Inhaled Vancomycin Tolerability, Safety and Pharmacokinetics

Phase 1

Completed

Conditions: Healthy
Cystic Fibrosis

Interventions: Drug: AeroVanc
Drug: IV vancomycin hydrochloride

Registration Number: NCT01537666

Lead Sponsor: Savara Inc.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aerovanc 16 mg in healthy volunteers	AeroVanc	-
AeroVanc 32 mg in healthy volunteers	AeroVanc	-
AeroVanc 80 mg in healthy volunteers	AeroVanc	-
IV vancomycin in healthy volunteers	IV vancomycin hydrochloride	-
AeroVanc 32 mg in CF patients	AeroVanc	-
AeroVanc 80 mg in CF patients	AeroVanc	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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.
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.
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 - 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.