Cystic Fibrosis
Conditions
Keywords
tobramycin
Brief summary
This study compares the safety of the tobramycin solution for inhalation with the tobramycin dry powder formulation, used with a simple inhaler
Interventions
Tobramycin Inhalation Powder (TIP) capsules for inhalation.
Tobramycin solution for inhalation (TOBI), supplied as 300 mg/5mL ampoules administered with a nebulizer
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of cystic fibrosis * Male and female patients at least 6 years of age at the time of screening. * Forced expiratory volume in one second (FEV1) at screening must be at least 25% and less than or equal to 75% of normal predicted values for age, sex, and height based on Knudson criteria. * Pseudomonas aeruginosa, a type of bacteria, must be present in a sputum/deep-throat cough swab culture (or bronchoalveolar lavage \[BAL\]) within 6 months prior to screening and in the sputum/ deep-throat cough swab culture at the screening visit. * Able to comply with all protocol requirements. * Clinically stable in the opinion of the investigator. * Use of an effective means of contraception in females of childbearing potential. * Provide written informed consent, Health Authority Portability and Accountability Act (HIPAA) authorization (where applicable), and assent (as appropriate) prior to the performance of any study-related procedure.
Exclusion criteria
* History of sputum culture or deep-throat cough swab (or BAL) culture yielding Burkholderia cepacia (B cepacia), a type of bacteria, within 2 years prior to screening and/or sputum culture yielding B cepacia at screening. * Coughing up more than 60 cc of blood from the respiratory tract at any time within 30 days prior to study drug administration. * Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics. * Females who are pregnant (positive pregnancy test), lactating, or are planning to become pregnant during the study. * History of hearing loss or chronic ringing in the ears deemed clinically significant by the investigator. * Use of systemic or inhaled antipseudomonal antibiotics within 28 days prior to study drug administration. * Use of loop diuretics within 7 days prior to study drug administration. * Use of any investigational treatment within 28 days prior to study drug administration. * Initiation of treatment with chronic macrolide therapy, dornase alpha treatment or inhaled corticosteroids within 28 days prior to study drug administration (patients may be taking these therapies at the time of enrollment, but they must have initiated treatment more than 28 days prior to study drug administration). Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events | 25 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Decrease From Baseline in Auditory Acuity | Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) | Audiology testing was performed only at selected centers. Auditory acuity was measured from 250 to 8000 Hertz using a standard dual-channel audiometer. |
| Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1) | Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25) | 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). |
| Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication | Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21). | 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. |
| Serum Tobramycin Concentrations | Weeks 1, 5, 17 and 21 | 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). |
| Change From Baseline in Tobramycin Minimum Inhibitory Concentration | Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25) | 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. |
| Antipseudomonal Antibiotic Usage During the Study | 25 Weeks | The average number of days patients required antipseudomonal antibiotics during the course of the study. |
| Hospitalization Due to Respiratory Events During the Study | 25 Weeks | The average number of days patients were hospitalized due to respiratory events during the course of the study. |
| Change From Baseline in Pseudomonas Aeruginosa Sputum Density | Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25). | 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. |
Countries
Australia, Canada, Chile, Colombia, France, Germany, Hungary, Israel, Italy, Mexico, Netherlands, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 308 |
| 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. | 209 |
| Total | 517 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Reason | 1 | 0 |
| Overall Study | Adverse Event or Death | 43 | 17 |
| Overall Study | Inappropriate Enrollment | 0 | 1 |
| Overall Study | Lost to Follow-up | 5 | 3 |
| Overall Study | Protocol Violation | 6 | 5 |
| Overall Study | Unable to classify | 4 | 3 |
| Overall Study | Withdrawal by Subject | 24 | 9 |
Baseline characteristics
| Characteristic | Tobramycin Solution for Inhalation (TOBI) | Total | Tobramycin Inhalation Powder (TIP) |
|---|---|---|---|
| Age Continuous | 25.2 years STANDARD_DEVIATION 10.2 | 25.6 years STANDARD_DEVIATION 10.9 | 25.9 years STANDARD_DEVIATION 11.36 |
| Age, Customized ≥13 to <20 years | 48 participants | 114 participants | 66 participants |
| Age, Customized ≥20 years | 143 participants | 357 participants | 214 participants |
| Age, Customized ≥6 to <13 years | 18 participants | 46 participants | 28 participants |
| Sex: Female, Male Female | 94 Participants | 231 Participants | 137 Participants |
| Sex: Female, Male Male | 115 Participants | 286 Participants | 171 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 241 / 308 | 148 / 209 |
| serious Total, serious adverse events | 85 / 308 | 61 / 209 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events
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.
