Background: As non-cystic fibrosis bronchiectasis (NCFB) progresses, patients suffer irreversible lung damage and deterioration in lung function. This study explored whether inhalational parameters (peak inspiratory flow [PIF, primary endpoint], inspiratory volume and time [secondary endpoints]) represent barriers to complete dosing in patients with poor lung function who are using Ciprofloxacin dry powder for inhalation (DPI) (a drug-device combination of the T-326 inhaler device and a Ciprofloxacin dry powder formulation). Methods: This open-label, multicenter study generated inspiratory flow rate data from patients with NCFB using the breath-actuated T-326 dry powder inhaler. These rates were compared against reference values to identify whether patients with all degrees of lung function impairment could generate sufficient flow rates to facilitate adequate drug delivery. Patients attended screening and a second visit 1 - 14 days later. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, and inspiratory capacity were measured via spirometry at both visits. Forty-two patients were screened for inclusion; 33 met eligibility criteria and were stratified into one of three groups based on their FEV1% predicted value (group 1: 25% ≤ FEV1% predicted <45%; group 2: 45% ≤ FEV1% predicted <70%; group 3: FEV1% predicted ≥70%). Results: No significant between-group differences occurred in PIF (mean flow rates 68.21, 66.01, and 65.18 L/min in groups 1, 2, and 3, respectively). Individual minimum PIFs of 46.0-49.0 L/min were observed across groups. These results all exceeded the reference value (minimum PIF 45 L/min for Ciprofloxacin DPI) indicating that regardless of the level of airflow obstruction, patients were capable of achieving sufficient PIFs to aerosolize and inhale Ciprofloxacin dry powder with the T-326 inhaler. Conclusions: Our data indicate that T-326 is suitable for use in the drug-device combination Ciprofloxacin DPI to provide targeted pulmonary delivery in patients with NCFB, including those with significantly impaired lung function.
Trial registration: ClinicalTrials.gov NCT02563197.
Keywords: dry powder for inhalation; inhaled antibiotics; non-CF bronchiectasis; peak inspiratory flow.