GSK2190915 Moderate to Severe Asthma Study

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00850642
• Collaborator: (none)
• Enrollment: 7
• Locations: 8
• Arms: 2
• Actual Duration (Months): 11.2
• Patients Per Site: 0.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A randomised, double-blind, placebo-controlled, parallel group study to evaluate the effect of treatment with GSK2190915, a FLAP inhibitor, as add-on to current inhaled corticosteroid therapy in patients with moderate to severe asthma with elevated sputum neutrophils.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: GSK2190195 100mg; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Efficacy of Orally Administered GSK2190915 as an add-on to Current Therapy in Subjects With Moderate to Severe Asthma Who Have Elevated Sputum Neutrophils
• Actual Study Start Date: Jun 26, 2009
• Actual Primary Completion Date: Jun 2, 2010
• Actual Study Completion Date: Jun 2, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 12 day repeat dosing with placebo	Drug: Placebo; Placebo : 2% (w/w) Ethanol, sucralose (5 mg/100 mL of oral solution) to 100 % (w/w) aqueous sodium carbonate buffer (0.010 M, pH 9-10)
Experimental: GSK2190915 100mg 12 day repeat dosing treatment phase with 100mg GSK2190915.	Drug: GSK2190195 100mg; GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor.

Outcome Measures

Primary Outcome Measures

1. The Numbers of Neutrophils in Induced Sputum-Absolute Neutrophil Count [Day -9 to -7, Day 1, Day 12 and follow-up (Day 24-28)]

   The neutrophils play an important role in participants with more severe asthma. The reduction in number of neutrophils in induced sputum was evaluated to study the effect of treatment with repeat oral doses of GSK2190915, in asthma participants. Sputum samples were evaluated at central laboratory. The samples were rejected, if the weight was less than 100 grams (g), or if excessive cell degeneration or due to excessive squamous cells and insufficient inflammatory cells. The total cell count of neutrophil was reported as total cell count × 10^6 /g.

2. Percentage of Neutrophils in Induced Sputum [Day -9 to -7, Day 1, Day 12 and follow-up (Day 24-28)]

   The neutrophils play an important role in participants with more severe asthma. The reduction in number of neutrophils in induced sputum was evaluated to study the effect of treatment with repeat oral doses of GSK2190915, in asthma participants. Sputum samples were evaluated at central laboratory. The samples were rejected, if the weight was less than 100 g, or if excessive cell degeneration or due to excessive squamous cells and insufficient inflammatory cells. The total cell count of neutrophil was reported as percentage of cells.

Secondary Outcome Measures

1. Assessment of FEV1 on Visit 2, 3 and Visit 4 [Visit 2 (Day 1), visit 3 (Day 5 to 7) and visit 4 (Day 12)]

   FEV1 is the amount of air which can be forcefully exhaled in 1 second. It was assessed using a spirometry. Due to early termination of the study, the data of individual participants is reported.

2. Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [From visit 1 (Day -7 to Day -9) to upto follow-up (upto Day 28)]

   An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.

3. Number of Participants With Vital Sign of Potential Clinical Concern (PCC) [Visit 2 (Day 1) to Upto follow-up (Day 28)]

   The vital sign measurement included measurement of systolic and diastolic blood pressure alongwith pulse rate. The PCC values reported for systolic blood pressure were < 85 millimeter of mercury (mmHg) and >160 mmHg; that for diastolic was <45 mmHg and >100 mmHg. The PCC values for pulse rate were <40 and > 110 beats per minute. The number of participants with values outside the PCC for systolic, diastolic blood pressure and vitals during the treatment duration were reported.

4. Number of Participants With Abnormal Electrocardiogram (ECG) Findings [Visit 2 (Day 1) to Upto follow-up (Day 28)]

   The number of participants with abnormal ECG values were reported. The data was reported as Abnormal clinically significant (CS), abnormal not clinically significant (NCS), and No result.

5. Number of Participants With Clinical Chemistry Values of PCC [Visit 2 (Day 1) to Upto follow-up (Day 28)]

   The clinical chemistry parameters evaluated were albumin, calcium, creatinine, glucose, magnesium, phosphorus, potassium, sodium, urea, gamma glutamyl transferase, and bicarbonate. The number of participants with values outside the PCC values were reported. The PCC value observed for bicarbonate was reported.

6. Number of Participants With Hematology Values of PCC [Visit 2 (Day 1) to Upto follow-up (Day 28)]

   The hematology parameters evaluated were white blood cells, neutrophils, hemoglobin, hematocrit, platelets and lymphocytes. The number of participants with values outside the PCC values were reported. The PCC value observed for lymphocyte was reported.

