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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00380133
Recruitment Status : Completed
First Posted : September 25, 2006
Last Update Posted : June 4, 2012
Information provided by (Responsible Party):

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

Condition or disease Intervention/treatment Phase
Pulmonary Disease, Chronic Obstructive Drug: SB681323 Drug: Prednisolone Drug: Placebo Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 Start Date : June 2005
Actual Primary Completion Date : April 2006
Actual Study Completion Date : April 2006

Arm Intervention/treatment
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.
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

Primary Outcome Measures :
  1. Pharmacodynamic effect of single, oral doses of SB-681323 and prednisolone [ Time Frame: 20 weeks ]
    Levels of ex-vivo LPS induced TNFα in whole blood at 1, 2, 6 and 24 hrs post-dose

Secondary Outcome Measures :
  1. Level of pHSP27 and mRNAs encoding inflammatory markers [ Time Frame: 20 weeks ]
    Levels obtained in sputum and whole blood samples

  2. CD11b and CD62L surface expression on neutrophils [ Time Frame: 20 weeks ]
    Levels obtained in whole blood samples

  3. Blood concentration of inflammatory markers [ Time Frame: 20 weeks ]
    GSK's COPD multiplex biomarker assay

  4. CRP levels [ Time Frame: 20 weeks ]
    Levels obtained in COPD patient sera

  5. Safety and tolerability of dinsgle doses of SB681323 and prednisolone [ Time Frame: 20 weeks ]
    Vitals, AEs, ECGs, safety laboratory, pulmonary function FEV1 and FVC

  6. Exploratory objective #1 [ Time Frame: 20 weeks ]
    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)

  7. Exploratory objective #2 [ Time Frame: 20 weeks ]
    Exploratory analysis of inflammatory biomarker concentrations in induced sputum supernatants (e.g. myeloperoxidase, IL-6, TNF-α, total protein) at 2 hours post-dose

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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00380133

United Kingdom
GSK Investigational Site
Manchester, Lancashire, United Kingdom, M23 9LT
Sponsors and Collaborators
Study Director: GSK Clinical Trials GlaxoSmithKline

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: GlaxoSmithKline Identifier: NCT00380133     History of Changes
Other Study ID Numbers: IPI100477
First Posted: September 25, 2006    Key Record Dates
Last Update Posted: June 4, 2012
Last Verified: March 2012

Keywords provided by GlaxoSmithKline:
COPD SB-681323 prednisolone biomarkers

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Chronic Disease
Respiratory Tract Diseases
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents