Inhaled Vancomycin Tolerability, Safety and Pharmacokinetics

Inclusion Criteria Healthy Volunteers:

• Healthy male volunteers between 18 and 50 years of age inclusive.
• Able to communicate with site personnel and to understand and voluntarily sign the Informed Consent Form.
• Able and willing to comply with the Protocol, including availability for all scheduled study visits.
• Body Mass Index (BMI) of 20 to 30 kg/m2 inclusive, and weight between 60-90 kg inclusive.
• No clinically significant abnormalities at screening determined by medical history, physical examination, blood chemistry, hematology, urinalysis, and 12-lead ECG. Negative urine screen for drugs of abuse and negative alcohol breath test at Screening and prior to dosing.
• Negative human immunodeficiency virus (HIV) and Hepatitis B and Hepatitis C screening test results.
• Spirometry (forced expiratory volume in 1 second (FEV1)) value at screening greater than 75% of predicted age-adjusted value.

Exclusion Criteria Healthy Volunteers:

• A history of pulmonary or other disorder likely to influence drug absorption.
• Evidence or suspicion of clinically significant respiratory, renal, hepatic, central nervous system, cardiovascular or metabolic dysfunction.
• A history of previous allergies or sensitivity to vancomycin, or other component(s) of the study drug or reference drug.
• Smokers (ex-smokers who quit smoking must have a one year period of not smoking prior to the study drug administration).
• Respiratory tract infection within the last two weeks prior to the first study drug administration.
• Treatment with any prescription medication and/or over-the-counter (OTC) products including vitamins or mineral supplements within 48 hours before Investigational Product administration.
• Vaccination within one month before the study drug administration.
• Systolic blood pressure 150 mmHg inclusive or diastolic blood pressure 90 mmHg inclusive.
• A history of drug or alcohol abuse.
• Participation in a clinical study within three months on Investigational Product administration.
• Donation of blood or plasma within three months of Investigational Product administration.
• Any other condition which in the view of the Investigator is likely to interfere with the study or put the subject at risk.

Inclusion Criteria CF Patients:

• Able to communicate with site personnel and to understand and voluntarily sign the Informed Consent Form.
• Able and willing to comply with the protocol, including availability for all scheduled study visits.
• Have a confirmed diagnosis of cystic fibrosis (by two established methods, e.g. positive sweat chloride value ≥ 60 mEq/L, nasal potential difference test, and/or genotype with two identifiable mutations consistent with CF, accompanied by one or more clinical features consistent with the CF phenotype).
• Be aged ≥ 18 years old
• Have FEV1 >40 % of predicted
• Be able to perform all the techniques necessary to measure lung function
• No liver enzymes increased by more than twice the upper limit of normal
• Ability to spontaneously produce bronchial sputum daily

Inclusion Criteria CF Patients:

• Administration of any investigational drug or device within 28 days of Screening and within six half-lives of the investigational drug.
• Oral corticosteroids in doses exceeding 10 mg per day or 16 mg every other day.
• History of sputum culture or throat swab culture yielding B. cepacia in the previous two years.
• History of positive MRSA culture, or sputum culture positive for MRSA at screening.
• Current daily continuous oxygen supplementation or requirement for more than 2 L/min at night.
• A history of previous allergies or sensitivity to vancomycin, or other component(s) of the study drug.
• Changes in antimicrobial, bronchodilator, anti-inflammatory or corticosteroid medications within 7 days prior to Screening.
• Changes in physiotherapy technique or schedule within 7 days prior to Screening.
• History of lung transplantation.
• A chest X-Ray at Screening