Time frame: 25 weeks
Population: All Randomized Safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Number of Participants With Treatment-emergent Adverse Events | Serious adverse event | 85 participants |
| Tobramycin Inhalation Powder (TIP) | Number of Participants With Treatment-emergent Adverse Events | Discontinued due to AE(s) | 46 participants |
| Tobramycin Inhalation Powder (TIP) | Number of Participants With Treatment-emergent Adverse Events | Death | 3 participants |
| Tobramycin Inhalation Powder (TIP) | Number of Participants With Treatment-emergent Adverse Events | Discontinued due to SAE(s) | 14 participants |
| Tobramycin Inhalation Powder (TIP) | Number of Participants With Treatment-emergent Adverse Events | Any adverse event | 278 participants |
| Tobramycin Solution for Inhalation (TOBI) | Number of Participants With Treatment-emergent Adverse Events | Discontinued due to SAE(s) | 6 participants |
| Tobramycin Solution for Inhalation (TOBI) | Number of Participants With Treatment-emergent Adverse Events | Any adverse event | 176 participants |
| Tobramycin Solution for Inhalation (TOBI) | Number of Participants With Treatment-emergent Adverse Events | Serious adverse event | 61 participants |
| Tobramycin Solution for Inhalation (TOBI) | Number of Participants With Treatment-emergent Adverse Events | Death | 0 participants |
| Tobramycin Solution for Inhalation (TOBI) | Number of Participants With Treatment-emergent Adverse Events | Discontinued due to AE(s) | 17 participants |
Secondary
Antipseudomonal Antibiotic Usage During the Study
The average number of days patients required antipseudomonal antibiotics during the course of the study.
Time frame: 25 Weeks
Population: Patients in the intent-to-treat population who required antipseudomonal antibiotics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Antipseudomonal Antibiotic Usage During the Study | 34.5 days | Standard Deviation 31.24 |
| Tobramycin Solution for Inhalation (TOBI) | Antipseudomonal Antibiotic Usage During the Study | 40.1 days | Standard Deviation 37.27 |
Secondary
Change From Baseline in Pseudomonas Aeruginosa Sputum Density
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | Change From Baseline in Pseudomonas Aeruginosa Sputum Density | Baseline [N=279, 192] | 7.23 log10 Colony forming units/g | Standard Deviation 1.49 |
| Tobramycin Solution for Inhalation (TOBI) | Change From Baseline in Pseudomonas Aeruginosa Sputum Density | Change from Baseline: Final Visit [N=263, 179] | -0.33 log10 Colony forming units/g | Standard Deviation 1.71 |
| Tobramycin Solution for Inhalation (TOBI) | Change From Baseline in Pseudomonas Aeruginosa Sputum Density | Baseline [N=279, 192] | 7.35 log10 Colony forming units/g | Standard Deviation 1.54 |
| Tobramycin Solution for Inhalation (TOBI) | Change From Baseline in Pseudomonas Aeruginosa Sputum Density | Change from Baseline at Week 5 [N=202, 145] | -1.32 log10 Colony forming units/g | Standard Deviation 2.03 |
| Tobramycin Solution for Inhalation (TOBI) | Change From Baseline in Pseudomonas Aeruginosa Sputum Density | Change from Baseline at Week 13 [N=170, 125] | -1.11 log10 Colony forming units/g | Standard Deviation 1.91 |
| Tobramycin Solution for Inhalation (TOBI) | Change From Baseline in Pseudomonas Aeruginosa Sputum Density | Change from Baseline at Week 21 [N= 157, 126] | -0.77 log10 Colony forming units/g | Standard Deviation 1.78 |
Secondary
Change From Baseline in Tobramycin Minimum Inhibitory Concentration
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | Change From Baseline in Tobramycin Minimum Inhibitory Concentration | Change from Baseline: Final Visit [N=298, 202] | 30.89 μg/mL | Standard Deviation 139.63 |
