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

NCT00380133 | Completed Phase 1

• 1 other identifier: IPI100477
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

COPD SB-681323 prednisolone biomarkers

Outcome Measures

Primary Outcomes (1)

• 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

  20 weeks

Secondary Outcomes (7)

• Level of pHSP27 and mRNAs encoding inflammatory markers

  20 weeks

• CD11b and CD62L surface expression on neutrophils

  20 weeks

• Blood concentration of inflammatory markers

  20 weeks

• CRP levels

  20 weeks

• Safety and tolerability of dinsgle doses of SB681323 and prednisolone

  20 weeks

Study Arms (1)

Randomised, double-blind, five-way crossover

EXPERIMENTAL

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; Drug: Prednisolone; Drug: Placebo

Interventions

SB681323 DRUG

5 mg and 2.5 mg tablets - The tablets will be round (9.0 mm in diameter) and white and provided in labelled bottles

Randomised, double-blind, five-way crossover

Prednisolone DRUG

5 mg size DB AA capsule shell (Swedish orange) with a powder backfill (lactose Anhydrous)

Randomised, double-blind, five-way crossover

Placebo DRUG

Tablets matched to SB681323 or prednisolone

Randomised, double-blind, five-way crossover

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Manchester, Lancashire, M23 9LT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 19880675 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

dilmapimod; Prednisolone

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2006
• First Posted: September 25, 2006
• Study Start: June 1, 2005
• Primary Completion: April 1, 2006
• Study Completion: April 1, 2006
• Last Updated: June 4, 2012

Record last verified: 2012-03

Locations

GB (1)