Clinical trial NCT01937338: Study to Investigate the Effect of a Single Dose of AZD7624 on Inflammation Caused by an Endotoxin Challenge
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: LPS Challenge, Neutrophils
Keywords: Healthy volunteers, Phase 1
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-09-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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

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.

Eligibility criteria: 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 -

Primary outcomes:
measure: Description of the pharmacodynamic Neutrophil lipopolysaccharide (LPS) response after a single dose AZD7624 in terms of % change in neutrophil differential from baseline
timeFrame: Sample taken at baseline visit (7-14 days before dose) and at 6h after dose day1 for each treatment. (up to 7 weeks)
Secondary outcomes:
measure: 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
timeFrame: Sample taken at baseline visit (7-14 days before dose) and at 6h after dose day1 for each treatment. (up to 7 weeks)
measure: 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
timeFrame: From Screening to follow up (up to 9 weeks)
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Quintiles London, UK
name: Saeed Khan, MBBS MRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca R&D Boston, United States
name: Naimish Patel
role: STUDY_CHAIR
References: