Inhaled Vancomycin Tolerability, Safety and Pharmacokinetics

NCT01537666 | Completed Phase 1 Results DMC

• 1 other identifier: SAV005-01
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

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.

Conditions

Healthy; Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• 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.

  Healthy volunteers = 2 weeks; CF Patients = 1 week

Secondary Outcomes (7)

• 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

• 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

• 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

• 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

• 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

Study Arms (6)

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

Interventions

AeroVanc DRUG

Vancomycin hydrochloride dry powder for inhalation

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 hydrochloride DRUG

Vancomycin hydrochloride solution for intravenous administration

IV vancomycin in healthy volunteers

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Spirometry (forced expiratory volume in 1 second (FEV1)) value at screening greater than 75% of predicted age-adjusted value.

You may not qualify if:

• 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.
• 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.
• 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).

Sponsors & Collaborators

• Savara Inc.: lead
• INC Research Limited: collaborator

Study Sites (2)

Mater Adult Hospital

Brisbane, Queensland, 4101, Australia

Location

Linear Clinical Research Ltd.

Perth, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Taneli Jouhikainen, MD, MBA; Chief Operating Officer
• Organization: Savara Inc.

info@savarapharma.com

(888) 302-4876

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2012
• First Posted: February 23, 2012
• Study Start: November 1, 2011
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: March 31, 2014
• Results First Posted: March 4, 2014

Record last verified: 2014-03

Locations

AU (2)