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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Tobramycin Inhalation Powder was administered via TOBI® Podhaler (T-326 inhaler).
Tobramycin inhalation solution was administered via nebuliser
Colistimethate was administered via nebuliser.
Novartis Investigative Site
Berlin, Germany
Novartis Investigative Site
Essen, Germany
Novartis Investigative Site
München, Germany
Novartis Investigative Site
Tübingen, Germany
Novartis Investigative Site
Galway, Ireland
Novartis Investigative Site
Seville, Andalusia, Spain
Novartis Investigative Site
Palma de Mallorca, Balearic Islands, Spain
Novartis Investigative Site
Barcelona, Catalonia, Spain
Novartis Investigative Site
Madrid, Madrid, Spain
Novartis Investigative Site
Valencia, Valencia, Spain
...and 11 more locations
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)
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)
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
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
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
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