Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis, Pseudomonas aeruginosa, FEV1, tobramycin inhalation powder, TOBI,, colistimethate, Cystic Fibrosis, Pseudomonas aeruginosa, FEV1, tobramycin inhalation powder, TOBI, colistimethate
Brief summary
The purpose of this interventional Phase IV study was to explore the ease of use of TIP and prevalence of microbial contamination of the T-326 Inhaler compared with TIS and colistimethate administered via nebuliser for the treatment of Cystic Fibrosis (CF) patients chronically infected with P. aeruginosa. It was anticipated that the data from this study would provide clinicians with further guidance on the relative differences between the speed and ease of use of these treatments as well as useful information on the prevalence of microbial contamination of the inhalation devices in real world use.
Detailed description
Patients who were on colistimethate (COLI), Tobramycin Inhalation Powder (TIP) or Tobramycin Inhalation Solution (TIS) were recruited for the study. They went through one treatment cycle on their usual inhaled antibiotic treatment, and were all transferred to TIP for the second treatment cycle. The primary endpoint was the total administration time of TIP vs TIS vs colistimethate, defined as the total time taken to prepare the delivery device and drug, administer the drug, and clean and disinfect the delivery device.
Interventions
DRUGColistimethate
Colistimethate was administered via nebuliser.
Tobramycin Inhalation Powder was administered via TOBI® Podhaler (T-326 inhaler).
Tobramycin inhalation solution was administered via nebuliser
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Provide written informed consent, HIPAA authorization, and assent (as appropriate for minors) prior to the performance of any study-related procedure * Confirmed diagnosis of Cystic Fibrosis (CF) * Male and female patients 6 years of age or older at screening * Forced Expiratory Volume in 1 second (FEV1) at screening (Visit 1) must be at least 25% and less than or equal to 90% of normal predicted values for age, sex, and height based on the NHANES III values (Hankinson, 1999) for patients 18 years of age or greater, and based on values from Wang (Wang 1993) for patients less than 18 years of age. * Documented use of any of the nebulized antibiotics based on local practice: * Tobramycin Inhalation Solution, colistimethate, or Tobramycin Inhalation Powder for at least 1 cycle within the last 6 months or * Colistimethate continuous use for at least 8 weeks within the last 6 months This cycle of treatment (or continuous colistimethate treatment period) is in addition to the treatment cycle during which the subject is being screened. * P. aeruginosa must be present in a sputum or deep cough throat swab culture or bronchoalveolar lavage (BAL) (only for BAL a threshold level of 10\^3 CFU/mL is required) within 6 months prior to screening, and in the sputum or deep cough throat swab culture at screening or rescreening (Visit 1); Key
Exclusion criteria
* History of sputum culture or deep cough throat swab (or BAL) culture yielding Burkholderia cenocepacia complex within 2 years prior to prescreening or sputum culture yielding B. cenocepacia complex at screening (Visit 1) * History of hearing loss or chronic tinnitus deemed clinically significant by the investigator * Serum creatinine 176.8 μmol/L (2 mg/dL) or greater, blood urea nitrogen (BUN) 14.28 mmol/L (40 mg/dL) or greater, or an abnormal urinalysis defined as 2+ or greater proteinuria at screening * Known local or systemic hypersensitivity to aminoglycosides * Regularly receiving more than 1 class of inhaled antipseudomonal antibiotic * Use of any investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening * Signs and symptoms of acute pulmonary disease, e.g., pneumonia, pneumothorax * Body mass index less than 12 kg/m2 * History of malignancy of any organ system, treated or untreated * Clinically significant laboratory abnormalities (not associated with the study indication) at screening (Visit 1) * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Total Administration Time | days 22 through 28 (cycle 1), days 78 through 84 (cycle 2) | The mean total time for administration of TIP via T-326 inhaler versus the total time for administration of COLI or TIS was assessed from information entered by participants into an ediary during the last 7 days prior to the last dose of a cycle. The total time included the setup, preparation, administration and cleaning/disinfection time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in P. Aeruginosa Sputum Density | days 1, 28 (cycle 1); 57, 84, 112 (cycle 2) | Sputum samples were sent to a central laboratory at the start and end of 2 treatment periods. The absolute change in the number of colony forming units (CFU) of Pseudomonas aeruginosa in sputum = the value of end of on/off treatment period of the cycle minus the pre-dose value at the start of that cycle. A negative change from baseline indicates improvement. |