7. Plasma Concentration of GSK2190915 [At Day 1, pre-dose; Day 1, 2 hour; Day 12, pre-dose; and Day 12, 2 hour]

   The blood samples for analysis of pharmacokinetic parameters were collected at pre-dose and 2 hours post dose on Day 1 and pre-dose trough and 2 hour post dose on Day 12, to evaluate the concentration of the drug GSK2190915 in plasma.

8. Percentage Change From Baseline Urine LTE4 Biomarker [Day 1 and Day 12]

   The urine spot samples were collected from the participants at pre-dose on day 1 and trough day 12 for evaluation of LTE4 biomarker. This evaluated the level of inflammation in the airways of the asthma participants. The percentage change from baseline was calculated by dividing the post randomization change by the baseline value from the individual and multiplying by a 100. If either the baseline or post-randomization value is missing, the change from baseline is set to missing. Baseline was defined as Day 1(pre-dose).

9. Percentage Change From Baseline of LTB4 Biomarker in Plasma [Day 1 and Day 12]

   The plasma samples were evaluated for presence of LTB4 biomarkers. The percentage change from baseline was calculated by dividing the post-randomization change by the baseline value from the individual and multiplying by a 100. If either the baseline or post-randomization value is missing, the change from baseline is set to missing. Baseline was defined as Day 1(pre-dose).

10. Concentration of LTB4 in Sputum [Day 1 and Day 12]

    The concentration of LTB4 levels in sputum were evaluated. However due to early termination of the study, the data was not collected.

11. Concentration of Interleukin (IL)-17 and High-sensitivity C-reactive Protein (hsCRP) in Blood [Day 1 and Day 12]

    The blood samples were collected to evaluate the concentration of IL-17 and hsCRP in blood. However due to early termination of the study, the data was not collected.

12. Assessment of Established Markers of Anti-inflammatory Activity in Sputum: the Measurements Will Include IL-17, Neutrophil Elastase, Myeloperoxidase and IL-8 [Day 1 and Day 12]

    During the study conduct it was observed that the levels of IL-17, measured in both blood and sputum were below limit of quantification; for neutrophil elastase, in sputum no inference could be made as most levels were above the limit of quantification. Thus due to limited amount of data the analysis was not summarized.

13. Asthma Control Questionnaire (ACQ) Assessment [At Day 1, Day 5 to 7 and Day 12]

    ACQ measures the adequacy of asthma control. It includes 5 questions about symptoms of asthma, 1 question about the rescue medication used and 1 about lung function (FEV1% predicted). This is a 7-item scale where the items are equally weighted and the ACQ score is the mean of 7 items which ranges from 0 to 6. 0= Well controlled and 6=extremely poorly controlled. Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma. Thus for ACQ a higher score indicates severe disease and a low score indicative of less severe disease.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

• Males and females aged 18 to 65 years inclusive.

• Body mass index within the range 18.5-37.0 kilograms/metre2 (kg/m2).

• An established clinical history of Asthma in accordance with the definition by the GINA Guidelines [GINA, 2006]. Subjects should have at screening or within the last year documented reversibility (>12 %) to short acting bronchodilator, or positive methacholine challenge, or positive histamine challenge (PC20 <8mg/ml).

• A female subject is eligible to participate if she is of: non-childbearing potential defined as pre-menopausal females with documented (medical report verification) hysterectomy or double oophrectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 40 pg/ml (<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy; childbearing potential and agrees to use one of the contracception methods listed in Section 8.1 for an appropriate period of time prior to the start of dosing and until 3 months after last dose.

• Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 3 months after the last dose.

• Subject with moderate to severe asthma with forced expiratory volume in one second (FEV1) ≥ 50% of predicted.

• Subject who are on regular inhaled corticosteroids without or in combination with a regular long acting Beta 2 Agonist. The dose should be stable for at least 4 weeks before screening.

• Subjects who are taking a minimum of FP 250mg BID or equivalent.

• Persistent sputum neutrophilia defined by sputum neutrophils ≥ 65% with TTC < 15 million cells/g with no evidence of eosinophilia (sputum eosinophils < 2%). Persistent is defined as the criteria being met at screening (or within the 6 months preceding screening) and on visit 1.

• 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.

Exclusion Criteria:

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

• 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).

• Clinically significant abnormalities in safety laboratory analysis at screening.

• Subject has uncontrolled hypertension or is hypertensive at screening. Hypertension at screening is defined as persistent systolic BP >150 mmHg or diastolic BP > 90mmHg.

• 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 hypercapnoea, respiratory arrest and/or hypoxic seizures.

• Subject is unable to abstain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements) including non-steroidal anti-inflammatory drugs (NSAIDs), anti-depressant drugs, anti-histamines and anti-asthma, anti-rhinitis or hay fever medication, with the exception of ICS, LABA and short action beta agonists, from 14 days before screening until the follow-up visit unless in the opinion of the Investigator and sponsor the medication will not interfere with the study

• Administration of oral or injectable steroids within 6 weeks of screening.

• 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.

• Administration of anti -leukotrienne therapies for 14 days before screening and during the study.

• Administration of any vaccinations within 1 month 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.

• There is a risk of non-compliance with study procedures.

• History of blood donation (500 mL) within 3 months of starting the clinical study.

• 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.

• The subject has a screening QTc value of >450msec, PR interval outside the range 120 to 220msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T-wave).

• The subject has tested positive for hepatitis C antibody or hepatitis B surface antigen.

• The subject has tested positive for HIV antibodies.

• 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, Barbituates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Hamilton	Ontario	Canada	L8N 4A6
2	GSK Investigational Site	Kingston	Ontario	Canada	K7L 2V6
3	GSK Investigational Site	Montreal	Quebec	Canada	H4J 1C5
4	GSK Investigational Site	Sainte-Foy	Quebec	Canada	G1V 4G5
5	GSK Investigational Site	Glasgow	Lanarkshire	United Kingdom	G12 0YN
6	GSK Investigational Site	Leicester	Leicestershire	United Kingdom	LE3 9QP
7	GSK Investigational Site	London		United Kingdom	NW10 7EW
8	GSK Investigational Site	Manchester		United Kingdom	M23 9QZ

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00850642
• Other Study ID Numbers: 112046; 2008-007244-33
• First Posted: Feb 25, 2009
• Last Update Posted: Nov 30, 2020
• Last Verified: Nov 1, 2020

• Keywords provided by GlaxoSmithKline: Sputum cell counts; Neutrophils; Severe Asthma; ICS; Inhaled corticosteroids
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Recruitment Details	The study was terminated prior to completion due to difficulties in recruiting the required participants. A total of 7 asthmatic participants completed the study prior to termination. The study was, conducted from 26 June 2009 to 02 June 2010, at three centers in Canada and three centers in the United Kingdom.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally, once daily for 12-days.	The eligible participants in this arm received GSK2190915 as 100 milligram (mg), orally once daily for 12-days.
Period Title: Overall Study
STARTED	3	4
COMPLETED	3	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	GSK2190915	Total
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days.	The eligible participants in this arm received GSK2190915 as 100 mg, orally, once daily for 12-days.	Total of all reporting groups
Overall Participants	3	4	7
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.0 (12.12)	57.8 (6.65)	55.3 (8.98)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	3 75%	4 57.1%
Male	2 66.7%	1 25%	3 42.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	3 100%	4 100%	7 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	The Numbers of Neutrophils in Induced Sputum-Absolute Neutrophil Count
Description	The neutrophils play an important role in participants with more severe asthma. The reduction in number of neutrophils in induced sputum was evaluated to study the effect of treatment with repeat oral doses of GSK2190915, in asthma participants. Sputum samples were evaluated at central laboratory. The samples were rejected, if the weight was less than 100 grams (g), or if excessive cell degeneration or due to excessive squamous cells and insufficient inflammatory cells. The total cell count of neutrophil was reported as total cell count × 10^6 /g.
Time Frame	Day -9 to -7, Day 1, Day 12 and follow-up (Day 24-28)

Outcome Measure Data

Analysis Population Description

All Subject Population was defined as all participants who receive at least one dose of study medication.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days
Measure Participants	3	4
Day -9 to -7	5.205 (2.8415)	3.096 (2.6093)
Day 1	3.142 (3.2449)	14.667 (20.8291)
Day 12	13.534 (13.6394)	0.396 (0.0801)
Follow-up	5.359 (1.1681)	2.995 (3.6389)

2. Primary Outcome

Title	Percentage of Neutrophils in Induced Sputum
Description	The neutrophils play an important role in participants with more severe asthma. The reduction in number of neutrophils in induced sputum was evaluated to study the effect of treatment with repeat oral doses of GSK2190915, in asthma participants. Sputum samples were evaluated at central laboratory. The samples were rejected, if the weight was less than 100 g, or if excessive cell degeneration or due to excessive squamous cells and insufficient inflammatory cells. The total cell count of neutrophil was reported as percentage of cells.
Time Frame	Day -9 to -7, Day 1, Day 12 and follow-up (Day 24-28)

