tobramycin Concentrations
Week 1: 2 to 5 hours (2nd sample) [N=25, 12]
|
0.68 μg/mL
Standard Deviation 0.24
|
0.54 μg/mL
Standard Deviation 0.25
|
|
Serum Tobramycin Concentrations
Week 5: Predose [N=23, 13]
|
0.47 μg/mL
Standard Deviation 0.73
|
0.21 μg/mL
Standard Deviation 0.15
|
|
Serum Tobramycin Concentrations
Week 5: 0 to 2 hours [N=23, 12]
|
1.39 μg/mL
Standard Deviation 0.80
|
1.18 μg/mL
Standard Deviation 0.72
|
|
Serum Tobramycin Concentrations
Week 5: 2 to 5 hours (1st sample) [N=23, 11]
|
1.41 μg/mL
Standard Deviation 0.60
|
1.08 μg/mL
Standard Deviation 0.55
|
|
Serum Tobramycin Concentrations
Week 5: 2 to 5 hours (2nd sample) [N=23, 8]
|
1.09 μg/mL
Standard Deviation 0.50
|
0.83 μg/mL
Standard Deviation 0.34
|
|
Serum Tobramycin Concentrations
Week 17: Predose [N=24, 13]
|
0.07 μg/mL
Standard Deviation 0.22
|
0.08 μg/mL
Standard Deviation 0.25
|
|
Serum Tobramycin Concentrations
Week 17: 0 to 2 hours [N=24, 13]
|
0.75 μg/mL
Standard Deviation 0.54
|
0.87 μg/mL
Standard Deviation 0.54
|
|
Serum Tobramycin Concentrations
Week 17: 2 to 5 hours (1st sample) [N=24, 12]
|
0.80 μg/mL
Standard Deviation 0.34
|
0.91 μg/mL
Standard Deviation 0.64
|
|
Serum Tobramycin Concentrations
Week 17: 2 to 5 hours (2nd sample) [N=23, 12]
|
0.74 μg/mL
Standard Deviation 0.30
|
0.67 μg/mL
Standard Deviation 0.40
|
|
Serum Tobramycin Concentrations
Week 21: Predose [N=24, 13]
|
0.36 μg/mL
Standard Deviation 0.29
|
0.24 μg/mL
Standard Deviation 0.26
|
|
Serum Tobramycin Concentrations
Week 21: 0 to 2 hours [N=24, 12]
|
1.22 μg/mL
Standard Deviation 0.57
|
1.10 μg/mL
Standard Deviation 0.64
|
|
Serum Tobramycin Concentrations
Week 21: 2 to 5 hours (1st sample) [N=22, 12]
|
1.19 μg/mL
Standard Deviation 0.50
|
1.02 μg/mL
Standard Deviation 0.52
|
|
Serum Tobramycin Concentrations
Week 21: 2 to 5 hours (2nd sample) [N=24, 11]
|
1.03 μg/mL
Standard Deviation 0.36
|
0.84 μg/mL
Standard Deviation 0.40
|
SECONDARY outcome
Timeframe: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21)Population: Audiology subpopulation
Audiology testing was performed only at selected centers. Auditory acuity was measured from 250 to 8000 Hertz using a standard dual-channel audiometer.
Outcome measures
| Measure |
Tobramycin Inhalation Powder (TIP)
n=73 Participants
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
n=42 Participants
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
|---|---|---|
|
Percentage of Participants With a Decrease From Baseline in Auditory Acuity
Cycle 1, Day 28 [N=60, 39]
|
13.3 percentage of participants
|
10.3 percentage of participants
|
|
Percentage of Participants With a Decrease From Baseline in Auditory Acuity
Cycle 2, Day 28 [N=55, 34]
|
12.7 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With a Decrease From Baseline in Auditory Acuity
Cycle 3, Day 28 [N=54, 34]
|
18.5 percentage of participants
|
11.8 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)Population: Intent to treat population for patients with available data. For Final Visit, the last available post-baseline measurement is reported.
Forced expiratory volume in one second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 is then converted to a percentage of normal (percent predicted) based on height, weight, and race. FEV1 was measured at Baseline (prior to beginning study treatment) and predose on Day 28 of Cycles 1, 2 and 3 and at the follow-up visit. Relative change = 100 \* ((Day 28 of Cycle 3 value - Baseline value)/ Baseline value).
Outcome measures
| Measure |
Tobramycin Inhalation Powder (TIP)
n=308 Participants
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
n=209 Participants
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
|---|---|---|
|
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1)
Baseline [N=308, 209]
|
52.9 percent of predicted
Standard Deviation 14.20
|
52.8 percent of predicted
Standard Deviation 15.95
|
|
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1)
Change from Baseline at Week 5 [N=268, 194]
|
2.8 percent of predicted
Standard Deviation 19.64
|
3.6 percent of predicted
Standard Deviation 14.33
|
|
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1)
Change from Baseline at Week 13 [N=252, 178]
|
2.3 percent of predicted
Standard Deviation 18.76
|
4.3 percent of predicted
Standard Deviation 16.63
|
|
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1)
Change from Baseline at Week 21 [N=227, 171]
|
3.1 percent of predicted
Standard Deviation 19.92
|
2.3 percent of predicted
Standard Deviation 17.57
|
|
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1)
Change from Baseline: Final Visit [N=307, 209]
|
-0.4 percent of predicted
Standard Deviation 17.15
|
-1.6 percent of predicted
Standard Deviation 17.38
|
SECONDARY outcome
Timeframe: Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21).Population: Intent-to-treat population for whom data were available.
Patient's self-reported treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM, a validated instrument) which was modified by adding four study-specific questions; the standard fourteen questions of the TSQM were not altered. Responses to nearly all items are rated on a five-point or seven-point rating scale and the items are factored into 4 domains. The TSQM domain scores range from 0 to 100 with higher scores representing higher satisfaction for that domain.
Outcome measures
| Measure |
Tobramycin Inhalation Powder (TIP)
n=308 Participants
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
n=209 Participants
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
|---|---|---|
|
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Cycle 1: Effectiveness [N=264, 189]
|
74.1 Scores on a scale
Standard Deviation 17.29
|
64.6 Scores on a scale
Standard Deviation 18.63
|
|
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Cycle 1: Side Effects [N=263, 190]
|
92.1 Scores on a scale
Standard Deviation 15.58
|
92.4 Scores on a scale
Standard Deviation 15.99
|
|
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Cycle 1: Convenience [N=264, 190]
|
82.3 Scores on a scale
Standard Deviation 14.95
|
58.1 Scores on a scale
Standard Deviation 20.64
|
|
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Cycle 1: Global Satisfaction [N=264, 190]
|
75.4 Scores on a scale
Standard Deviation 20.19
|
20.19 Scores on a scale
Standard Deviation 18.67
|
|
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Cycle 2: Effectiveness [N=241, 170]
|
74.5 Scores on a scale
Standard Deviation 17.62
|
64.6 Scores on a scale
Standard Deviation 17.42
|
|
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Cycle 2: Side Effects [N=239, 170]
|
93.6 Scores on a scale
Standard Deviation 14.06
|
93.8 Scores on a scale
Standard Deviation 13.41
|
|
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Cycle 2:Convenience [N=241, 170]
|
81.1 Scores on a scale
Standard Deviation 16.61
|
57.0 Scores on a scale
Standard Deviation 20.40
|
|
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Cycle 2: Global Satisfaction [N=241, 170]
|
76.6 Scores on a scale
Standard Deviation 19.16
|
70.2 Scores on a scale
Standard Deviation 19.40
|
|
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Cycle 3: Effectiveness [N=221, 162]
|
74.9 Scores on a scale
Standard Deviation 20.25
|
65.5 Scores on a scale
Standard Deviation 17.42
|
|
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Cycle 3: Side Effects [N=215, 158]
|
91.5 Scores on a scale
Standard Deviation 17.78
|
94.1 Scores on a scale
Standard Deviation 14.48
|
|
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Cycle 3: Convenience [N=221, 162]
|
81.6 Scores on a scale
Standard Deviation 16.89
|
56.6 Scores on a scale
Standard Deviation 20.90
|
|
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Cycle 3: Global Satisfaction [N=221, 162]
|
75.2 Scores on a scale
Standard Deviation 24.00
|
72.2 Scores on a scale
Standard Deviation 17.90
|
SECONDARY outcome
Timeframe: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25).Population: Intent to treat population for patients with available data. For Final Visit, the last available post-baseline measurement is reported.
Three Pseudomonas aeruginosa biotypes were assessed in patient's sputum; mucoid, dry and small colony variant. Overall density is defined as the sum of all bio-types in Pseudomonas aeruginosa density.