| Number of Participants With Any Contaminated Delivery Device | days (d) 1, 28, 57, 84 | Devices used to administer the drugs (the T-326 inhaler and nebulisers) were swabbed for contamination testing at the start and end of each treatment cycle (or discontinuation visit if the participant withdrew). No assessments were required from the T-326 inhaler when participants started the treatment period (days 1 and 57). Microbial contamination was measured according to device type and the frequency of organism growth (light/ moderate/ heavy). All nebulisers (neb) used by the participants were analyzed, including those for inhaling other medications, like mucolytics. |
| Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | days 1, 28, 57, 84, 112 | MIC50/90 is the lowest concentration required to inhibit 50%/90% of the isolates tested. The MIC50/90 of a range of antibiotics for P.aeruginosa was determined at the start and end of each treatment cycle, and at the end of the off-treatment period of the second cycle. |
| Number of Participants With Post-inhalation Bronchospasm | days 1, 28, 57, 84 | Bronchospasm was defined as the relative decrease of 20% or more in forced expiratory volume in 1 second (FEV1) percent predicted from pre-dose to 15 to 45 minutes post-dose. |
Countries
Germany, Ireland, Spain, Switzerland, United Kingdom
Participant flow
Pre-assignment details
Each participant was assigned to 1 of 3 treatment arms, TIS/TIP, COLI/TIP, or TIP/TIP with the first treatment cycle based on the participant's usual antibiotic treatment. Then all participants were crossed-over to receive TIP for the second cycle of treatment.
Participants by arm
| Arm | Count |
|---|---|
| TIS/TIP During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment. | 14 |
| COLI/TIP During the first cycle, participants received nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant's usual dose and regimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off-treatment (cycling regimen), depending on local treatment guidelines. During the second cycle, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment. | 28 |
| TIP/TIP During the first and second cycles, participants received TIP 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment. | 18 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 2 |
| Overall Study | Protocol deviation | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | TIS/TIP | COLI/TIP | TIP/TIP | Total |
|---|---|---|---|---|
| Age, Continuous | 27.4 Years STANDARD_DEVIATION 6.82 | 28.4 Years STANDARD_DEVIATION 9.86 | 26.6 Years STANDARD_DEVIATION 7.25 | 27.6 Years STANDARD_DEVIATION 8.4 |
| Sex: Female, Male Female | 4 Participants | 10 Participants | 7 Participants | 21 Participants |
| Sex: Female, Male Male | 10 Participants | 18 Participants | 11 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 14 | 6 / 12 | 13 / 28 | 12 / 25 | 10 / 18 | 10 / 15 | 28 / 52 |
| serious Total, serious adverse events | 3 / 14 | 3 / 12 | 9 / 28 | 3 / 25 | 3 / 18 | 2 / 15 | 8 / 52 |
Outcome results
Primary
Mean Total Administration Time
The mean total time for administration of TIP via T-326 inhaler versus the total time for administration of COLI or TIS was assessed from information entered by participants into an ediary during the last 7 days prior to the last dose of a cycle. The total time included the setup, preparation, administration and cleaning/disinfection time.
Time frame: days 22 through 28 (cycle 1), days 78 through 84 (cycle 2)
Population: The full analysis set (FAS) was considered for this analysis. The FAS included participants who received at least 1 dose of treatment. Only participants (n), with non-missing mean total administration time of initial and second cycles, were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIS/TIP | Mean Total Administration Time | Cycle 1 (n=8,17,14) | 37.0 minutes | Standard Deviation 22.06 |
| TIS/TIP | Mean Total Administration Time | Cycle 2 (n=10,16,11) | 5.0 minutes | Standard Deviation 2.04 |
| COLI/TIP | Mean Total Administration Time | Cycle 1 (n=8,17,14) | 16.4 minutes | Standard Deviation 9.54 |
| COLI/TIP | Mean Total Administration Time | Cycle 2 (n=10,16,11) | 3.8 minutes | Standard Deviation 1.7 |
| TIP/TIP | Mean Total Administration Time | Cycle 1 (n=8,17,14) | 4.2 minutes | Standard Deviation 2.02 |
| TIP/TIP | Mean Total Administration Time | Cycle 2 (n=10,16,11) | 3.4 minutes | Standard Deviation 2.06 |
Secondary
Change in P. Aeruginosa Sputum Density
Sputum samples were sent to a central laboratory at the start and end of 2 treatment periods. The absolute change in the number of colony forming units (CFU) of Pseudomonas aeruginosa in sputum = the value of end of on/off treatment period of the cycle minus the pre-dose value at the start of that cycle. A negative change from baseline indicates improvement.
