Clinical trial NCT00380133: Study of SB681323 and Prednisolone on Biomarkers in COPD (Chronic Obstructive Pulmonary Disease) 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: COPD SB-681323 prednisolone biomarkers
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-09-25
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Pharmacodynamic effect of single, oral doses of SB-681323 and prednisolone
timeFrame: 20 weeks
Secondary outcomes:
measure: Level of pHSP27 and mRNAs encoding inflammatory markers
timeFrame: 20 weeks
measure: CD11b and CD62L surface expression on neutrophils
timeFrame: 20 weeks
measure: Blood concentration of inflammatory markers
timeFrame: 20 weeks
measure: CRP levels
timeFrame: 20 weeks
measure: Safety and tolerability of dinsgle doses of SB681323 and prednisolone
timeFrame: 20 weeks
measure: Exploratory objective #1
timeFrame: 20 weeks
measure: Exploratory objective #2
timeFrame: 20 weeks
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
state: Lancashire
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Singh D, Smyth L, Borrill Z, Sweeney L, Tal-Singer R. A randomized, placebo-controlled study of the effects of the p38 MAPK inhibitor SB-681323 on blood biomarkers of inflammation in COPD patients. J Clin Pharmacol. 2010 Jan;50(1):94-100. doi: 10.1177/0091270009347873. Epub 2009 Oct 30.