The human nasal lipopolysaccharide (LPS) challenge model reflects inflammatory events in the lower airways, illustrated by CXCR2 inhibition of neutrophil recruitment

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 18

Inclusion Criteria

1. Provision of informed consent prior to any study specific procedures
2. Be willing and able to comply with study procedures
3. Healthy men or women aged 18 to 50 years (inclusive). Women must be of non-childbearing potential, that is women who are permanently sterilized (hysterectomy and/or bilateral oophorectomy or salpingectomy).
4. Have a body mass index (BMI) between 18 and 30 kg/m2 (inclusive) and minimum body weight of 50 kg
5. A blood neutrophil count above 2.2 x 10^9/L
6. Be non-smokers, or ex-smokers who have not smoked (or used any other nicotine products) in the 12 months preceding Visit 1 with a pack-year history of less than 10

Exclusion Criteria

1. Any clinically relevant disease and/or abnormality (past or present), which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results of the study, or the subject's ability to participate in the study
2. A definite or suspected personal or family history of intolerance or hypersensitivity to drugs and/or their excipients, judged to be clinically relevant by the investigator
3. Surgery or significant trauma within 3 months of Visit 1
4. Symptoms, signs or laboratory findings suggestive of an ongoing infective illness, as judged by the investigator, at Visit 1
5. Current or recurrent atopic symptoms, ie, rhinitis, asthma or conjunctivitis of clinical relevance as judged by the investigator
6. Participation in any clinical study with an investigational drug or new formulation of a marketed drug in the 3 months prior to Visit 1, or participation in a methodology study 1 month prior to Visit 1 (Note: participation is identified as the completion of a treatment-related visit)
7. Donation of blood within 3 months and plasma within 14 days prior to Visit 1
8. Use of any medication (other than hormone replacement therapy [HRT]), including vaccinations or over-the-counter medication (e.g., herbal remedies, vitamins or nutritional supplements) within 2 weeks in relation to first administration of study drug (or longer if the medication has a half-life long enough to potentially expose the subject to any significant systemic exposure that may interfere with the objectives of the study or the safety of the subjects), as judged by the investigator. Occasional intake of paracetamol, maximum 1 g 4 times daily (qid), is allowed.
9. Past or present alcohol or drug abuse, as judged by the investigator, or positive drugs of abuse test
10. Positive results on screening tests for serum hepatitis B surface antigen, hepatitis C antibodies and/or human immunodeficiency virus (HIV)
11. A suspected/manifested infection according to World Health Organization (WHO) risk classification 2, 3 or 4
12. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
13. Previous randomisation into the present study
14. Subjects, who in the opinion of the investigator, should not participate in the study
15. Subjects being recently extensively exposed to passive smoking or environmental LPS (eg, swine farms) as judged by the investigator
16. Previous participation in another LPS study during the last 12 months
17. Suspicion of Gilbert's syndrome
18. Structural abnormalities of the nose or nasal disorder symptomatic enough to cause significant nasal obstruction, as judged by the investigator

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
eutrophil numbers in nasal lavage, measured 24 hours post-LPS challenge<br>

Secondary Outcome Measures

Name	Time	Method
1. Other cells in nasal lavage: total leucocytes, macrophages, lymphocytes, eosinophils and epithelial cells, measured 24 hours post-LPS challenge<br>2. Inflammatory biomarkers in nasal lavage, which may include, but not be restricted to: IL-8, GROa, LTB4 and neutrophil elastase activity, measured 24 hours post-LPS challenge<br>3. Cells in blood: total leucocytes, neutrophils, monocytes, lymphocytes, basophils and eosinophils, measured 24 hours post-LPS challenge<br>4. Inflammatory biomarkers in blood, which may include, but not be restricted to: TNFa, high sensitivity CRP, IL-6, IL-8, GROa and serum amyloid A, measured 24 hours post-LPS challenge<br>5. Safety:<br>5.1. Incidence and nature of adverse events<br>5.2. Nasal symptoms (total nasal symptom scores) and nasal airway resistance (peak nasal inspiratory flow)<br>5.3. Clinically significant abnormalities in pulse, blood pressure, body temperature and liver enzymes (aspartate aminotransferase, alanine aminotransferase and bilirubin)