Outcome measures
| Measure |
Tobramycin Inhalation Powder (TIP)
n=308 Participants
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
n=209 Participants
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
|---|---|---|
|
Change From Baseline in Pseudomonas Aeruginosa Sputum Density
Change from Baseline: Final Visit [N=263, 179]
|
-0.53 log10 Colony forming units/g
Standard Deviation 1.92
|
-0.33 log10 Colony forming units/g
Standard Deviation 1.71
|
|
Change From Baseline in Pseudomonas Aeruginosa Sputum Density
Baseline [N=279, 192]
|
7.23 log10 Colony forming units/g
Standard Deviation 1.49
|
7.35 log10 Colony forming units/g
Standard Deviation 1.54
|
|
Change From Baseline in Pseudomonas Aeruginosa Sputum Density
Change from Baseline at Week 5 [N=202, 145]
|
-1.76 log10 Colony forming units/g
Standard Deviation 1.96
|
-1.32 log10 Colony forming units/g
Standard Deviation 2.03
|
|
Change From Baseline in Pseudomonas Aeruginosa Sputum Density
Change from Baseline at Week 13 [N=170, 125]
|
-1.54 log10 Colony forming units/g
Standard Deviation 1.99
|
-1.11 log10 Colony forming units/g
Standard Deviation 1.91
|
|
Change From Baseline in Pseudomonas Aeruginosa Sputum Density
Change from Baseline at Week 21 [N= 157, 126]
|
-1.61 log10 Colony forming units/g
Standard Deviation 2.03
|
-0.77 log10 Colony forming units/g
Standard Deviation 1.78
|
SECONDARY outcome
Timeframe: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)Population: Intent to treat population for patients with available data. For Final Visit, the last available post-baseline measurement is reported.
The minimum inhibitory concentration (MIC) is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. The MIC of tobramycin against total Pseudomonas aeruginosa colonization was assessed over the course of the study.
Outcome measures
| Measure |
Tobramycin Inhalation Powder (TIP)
n=308 Participants
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
n=209 Participants
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
|---|---|---|
|
Change From Baseline in Tobramycin Minimum Inhibitory Concentration
Baseline [N=308, 208]
|
35.39 μg/mL
Standard Deviation 107.58
|
42.45 μg/mL
Standard Deviation 116.40
|
|
Change From Baseline in Tobramycin Minimum Inhibitory Concentration
Change from Baseline at Week 5 [N=239, 173]
|
38.47 μg/mL
Standard Deviation 148.34
|
5.80 μg/mL
Standard Deviation 112.96
|
|
Change From Baseline in Tobramycin Minimum Inhibitory Concentration
Change from Baseline at Week 8 [N=215, 157]
|
35.59 μg/mL
Standard Deviation 148.03
|
20.68 μg/mL
Standard Deviation 130.57
|
|
Change From Baseline in Tobramycin Minimum Inhibitory Concentration
Change from Baseline at Week 21 [N=199, 154]
|
29.83 μg/mL
Standard Deviation 139.85
|
14.13 μg/mL
Standard Deviation 117.54
|
|
Change From Baseline in Tobramycin Minimum Inhibitory Concentration
Change from Baseline: Final Visit [N=298, 202]
|
30.89 μg/mL
Standard Deviation 139.63
|
3.27 μg/mL
Standard Deviation 107.80
|
SECONDARY outcome
Timeframe: 25 WeeksPopulation: Patients in the intent-to-treat population who required antipseudomonal antibiotics.
The average number of days patients required antipseudomonal antibiotics during the course of the study.
Outcome measures
| Measure |
Tobramycin Inhalation Powder (TIP)
n=202 Participants
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
n=115 Participants
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
|---|---|---|
|
Antipseudomonal Antibiotic Usage During the Study
|
34.5 days
Standard Deviation 31.24
|
40.1 days
Standard Deviation 37.27
|
SECONDARY outcome
Timeframe: 25 WeeksPopulation: Patients in the intent-to-treat population who were hospitalized due to respiratory events.
The average number of days patients were hospitalized due to respiratory events during the course of the study.
