LPS Challenge, Neutrophils Clinical Trial
Official title:
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.
| Status | Completed |
| Enrollment | 60 |
| Est. completion date | April 2014 |
| Est. primary completion date | April 2014 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Both |
| Age group | 18 Years to 55 Years |
| Eligibility |
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 - |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science
| Country | Name | City | State |
|---|---|---|---|
| United Kingdom | Research Site | London |
| Lead Sponsor | Collaborator |
|---|---|
| AstraZeneca |
United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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) | No | |
| Secondary | Description of the efficacy in terms of effect of a single dose of inhaled AZD7624 on levels of TNF-a 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) | No | |
| Secondary | 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) | Yes |