HealthyPhase 1NCT01537666
Inhaled Vancomycin Tolerability, Safety and Pharmacokinetics
A Phase 1 study testing AeroVanc and IV vancomycin hydrochloride in people with Healthy and Cystic Fibrosis, run by Savara Inc. at 2 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy, Cystic Fibrosis
- What is being tested?
- AeroVanc and IV vancomycin hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesAustralia
- Study dates
- Nov 2011to Mar 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- Spirometry (forced expiratory volume in 1 second (FEV1)) value at screening greater than 75% of predicted age-adjusted value.
- 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
- 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 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).
- Positive pregnancy test. All women of childbearing potential will be tested.
- 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).
- Findings at Screening that, in the investigator's opinion, would compromise the safety of the subject or the quality of the study data.
- History of severe cough/bronchospasm upon inhalation of dry powder inhalation product.
- Considered "terminally ill" or eligible for lung transplantation.
- Have had a significant episode of hemoptysis (>60 mL) in the three months prior to enrolment.
Who cannot join
- 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.
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- Vaccination within one month before the study drug administration.
- Systolic blood pressure <110 mmHg or >150 mmHg inclusive or diastolic blood pressure <60 mmHg or >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.
Trial locations and contacts
2 sites in 1 country.
Australia2 sites
Mater Adult Hospital
Brisbane, Queensland, 4101
Linear Clinical Research Ltd.
Perth, Western Australia, 6009
About this study
Official title: Phase I, Reference-controlled, Dose Escalating Study to Examine the Pharmacokinetics and Safety of AeroVanc Inhalation Powder.
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.
Read the detailed description
The study has three main objectives:
- To evaluate the safety, and tolerability of AeroVanc inhalation powder in healthy volunteers, and in patients with CF.
- To determine the systemic bioavailability of vancomycin in healthy volunteers following single dose pulmonary administration of 16 mg, 32 mg, and 80 mg doses of AeroVanc in comparison with a 250 mg dose of vancomycin administered intravenously.
- To estimate the lung sputum concentrations of vancomycin in patients with cystic fibrosis (CF) following single dose pulmonary administration of 32 mg and 80 mg doses of AeroVanc.
- Conditions
- Healthy, Cystic Fibrosis
- Being tested
- AeroVanc, IV vancomycin hydrochloride
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AeroVancDrug
Vancomycin hydrochloride dry powder for inhalation
IV vancomycin hydrochlorideDrug
Vancomycin hydrochloride solution for intravenous administration
| Study group | Role | What they receive |
|---|---|---|
| Aerovanc 16 mg in healthy volunteers | Experimental | Not described Receives: Drug: AeroVanc |
| AeroVanc 32 mg in healthy volunteers | Experimental | Not described Receives: Drug: AeroVanc |
| AeroVanc 80 mg in healthy volunteers | Experimental | Not described Receives: Drug: AeroVanc |
| IV vancomycin in healthy volunteers | Active comparator | Not described Receives: Drug: IV vancomycin hydrochloride |
| AeroVanc 32 mg in CF patients | Experimental | Not described Receives: Drug: AeroVanc |
| AeroVanc 80 mg in CF patients | Experimental | Not described Receives: Drug: AeroVanc |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Healthy volunteers = 2 weeks; CF Patients = 1 week
Secondary outcomes (7)
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%.
Measured: 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)
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.
Measured: 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)
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.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 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)
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.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
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.
Measured: 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)
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.
Measured: 1, 8 and 24 hours post-dose
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.
Measured: 1, 8 and 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2012 (estimated)
- Study startNov 2011
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Savara Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- INC Research Limited
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01537666
- Sponsor's protocol ID
- SAV005-01
- Status last verified
- Mar 2014
- First submitted
- 17 Feb 2012
- Last updated
- 31 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Reference-controlled, Dose Escalating Study to Examine the Pharmacokinetics and Safety of AeroVanc Inhalation Powder.
- ClinicalTrials.gov ID
- NCT01537666
- Acronym / sponsor ID
- SAV005-01
- Conditions
- Healthy, Cystic Fibrosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Savara Inc.Industry (pharma, biotech, devices)
- Collaborators
- INC Research Limited
- Study start
- Nov 2011
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 23 Feb 2012 (estimated)
- Results
- Posted 4 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study has three main objectives:
- To evaluate the safety, and tolerability of AeroVanc inhalation powder in healthy volunteers, and in patients with CF.
- To determine the systemic bioavailability of vancomycin in healthy volunteers following single dose pulmonary administration of 16 mg, 32 mg, and 80 mg doses of AeroVanc in comparison with a 250 mg dose of vancomycin administered intravenously.
- To estimate the lung sputum concentrations of vancomycin in patients with cystic fibrosis (CF) following single dose pulmonary administration of 32 mg and 80 mg doses of AeroVanc.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Aerovanc 16 mg in healthy volunteers | Experimental | Drug: AeroVanc |
| AeroVanc 32 mg in healthy volunteers | Experimental | Drug: AeroVanc |
| AeroVanc 80 mg in healthy volunteers | Experimental | Drug: AeroVanc |
| IV vancomycin in healthy volunteers | Active comparator | Drug: IV vancomycin hydrochloride |
| AeroVanc 32 mg in CF patients | Experimental | Drug: AeroVanc |
| AeroVanc 80 mg in CF patients | Experimental | Drug: AeroVanc |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (31 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AeroVancVancomycin hydrochloride dry powder for inhalation | Drug | AeroVanc 32 mg in CF patients, AeroVanc 32 mg in healthy volunteers, AeroVanc 80 mg in CF patients, AeroVanc 80 mg in healthy volunteers, Aerovanc 16 mg in healthy volunteers |
| IV vancomycin hydrochlorideVancomycin hydrochloride solution for intravenous administration | Drug | IV vancomycin in healthy volunteers |
Primary outcome
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
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.
7 secondary outcomes
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 - 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
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 - 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
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
Lung Pharmacokinetics - Minimum Sputum Concentration (Cmin)
Time frame: 1, 8 and 24 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AeroVanc and IV vancomycin hydrochloride in people with Healthy and Cystic Fibrosis, run by Savara Inc. at 2 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2014.