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

Pulmonary Disease, Chronic Obstructive Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00380133
• Other study ID #: IPI100477
• Status: Completed
• Phase: Phase 1
• First received: September 21, 2006
• Last updated: May 31, 2012
• Start date: June 2005
• Est. completion date: April 2006

Study information

• Verified date: March 2012
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2006
• Est. primary completion date: April 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

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
• Prednisolone
5 mg size DB AA capsule shell (Swedish orange) with a powder backfill (lactose Anhydrous)
• Placebo
Tablets matched to SB681323 or prednisolone

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	Manchester	Lancashire

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacodynamic effect of single, oral doses of SB-681323 and prednisolone	Levels of ex-vivo LPS induced TNFa in whole blood at 1, 2, 6 and 24 hrs post-dose	20 weeks	No
Secondary	Level of pHSP27 and mRNAs encoding inflammatory markers	Levels obtained in sputum and whole blood samples	20 weeks	No
Secondary	CD11b and CD62L surface expression on neutrophils	Levels obtained in whole blood samples	20 weeks	No
Secondary	Blood concentration of inflammatory markers	GSK's COPD multiplex biomarker assay	20 weeks	No
Secondary	CRP levels	Levels obtained in COPD patient sera	20 weeks	No
Secondary	Safety and tolerability of dinsgle doses of SB681323 and prednisolone	Vitals, AEs, ECGs, safety laboratory, pulmonary function FEV1 and FVC	20 weeks	No
Secondary	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)	20 weeks	No
Secondary	Exploratory objective #2	Exploratory analysis of inflammatory biomarker concentrations in induced sputum supernatants (e.g. myeloperoxidase, IL-6, TNF-a, total protein) at 2 hours post-dose	20 weeks	No