| Tobramycin Inhalation Powder (TIP) | Change From Baseline in Tobramycin Minimum Inhibitory Concentration | Baseline [N=308, 208] | 35.39 μg/mL | Standard Deviation 107.58 |
| Tobramycin Solution for Inhalation (TOBI) | Change From Baseline in Tobramycin Minimum Inhibitory Concentration | Change from Baseline: Final Visit [N=298, 202] | 3.27 μg/mL | Standard Deviation 107.8 |
| Tobramycin Solution for Inhalation (TOBI) | Change From Baseline in Tobramycin Minimum Inhibitory Concentration | Baseline [N=308, 208] | 42.45 μg/mL | Standard Deviation 116.4 |
| Tobramycin Solution for Inhalation (TOBI) | Change From Baseline in Tobramycin Minimum Inhibitory Concentration | Change from Baseline at Week 5 [N=239, 173] | 5.80 μg/mL | Standard Deviation 112.96 |
| Tobramycin Solution for Inhalation (TOBI) | Change From Baseline in Tobramycin Minimum Inhibitory Concentration | Change from Baseline at Week 8 [N=215, 157] | 20.68 μg/mL | Standard Deviation 130.57 |
| Tobramycin Solution for Inhalation (TOBI) | Change From Baseline in Tobramycin Minimum Inhibitory Concentration | Change from Baseline at Week 21 [N=199, 154] | 14.13 μg/mL | Standard Deviation 117.54 |
Secondary
Hospitalization Due to Respiratory Events During the Study
The average number of days patients were hospitalized due to respiratory events during the course of the study.
Time frame: 25 Weeks
Population: Patients in the intent-to-treat population who were hospitalized due to respiratory events.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Hospitalization Due to Respiratory Events During the Study | 15.6 days | Standard Deviation 13.31 |
| Tobramycin Solution for Inhalation (TOBI) | Hospitalization Due to Respiratory Events During the Study | 15.3 days | Standard Deviation 10.23 |
Secondary
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
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.
Time frame: Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21).
Population: Intent-to-treat population for whom data were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Solution for Inhalation (TOBI) | Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication | Cycle 3: Global Satisfaction [N=221, 162] | 72.2 Scores on a scale | Standard Deviation 17.9 |
| Tobramycin Solution for Inhalation (TOBI) | Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication | Cycle 1: Effectiveness [N=264, 189] | 64.6 Scores on a scale | Standard Deviation 18.63 |
| Tobramycin Solution for Inhalation (TOBI) | Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication | Cycle 1: Side Effects [N=263, 190] | 92.4 Scores on a scale | Standard Deviation 15.99 |
| Tobramycin Solution for Inhalation (TOBI) | Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication | Cycle 1: Convenience [N=264, 190] | 58.1 Scores on a scale | Standard Deviation 20.64 |
| Tobramycin Solution for Inhalation (TOBI) | Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication | Cycle 1: Global Satisfaction [N=264, 190] | 20.19 Scores on a scale | Standard Deviation 18.67 |
| Tobramycin Solution for Inhalation (TOBI) | Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication | Cycle 2: Effectiveness [N=241, 170] | 64.6 Scores on a scale | Standard Deviation 17.42 |
| Tobramycin Solution for Inhalation (TOBI) | Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication | Cycle 2: Side Effects [N=239, 170] | 93.8 Scores on a scale | Standard Deviation 13.41 |
| Tobramycin Solution for Inhalation (TOBI) | Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication | Cycle 2:Convenience [N=241, 170] | 57.0 Scores on a scale | Standard Deviation 20.4 |
| Tobramycin Solution for Inhalation (TOBI) | Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication | Cycle 2: Global Satisfaction [N=241, 170] | 70.2 Scores on a scale | Standard Deviation 19.4 |
| Tobramycin Solution for Inhalation (TOBI) | Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication | Cycle 3: Effectiveness [N=221, 162] | 65.5 Scores on a scale | Standard Deviation 17.42 |
| Tobramycin Solution for Inhalation (TOBI) | Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication | Cycle 3: Side Effects [N=215, 158] | 94.1 Scores on a scale | Standard Deviation 14.48 |
| Tobramycin Solution for Inhalation (TOBI) | Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication | Cycle 3: Convenience [N=221, 162] | 56.6 Scores on a scale | Standard Deviation 20.9 |
Secondary
Percentage of Participants With a Decrease From Baseline in Auditory Acuity
Audiology testing was performed only at selected centers. Auditory acuity was measured from 250 to 8000 Hertz using a standard dual-channel audiometer.
Time frame: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21)
Population: Audiology subpopulation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Percentage of Participants With a Decrease From Baseline in Auditory Acuity | Cycle 1, Day 28 [N=60, 39] | 13.3 percentage of participants |
| Tobramycin Inhalation Powder (TIP) | Percentage of Participants With a Decrease From Baseline in Auditory Acuity | Cycle 2, Day 28 [N=55, 34] | 12.7 percentage of participants |
| Tobramycin Inhalation Powder (TIP) | Percentage of Participants With a Decrease From Baseline in Auditory Acuity | Cycle 3, Day 28 [N=54, 34] | 18.5 percentage of participants |
| Tobramycin Solution for Inhalation (TOBI) | Percentage of Participants With a Decrease From Baseline in Auditory Acuity | Cycle 3, Day 28 [N=54, 34] | 11.8 percentage of participants |
| Tobramycin Solution for Inhalation (TOBI) | Percentage of Participants With a Decrease From Baseline in Auditory Acuity | Cycle 1, Day 28 [N=60, 39] | 10.3 percentage of participants |
| Tobramycin Solution for Inhalation (TOBI) | Percentage of Participants With a Decrease From Baseline in Auditory Acuity | Cycle 2, Day 28 [N=55, 34] | 0.0 percentage of participants |
Secondary
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1)
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 |
| Tobramycin Inhalation Powder (TIP) | 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 14.2 |
| Tobramycin Solution for Inhalation (TOBI) | Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1) | Change from Baseline: Final Visit [N=307, 209] | -1.6 percent of predicted | Standard Deviation 17.38 |
| Tobramycin Solution for Inhalation (TOBI) | Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1) | Baseline [N=308, 209] | 52.8 percent of predicted | Standard Deviation 15.95 |
| Tobramycin Solution for Inhalation (TOBI) | Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1) | Change from Baseline at Week 5 [N=268, 194] | 3.6 percent of predicted | Standard Deviation 14.33 |
| Tobramycin Solution for Inhalation (TOBI) | Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1) | Change from Baseline at Week 13 [N=252, 178] | 4.3 percent of predicted | Standard Deviation 16.63 |
| Tobramycin Solution for Inhalation (TOBI) | Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1) | Change from Baseline at Week 21 [N=227, 171] | 2.3 percent of predicted | Standard Deviation 17.57 |
Secondary
Serum Tobramycin Concentrations
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).
