A Randomised, Double-Blind, Placebo-Controlled, Two-Way Crossover Study in Healthy Volunteers to Investigate the Effect of Oral Dosing with AZD9668 on Airway Inflammation as Assessed in Induced Sputum after Challenge with Inhaled Lipopolysaccharide (LPS)

• Conditions: Chronic Obstructive Pulmonary Disease (COPD); MedDRA version: 9.1Level: LLTClassification code 10010952Term: COPD

• Registration Number: EUCTR2007-004584-22-GB
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10-16
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Provision of informed consent
2. Healthy male or female of non-childbearing potential (defined as cessation of regular menses for more than 12 months and an FSH of >20 IU/L or surgically sterile).
3. Aged 18-50 years inclusive.
4. Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and minimum body weight of 50 kg.
5. Have a normal physical examination, laboratory values, 12-lead ECG and vital signs (blood pressure and pulse), unless the investigator considers an abnormality to be clinically irrelevant.
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.
7. Demonstrate an FEV1 =80% of their predicted normal.
8. Demonstrate no evidence of airway obstruction by having an FEV1/FVC ratio >70%.
9. Have normal airway responsiveness to inhaled methacholine with a PC20 =16 mg/mL.
10. Have negative screens for serum Hepatitis B surface antigen, Hepatitis C antibodies and HIV.
11. Be able to produce a minimum of 200 µL sputum volume after induction with inhaled hypertonic saline.
12. Have a sputum eosinophilia =2% and a sputum neutrophilia =80%.

Pharmacognetics - For inclusion in the genetic research, subjects must fulfil the following criterion:
1. Provision of informed consent for genetic research

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. A history or presence of conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs eg., haematological, gastrointestinal, hepatic or renal disease etc.
2. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff and staff at the study site).
3. History of exposure to environmental LPS eg. swine farmers or extensive exposure to passive smoking.
4. Previous enrolment or randomisation to treatment in the present study.
5. 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.
6. Surgery or significant trauma within 3 months of Visit 1.
7. Symptoms, signs or laboratory findings suggestive of an ongoing infective illness at the time of enrolment.
8. A history of respiratory disease including asthma.
9. Participation in another study involving an LPS challenge during the past 12 months.
10. Participation in any clinical study with an investigational drug in the 4 months prior to Visit 1, or participation in a study with a new formulation of a marketed drug in the 3 months prior to Visit 1, or participation in a methodology study in the month prior to Visit 1 (Note: participation is identified as the completion of a treatment-related visit).
11. Donation of more than 1200 mL of blood within 12 months of Visit 1, or donation of blood in total >500 mL within 3 months prior to Visit 1.
12. Symptoms of any clinically significant illness within 2 weeks prior to Visit 1.
13. Use of any prescribed medication in the 3 weeks prior to Visit 1 (other than paracetamol (up to 4 g/day), hormone replacement therapy (HRT) or over-the-counter preparations , herbal preparations or vitamins in the previous 7 days judged to be clinically irrelevant by the Investigator.
14. Subjects who are pyrexial with a body temperature of greater than 37.7°C .
15. A significant history of alcohol abuse or consumption of more than 28 units (male) or 21 units (female) of alcohol per week.
16. A significant history of drug abuse (including benzodiazepines) or positive drugs of abuse test.
17. Subjects who admit to belonging to a high-risk group for HIV infection according to the site’s standard practice.
18. Anticipated difficulty with venous access.
19. Subjects who in the opinion of the investigator should not, for reasons of the safety or compliance, participate in the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified