Inhaled Vancomycin Tolerability, Safety and Pharmacokinetics

Phase I, Reference-controlled, Dose Escalating Study to Examine the Pharmacokinetics and Safety of AeroVanc Inhalation Powder.

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01537666

Enrollment

Registered

2012-02-23

Start date

2011-11-30

Completion date

2012-03-31

Last updated

2014-03-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cystic Fibrosis, Healthy

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.

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.

Interventions

DRUGAeroVanc

Vancomycin hydrochloride dry powder for inhalation

DRUGIV vancomycin hydrochloride

Vancomycin hydrochloride solution for intravenous administration

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 50 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
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)	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.

Secondary

Measure	Time frame	Description
Plasma Pharmacokinetics - Time to Reach the Maximum Plasma Concentration (Tmax)	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose	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.
Plasma Pharmacokinetics - Maximum Plasma Concentration (Cmax)	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose	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.
Plasma Pharmacokinetics - Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt)	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose	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.
Plasma Pharmacokinetics - Elimination Half Life (t½)	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose	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%.
Lung Pharmacokinetics - Maximum Sputum Concentration (Cmax)	1, 8 and 24 hours post-dose	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.
Lung Pharmacokinetics - Minimum Sputum Concentration (Cmin)	1, 8 and 24 hours post-dose	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.
Plasma Pharmacokinetics - Area Under the Plasma Concentration-time Curve From Time 0 to Infinite Time (AUCinf)	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose	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.

Countries

Australia

Participant flow

Participants by arm

Arm	Count
Aerovanc 16 mg (Subset IV Vancomycin) in Healthy Volunteers AeroVanc : Vancomycin hydrochloride dry powder for inhalation (N=6)/ Subset received IV vancomycin hydrochloride : Vancomycin hydrochloride solution for intravenous administration (N=2 from this group, 6 overall)	6
AeroVanc 32 mg (Subset IV Vancomycin) in Healthy Volunteers AeroVanc : Vancomycin hydrochloride dry powder for inhalation (N=6)/ Subset received IV vancomycin hydrochloride : Vancomycin hydrochloride solution for intravenous administration (N=2 from this group, 6 overall)	6
AeroVanc 80 mg (Subset IV Vancomycin) in Healthy Volunteers AeroVanc : Vancomycin hydrochloride dry powder for inhalation (N=6)/ Subset received IV vancomycin hydrochloride : Vancomycin hydrochloride solution for intravenous administration (N=2 from this group, 6 overall)	6
AeroVanc 32 and 80 mg in CF Patients AeroVanc : Vancomycin hydrochloride dry powder for inhalation	7
Total	25

Baseline characteristics

Characteristic	AeroVanc 32 mg (Subset IV Vancomycin) in Healthy Volunteers	AeroVanc 80 mg (Subset IV Vancomycin) in Healthy Volunteers	Aerovanc 16 mg (Subset IV Vancomycin) in Healthy Volunteers	AeroVanc 32 and 80 mg in CF Patients	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	6 Participants	6 Participants	6 Participants	7 Participants	25 Participants
Age, Continuous	24.7 years STANDARD_DEVIATION 3.7	22.2 years STANDARD_DEVIATION 2.8	28.2 years STANDARD_DEVIATION 10.5	29.7 years STANDARD_DEVIATION 7.8	26.3 years STANDARD_DEVIATION 7.2
Region of Enrollment Australia	6 participants	6 participants	6 participants	7 participants	25 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	3 Participants	3 Participants
Sex: Female, Male Male	6 Participants	6 Participants	6 Participants	4 Participants	22 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	2 / 6	5 / 6	2 / 6	6 / 6	5 / 6	2 / 6
serious Total, serious adverse events	0 / 6	0 / 6	0 / 6	1 / 6	0 / 6	0 / 6

Outcome results

Primary

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.

Time frame: Healthy volunteers = 2 weeks; CF Patients = 1 week

Population: All 18 healthy volunteers who received single doses of AeroVanc, 6 of which also received a single dose of IV vancomycin. All 7 Cystic Fibrosis patients who received at least one single dose of AeroVanc.