Time frame: Weeks 1, 5, 17 and 21
Population: Pharmacokinetic subpopulation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 1: Predose [N=28, 14] | 0.00 μg/mL | Standard Deviation 0.02 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 1: 0 to 2 hours [N=28, 14] | 0.82 μg/mL | Standard Deviation 0.39 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 1: 2 to 5 hours (1st sample) [N=26, 14] | 0.74 μg/mL | Standard Deviation 0.34 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 1: 2 to 5 hours (2nd sample) [N=25, 12] | 0.68 μg/mL | Standard Deviation 0.24 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 5: Predose [N=23, 13] | 0.47 μg/mL | Standard Deviation 0.73 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 5: 0 to 2 hours [N=23, 12] | 1.39 μg/mL | Standard Deviation 0.8 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 5: 2 to 5 hours (1st sample) [N=23, 11] | 1.41 μg/mL | Standard Deviation 0.6 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 5: 2 to 5 hours (2nd sample) [N=23, 8] | 1.09 μg/mL | Standard Deviation 0.5 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 17: Predose [N=24, 13] | 0.07 μg/mL | Standard Deviation 0.22 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 17: 0 to 2 hours [N=24, 13] | 0.75 μg/mL | Standard Deviation 0.54 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 17: 2 to 5 hours (1st sample) [N=24, 12] | 0.80 μg/mL | Standard Deviation 0.34 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 17: 2 to 5 hours (2nd sample) [N=23, 12] | 0.74 μg/mL | Standard Deviation 0.3 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 21: Predose [N=24, 13] | 0.36 μg/mL | Standard Deviation 0.29 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 21: 0 to 2 hours [N=24, 12] | 1.22 μg/mL | Standard Deviation 0.57 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 21: 2 to 5 hours (1st sample) [N=22, 12] | 1.19 μg/mL | Standard Deviation 0.5 |
| Tobramycin Inhalation Powder (TIP) | Serum Tobramycin Concentrations | Week 21: 2 to 5 hours (2nd sample) [N=24, 11] | 1.03 μg/mL | Standard Deviation 0.36 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 21: 2 to 5 hours (2nd sample) [N=24, 11] | 0.84 μg/mL | Standard Deviation 0.4 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 1: Predose [N=28, 14] | 0.02 μg/mL | Standard Deviation 0.05 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 17: Predose [N=24, 13] | 0.08 μg/mL | Standard Deviation 0.25 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 1: 0 to 2 hours [N=28, 14] | 0.61 μg/mL | Standard Deviation 0.35 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 21: Predose [N=24, 13] | 0.24 μg/mL | Standard Deviation 0.26 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 1: 2 to 5 hours (1st sample) [N=26, 14] | 0.69 μg/mL | Standard Deviation 0.39 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 17: 0 to 2 hours [N=24, 13] | 0.87 μg/mL | Standard Deviation 0.54 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 1: 2 to 5 hours (2nd sample) [N=25, 12] | 0.54 μg/mL | Standard Deviation 0.25 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 21: 2 to 5 hours (1st sample) [N=22, 12] | 1.02 μg/mL | Standard Deviation 0.52 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 5: Predose [N=23, 13] | 0.21 μg/mL | Standard Deviation 0.15 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 17: 2 to 5 hours (1st sample) [N=24, 12] | 0.91 μg/mL | Standard Deviation 0.64 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 5: 0 to 2 hours [N=23, 12] | 1.18 μg/mL | Standard Deviation 0.72 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 21: 0 to 2 hours [N=24, 12] | 1.10 μg/mL | Standard Deviation 0.64 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 5: 2 to 5 hours (1st sample) [N=23, 11] | 1.08 μg/mL | Standard Deviation 0.55 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 17: 2 to 5 hours (2nd sample) [N=23, 12] | 0.67 μg/mL | Standard Deviation 0.4 |
| Tobramycin Solution for Inhalation (TOBI) | Serum Tobramycin Concentrations | Week 5: 2 to 5 hours (2nd sample) [N=23, 8] | 0.83 μg/mL | Standard Deviation 0.34 |