This is a single center, open label, Phase IIa, multiple-ascending dose study in which subjects with mild to moderate Cystic Fibrosis and non CF bronchiectasis (n≤12) will be enrolled.

The safety and tolerability of S-1226 composed of PFOB with ascending doses of carbon dioxide (4%, 8%, and 12% CO2) administered twice daily in subjects with Cystic Fibrosis and non CF bronchiectasis will be evaluated. This will be followed by 5 day consecutive treatment using the highest tolerated dose of S1226. Participants can choose additional use of a further four weeks (28 days) of S-1226 therapy at home, using same or a lower tolerated dose.

This is a single center, open label, Phase IIa, multiple-ascending dose study in which subjects with mild to moderate Cystic Fibrosis and non CF bronchiectasis (n≤12) will be enrolled.

The study will consist of a screening period, a run-in and two dosing and evaluation periods (with a minimum two-day break in between) and a follow-up period.

The dosing and evaluation period of the study is divided into two consecutive components:

1. Dose escalation study

   - This segment of the treatment period is designed to assess the safety and tolerability of escalating doses of S-1226 (4%, 8% and 12%) in those with mild-moderate CF and non CF bronchiectasis

2. Daily dosing study - This segment of the treatment period is designed to assess the short term (5 day) safety and tolerability of twice daily administration of a fixed dose of S-1226 in subjects with mild-moderate CF and non CF bronchiectasis.

The primary aim of this study of S-1226 is to capture information to inform follow-up S-1226 clinical studies in CF and non CF bronchiectasis. Important in this regard will be data on safety, tolerability, dosing and efficacy. Specifically, regarding efficacy, the investigators want to examine for optimal dose ranging and magnitude of the effect to determine the power calculations for any follow-up studies and to determine which outcome measures best reflect the effects of the drug. Because the study is investigational in nature, it will be un-blinded and information will be analyzed as it is collected.

During the screening and the run-in period, the subjects will have safety assessments and all eligibility criteria confirmed. The run-in period involves meeting with the study subjects 1 - 2 weeks prior to the start of the treatment for a physical exam, concomitant medication review, spirometry and information regarding the study. The consent process will also take place at this stage.

The dose escalation period will include 3 days of twice daily treatment of the study drug with a washout period in between. The dose of CO2 in S-1226 will be sequentially escalated for the particular subject from the starting dose of 4% CO2. Planned subsequent dose levels are 8% and 12% CO2, although doses may be adjusted within this range based on safety and tolerability data from the completed dosing days. Subjects will not be dosed with a higher CO2 level until drug administration of the preceding dose level has been completed and safety data reviewed by the Safety Committee and a decision taken to proceed or not with the next sequential dose level.

There will be a washout period between the dose escalation and the daily dosing study. The daily dosing study will include 5 days of twice daily treatment of the study drug based on the results of the dose escalation study. Lung function tests will be performed before and after the treatment.

Subjects in the Home Extension Study will receive S-1226 twice daily for 28 consecutive days. Subjects will monitor daily symptom scores. Oxygen saturation values, as determined by pulse oximetry, will be monitored 2 minutes prior to therapy, during therapy and for up to 30 minutes post therapy. Pulmonary function studies will be assessed weekly by the designated respiratory therapist between 4-7 pm.

The follow-up phase will occur 10-14 days after completion of the final dose. This will involve a clinical exam, spirometry and completion of CFQ-R.

Inclusion Criterian(CF lung disease):

• Confirmed diagnosis of Cystic Fibrosis by sweat chloride concentration over 60 mosm/L and/or genotype analysis identifying two disease causing mutations

• Male or Female over the age of 14

• Followed in CF clinic at Foothills Hospital or Alberta Children's Hospital

• Known lung involvement

  1. Recommended airway clearance daily or twice daily
  2. FEV1, % predicted, between 40-80%
  3. Evidence of Cystic Fibrosis lung involvement on Imaging, if available

• Competent at providing reliable and accurate pulmonary function studies

• Clinically stable - no pulmonary exacerbation of CF for which the patient has been hospitalized or received intravenous antibiotics for 4 weeks, no change in frequency of airway clearance

Exclusion Criteria CF lung disease:

• Gross Hemoptysis in previous 4 weeks
• Pneumothorax in previous 4 weeks
• Pregnancy or of child bearing age without adequate contraception
• Inability to produce acceptable and reproducible pulmonary function studies
• Evidence of elevated PaCO2 in recent 6 months
• Inability to perform airway clearance twice a day for the duration of the study
• History of anxiety/panic disorders
• Breast-feeding subject.
• Positive pregnancy test at screening.
• Subject, who in the opinion of the Investigator, is mentally or emotionally unsuitable to participate, or unable/unwilling to comply with the study assessments.

Gross Hemoptysis in previous 4 weeks Pneumothorax in previous 4 weeks Pregnancy or of child bearing age without adequate contraception Inability to produce acceptable and reproducible pulmonary function studies Evidence of elevated PaCO2 in recent 6 months Inability to perform airway clearance twice a day for the duration of the study History of anxiety/panic disorders Breast-feeding subject. Positive pregnancy test at screening. Subject, who in the opinion of the Investigator, is mentally or emotionally unsuitable to participate, or unable/unwilling to comply with the study assessments.

Inclusion Criteria (Non-CF bronchiectasis)

• Male or Female including and over the age of 14

• Known lung involvement

  1. FEV1, % predicted, between 40-80%
  2. Evidence of bronchiectasis on Imaging

• Competent at providing reliable and accurate pulmonary function studies

• Clinically stable - no pulmonary exacerbation for which the patient has been hospitalized or received intravenous antibiotics for 4 weeks

Exclusion Criteria (Non-CF bronchiectasis)

• Diagnosis of Cystic Fibrosis
• Active tuberculosis and/or non-tuberculosis mycobacterial infection
• Active allergic bronchopulmonary aspergillosis
• Traction bronchiectasis due to pulmonary fibrosis
• Gross Hemoptysis in previous 4 weeks
• Pneumothorax in previous 4 weeks
• Pregnancy or of child bearing age without adequate contraception
• Inability to produce acceptable and reproducible pulmonary function studies
• Evidence of elevated PaCO2 in recent 6 months
• Inability to perform airway clearance twice a day for the duration of the study
• History of anxiety/panic disorders
• Breast-feeding subject.
• Positive pregnancy test at screening.
• Subject, who in the opinion of the Investigator, is mentally or emotionally unsuitable to participate, or unable/unwilling to comply with the study assessments.