Inhaled Vancomycin Tolerability, Safety and Pharmacokinetics
Condition: Healthy; Cystic Fibrosis
MeSH terms: Cystic Fibrosis
Intervention: AeroVanc; IV vancomycin hydrochloride
Intervention description: Vancomycin hydrochloride dry powder for inhalation; Vancomycin hydrochloride solution for intravenous administration
Intervention MeSH terms: Vancomycin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The study is carried out to evaluate the safety, tolerability and pharmacokinetics of
      AeroVanc inhalation powder in healthy volunteers, and in patients with cystic fibrosis.
    

Eligibility criteria:

        Inclusion Criteria Healthy Volunteers:

          1. Healthy male volunteers between 18 and 50 years of age inclusive.

          2. Able to communicate with site personnel and to understand and voluntarily sign the
             Informed Consent Form.

          3. Able and willing to comply with the Protocol, including availability for all scheduled
             study visits.

          4. Body Mass Index (BMI) of 20 to 30 kg/m2 inclusive, and weight between 60-90 kg
             inclusive.

          5. 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.

          6. Negative human immunodeficiency virus (HIV) and Hepatitis B and Hepatitis C screening
             test results.

          7. Spirometry (forced expiratory volume in 1 second (FEV1)) value at screening greater
             than 75% of predicted age-adjusted value.

        Exclusion Criteria Healthy Volunteers:

          1. A history of pulmonary or other disorder likely to influence drug absorption.

          2. Evidence or suspicion of clinically significant respiratory, renal, hepatic, central
             nervous system, cardiovascular or metabolic dysfunction.

          3. A history of previous allergies or sensitivity to vancomycin, or other component(s) of
             the study drug or reference drug.

          4. Smokers (ex-smokers who quit smoking must have a one year period of not smoking prior
             to the study drug administration).

          5. Respiratory tract infection within the last two weeks prior to the first study drug
             administration.

          6. Treatment with any prescription medication and/or over-the-counter (OTC) products
             including vitamins or mineral supplements within 48 hours before Investigational
             Product administration.

          7. Vaccination within one month before the study drug administration.

          8. Systolic blood pressure <110 mmHg or >150 mmHg inclusive or diastolic blood pressure
             <60 mmHg or >90 mmHg inclusive.

          9. A history of drug or alcohol abuse.

         10. Participation in a clinical study within three months on Investigational Product
             administration.

         11. Donation of blood or plasma within three months of Investigational Product
             administration.

         12. 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:

          1. Able to communicate with site personnel and to understand and voluntarily sign the
             Informed Consent Form.

          2. Able and willing to comply with the protocol, including availability for all scheduled
             study visits.

          3. 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).

          4. Be aged ≥ 18 years old

          5. Have FEV1 >40 % of predicted

          6. Be able to perform all the techniques necessary to measure lung function

          7. No liver enzymes increased by more than twice the upper limit of normal

          8. Ability to spontaneously produce bronchial sputum daily

        Inclusion Criteria CF Patients:

          1. Administration of any investigational drug or device within 28 days of Screening and
             within six half-lives of the investigational drug.

          2. Oral corticosteroids in doses exceeding 10 mg per day or 16 mg every other day.

          3. History of sputum culture or throat swab culture yielding B. cepacia in the previous
             two years.

          4. History of positive MRSA culture, or sputum culture positive for MRSA at screening.

          5. Current daily continuous oxygen supplementation or requirement for more than 2 L/min
             at night.

          6. A history of previous allergies or sensitivity to vancomycin, or other component(s) of
             the study drug.

          7. Changes in antimicrobial, bronchodilator, anti-inflammatory or corticosteroid
             medications within 7 days prior to Screening.

          8. Changes in physiotherapy technique or schedule within 7 days prior to Screening.

          9. History of lung transplantation.

         10. A chest X-Ray at Screening or within the previous 90 days of Screening, with
             abnormalities indicating a significant acute finding (e.g., lobar infiltrate and
             atelectasis, pneumothorax, or pleural effusion).

         11. Positive pregnancy test. All women of childbearing potential will be tested.

         12. Female of childbearing potential who is lactating or is not practicing acceptable
             method of birth control (e.g., hormonal or barrier methods, or intrauterine device).

         13. Findings at Screening that, in the investigator's opinion, would compromise the safety
             of the subject or the quality of the study data.

         14. History of severe cough/bronchospasm upon inhalation of dry powder inhalation product.

         15. Considered "terminally ill" or eligible for lung transplantation.

         16. Have had a significant episode of hemoptysis (>60 mL) in the three months prior to
             enrolment.