Pulmonary Disease, Chronic ObstructivePhase 1NCT00380133
Study of SB681323 and Prednisolone on Biomarkers in COPD (Chronic Obstructive Pulmonary Disease) Patients
A Phase 1 study testing SB681323 and Prednisolone in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in United Kingdom.
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 Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- SB681323 and Prednisolone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2005to Apr 2006
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
GSK Investigational Site
Manchester, Lancashire, M23 9LT
About this study
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.
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
- Being tested
- SB681323, Prednisolone, Placebo
- Keywords
- COPD SB-681323 prednisolone biomarkers
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SB681323Drug
5 mg and 2.5 mg tablets - The tablets will be round (9.0 mm in diameter) and white and provided in labelled bottles
PrednisoloneDrug
5 mg size DB AA capsule shell (Swedish orange) with a powder backfill (lactose Anhydrous)
PlaceboDrug
Tablets matched to SB681323 or prednisolone
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: SB681323; Drug: Prednisolone; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 20 weeks
Secondary outcomes (7)
Level of pHSP27 and mRNAs encoding inflammatory markers
Levels obtained in sputum and whole blood samples
Measured: 20 weeks
CD11b and CD62L surface expression on neutrophils
Levels obtained in whole blood samples
Measured: 20 weeks
Blood concentration of inflammatory markers
GSK's COPD multiplex biomarker assay
Measured: 20 weeks
CRP levels
Levels obtained in COPD patient sera
Measured: 20 weeks
Safety and tolerability of dinsgle doses of SB681323 and prednisolone
Vitals, AEs, ECGs, safety laboratory, pulmonary function FEV1 and FVC
Measured: 20 weeks
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)
Measured: 20 weeks
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
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2006 (estimated)
- Study startJun 2005
- Primary completionApr 2006
- Study completionApr 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00380133
- Sponsor's protocol ID
- IPI100477
- Status last verified
- Mar 2012
- First submitted
- 21 Sep 2006
- Last updated
- 4 Jun 2012
- Results posted
- No
Publications
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.
PubMed 19880675
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00380133
- Acronym / sponsor ID
- IPI100477
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- COPD SB-681323 prednisolone biomarkers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jun 2005
- Primary completion
- Apr 2006 (actual)
- Study completion
- Apr 2006 (actual)
- First posted
- 25 Sep 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the effects of single oral doses of SB681323 and prednisolone on biomarkers in induced sputum and blood COPD patients
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Randomised, double-blind, five-way crossover | Experimental | Drug: SB681323, Drug: Prednisolone, Drug: PlaceboA 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. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SB6813235 mg and 2.5 mg tablets - The tablets will be round (9.0 mm in diameter) and white and provided in labelled bottles | Drug | Randomised, double-blind, five-way crossover |
| Prednisolone5 mg size DB AA capsule shell (Swedish orange) with a powder backfill (lactose Anhydrous) | Drug | Randomised, double-blind, five-way crossover |
| PlaceboTablets matched to SB681323 or prednisolone | Drug | Randomised, double-blind, five-way crossover |
Primary outcome
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
7 secondary outcomes
Level of pHSP27 and mRNAs encoding inflammatory markers
Time frame: 20 weeks
CD11b and CD62L surface expression on neutrophils
Time frame: 20 weeks
Blood concentration of inflammatory markers
Time frame: 20 weeks
CRP levels
Time frame: 20 weeks
Safety and tolerability of dinsgle doses of SB681323 and prednisolone
Time frame: 20 weeks
Exploratory objective #1
Time frame: 20 weeks
Exploratory objective #2
Time frame: 20 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2012.
- Derived from this study: PubMed 19880675Singh 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SB681323 and Prednisolone in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacodynamic effect of single, oral doses of SB-681323 and prednisolone (time frame: 20 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00380133, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2012.