Study of SB681323 and Prednisolone on Biomarkers in COPD (Chronic Obstructive Pulmonary Disease) Patients

Condition(s) targeted: Chronic Obstructive Pulmonary Disease

Intervention: SB681323 (Drug); Prednisolone (Drug)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, MD, Study Director, Affiliation: GlaxoSmithKline

This study will assess the effects of single oral doses of SB681323 and prednisolone on biomarkers in induced sputum and blood COPD patients

Official title: A Randomised, Double-Blind, Double-Dummy, Placebo-Controlled, Five-Way Crossover Study to Assess the Effects of Single Oral Doses of SB-681323 (7.5 Mg and 25 Mg) and Prednisolone (10 Mg and 30 Mg) on Biomarkers in Induced Sputum and Blood in COPD Patients.

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Safety Study

Primary outcome: Levels of ex vivo lipopolysaccharide (LPS) - induced tumor necrosis factor-alpha (TNF-a) production in whole blood of COPD patients

Secondary outcome: Level of pHSP27 and mRNAs encoding inflammatory biomarkers (including but not limited to IL-1ß,-6, 8, TNFa, HSP27)

Minimum age: 40 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion criteria:

- Subject is current smoker or ex-smoker with a smoking history of at least 10 pack

years (number of pack years = [number of cigarettes per day/20] x number of years smoked).

- The patient has serum CRP ≥ 3 mg/L at screening

- Subjects able to understand and comply with protocol requirements, instructions and

protocol-stated restrictions.

Exclusion criteria:

- Any clinically relevant abnormality identified on medical assessment, laboratory

examination, or 12-lead ECG which in the opinion of the investigator, will lead to an unacceptable increase in the risk of study participation or will call into question the validity of the outcome measures.

- Subjects who are obese, defined as having a BMI > 40

- Subject has a diagnosis of asthma that is confirmed by the investigator.

- Subject has poorly controlled COPD, defined as the occurrence of any of the following

in the 2 weeks prior to visit 1: acute worsening of COPD that is managed by the subject at home by self-treatment with corticosteroids or antibiotics, or that requires treatment by a physician.

- Subject has active tuberculosis, lung cancer or clinically overt bronchiectasis.

- Symptoms of "cold or flu" or any respiratory infection/symptoms at the start of the

study

- Subject has cardiac, gastrointestinal, neurological, renal, endocrine or psychiatric

disease that is uncontrolled on permitted medication

- Subject has history of allergic rhinitis.

- Subjects with a history of any type of malignancy with the exception of successfully

treated basal cell cancer of the skin.

- Subjects with rheumatoid arthritis, connective tissue disorders and other conditions

known to be associated with chronic inflammation (e. g. Inflammatory Bowel Disease).

- Subjects with chronic infections such as gingivitis, periodontitis, prostatitis,

gastritis, and urinary tract infections.

- Subjects with history of hepatic disease.

- History of increased liver function tests (ALT, AST) above upper limit of normal in

the past 6 months and/or liver function tests (bilirubin, ALT, AST) above upper limit of normal at screening.

- History of positive HIV, Hepatitis B /C antibody test result, a positive Hep B/C

result at screen or a risk factor for these diseases.

- History of drug or other allergy, which, in the opinion of the Investigator precludes

participation in the study.

GSK Clinical Trials Call Center, Manchester M23 9LT, United Kingdom

Starting date: August 2005
Last updated: September 21, 2006