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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
History of Changes
  Purpose

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


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
 Drug: SB681323
Drug: Prednisolone
Drug: Placebo
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, 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.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Enrollment: 20
Study Start Date: June 2005
Study Completion Date: April 2006
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00380133

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

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00380133     History of Changes
Other Study ID Numbers: IPI100477
Study First Received: September 21, 2006
Last Updated: May 31, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
COPD SB-681323 prednisolone biomarkers

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

ClinicalTrials.gov processed this record on May 19, 2013