EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Percent count of neutrophils in induced sputum following repeat dosing on Visit 4 and Visit 5
Timeframe: Visit 4 (Days 12 to 15) and Visit 5 (Days 13 to 16)
Sputum neutrophil absolute count by method 1, method 2 and method 3 in induced sputum following repeat dosing on Visit 4 and Visit 5
Timeframe: Visit 4 (Days 12 to 15) and Visit 5 (Days 13 to 16)
Secondary outcomes:
Mean Leukotriene E4 (LTE4) levels in urine
Timeframe: Visit 4 (Days 12 to 15) and Visit 5 (Days 13 to 16)
Mean Leukotriene B4 (LTB4)-glucuronide in urine
Timeframe: Visit 4 (Days 12 to 15) and Visit 5 (Days 13 to 16)
Mean LTB4 in sputum supernatant
Timeframe: Visit 4 (Days 12 to 15) and Visit 5 (Days 13 to 16)
Mean high sensitivity C-reactive protein (hsCRP) at Visit 4 and Visit 5
Timeframe: Visit 4 (Days 12 to 15) and Visit 5 (Days 13 to 16)
Mean Interleukin 8 (IL-8) at different visits
Timeframe: Visit 4 (Days 12 to 15) and Visit 5 (Days 13 to 16)
Mean myeloperoxidase (MPO) and neutrophil elastase (NE)
Timeframe: Visit 4 (Days 12 to 15) and Visit 5 (Days 13 to 16)
Asthma control questionnaire (ACQ) score throughout the study
Timeframe: Up to Follow-up (Up to Day 67)
Mean Forced Expiratory Volume over 1 second (FEV1) at visits throughout the study
Timeframe: Up to Visit 5 (Day 53)
Plasma concentration of GSK2190915 at Visit 4 and Visit 5
Timeframe: Visit 4 (Days 12 to 15) and Visit 5 (Days 13 to 16)
Number of participants with treatment emergent adverse events throughout the study
Timeframe: Up to 67 days
Number of participants with vital signs of potential clinical concern
Timeframe: Up to Follow-up (Day 67)
Number of participants with abnormal electrocardiogram (ECG) findings
Timeframe: Up to 67 days
Number of participants with Hematology Abnormalities of Potential Clinical Importance
Timeframe: Up to Follow up (67 days)
Number of participants with Clinical Chemistry Abnormalities of Potential Clinical Importance
Timeframe: Up to Follow up (Up to 67 days)
Mean Peak Expiratory Flow (PEF) rate
Timeframe: Up to Visit 5 (Day 53)
Interventions:
Enrollment:
14
Primary completion date:
2012-17-05
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Chaudhuri R, Norris V, Kelly K, Zhu C, Ambery C, Lafferty J, Cameron E, Thompson N. FLAPi-1MS-00016349 A randomised, double-blind, placebo-controlled, corss-over study to evaluate the effcte 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.Pulm Pharmacol Ther.2014;27(1):62-69doi: 10.1016/j.pupt.2013.11.007
Medical condition
Asthma
Product
fiboflapon
Collaborators
Not applicable
Study date(s)
June 2011 to May 2012
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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.
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- 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%.
- 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.
A female subject is eligible to participate if she is of:
Exclusion criteria:
- 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.
- 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 location(s)
Location
GSK Investigational Site
Glasgow, Lanarkshire, United Kingdom, G12 0YN
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2012-17-05
Actual study completion date
2012-17-05
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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