Time frame: days 1, 28 (cycle 1); 57, 84, 112 (cycle 2)
Population: The FAS was considered and included participants who received at least 1 dose of treatment. Only participants (n), with values at the start and end of an on-treatment period (on-treatment change), and/or with values at the start of an on-treatment period and end of an off-treatment period (off-treatment change), were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIS/TIP | Change in P. Aeruginosa Sputum Density | Cycle 1, on-treatment change (n=11,22,9) | -1.4 log10 CFU/mL | Standard Deviation 1.85 |
| TIS/TIP | Change in P. Aeruginosa Sputum Density | Cycle 1, off-treatment change (n=10,20,8) | 0.2 log10 CFU/mL | Standard Deviation 1.98 |
| TIS/TIP | Change in P. Aeruginosa Sputum Density | Cycle 2, on-treatment (n=9,16,5) | -0.9 log10 CFU/mL | Standard Deviation 1.66 |
| TIS/TIP | Change in P. Aeruginosa Sputum Density | Cycle 2, off-treatment (n=9,18,5) | 0.0 log10 CFU/mL | Standard Deviation 0.95 |
| COLI/TIP | Change in P. Aeruginosa Sputum Density | Cycle 2, off-treatment (n=9,18,5) | 0.5 log10 CFU/mL | Standard Deviation 2.55 |
| COLI/TIP | Change in P. Aeruginosa Sputum Density | Cycle 1, on-treatment change (n=11,22,9) | -0.6 log10 CFU/mL | Standard Deviation 1.88 |
| COLI/TIP | Change in P. Aeruginosa Sputum Density | Cycle 2, on-treatment (n=9,16,5) | -0.5 log10 CFU/mL | Standard Deviation 1.65 |
| COLI/TIP | Change in P. Aeruginosa Sputum Density | Cycle 1, off-treatment change (n=10,20,8) | -0.6 log10 CFU/mL | Standard Deviation 2.36 |
| TIP/TIP | Change in P. Aeruginosa Sputum Density | Cycle 2, off-treatment (n=9,18,5) | 0.0 log10 CFU/mL | Standard Deviation 0.91 |
| TIP/TIP | Change in P. Aeruginosa Sputum Density | Cycle 1, off-treatment change (n=10,20,8) | -0.2 log10 CFU/mL | Standard Deviation 1.56 |
| TIP/TIP | Change in P. Aeruginosa Sputum Density | Cycle 2, on-treatment (n=9,16,5) | -1.6 log10 CFU/mL | Standard Deviation 1.53 |
| TIP/TIP | Change in P. Aeruginosa Sputum Density | Cycle 1, on-treatment change (n=11,22,9) | -1.7 log10 CFU/mL | Standard Deviation 2.87 |
Secondary
Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values
MIC50/90 is the lowest concentration required to inhibit 50%/90% of the isolates tested. The MIC50/90 of a range of antibiotics for P.aeruginosa was determined at the start and end of each treatment cycle, and at the end of the off-treatment period of the second cycle.
