Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia

Inclusion Criteria

• The subject must have evidence supportive of a PCD diagnosis.
• Subjects with percent predicted FEV1 of ≥40 to <90 percentage points
• Non-smoker for at least 90 days prior to the Screening Visit and less than a 5 pack-year lifetime history of smoking
• Stable regimen of medications and chest physiotherapy for the 28 days prior to Day 1
• If currently using daily inhaled HS, must be able to discontinue its use for the duration of the study.
• If taking daily chronic or chronic cycling antibiotics, has been on a consistent regimen for at least 4 months prior to the Screening Visit.
• Clinically stable (as deemed by the investigator) for at least 14 days prior to the Screening Visit
• Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening Visit. Subjects of childbearing potential and who are sexually active must meet the contraception requirements.

Exclusion Criteria

• Diagnosis of CF based on results of sweat chloride or nasal potential difference (NPD) tests or presence of 2 CF-causing mutations in CFTR gene.
• History of any organ transplantation or lung resection or chest wall surgery.
• Significant congenital heart defects, other than a laterality defect, at the discretion of the investigator
• Diagnosis of Cri du chat syndrome (chromosome 5p deletion syndrome).
• Inability to withhold short-acting bronchodilator use for 4 hours prior to clinic visit and long-acting bronchodilator use the night before the first and last clinic visit of each treatment period.
• Use of diuretics (including amiloride) or renin-angiotensin antihypertensive drugs
• Symptoms of acute upper or lower respiratory tract infection, acute pulmonary exacerbation, or treatment or was treated with systemic antibiotics for ear or sinus disease within 28 days before Day 1 (topical otic antibiotics allowed).
• History of significant intolerance to inhaled HS
• Pregnant and/or nursing females
• Any clinically significant laboratory abnormalities
• History of chronic B. cepacia complex or M. abscessus or M. avium
• Surgery that required general anesthesia and hospitalization within 3 months of Day 1

Additional Exclusion Criteria for Part B:

• In addition to the exclusion criteria above, subjects who participate in Part B and meet any of the following exclusion criteria will not be eligible to continue into Part B
• Unable to swallow tablets.
• Concomitant use of strong or moderate inhibitors or inducers of cytochrome P450 (CYP) 3A, including consumption of certain herbal medications (e.g., St. John's Wort), and grapefruit/grapefruit juice.
• Known hypersensitivity to ivacaftor.