MP-376 (Aeroquin™, Levofloxacin for Inhalation) in Patients With Cystic Fibrosis

The start of the exacerbation was determined by the earliest date at which a participant concurrently met at least 4 of the 12 modified Fuchs symptoms/signs; discontinued from the study early; died; or received an antipseudomonal agent for an event that did not meet modified Fuchs criteria but was determined to be an exacerbation by the Blinded Exacerbation.

Fuchs symptoms/signs;

• Change in sputum
• New or increased hemoptysis
• Increased cough
• Increased dyspnea
• Malaise, fatigue or lethargy
• Temperature above 38oC
• Anorexia or weight loss
• Sinus pain or tenderness
• Change in sinus discharge
• Change in physical examination of the chest
• Decrease in pulmonary function by 10 percent or more from a previously recorded value
• Radiographic changes indicative of pulmonary infection

Median and 95%Ci were estimated using Kaplan Meier estimates.

FEV1 was the volume of air exhaled in first second of a forced expiration as measured by spirometer. Least squares (LS) mean and standard error are determined from a repeated measures model with terms for treatment, visit, treatment*visit, region (US, non-US), age (12-18 years, >18 years), and baseline FEV1 (<55%, >=55%).

Pseudomonas aeruginosa density was measured as log10 colony-forming units [CFU] per gram sputum. LSMean and standard are determined from a repeated measures model with terms for treatment, visit, treatment*visit, region (US, non-US), age (12-18 years, >18 years), baseline FEV1 (<55%, >=55%), and baseline organism log density.

The Cystic Fibrosis Questionnaire (CFQ-R) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents and adults with cystic fibrosis (CF). Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. LSMean and standard error were determined from a repeated measures model with terms for treatment, visit, treatment*visit, region (US, non-US), age (12 to 18 years, > 18 years), Baseline FEV1 (<55%, ≥ 55%), and Baseline value.

FEV1 was the volume of air exhaled in first second of a forced expiration as measured by spirometer. Least squares (LS) mean and standard error are determined from a repeated measures model with terms for treatment, visit, treatment*visit, region (US, non-US), age (12-18 years, >18 years), and baseline FEV1 (<55%, >=55%).

Participants who had at least one of four worsening respiratory symptoms (increased cough, increased sputum/chest congestion, decreased exercise tolerance, decreased appetite) at the time of administration of the anti-pseudomonal antimicrobial agent were included in the analysis. Median and 95% CI are estimated using Kaplan Meier estimates.

Median and 95%CI was estimated using Kaplan Meier estimates.

An AE was defined as any unfavorable or unintended sign, symptom, or disease temporally associated with the use of a Study Drug, whether or not considered related to the Study Drug.

An AE could potentially be a new disease, any untoward event, or an exacerbation of a pre-existing condition. AEs included, but were not limited to:

• Any symptom not previously reported by the patient (medical history)
• An exacerbation of a pre-existing illness
• An increase in frequency or intensity of a pre-existing episodic event or condition
• A condition first detected or diagnosed after Study Drug administration even though the condition may have been present before the start of the study
• Overdose of Study Drug