Study of SB681323 and Prednisolone on Biomarkers in COPD (Chronic Obstructive Pulmonary Disease) Patients
Primary Purpose
Pulmonary Disease, Chronic Obstructive
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
SB681323
Prednisolone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive focused on measuring COPD SB-681323 prednisolone biomarkers
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.
Sites / Locations
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Randomised, double-blind, five-way crossover
Arm Description
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.
Outcomes
Primary Outcome Measures
Pharmacodynamic effect of single, oral doses of SB-681323 and prednisolone
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
Levels obtained in sputum and whole blood samples
CD11b and CD62L surface expression on neutrophils
Levels obtained in whole blood samples
Blood concentration of inflammatory markers
GSK's COPD multiplex biomarker assay
CRP levels
Levels obtained in COPD patient sera
Safety and tolerability of dinsgle doses of SB681323 and prednisolone
Vitals, AEs, ECGs, safety laboratory, pulmonary function FEV1 and FVC
Exploratory objective #1
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
Exploratory analysis of inflammatory biomarker concentrations in induced sputum supernatants (e.g. myeloperoxidase, IL-6, TNF-α, total protein) at 2 hours post-dose
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00380133
Brief Title
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
2. Study Status
Record Verification Date
March 2012
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
April 2006 (Actual)
Study Completion Date
April 2006 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
Keywords
COPD SB-681323 prednisolone biomarkers
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Randomised, double-blind, five-way crossover
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
SB681323
Intervention Description
5 mg and 2.5 mg tablets - The tablets will be round (9.0 mm in diameter) and white and provided in labelled bottles
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Intervention Description
5 mg size DB AA capsule shell (Swedish orange) with a powder backfill (lactose Anhydrous)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablets matched to SB681323 or prednisolone
Primary Outcome Measure Information:
Title
Pharmacodynamic effect of single, oral doses of SB-681323 and prednisolone
Description
Levels of ex-vivo LPS induced TNFα in whole blood at 1, 2, 6 and 24 hrs post-dose
Time Frame
20 weeks
Secondary Outcome Measure Information:
Title
Level of pHSP27 and mRNAs encoding inflammatory markers
Description
Levels obtained in sputum and whole blood samples
Time Frame
20 weeks
Title
CD11b and CD62L surface expression on neutrophils
Description
Levels obtained in whole blood samples
Time Frame
20 weeks
Title
Blood concentration of inflammatory markers
Description
GSK's COPD multiplex biomarker assay
Time Frame
20 weeks
Title
CRP levels
Description
Levels obtained in COPD patient sera
Time Frame
20 weeks
Title
Safety and tolerability of dinsgle doses of SB681323 and prednisolone
Description
Vitals, AEs, ECGs, safety laboratory, pulmonary function FEV1 and FVC
Time Frame
20 weeks
Title
Exploratory objective #1
Description
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)
Time Frame
20 weeks
Title
Exploratory objective #2
Description
Exploratory analysis of inflammatory biomarker concentrations in induced sputum supernatants (e.g. myeloperoxidase, IL-6, TNF-α, total protein) at 2 hours post-dose
Time Frame
20 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Manchester
State/Province
Lancashire
ZIP/Postal Code
M23 9LT
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
19880675
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.
Results Reference
derived
Learn more about this trial
Study of SB681323 and Prednisolone on Biomarkers in COPD (Chronic Obstructive Pulmonary Disease) Patients
We'll reach out to this number within 24 hrs