Inhaled Vancomycin Tolerability, Safety and Pharmacokinetics

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01537666
• Date of registration: 17/02/2012
• Prospective Registration: No
• Primary sponsor: Savara Inc.
• Public title: Inhaled Vancomycin Tolerability, Safety and Pharmacokinetics
• Scientific title: Phase I, Reference-controlled, Dose Escalating Study to Examine the Pharmacokinetics and Safety of AeroVanc Inhalation Powder.
• Date of first enrolment: November 2011
• Target sample size: 25
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01537666
• Study type: Interventional
• Phase: Phase 1

Countries of recruitment

Australia

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 50 Years
Gender: All

Health Condition(s) or Problem(s) studied

Healthy

Cystic Fibrosis

Intervention(s)

Drug: IV vancomycin hydrochloride

Drug: AeroVanc

Primary Outcome(s)

Safety and Tolerability - Number of Participants With Treatment Emergent Adverse Events (TEAEs = Adverse Events That Started During or After the First Dose of Study Drug) [Time Frame: Healthy volunteers = 2 weeks; CF Patients = 1 week]

Secondary Outcome(s)

Plasma Pharmacokinetics - Elimination Half Life (t½) [Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose]

Plasma Pharmacokinetics - Maximum Plasma Concentration (Cmax) [Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose]

Plasma Pharmacokinetics - Time to Reach the Maximum Plasma Concentration (Tmax) [Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose]

Lung Pharmacokinetics - Minimum Sputum Concentration (Cmin) [Time Frame: 1, 8 and 24 hours post-dose]

Plasma Pharmacokinetics - Area Under the Plasma Concentration-time Curve From Time 0 to Infinite Time (AUCinf) [Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose]

Lung Pharmacokinetics - Maximum Sputum Concentration (Cmax) [Time Frame: 1, 8 and 24 hours post-dose]

Plasma Pharmacokinetics - Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) [Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose]

Secondary ID(s)

SAV005-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

INC Research Limited

Results

• Results available: Yes
• Date Posted: 04/03/2014
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01537666