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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00380133
First received: September 21, 2006
Last updated: May 31, 2012
Last verified: March 2012

September 21, 2006
May 31, 2012
June 2005
April 2006   (final data collection date for primary outcome measure)
Pharmacodynamic effect of single, oral doses of SB-681323 and prednisolone [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Levels of ex-vivo LPS induced TNFα in whole blood at 1, 2, 6 and 24 hrs post-dose
Levels of ex vivo lipopolysaccharide (LPS) - induced tumor necrosis factor-alpha (TNF-a) production in whole blood of COPD patients
Complete list of historical versions of study NCT00380133 on ClinicalTrials.gov Archive Site
  • Level of pHSP27 and mRNAs encoding inflammatory markers [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    Levels obtained in sputum and whole blood samples
  • CD11b and CD62L surface expression on neutrophils [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    Levels obtained in whole blood samples
  • Blood concentration of inflammatory markers [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    GSK's COPD multiplex biomarker assay
  • CRP levels [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    Levels obtained in COPD patient sera
  • Safety and tolerability of dinsgle doses of SB681323 and prednisolone [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    Vitals, AEs, ECGs, safety laboratory, pulmonary function FEV1 and FVC
  • Exploratory objective #1 [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    Transcriptomic profiles of induced sputum cells and whole blood Exploratory micro-array analysis of mRNA biomarkers in induced sputum samples at 2 hrs post-dose and whole blood samples at baseline (pre-dose), and 6 hrs post-dose (earlier post-dose blood samples (1 and 2 hrs ) may also be examined)
  • Exploratory objective #2 [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    Exploratory analysis of inflammatory biomarker concentrations in induced sputum supernatants (e.g. myeloperoxidase, IL-6, TNF-α, total protein) at 2 hours post-dose
Level of pHSP27 and mRNAs encoding inflammatory biomarkers (including but not limited to IL-1ß,-6, 8, TNFa, HSP27)
Not Provided
Not Provided
 
Study of SB681323 and Prednisolone on Biomarkers in COPD (Chronic Obstructive Pulmonary Disease) Patients
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.

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

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Pulmonary Disease, Chronic Obstructive
  • Drug: SB681323
    5 mg and 2.5 mg tablets - The tablets will be round (9.0 mm in diameter) and white and provided in labelled bottles
  • Drug: Prednisolone
    5 mg size DB AA capsule shell (Swedish orange) with a powder backfill (lactose Anhydrous)
  • Drug: Placebo
    Tablets matched to SB681323 or prednisolone
Experimental: Randomised, double-blind, five-way crossover
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.
Interventions:
  • Drug: SB681323
  • Drug: Prednisolone
  • Drug: Placebo
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. Epub 2009 Oct 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
April 2006
April 2006   (final data collection date for primary outcome measure)

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.
Both
40 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT00380133
IPI100477
Not Provided
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP