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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01537666




Registration number
NCT01537666
Ethics application status
Date submitted
17/02/2012
Date registered
23/02/2012
Date last updated
31/03/2014

Titles & IDs
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.
Secondary ID [1] 0 0
SAV005-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy 0 0
Cystic Fibrosis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AeroVanc
Treatment: Drugs - IV vancomycin hydrochloride

Experimental: Aerovanc 16 mg in healthy volunteers -

Experimental: AeroVanc 32 mg in healthy volunteers -

Experimental: AeroVanc 80 mg in healthy volunteers -

Active Comparator: IV vancomycin in healthy volunteers -

Experimental: AeroVanc 32 mg in CF patients -

Experimental: AeroVanc 80 mg in CF patients -


Treatment: Drugs: AeroVanc
Vancomycin hydrochloride dry powder for inhalation

Treatment: Drugs: IV vancomycin hydrochloride
Vancomycin hydrochloride solution for intravenous administration

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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) - Each participant was monitored regularly for Adverse Events (AEs) throughout the study. The Investigator or designee enquired about AEs by asking participants non-leading questions such as: "How do you feel?" or "Have you had any (other) medical problems since your last visit/assessment?" Additionally, several safety procedures (physical examinations, vital signs, safety laboratory tests, 12-lead ECGs, and spirometry) were conducted on participants at regular intervals. All AEs reported spontaneously by participants or in response to questioning or observation by the Investigator, including those related to safety procedures, were recorded. For each AE, the Investigator recorded the following assessments: seriousness, severity (Mild, Moderate, or Severe), and relationship to study drug (Not Related, Remote, Possible, Probable, or Highly Probable). AEs were considered drug-related if given a relationship of Possible, Probable, or Highly Probable.
Timepoint [1] 0 0
Healthy volunteers = 2 weeks; CF Patients = 1 week
Secondary outcome [1] 0 0
Plasma Pharmacokinetics - Elimination Half Life (t½) - Blood samples were obtained from the healthy volunteers to evaluate systemic pharmacokinetics of vancomycin after a single dose administration of AeroVanc or a single dose of IV vancomycin.
Half-life is the time it takes for the concentration of drug to decline by 50%.
Timepoint [1] 0 0
Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
Secondary outcome [2] 0 0
Plasma Pharmacokinetics - Time to Reach the Maximum Plasma Concentration (Tmax) - Blood samples were obtained from the healthy volunteers to evaluate systemic pharmacokinetics of vancomycin after a single dose administration of AeroVanc or a single dose of IV vancomycin.
Tmax is the time it takes to reach the maximum plasma concentration of a drug.
Timepoint [2] 0 0
Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
Secondary outcome [3] 0 0
Plasma Pharmacokinetics - Maximum Plasma Concentration (Cmax) - Blood samples were obtained from the healthy volunteers to evaluate systemic pharmacokinetics of vancomycin after a single dose administration of AeroVanc or a single dose of IV vancomycin.
Cmax is the maximum observed concentration of a drug.
Timepoint [3] 0 0
Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
Secondary outcome [4] 0 0
Plasma Pharmacokinetics - Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) - Blood samples were obtained from the healthy volunteers to evaluate systemic pharmacokinetics of vancomycin after a single dose administration of AeroVanc or a single dose of IV vancomycin.
AUCt is a way of expressing the total amount of drug exposure over a specified time period.
Timepoint [4] 0 0
Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
Secondary outcome [5] 0 0
Plasma Pharmacokinetics - Area Under the Plasma Concentration-time Curve From Time 0 to Infinite Time (AUCinf) - Blood samples were obtained from the healthy volunteers to evaluate systemic pharmacokinetics of vancomycin after a single dose administration of AeroVanc or a single dose of IV vancomycin.
AUCinf is a way of estimating the total amount of drug exposure over an infinite time period.
Timepoint [5] 0 0
Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
Secondary outcome [6] 0 0
Lung Pharmacokinetics - Maximum Sputum Concentration (Cmax) - Sputum samples were obtained from the patients with cystic fibrosis to evaluate lung pharmacokinetics of vancomycin after a single dose administration of AeroVanc.
Cmax is the maximum observed concentration of a drug.
Timepoint [6] 0 0
1, 8 and 24 hours post-dose
Secondary outcome [7] 0 0
Lung Pharmacokinetics - Minimum Sputum Concentration (Cmin) - Sputum samples were obtained from the patients with cystic fibrosis to evaluate lung pharmacokinetics of vancomycin after a single dose administration of AeroVanc.
Cmin is the minimum observed concentration of a drug.
Timepoint [7] 0 0
1, 8 and 24 hours post-dose

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,WA
Recruitment hospital [1] 0 0
Mater Adult Hospital - Brisbane
Recruitment hospital [2] 0 0
Linear Clinical Research Ltd. - Perth
Recruitment postcode(s) [1] 0 0
4101 - Brisbane
Recruitment postcode(s) [2] 0 0
6009 - Perth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Savara Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
INC Research Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT01537666
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications