Following are the major changes in amendment-1: 1. Allowing randomization from throat swab, sputum or nasopharyngeal aspiration samples culture tested P. aeruginosa-positive at local site laboratory following local microbiology standard operating procedures. With view to maintain data integrity and primary endpoint robustness, re-identification and susceptibility testing of the P. aeruginosa isolates and the subtypes was to be performed at central laboratory. Hence allowing the screening and randomization visits to occur on the same day and the patient to start study medication immediately. 2. Allowing patients to be randomized from local laboratory safety results. Central safety laboratory results were available to the site within 7 days after samples are taken. The patient was to be discontinued in the event of clinically significant abnormal results as defined in the protocol. 3. Reduction of sample size based on revised realistic active and placebo treatment effects. The initial assumptions for the placebo effect were very conservative, as stated in the protocol. Published data in this population and with placebo-controlled trials are extremely limited; however, in a prospective, randomized, placebo-controlled, double-blind study enrolling 22 patients (Wiesemann et al 1998), 8 out of 10 patients in the placebo arm were still P. aeruginosa-positive after 1 month of treatment. Thus adopting a 30% placebo effect still remained conservative. 4. Performing an analysis and generating a report focusing on the double-blind randomized study results.

Amendment 2 included the following changes: 1. It was required to ensure consistency throughout the protocol that audiology assessments were only to be done by the patients at sites which are able to perform this assessment. Therefore the number of patients to have audiology assessments was based on site capabilities. 2. Any reference to the assent form in the protocol was deleted as the assent form was not required by any active site and therefore was not signed by any patient. 3. Exclusion criterion no. 1 was changed in order to clarify that any anti-pseudomonal antibiotic treatment within 1 year prior to randomization was prohibited. 4. The overview of visit paths during the treatment phase was corrected and clarified in order to be in line with the protocol design and text within the protocol. 5. Finally, the statistical section was updated to document that the primary analysis would be performed after all patients had completed the treatment phase of the study as this was missing previously.