Outcome measures
| Measure |
Tobramycin Inhalation Powder (TIP)
n=75 Participants
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
n=46 Participants
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
|---|---|---|
|
Hospitalization Due to Respiratory Events During the Study
|
15.6 days
Standard Deviation 13.31
|
15.3 days
Standard Deviation 10.23
|
Adverse Events
Tobramycin Inhalation Powder (TIP)
Serious events: 85 serious events
Other events: 241 other events
Deaths: 0 deaths
Tobramycin Solution for Inhalation (TOBI)
Serious events: 61 serious events
Other events: 148 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tobramycin Inhalation Powder (TIP)
n=308 participants at risk
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
n=209 participants at risk
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
|---|---|---|
|
Congenital, familial and genetic disorders
Cystic fibrosis lung
|
0.65%
2/308
|
0.96%
2/209
|
|
Gastrointestinal disorders
Abdominal pain
|
0.32%
1/308
|
0.48%
1/209
|
|
Gastrointestinal disorders
Crohn's disease
|
0.00%
0/308
|
0.48%
1/209
|
|
Gastrointestinal disorders
Diarrhoea
|
0.32%
1/308
|
0.00%
0/209
|
|
Gastrointestinal disorders
Distal ileal obstruction syndrome
|
0.32%
1/308
|
0.00%
0/209
|
|
Gastrointestinal disorders
Distal intestinal obstruction syndrome
|
0.32%
1/308
|
0.48%
1/209
|
|
Gastrointestinal disorders
Frequent bowel movements
|
0.32%
1/308
|
0.00%
0/209
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/308
|
0.48%
1/209
|
|
Gastrointestinal disorders
Pancreatic insufficiency
|
0.00%
0/308
|
0.48%
1/209
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/308
|
0.48%
1/209
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/308
|
0.48%
1/209
|
|
General disorders
Chest pain
|
0.32%
1/308
|
0.00%
0/209
|
|
General disorders
Fatigue
|
0.97%
3/308
|
0.00%
0/209
|
|
General disorders
Pyrexia
|
0.32%
1/308
|
0.96%
2/209
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/308
|
0.48%
1/209
|
|
Hepatobiliary disorders
Hepatosplenomegaly
|
0.32%
1/308
|
0.00%
0/209
|
|
Infections and infestations
Appendicitis
|
0.32%
1/308
|
0.00%
0/209
|
|
Infections and infestations
Bronchitis
|
1.9%
6/308
|
0.48%
1/209
|
|
Infections and infestations
Bronchopneumonia
|
0.32%
1/308
|
0.96%
2/209
|
|
Infections and infestations
Bronchopulmonary aspergillosis allergic
|
0.00%
0/308
|
0.48%
1/209
|
|
Infections and infestations
Influenza
|
0.32%
1/308
|
0.00%
0/209
|
|
Infections and infestations
Lower respiratory tract infection
|
0.65%
2/308
|
0.96%
2/209
|
|
Infections and infestations
Lung abscess
|
0.32%
1/308
|
0.48%
1/209
|
|
Infections and infestations
Lung infection pseudomonal
|
0.65%
2/308
|
0.48%
1/209
|
|
Infections and infestations
Pneumonia
|
0.65%
2/308
|
0.96%
2/209
|
|
Infections and infestations
Pneumonia bacterial
|
0.65%
2/308
|
0.96%
2/209
|
|
Infections and infestations
Pseudomonas bronchitis
|
0.32%
1/308
|
0.00%
0/209
|
|
Infections and infestations
Pseudomonas infection
|
0.32%
1/308
|
0.96%
2/209
|
|
Infections and infestations
Respiratory tract infection
|
0.32%
1/308
|
0.48%
1/209
|
|
Infections and infestations
Sinusitis
|
0.65%
2/308
|
0.48%
1/209
|
|
Infections and infestations
Upper respiratory tract infection
|
0.32%
1/308
|
0.00%
0/209
|
|
Infections and infestations
Urinary tract infection
|
0.32%
1/308
|
0.00%
0/209
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.32%
1/308
|
0.00%
0/209
|
|
Injury, poisoning and procedural complications
Ulna fracture
|
0.00%
0/308
|
0.48%
1/209
|
|
Investigations
Blood glucose increased
|
0.32%
1/308
|
0.00%
0/209
|
|
Investigations
Chest X-ray abnormal
|
0.00%
0/308
|
0.48%
1/209
|
|
Investigations
Forced expiratory volume decreased
|
0.32%
1/308
|
0.48%
1/209
|
|
Investigations
Oxygen saturation
|
0.32%
1/308
|
0.00%
0/209
|
|
Investigations
Pulmonary function test decreased
|
1.3%
4/308
|
1.4%
3/209
|
|
Investigations
Weight decreased
|
0.00%
0/308
|
1.4%
3/209
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.32%
1/308
|
0.00%
0/209
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/308
|
0.48%
1/209
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/308
|
0.48%
1/209
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/308
|
0.48%
1/209
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.32%
1/308
|