Arm	Measure	Group	Value (NUMBER)
AeroVanc 16 mg in Healthy Volunteers	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)	Subset of total with serious, drug-related TEAEs	0 participants
AeroVanc 16 mg in Healthy Volunteers	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)	Subset of total with severe, drug-related TEAEs	0 participants
AeroVanc 16 mg in Healthy Volunteers	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)	Total with at least one TEAE	2 participants
AeroVanc 16 mg in Healthy Volunteers	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)	Subset of total with drug-related TEAEs	2 participants
AeroVanc 16 mg in Healthy Volunteers	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)	Subset of total with serious TEAEs	0 participants
AeroVanc 16 mg in Healthy Volunteers	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)	Subset of total with severe TEAEs	0 participants
AeroVanc 32 mg in Healthy Volunteers	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)	Total with at least one TEAE	5 participants
AeroVanc 32 mg in Healthy Volunteers	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)	Subset of total with severe TEAEs	0 participants
AeroVanc 32 mg in Healthy Volunteers	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)	Subset of total with serious TEAEs	0 participants
AeroVanc 32 mg in Healthy Volunteers	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)	Subset of total with drug-related TEAEs	3 participants
AeroVanc 32 mg in Healthy Volunteers	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)	Subset of total with severe, drug-related TEAEs	0 participants
AeroVanc 32 mg in Healthy Volunteers	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)	Subset of total with serious, drug-related TEAEs	0 participants
AeroVanc 80 mg in Healthy Volunteers	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)	Subset of total with severe, drug-related TEAEs	0 participants
AeroVanc 80 mg in Healthy Volunteers	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)	Subset of total with serious, drug-related TEAEs	0 participants
AeroVanc 80 mg in Healthy Volunteers	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)	Subset of total with drug-related TEAEs	2 participants
AeroVanc 80 mg in Healthy Volunteers	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)	Total with at least one TEAE	2 participants
AeroVanc 80 mg in Healthy Volunteers	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)	Subset of total with severe TEAEs	0 participants
AeroVanc 80 mg in Healthy Volunteers	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)	Subset of total with serious TEAEs	0 participants
IV Vancomycin 250 mg in Healthy Volunteers	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)	Subset of total with severe, drug-related TEAEs	0 participants
IV Vancomycin 250 mg in Healthy Volunteers	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)	Total with at least one TEAE	2 participants
IV Vancomycin 250 mg in Healthy Volunteers	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)	Subset of total with drug-related TEAEs	1 participants
IV Vancomycin 250 mg in Healthy Volunteers	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)	Subset of total with serious TEAEs	0 participants
IV Vancomycin 250 mg in Healthy Volunteers	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)	Subset of total with serious, drug-related TEAEs	0 participants
IV Vancomycin 250 mg in Healthy Volunteers	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)	Subset of total with severe TEAEs	0 participants
AeroVanc 32 mg in Cystic Fibrosis Patients	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)	Subset of total with serious, drug-related TEAEs	0 participants
AeroVanc 32 mg in Cystic Fibrosis Patients	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)	Subset of total with drug-related TEAEs	4 participants
AeroVanc 32 mg in Cystic Fibrosis Patients	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)	Total with at least one TEAE	6 participants
AeroVanc 32 mg in Cystic Fibrosis Patients	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)	Subset of total with serious TEAEs	1 participants
AeroVanc 32 mg in Cystic Fibrosis Patients	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)	Subset of total with severe, drug-related TEAEs	0 participants
AeroVanc 32 mg in Cystic Fibrosis Patients	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)	Subset of total with severe TEAEs	1 participants
AeroVanc 80 mg in Cystic Fibrosis Patients	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)	Subset of total with severe TEAEs	0 participants
AeroVanc 80 mg in Cystic Fibrosis Patients	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)	Subset of total with drug-related TEAEs	4 participants
AeroVanc 80 mg in Cystic Fibrosis Patients	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)	Total with at least one TEAE	5 participants
AeroVanc 80 mg in Cystic Fibrosis Patients	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)	Subset of total with serious, drug-related TEAEs	0 participants
AeroVanc 80 mg in Cystic Fibrosis Patients	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)	Subset of total with severe, drug-related TEAEs	0 participants
AeroVanc 80 mg in Cystic Fibrosis Patients	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)	Subset of total with serious TEAEs	0 participants

Secondary

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.

Time frame: 1, 8 and 24 hours post-dose

Population: All CF patients who received a 32 mg dose of AeroVanc followed at least one week later by an 80 mg dose of AeroVanc (N=5). One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.

Arm	Measure	Value (MEAN)	Dispersion
AeroVanc 16 mg in Healthy Volunteers	Lung Pharmacokinetics - Maximum Sputum Concentration (Cmax)	95.775 µg/ml	Standard Deviation 171.544
AeroVanc 32 mg in Healthy Volunteers	Lung Pharmacokinetics - Maximum Sputum Concentration (Cmax)	269.17 µg/ml	Standard Deviation 510.98

Secondary

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.

Time frame: 1, 8 and 24 hours post-dose

Arm	Measure	Value (MEAN)	Dispersion
AeroVanc 16 mg in Healthy Volunteers	Lung Pharmacokinetics - Minimum Sputum Concentration (Cmin)	3.050 µg/ml	Standard Deviation 3.679
AeroVanc 32 mg in Healthy Volunteers	Lung Pharmacokinetics - Minimum Sputum Concentration (Cmin)	7.990 µg/ml	Standard Deviation 8.066

Secondary

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.