Lung Pharmacokinetics (PK) in Epithelial Lining Fluid (ELF)

July 13, 2020 updated by: Allecra

A Phase I Open-Label, Single-Centre Study to Assess the Concentration of AAI101 and Cefepime in Epithelial Lining Fluid and Plasma in Healthy Volunteers

The primary objective of this study is to measure and compare the concentration of AAI101 and cefepime in bronchial epithelial lining fluid (ELF) and plasma following administration of cefepime/AAI101 combination in healthy subjects.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Liverpool, United Kingdom, L69 3GL
        • University of Liverpool

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

  1. Provision of signed and dated, written informed consent prior to any study-specific procedures.
  2. Healthy male and female subjects aged 18 to 65 years with veins suitable for cannulation or repeated venipuncture. Female patients can participate if at least 1 of the following criteria are met:

    • Are of non-childbearing potential defined as
    • Permanently sterile following hysterectomy, bilateral salpingectomy, bilateral oophorectomy or confirmed tubal occlusion (not tubal ligation);
    • Postmenopausal, as defined as at least 1 year post-cessation of menses (without an alternative medical cause), and per documentation provided by a medical professional;
    • Postmenopausal status will be confirmed with a screening serum follicle stimulating hormone (FSH) level greater than 40 milli-international units per milliliter (mlU/mL).
    • Patient has a negative urine and/or serum pregnancy test (serum β-human chorionic gonadotropin) within 1 day prior to study entry, and agrees to use highly effective contraception methods during treatment and for at least 7 days after the last dose of i.v. study therapy;
  3. Have a body mass index (BMI) between 18 and 32 kg/m2.
  4. As judged by the Investigator, all the subjects must be able to understand and be willing to comply with study procedures, restrictions and requirements.

4.2 Exclusion criteria

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

  1. Male subjects who do not agree to follow contraception restrictions.
  2. Female subjects who are pregnant or currently lactating
  3. Female subjects who are of child bearing potential who do not agree to follow contraception restrictions as detailed in section 5.1.10.
  4. Donated blood in the 3 months prior to screening, plasma in the 7 days prior to screening, platelets in the 6 weeks prior to screening
  5. Consume more than 28 units of alcohol per week if male, or 21 units of alcohol per week if female or any significant history of alcohol / substance misuse as determined by the investigator
  6. Unwilling to abstain from vigorous exercise for 48 hours prior to any study visit
  7. Unwilling to abstain from alcohol for 48 hours prior to any study visit
  8. Used cigarettes or vapor e-cigarettes, cigars or other nicotine-containing products (with the exception of nicotine replacement products not covered above) within 3 months before bronchoscopy or have a smoking history greater than 10 pack years.
  9. Received any medication, including St John's Wort, known to chronically alter drug absorption or elimination within 30 days prior to first dose administration unless in the opinion of the investigator it will not interfere with study procedures or compromise safety
  10. Received any prescribed systemic or topical medication within 14 days prior to the first dose administration (with the exception of the oral contraceptive pill)
  11. Received any non-prescribed systemic or topical medication, herbal remedy or vitamin / mineral supplementation within 14 days prior to the first dose administration (with the exception of paracetamol).
  12. Subjects who have any abnormality of vital signs prior to the first dose administration that, in the opinion of the investigator, would increase the risk of participating in the study
  13. Subjects who have any clinically significant abnormal physical examination finding
  14. Subjects who have any clinically significant 12 lead ECG abnormality that, in the opinion of the investigator, would increase the risk of participating in the study
  15. Subjects who have, or have any history of, any clinically significant cardiovascular, respiratory, gastrointestinal, neurological, psychiatric, metabolic, endocrine, renal, hepatic, haematological or other major disorder as determined by the investigator
  16. Subjects who have any significant condition that may preclude nasal or oral intubation with a bronchoscope as determined by the investigator
  17. Subjects who have any clinically significant allergy or allergic condition as determined by the investigator (with the exception of non-active hay fever)
  18. Subjects who have had previous adverse reactions to benzodiazepines or anaesthetic agents (lidocaine or xylocaine) including reversal agents such as flumazenil
  19. Subjects who have any clinically significant abnormal laboratory safety results as determined by the investigator with specific exclusions of any aspartate aminotransferase (AST) or alanine aminotransferase (ALT)upper limit of normal greater than or equal to 1.5 times upper limit of normal (ULN) at screening or day -1; total bilirubin > ULN (Gilbert's syndrome is acceptable), haemoglobin <12.0 g/dL or prothrombin time > 13 seconds (one repeat assessment is acceptable at screening)
  20. Subjects who have hepatitis B or C or are carriers of HBsAg or are carriers of hepatitis C virus (HCV= Ab or are positive for HIV 1/2 antibodies.
  21. Subjects who have a positive alcohol breath test or a positive urine drug screen ( a repeat assessment is acceptable)
  22. Subjects who are still participating in another clinical study or who have participated in a clinical study involving administration of an investigational product in the 3 months (or 5 half-lives, whichever is longer) prior to first dose administration
  23. Subjects who, in the opinion of the investigator, should not participate in this study For procedures for withdrawal of incorrectly enrolled subjects, see Section 5.3. Subjects who drop out will be replaced.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cefepime 2 gram + AAI101 1 gram
cefepime 2 grams in combination with AAI101 1 gram intravenous infusion
Combination of cefepime 2 gram with AAI101 1 gram
Other Names:
  • AAI101

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum concentration of cefepime and AAI101 in the lung
Time Frame: Change from baseline to 2 hours, 4 hours, 6 hours and 8 hours post dose
Maximum concentration of cefepime and AAI101 in Bronchoalveolar lavage (BAL) samples
Change from baseline to 2 hours, 4 hours, 6 hours and 8 hours post dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum concentration of cefepime and AAI101 in plasma
Time Frame: Change from baseline to 2 hours, 4 hours, 6 hours and 8 hours post dose
Maximum concentration of cefepime and AAI101 in plasma samples
Change from baseline to 2 hours, 4 hours, 6 hours and 8 hours post dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2017

Primary Completion (Actual)

April 30, 2019

Study Completion (Actual)

April 30, 2019

Study Registration Dates

First Submitted

July 25, 2018

First Submitted That Met QC Criteria

September 20, 2018

First Posted (Actual)

September 21, 2018

Study Record Updates

Last Update Posted (Actual)

July 14, 2020

Last Update Submitted That Met QC Criteria

July 13, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AT-103

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Healthy Subjects

Clinical Trials on Cefepime 2 gram

3
Subscribe