AsthmaPhase 2NCT01471665
GSK2190915 Neutrophilic Asthma Study
A Phase 2 study testing GSK2190915 100mg in people with Asthma, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
The purpose of this study is to investigate the effect on repeat doses of GSK2190915 in asthmatic patients with a high percentage of neutrophils in their sputum. GSK2190915 will be given as an add on to current therapy, and its effects on the percentage of sputum neutrophils in the patients will be assessed. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Asthma
- What is being tested?
- GSK2190915 100mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2011to May 2012
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) < 2xUpper limit of normal (ULN); alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Males and females ages 18 years old and above.
- An established clinical history of asthma in accordance with the definition by the GINA Guidelines.
- Subjects who are stable on their current treatment for at least one month prior to first dose and for the duration of the study.
- Persistent sputum neutrophilia in the absence of infection. Persistent is defined at being met at Screening and Visit 1 of Treatment Period 1. At least one sputum sample must show neutrophils ≥ 50%. The other sample must be > 45%.
- A female subject is eligible to participate if she is of:
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- Non-childbearing potential defined as pre-menopausal females with a documented (medical report verification) hysterectomy or double oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels > 40 mIU/mL and estradiol < 40 pg/ml (<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods specified in the protocol if they wish to continue their Hormone Replacement Therapy (HRT) during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
- Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow up visit, or at least 6 days after last dose.
- Signed and dated written informed consent is obtained from the subject
- The subject is able to understand and comply with the protocol requirements, instructions and protocol-stated restrictions.
Who cannot join
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- The subject has tested positive for Human Immunodeficiency Virus ev1(HIV) antibodies.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Past or present disease, which as judged by the investigator or medical monitor, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, gastrointestinal disease, hepatic disease, renal disease, haematological disease, neurological disease, endocrine disease or pulmonary disease (excluding asthma but including but not confined to chronic bronchitis, emphysema, bronchiectasis, eosinophilic bronchitis or pulmonary fibrosis).
- History of asthma exacerbations or acute intercurrent respiratory illness (viral respiratory syndrome, bronchitis, pneumonia) for a four week period before the screening visit.
- History of life-threatening asthma, defined as an asthma episode that required intubations and/or was associated with hypercapnia, respiratory arrest and/or hypoxic seizures.
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- FEV1 < 1 litre post salbutamol.
- Clinically significant abnormalities in vital signs or safety laboratory analysis at screening.
- The subject has a clinically significant QT duration corrected for heart rate (QTc) value at screening.
- The subject has a positive pre-study urine drug or urine or breath alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.
- Administration of injectable steroids within 6 weeks of screening.
- Administration of any vaccinations within 2 weeks of screening or during the study.
- Administration of biological therapies within 3 months of the screening visit or during the study.
- Subject is undergoing allergen desensitisation therapy.
- Administration of OATP1B1 substrates from 2 weeks before dosing, and until all follow up assessments are completed.
- Subject is unable to abstain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements) including non-steroidal antiinflammatory drugs (NSAIDs), anti-depressant drugs, anti-histamines and antiasthma, anti-rhinitis or hay fever medication, with the exception of ICS, Long Acting Beta Agonist (LABA), montelukast and short action beta agonists, within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study.
- The subject has participated in a study with a new molecular entity during the previous 3 months or has participated in 4 or more clinical studies in the previous 12 months prior to the first dosing day.
- History of blood donation (500 mL) within 3 months of starting the clinical study.
- History of alcohol abuse or the subject regularly drinks more than 28 units of alcohol in a week if male, or 21 units per week if female. One unit of alcohol is defined as a medium (125 ml) glass of wine, half a pint (250 ml) of beer or one measure (25 ml) of spirits.
- There is a risk of non-compliance with study procedures.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
GSK Investigational Site
Glasgow, Lanarkshire, G12 0YN
About this study
Official title: A Randomised, Double-blind, Placebo-controlled, Cross-over Study to Evaluate the Effect of Treatment With Repeat Dose GSK2190915 as an add-on to Current Therapy on the Percentage of Neutrophils in Induced Sputum in Asthmatic Patients With Elevated Sputum Neutrophils
The purpose of this study is to investigate the effect on repeat doses of GSK2190915 in asthmatic patients with a high percentage of neutrophils in their sputum. GSK2190915 will be given as an add on to current therapy, and its effects on the percentage of sputum neutrophils in the patients will be assessed.
Read the detailed description
This is a randomised, double blind, placebo-controlled, two-way cross-over study to evaluate the effect of treatment with repeat dose GSK2190915, a 5-lipoxygenase-activating protein (FLAP) inhibitor, as an add-on to current therapy on the percentage of neutrophils in induced sputum in asthmatic patients with elevated sputum neutrophils. Approximately 20 subjects will be enrolled onto the study to ensure that approximately 14 evaluable subjects complete the study. All subjects will receive oral placebo and GSK2190915 100mg once daily for up to 16 days. Sputum neutrophilia will be assessed prior to treatment and on treatment. Key assessments: sputum cell counts, biomarker samples in sputum, blood and urine, and pharmacokinetics. Safety will be assessed by vital signs, electrocardiograms (ECGs), clinical laboratory safety tests and collection of adverse events (AEs).
GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that attenuates the production of leukotrienes, through the blockage of the first committed step in the leukotriene pathway, 5-lipoxygenase (5-LO) activation. Leukotrienes are potent inflammatory molecules produced mainly by mast cells, eosinophils, monocytes/macrophage and neutrophils in response to allergic or inflammatory stimuli. As GSK2190915 reproducibly inhibits the production of leukotriene B4 (LTB4) and cysteinyl leukotrienes (cysLTs) both in vitro and in vivo it has strong potential utility in the treatment of asthma.
- Conditions
- Asthma
- Being tested
- GSK2190915 100mg, Placebo
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2190915 100mgDrug
GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor. Dosing will occur once daily for up to 16 days.
PlaceboDrug
Placebo will be administered once daily for up to 16 days.
| Study group | Role | What they receive |
|---|---|---|
| GSK2190915 100mg | Experimental | This is a crossover study so patients will receive 100mg of GSK2190915 once daily for up to 16 days followed by a wash out period of at least 14 days before they cross over onto the placebo arm of the study. Receives: Drug: GSK2190915 100mg |
| Placebo | Placebo comparator | This is a crossover study so patients will receive placebo once daily for up to 16 days followed by a wash out period of at least 14 days before they cross over onto the GSK2190915 100mg arm of the study. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The numbers of neutrophils in induced sputum in asthmatic subjects (average of absolute and percentage count on Visit 4 and Visit 5)
Pharmacodynamics
Measured: 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
Secondary outcomes (7)
The levels of LTE4 in urine, LTB4-glucuronide in urine and LTB4 in sputum supernatant in asthmatic subjects
Pharmacodynamics
Measured: Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
The levels of high sensitive C-reactive protein (hsCRP) and other biomarkers (for example IL-17) in blood in asthmatic subjects
Pharmacodynamics
Measured: Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
Changes in symptoms in asthmatic subjects compared to placebo using the asthma control questionnaire
Safety and tolerability and efficacy
Measured: Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
Changes in lung function as measured by Forced Expiratory Volume in one second (FEV1) in subjects with asthma
Safety and tolerability and efficacy
Measured: Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
Plasma concentrations of GSK2190915 following repeated doses in asthmatic subjects
Pharmacokinetics
Measured: On days 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
Incidence of treatment emergent adverse events in asthmatic subjects and vital signs, electrocardiograms and safety laboratory parameters in asthmatic subjects
Safety and tolerability and effiacy
Measured: Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
The levels of biomarkers in sputum supernatant, for example IL-17, IL-8, neutrophil elastase and myeloperoxidase, as samples permit, in asthmatic subjects
Pharmacodynamics
Measured: Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2011 (estimated)
- Study startJun 2011
- Primary completionMay 2012
- Study completionMay 2012
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 AsthmaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 14 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
- NCT01471665
- Sponsor's protocol ID
- 115134
- Status last verified
- Nov 2016
- First submitted
- 18 Aug 2011
- Last updated
- 22 Nov 2016
- Results posted
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
Chaudhuri R, Norris V, Kelly K, Zhu CQ, Ambery C, Lafferty J, Cameron E, Thomson NC. Effects of a FLAP inhibitor, GSK2190915, in asthmatics with high sputum neutrophils. Pulm Pharmacol Ther. 2014 Feb;27(1):62-9. doi: 10.1016/j.pupt.2013.11.007. Epub 2013 Dec 10.
PubMed 24333186
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo-controlled, Cross-over Study to Evaluate the Effect of Treatment With Repeat Dose GSK2190915 as an add-on to Current Therapy on the Percentage of Neutrophils in Induced Sputum in Asthmatic Patients With Elevated Sputum Neutrophils
- ClinicalTrials.gov ID
- NCT01471665
- Acronym / sponsor ID
- 115134
- Conditions
- Asthma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jun 2011
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 16 Nov 2011 (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.
The purpose of this study is to investigate the effect on repeat doses of GSK2190915 in asthmatic patients with a high percentage of neutrophils in their sputum. GSK2190915 will be given as an add on to current therapy, and its effects on the percentage of sputum neutrophils in the patients will be assessed.
Detailed description
This is a randomised, double blind, placebo-controlled, two-way cross-over study to evaluate the effect of treatment with repeat dose GSK2190915, a 5-lipoxygenase-activating protein (FLAP) inhibitor, as an add-on to current therapy on the percentage of neutrophils in induced sputum in asthmatic patients with elevated sputum neutrophils. Approximately 20 subjects will be enrolled onto the study to ensure that approximately 14 evaluable subjects complete the study. All subjects will receive oral placebo and GSK2190915 100mg once daily for up to 16 days. Sputum neutrophilia will be assessed prior to treatment and on treatment. Key assessments: sputum cell counts, biomarker samples in sputum, blood and urine, and pharmacokinetics. Safety will be assessed by vital signs, electrocardiograms (ECGs), clinical laboratory safety tests and collection of adverse events (AEs).
GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that attenuates the production of leukotrienes, through the blockage of the first committed step in the leukotriene pathway, 5-lipoxygenase (5-LO) activation. Leukotrienes are potent inflammatory molecules produced mainly by mast cells, eosinophils, monocytes/macrophage and neutrophils in response to allergic or inflammatory stimuli. As GSK2190915 reproducibly inhibits the production of leukotriene B4 (LTB4) and cysteinyl leukotrienes (cysLTs) both in vitro and in vivo it has strong potential utility in the treatment of asthma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GSK2190915 100mg | Experimental | Drug: GSK2190915 100mgThis is a crossover study so patients will receive 100mg of GSK2190915 once daily for up to 16 days followed by a wash out period of at least 14 days before they cross over onto the placebo arm of the study. |
| Placebo | Placebo comparator | Drug: PlaceboThis is a crossover study so patients will receive placebo once daily for up to 16 days followed by a wash out period of at least 14 days before they cross over onto the GSK2190915 100mg arm of the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) < 2xUpper limit of normal (ULN); alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Males and females ages 18 years old and above.
- An established clinical history of asthma in accordance with the definition by the GINA Guidelines.
- Subjects who are stable on their current treatment for at least one month prior to first dose and for the duration of the study.
- Persistent sputum neutrophilia in the absence of infection. Persistent is defined at being met at Screening and Visit 1 of Treatment Period 1. At least one sputum sample must show neutrophils ≥ 50%. The other sample must be > 45%.
Key exclusion criteria (20 listed)
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- The subject has tested positive for Human Immunodeficiency Virus ev1(HIV) antibodies.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Past or present disease, which as judged by the investigator or medical monitor, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, gastrointestinal disease, hepatic disease, renal disease, haematological disease, neurological disease, endocrine disease or pulmonary disease (excluding asthma but including but not confined to chronic bronchitis, emphysema, bronchiectasis, eosinophilic bronchitis or pulmonary fibrosis).
- History of asthma exacerbations or acute intercurrent respiratory illness (viral respiratory syndrome, bronchitis, pneumonia) for a four week period before the screening visit.
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 |
|---|---|---|
| GSK2190915 100mgGSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor. Dosing will occur once daily for up to 16 days. | Drug | GSK2190915 100mg |
| PlaceboPlacebo will be administered once daily for up to 16 days. | Drug | Placebo |
Primary outcome
The numbers of neutrophils in induced sputum in asthmatic subjects (average of absolute and percentage count on Visit 4 and Visit 5)
Time frame: 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
Pharmacodynamics
7 secondary outcomes
The levels of LTE4 in urine, LTB4-glucuronide in urine and LTB4 in sputum supernatant in asthmatic subjects
Time frame: Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
The levels of high sensitive C-reactive protein (hsCRP) and other biomarkers (for example IL-17) in blood in asthmatic subjects
Time frame: Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
Changes in symptoms in asthmatic subjects compared to placebo using the asthma control questionnaire
Time frame: Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
Changes in lung function as measured by Forced Expiratory Volume in one second (FEV1) in subjects with asthma
Time frame: Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
Plasma concentrations of GSK2190915 following repeated doses in asthmatic subjects
Time frame: On days 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
Incidence of treatment emergent adverse events in asthmatic subjects and vital signs, electrocardiograms and safety laboratory parameters in asthmatic subjects
Time frame: Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
The levels of biomarkers in sputum supernatant, for example IL-17, IL-8, neutrophil elastase and myeloperoxidase, as samples permit, in asthmatic subjects
Time frame: Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily
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 22 Nov 2016.
- Derived from this study: PubMed 24333186Chaudhuri R, Norris V, Kelly K, Zhu CQ, Ambery C, Lafferty J, Cameron E, Thomson NC. Effects of a FLAP inhibitor, GSK2190915, in asthmatics with high sputum neutrophils. Pulm Pharmacol Ther. 2014 Feb;27(1):62-9. doi: 10.1016/j.pupt.2013.11.007. Epub 2013 Dec 10.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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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 2 study testing GSK2190915 100mg in people with Asthma, 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 10 inclusion and 20 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 22 Nov 2016. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The numbers of neutrophils in induced sputum in asthmatic subjects (average of absolute and percentage count on Visit 4 and Visit 5) (time frame: 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily). 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 NCT01471665, 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 22 Nov 2016.