0.00%
0/209
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.32%
1/308
|
0.00%
0/209
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign lung neoplasm
|
0.00%
0/308
|
0.48%
1/209
|
|
Nervous system disorders
Cervicobrachial syndrome
|
0.32%
1/308
|
0.00%
0/209
|
|
Nervous system disorders
Headache
|
0.32%
1/308
|
0.00%
0/209
|
|
Nervous system disorders
Sinus headache
|
0.32%
1/308
|
0.00%
0/209
|
|
Psychiatric disorders
Depression
|
0.00%
0/308
|
0.48%
1/209
|
|
Psychiatric disorders
Panic attack
|
0.32%
1/308
|
0.00%
0/209
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.32%
1/308
|
0.00%
0/209
|
|
Respiratory, thoracic and mediastinal disorders
Bronchiectasis
|
0.00%
0/308
|
0.96%
2/209
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.3%
7/308
|
2.4%
5/209
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.6%
5/308
|
1.9%
4/209
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.65%
2/308
|
0.00%
0/209
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.65%
2/308
|
0.48%
1/209
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
2.6%
8/308
|
1.9%
4/209
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/308
|
0.96%
2/209
|
|
Respiratory, thoracic and mediastinal disorders
Increased bronchial secretion
|
0.32%
1/308
|
0.00%
0/209
|
|
Respiratory, thoracic and mediastinal disorders
Lung consolidation
|
0.32%
1/308
|
0.00%
0/209
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
19.5%
60/308
|
18.7%
39/209
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.32%
1/308
|
0.00%
0/209
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/308
|
0.48%
1/209
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.32%
1/308
|
0.00%
0/209
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.32%
1/308
|
0.00%
0/209
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/308
|
0.48%
1/209
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
0.32%
1/308
|
0.48%
1/209
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
0.32%
1/308
|
0.00%
0/209
|
|
Respiratory, thoracic and mediastinal disorders
Sputum discoloured
|
0.32%
1/308
|
0.00%
0/209
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
1.6%
5/308
|
0.48%
1/209
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/308
|
0.48%
1/209
|
Other adverse events
| Measure |
Tobramycin Inhalation Powder (TIP)
n=308 participants at risk
Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
Tobramycin Solution for Inhalation (TOBI)
n=209 participants at risk
Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
3.9%
12/308
|
8.1%
17/209
|
|
Gastrointestinal disorders
Nausea
|
7.5%
23/308
|
9.1%
19/209
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
19/308
|
5.3%
11/209
|
|
General disorders
Chest discomfort
|
6.5%
20/308
|
2.9%
6/209
|
|
General disorders
Fatigue
|
5.8%
18/308
|
4.8%
10/209
|
|
General disorders
Pyrexia
|
15.3%
47/308
|
12.0%
25/209
|
|
Infections and infestations
Sinusitis
|
5.5%
17/308
|
7.2%
15/209
|
|
Infections and infestations
Upper respiratory tract infection
|
6.8%
21/308
|
8.6%
18/209
|
|
Investigations
Pulmonary function test decreased
|
5.8%
18/308
|
6.7%
14/209
|
|
Nervous system disorders
Headache
|
11.0%
34/308
|
12.0%
25/209
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
47.1%
145/308
|
30.1%
63/209
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
13.6%
42/308
|
3.8%
8/209
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
14.3%
44/308
|
10.5%
22/209
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
11.4%
35/308
|
11.0%
23/209
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
18.5%
57/308
|
15.8%
33/209
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
8.1%
25/308
|
7.2%
15/209
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
14.0%
43/308
|
10.5%
22/209
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
5.5%
17/308
|
3.8%
8/209
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
6.8%
21/308
|
6.2%
13/209
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
7.1%
22/308
|
7.2%
15/209
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
15.9%
49/308
|
16.7%
35/209
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
6.8%
21/308
|
6.2%
13/209
|
Additional Information
Study Director
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.
- Publication restrictions are in place
Restriction type: OTHER