Time frame: days 1, 28, 57, 84, 112
Population: The FAS was considered for the analysis and included participants who had at least one dose of study treatment. Only participants (n), with values on a given day, were analyzed for that day. The number of isolates tested = m.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIS/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 1, n=14,27,18; m=27,51,29 | 2 ug/mL |
| TIS/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 28, n=13,23,13; m=25,46,21 | 2 ug/mL |
| TIS/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 57, n=11,19,15; m=23,34,24 | 4 ug/mL |
| TIS/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 84, n=12,17,11; m=25,29,18 | 4 ug/mL |
| TIS/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 112, n=12,19,12; m=24,33,19 | 2 ug/mL |
| TIS/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 1, n=14,27,18; m=27,51,29 | 256 ug/mL |
| TIS/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 28, n=13,23,13; m=25,46,21 | 256 ug/mL |
| TIS/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 57, n=11,19,15; m=23,34,24 | 64 ug/mL |
| TIS/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 84, n=12,17,11; m=25,29,18 | 512 ug/mL |
| TIS/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 112, n=12,19,12; m=24,33,19 | 32 ug/mL |
| COLI/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 1, n=14,27,18; m=27,51,29 | 16 ug/mL |
| COLI/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 1, n=14,27,18; m=27,51,29 | 2 ug/mL |
| COLI/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 112, n=12,19,12; m=24,33,19 | 2 ug/mL |
| COLI/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 112, n=12,19,12; m=24,33,19 | 32 ug/mL |
| COLI/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 28, n=13,23,13; m=25,46,21 | 2 ug/mL |
| COLI/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 84, n=12,17,11; m=25,29,18 | 32 ug/mL |
| COLI/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 57, n=11,19,15; m=23,34,24 | 16 ug/mL |
| COLI/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 57, n=11,19,15; m=23,34,24 | 4 ug/mL |
| COLI/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 28, n=13,23,13; m=25,46,21 | 16 ug/mL |
| COLI/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 84, n=12,17,11; m=25,29,18 | 4 ug/mL |
| TIP/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 57, n=11,19,15; m=23,34,24 | 64 ug/mL |
| TIP/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 84, n=12,17,11; m=25,29,18 | 2 ug/mL |
| TIP/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 112, n=12,19,12; m=24,33,19 | 32 ug/mL |
| TIP/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 112, n=12,19,12; m=24,33,19 | 1 ug/mL |
| TIP/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 84, n=12,17,11; m=25,29,18 | 64 ug/mL |
| TIP/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 1, n=14,27,18; m=27,51,29 | 64 ug/mL |
| TIP/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC90: Day 28, n=13,23,13; m=25,46,21 | 64 ug/mL |
| TIP/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 1, n=14,27,18; m=27,51,29 | 2 ug/mL |
| TIP/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 28, n=13,23,13; m=25,46,21 | 2 ug/mL |
| TIP/TIP | Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values | MIC50: Day 57, n=11,19,15; m=23,34,24 | 2 ug/mL |
Secondary
Number of Participants With Any Contaminated Delivery Device
Devices used to administer the drugs (the T-326 inhaler and nebulisers) were swabbed for contamination testing at the start and end of each treatment cycle (or discontinuation visit if the participant withdrew). No assessments were required from the T-326 inhaler when participants started the treatment period (days 1 and 57). Microbial contamination was measured according to device type and the frequency of organism growth (light/ moderate/ heavy). All nebulisers (neb) used by the participants were analyzed, including those for inhaling other medications, like mucolytics.
Time frame: days (d) 1, 28, 57, 84
Population: The FAS was considered for the analysis and included participants who had at least one dose of study treatment. Only participants (n), with an available culture from the delivery device, were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | C. indologenes,d28,neb,moderate,n=0,6,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | P. putida,d1,neb,light,n=0,7,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | P. a biotype 2 - dry,d1,neb, moderate,(n=0,0,1) | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | Acinetobacter species,d28,neb,light,n=0,6,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | P. stutzeri,d1,neb,moderate,n=0,7,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | S. aureus,d28,neb,light,n=0,6,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | S. maltophilia,d1,neb,light,n=0,7,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | S.liquefaciens,d1,neb,light,n=0,7,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | A.lwoffi,d1,neb,light,n=0,7,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | S. multivorum,d1,neb,light,n=0,7,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | A. baumannii,d1,neb,heavy,n=0,7,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | S. paucimobilis,d28,neb,heavy,n=0,6,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | H. parainfluenza,d1,neb,light,n=0,7,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | A. junii,d1,neb,moderate,n=0,7,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | P. fluorescens,d28,neb,light,n=0,6,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | O. anthropic,d1,neb,heavy,n=0,7,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | S. aureus,d84,T-326,light,n=1,0,0 | 1 Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | D. acidovorans,d 28,neb,light,n=0,6,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | P. fluorescens,d1,neb,light,n=0,7,0 | NA Participants |
