Open Label Extension to Bridging Study CTBM100C2303

AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal product.

SAEs included adverse events that resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.

AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal product. SAEs included adverse events that resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.

Shift from baseline in hematology and biochemistry values to above upper/below lower limit of normal at any time post-baseline were reported. Baseline for safety analyses was defined as the last measurement prior to first dose of study drug in the core study CTBM100C2303. Change to low referred to number of participants with normal or high values at baseline. Change to high referred to number of participants with normal or low values at baseline.

Airway Reactivity was defined as ≥20% FEV1 relative decrease in percent predicted from pre dose to 30 minutes post dose. FEV1 was defined as the volume of air expired in 1 second. FEV1 % predicted was a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. Relative change in FEV1 % predicted = 100* (30 minutes post dose - pre dose) / pre dose assessed by number and percentage of participants with a decrease in ≥20% FEV1 percent predicted from pre dose to 30 minutes post dose. Baseline for was defined as the last measurement prior to first dose of study drug in the core study CTBM100C2303.

Auditory acuity of participants was measured using a standard dual-channel audiometer at frequencies from 250 to 8000 Hertz, and an audiogram (pure-tone air conduction) and tympanogram were performed by an audiologist. The categories reported includes >= 10dB decrease in 3 consecutive frequencies in either ear, >= 15dB decrease in 2 consecutive frequencies in either ear, and >= 20dB decrease in at least one frequency in either ear.

AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal product. SAEs included adverse events that resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.

FEV1 was defined as the volume of air expired in 1 second. FEV1 % predicted was a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. Relative change in FEV1 % predicted = 100* (30 minutes post dose - pre dose) / pre dose assessed by number and percentage of participants with a decrease in ≥20% FEV1 percent predicted from pre dose to 30 minutes post dose. Baseline for was defined as the last measurement prior to first dose of study drug in the core study CTBM100C2303. Termination referred to the last available pre dose post-baseline measurement.

Relative change from baseline in FVC % predicted to end of dosing in each cycle and study completion were reported. Relative change from baseline was defined as: Relative change = 100* (Post baseline- baseline) / baseline. Baseline was defined as last measurement prior to first dose of study drug in the core study CTBM100C2303. Termination referred to the last available pre dose post-baseline measurement.

Relative change from baseline in FEF25-75% predicted to end of dosing in each cycle and study completion were reported. Relative change from baseline was defined as: Relative change = 100* (Post baseline- baseline) / baseline. Baseline was defined as last measurement prior to first dose of study drug in the core study CTBM100C2303. Termination referred to the last available pre dose post-baseline measurement.

P. aeruginosa sputum density referred to overall density, defined as the sum of biotypes (mucoid, dry and small colony variant). If sub-isolates existed for CFU biotype mucoid or dry, then the sum of sub-isolates was analyzed. Absolute change from baseline was defined as: Absolute change = Post Baseline - Baseline. Baseline was defined as last measurement prior to first dose of study drug in the core study CTBM100C2303. Termination referred to the last available pre dose post-baseline measurement.

Change in tobramycin MIC values for P. aeruginosa were reported for specimens and were used to assess the change in pathogen susceptibility to tobramycin before (baseline) and after (post-baseline) the treatment. Maximum MIC values from all biotypes were used. Change from baseline was defined as: Change = Post-baseline - Baseline. Baseline was defined as last measurement prior to first dose of study drug in the core studyCTBM100C2303.Termination referred to the last available pre dose post-baseline measurement.

SAEs included adverse events that resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. For calculation of days in hospitalization due to respiratory events, the end date was defined as the discharge date (if provided and even if after the end of the extension study), and otherwise as the date of last visit.