A Double-Blind, Active-Controlled, Multiple-Ascending Dose Study of Aerosolized RSP-1502 in Subjects With CF and Chronic PA Lung Infection

Exclusion Criteria20

• A history of previous allergy or sensitivity to components of RSP 1502.
• A history of intolerance to inhaled tobramycin (TOBI®, BETHKIS®, TOBI® Podhaler®, tobramycin inhalation solution).
• eGFR \< 40 mL/min, or serum total bilirubin \> 2X or serum transaminases \> 3X the upper limit of normal range at screening.
• Currently taking other medications with known nephrotoxic, neurotoxic, or ototoxic potential (subjects receiving inhaled tobramycin in conjunction with low dose azithromycin prior to study participation without evidence of ototoxicity may continue taking low dose azithromycin during the study).
• Currently taking ethacrynic acid, furosemide, urea, or intravenous mannitol.
• Lung infection with organisms associated with a more rapid decline in pulmonary status (including, but not limited to, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus). For subjects who have had a history of a positive culture, the investigator will apply the following criteria to establish whether the subject is free of infection with such organisms:
• The subject has not had a respiratory tract culture positive for these organisms within the 12 months before the date of informed consent.
• The subject has had at least 2 respiratory tract cultures negative for such organisms within the 12 months before the date of informed consent, with the first and last of these separated by at least 3 months, and the most recent one within the 6 months before the date of informed consent.
• Consistent inability to produce sputum and unwillingness to perform sputum induction.
• Any acute upper or lower respiratory tract infection or pulmonary exacerbation requiring changes in therapy (including systemic antibiotics), or other significant clinical/laboratory/radiological/spirometric sign of unstable or unexpectedly deteriorating respiratory disease within 30 days prior to the first study drug administration.
• Initiation or adjustment of chronic airway medications (eg, inhaled corticosteroids; chronic suppressive antibacterial treatment) or airway clearance regimen (eg, nebulized saline, rhDNase, initiation of mechanical vest or handheld airway clearance device) within 28 days prior to screening. Individuals can be rescreened 28 days after these agents/therapies have been established for at least 28 days.
• Is immunocompromised due to illness, or solid or hematological organ transplant.
• Requires systemic prednisone (or equivalent) \> 10 mg daily.
• Vaping or smoking tobacco or any other substance within 1 month prior to screening and anticipated inability to refrain from vaping or smoking throughout the study.
• Female subjects who are pregnant, lactating, or have a positive urine human chorionic gonadotropin (pregnancy) test, as determined by laboratory testing.
• HIV positive.
• Active Hepatitis B or C.
• History of recreational drug or alcohol use/abuse which in the opinion of the investigator will compromise the patient's ability to comply with the study protocol.
• Participation in a clinical study with administration of an investigational drug product within the previous 30 days, or five half-lives of the previously administered investigational product.
• Has any other medical condition(s) which, in the opinion of the Principal Investigator, would jeopardize the safety of the study subject or impact the validity of the study results.