| TIS/TIP | Number of Participants With Any Contaminated Delivery Device | P. a biotype 2 - dry,d57,neb,light,n=1,0,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | A. junii,d1,neb,moderate,n=0,7,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | P. a biotype 2 - dry,d1,neb, moderate,(n=0,0,1) | NA Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | A. baumannii,d1,neb,heavy,n=0,7,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | A.lwoffi,d1,neb,light,n=0,7,0 | 2 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | H. parainfluenza,d1,neb,light,n=0,7,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | O. anthropic,d1,neb,heavy,n=0,7,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | P. fluorescens,d1,neb,light,n=0,7,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | P. putida,d1,neb,light,n=0,7,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | P. stutzeri,d1,neb,moderate,n=0,7,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | S.liquefaciens,d1,neb,light,n=0,7,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | S. multivorum,d1,neb,light,n=0,7,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | S. maltophilia,d1,neb,light,n=0,7,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | Acinetobacter species,d28,neb,light,n=0,6,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | C. indologenes,d28,neb,moderate,n=0,6,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | D. acidovorans,d 28,neb,light,n=0,6,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | P. fluorescens,d28,neb,light,n=0,6,0 | 2 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | S. paucimobilis,d28,neb,heavy,n=0,6,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | S. aureus,d28,neb,light,n=0,6,0 | 1 Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | P. a biotype 2 - dry,d57,neb,light,n=1,0,0 | NA Participants |
| COLI/TIP | Number of Participants With Any Contaminated Delivery Device | S. aureus,d84,T-326,light,n=1,0,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | P. fluorescens,d1,neb,light,n=0,7,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | S. aureus,d28,neb,light,n=0,6,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | O. anthropic,d1,neb,heavy,n=0,7,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | A. baumannii,d1,neb,heavy,n=0,7,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | D. acidovorans,d 28,neb,light,n=0,6,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | H. parainfluenza,d1,neb,light,n=0,7,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | S. aureus,d84,T-326,light,n=1,0,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | P. fluorescens,d28,neb,light,n=0,6,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | A.lwoffi,d1,neb,light,n=0,7,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | P. a biotype 2 - dry,d57,neb,light,n=1,0,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | S.liquefaciens,d1,neb,light,n=0,7,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | S. paucimobilis,d28,neb,heavy,n=0,6,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | S. multivorum,d1,neb,light,n=0,7,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | P. stutzeri,d1,neb,moderate,n=0,7,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | A. junii,d1,neb,moderate,n=0,7,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | S. maltophilia,d1,neb,light,n=0,7,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | P. putida,d1,neb,light,n=0,7,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | C. indologenes,d28,neb,moderate,n=0,6,0 | NA Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | P. a biotype 2 - dry,d1,neb, moderate,(n=0,0,1) | 1 Participants |
| TIP/TIP | Number of Participants With Any Contaminated Delivery Device | Acinetobacter species,d28,neb,light,n=0,6,0 | NA Participants |
Secondary
Number of Participants With Post-inhalation Bronchospasm
Bronchospasm was defined as the relative decrease of 20% or more in forced expiratory volume in 1 second (FEV1) percent predicted from pre-dose to 15 to 45 minutes post-dose.
Time frame: days 1, 28, 57, 84
Population: The FAS was considered for the analysis and included participants who had at least one dose of study treatment. Only participants (n), with values on a given day, were analyzed for that day.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIS/TIP | Number of Participants With Post-inhalation Bronchospasm | Day 1, n=8,17,14 | 0 Participants |
| TIS/TIP | Number of Participants With Post-inhalation Bronchospasm | Day 28, n=6,19,14 | 0 Participants |
| TIS/TIP | Number of Participants With Post-inhalation Bronchospasm | Day 57, n=10,22,13 | 0 Participants |
| TIS/TIP | Number of Participants With Post-inhalation Bronchospasm | Day 84, n=8,14,10 | 0 Participants |
| COLI/TIP | Number of Participants With Post-inhalation Bronchospasm | Day 84, n=8,14,10 | 0 Participants |
| COLI/TIP | Number of Participants With Post-inhalation Bronchospasm | Day 1, n=8,17,14 | 1 Participants |
| COLI/TIP | Number of Participants With Post-inhalation Bronchospasm | Day 57, n=10,22,13 | 0 Participants |
| COLI/TIP | Number of Participants With Post-inhalation Bronchospasm | Day 28, n=6,19,14 | 1 Participants |
| TIP/TIP | Number of Participants With Post-inhalation Bronchospasm | Day 84, n=8,14,10 | 0 Participants |
| TIP/TIP | Number of Participants With Post-inhalation Bronchospasm | Day 28, n=6,19,14 | 0 Participants |
| TIP/TIP | Number of Participants With Post-inhalation Bronchospasm | Day 57, n=10,22,13 | 1 Participants |
| TIP/TIP | Number of Participants With Post-inhalation Bronchospasm | Day 1, n=8,17,14 | 0 Participants |