Tolerability and Safety of Inhaled Colistimethate Sodium (CMS) Administered Once Daily Compared to Twice Daily Dosing in Adult and Adolescent Subjects with Cystic Fibrosis and Chronic Pseudomonas Aeruginosa Lung Infection (COPILOT)

Inclusion Criteria22

• Male and female subjects, ages 12 years and older:
• a. Step A: ages 18 years and older (adults)
• b. Step B: ages 12 years and older (children, adolescents, and adults)
• Previous diagnosis of cystic fibrosis as confirmed by:
• a. documented sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test prior to initiation of therapy with CFTR modulators (e.g., elexacaftor, tezacaftor, ivacaftor), if applicable; or
• b. two well-characterized genetic mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene; and
• c. symptoms characteristic of cystic fibrosis
• Persistent airways infection with P. aeruginosa as evidenced by:
• a. positive P. aeruginosa in a sputum/deep-throat cough swab culture (or bronchoalveolar lavage [BAL]) within 6 months prior to Screening; or
• b. history of inhaled antibiotic treatment for suppression of P. aeruginosa
• Stable treatment regimen of CF therapeutics for at least 2 months prior to randomization defined as:
• a. regimen of inhaled antibacterials for either at least 2 months of continuous therapy or at least a total of 56 days of consecutive on-treatment periods in case of cyclical therapy (e.g., 28 days on treatment, followed by 28 days off treatment, followed by another 28 days on treatment) prior to randomization AND
• b. no changes in either any current treatment regimen or initiation of treatment with hypertonic saline, dornase alfa, CFTR modulators or other CF specific therapeutics.
• Ability to perform reproducible pulmonary function tests.
• FEV1 at Screening of greater than or equal to 30% of predicted values
• Arterial oxygen saturation (SpO2) greater than or equal to 90% on room air at Screening
• Clinically stable in the opinion of the Investigator
• Female subjects of childbearing potential must have a negative pregnancy test at the Screening Visit and must use a highly acceptable method of contraception after the first dose of trial drug and for 28 days after the last dose of trial drug, as defined in the protocol. To be considered “not of childbearing potential”:
• a. female subjects must be postmenopausal for at least 1 year as confirmed by an elevated follicle-stimulating hormone (FSH) level (greater than or equal to 30 mIU/mL) at Screening and 1 year of amenorrhea, or have been irreversibly surgically sterilized by hysterectomy, oophorectomy, or bilateral tubal ligation for at least 3 months prior to the first dose of trial drug; or
• b. female subjects must be before their first menstrual cycle (i.e., menarche)
• Male subjects whose female partners are of childbearing potential (definition as above) must agree to use an acceptable method of birth control for the duration of trial treatment and for 28 days after the last dose of trial drug.
• Signed written informed consent.