Study to Investigate the Effect of a Single Dose of AZD7624 on Inflammation Caused by an Endotoxin Challenge

A Double Blind, Randomised, Placebo-controlled, 2-period, Cross-over Study in Healthy Volunteers to Investigate the Effects of a Single Dose of Inhaled AZD7624 on White Blood Cells and Inflammatory Markers in Induced Sputum and Blood After Oral Inhalation of 45,000 Endotoxin Units Lipopolysaccharide (LPS)

Study to investigate the effect of a single dose of AZD7624 on inflammation caused by an endotoxin challenge.

Study Overview

• Status: Completed
• Conditions: LPS Challenge, Neutrophils
• Intervention / Treatment: Drug: AZD7624; Drug: Placebo

Detailed Description

This is a double-blind, randomised, placebo controlled, 2-way cross-over study to investigate the effects of a single dose of inhaled AZD7624 on white blood cells and inflammatory markers in induced sputum and blood after oral inhalation of LPS as well as the safety, tolerability and pharmacokinetics (PK) of AZD7624 following a single inhaled dose.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male and/or female volunteers aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture. (Healthy as determined by medical history and physical examination, laboratory parameters, and ECG performed before the first administration of the IP)
2. Female volunteers must have a negative pregnancy test at Visit 1 and on admission (Day -1 of Visit 3 and Visit 5) to the study centre, must not be lactating and must be of non childbearing potential
3. Be able to produce a minimum of 100 mg sputum (pellet weight) of good quality with total cell count (defined as total cell count <14 x 106/g, eosinophils <3%, sputum neutrophil % differential <65%, <30% squamous cell contamination and a minimum of 50% ce
4. Have normoresponsive airways with a methacholine PC20 >16 mg/mL. Screening methacholine provocation is not required if the volunteer has been tested by the centre in the past 1 year, with documented records of this testing
5. Be able to inhale from SPIRA nebuliser

Exclusion Criteria:

1. History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate
2. Any infection within the previous 4 weeks. Volunteers who get an infection between Visit 1 and admission to the centre can be rescreened
3. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator or reason to expect untoward reactions to LPS and/or AZD7624
4. History of chronic respiratory disease
5. Volunteers who are vegans or have medical dietary restrictions -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; nebuliser solution for inhalation
Experimental: AZD7624	Drug: AZD7624; nebuliser solution; 20 mg/mL for inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Description of the pharmacodynamic Neutrophil lipopolysaccharide (LPS) response after a single dose AZD7624 in terms of % change in neutrophil differential from baseline	Sample taken at baseline visit (7-14 days before dose) and at 6h after dose day1 for each treatment. (up to 7 weeks)

Secondary Outcome Measures

Outcome Measure	Time Frame
Description of the efficacy in terms of effect of a single dose of inhaled AZD7624 on levels of TNF-α induced sputum after oral inhalation of LPS will be evaluated compared to placebo	Sample taken at baseline visit (7-14 days before dose) and at 6h after dose day1 for each treatment. (up to 7 weeks)
Description of the safety profile in terms of Adverse events; blood pressure, heart rate and body temperature; electrocardiograms; clinical chemistry ,Creatinin kinase and myoglobin; haematology assessments, and forced expiratory volume in one second	From Screening to follow up (up to 9 weeks)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Saeed Khan, MBBS MRCP, Quintiles London, UK; Study Chair: Naimish Patel, AstraZeneca R&D Boston, United States

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: September 4, 2013
• First Submitted That Met QC Criteria: September 4, 2013
• First Posted (Estimate): September 9, 2013

Study Record Updates

• Last Update Posted (Estimate): May 7, 2014
• Last Update Submitted That Met QC Criteria: May 6, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Healthy volunteers, Phase 1
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; AZD7624
• Other Study ID Numbers: D2550C00004