Outcome Measure Data

Analysis Population Description

All Subject Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days.	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days.
Measure Participants	3	4
Day -9 to -7	84.00 (9.469)	74.88 (2.269)
Day 1, pre-dose	68.00 (10.607)	74.77 (18.351)
Day 12, 2 hour	86.30 (16.263)	56.33 (19.732)
Follow-up	65.75 (0.071)	78.33 (14.640)

3. Secondary Outcome

Title	Assessment of FEV1 on Visit 2, 3 and Visit 4
Description	FEV1 is the amount of air which can be forcefully exhaled in 1 second. It was assessed using a spirometry. Due to early termination of the study, the data of individual participants is reported.
Time Frame	Visit 2 (Day 1), visit 3 (Day 5 to 7) and visit 4 (Day 12)

Outcome Measure Data

Analysis Population Description

All Subject population. Individual participant data reported, due to early termination of study. Data for only those participants available at the indicated time points were collected and analyzed. Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days.	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days.
Measure Participants	3	4
Particpant 1, Day 1, Pre-dose	2.33
Particpant 1, Day 1, 2 hour	2.55
Participant 1, Day 5 to 7/ Visit 3	2.56
Participant 1, Day 12, Pre-dose	2.83
Particpant 1, Day 12, 2 hour	2.77
Particpant 2, Day 1, Pre-dose	2.88
Particpant 2, Day 1, 2 hour	3.06
Participant 2, Day 5 to 7/Visit 3	2.96
Participant 2, Day 12, Pre-dose	3.26
Particpant 2, Day 12, 2 hour	3.14
Particpant 3, Day 1, Pre-dose	1.65
Particpant 3, Day 1, 2 hour	1.98
Participant 3, Day 5 to 7/ Visit 3	1.92
Participant 3, Day 12, Pre-dose	1.81
Particpant 3, Day 12, 2 hour	1.83
Particpant 4, Day 1, Pre-dose	1.97
Particpant 4, Day 1, 2 hour	2.14
Participant 4, Day 5 to 7/ Visit 3	2.22
Participant 4, Day 12, Pre-dose	2.02
Particpant 4, Day 12, 2 hour	1.90
Particpant 5, Day 1, Pre-dose	2.24
Particpant 5, Day 1, 2 hour	2.78
Participant 5, Day 5 to 7/ Visit 3	2.07
Participant 5, Day 12, Pre-dose	1.89
Particpant 5, Day 12, 2 hour	2.02
Particpant 6, Day 1, Pre-dose	1.10
Particpant 6, Day 1, 2 hour	1.22
Participant 6, Day 5 to 7/ Visit 3	1.22
Participant 6, Day 12, Pre-dose	1.10
Particpant 6, Day 12, 2 hour	1.19
Particpant 7, Day 1, Pre-dose	1.03
Particpant 7, Day 1, 2 hour	1.13
Participant 7, Day 5 to 7/ Visit 3	1.14
Participant 7, Day 12, Pre-dose	1.11

4. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Time Frame	From visit 1 (Day -7 to Day -9) to upto follow-up (upto Day 28)

Outcome Measure Data

Analysis Population Description

All Subject Population.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days
Measure Participants	3	4
Any AE	2 66.7%	3 75%
Any SAE	0 0%	0 0%

5. Secondary Outcome

Title	Number of Participants With Vital Sign of Potential Clinical Concern (PCC)
Description	The vital sign measurement included measurement of systolic and diastolic blood pressure alongwith pulse rate. The PCC values reported for systolic blood pressure were < 85 millimeter of mercury (mmHg) and >160 mmHg; that for diastolic was <45 mmHg and >100 mmHg. The PCC values for pulse rate were <40 and > 110 beats per minute. The number of participants with values outside the PCC for systolic, diastolic blood pressure and vitals during the treatment duration were reported.
Time Frame	Visit 2 (Day 1) to Upto follow-up (Day 28)

Outcome Measure Data

Analysis Population Description

All subject population.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days.	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days.
Measure Participants	3	4
Systolic blood pressure	0 0%	0 0%
Diastolic blood pressure	0 0%	0 0%
Heart rate	0 0%	0 0%

6. Secondary Outcome

Title	Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Description	The number of participants with abnormal ECG values were reported. The data was reported as Abnormal clinically significant (CS), abnormal not clinically significant (NCS), and No result.
Time Frame	Visit 2 (Day 1) to Upto follow-up (Day 28)

Outcome Measure Data

Analysis Population Description

All Subject Population.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days
Measure Participants	3	4
Abnormal NCS, Day 1, pre-dose	1 33.3%	1 25%
No results, Day 1 pre-dose 2	1 33.3%	0 0%
No results, Day 1 pre-dose 3	1 33.3%	0 0%
Abnormal NCS, Day 1, pre-dose 2 hour	1 33.3%	0 0%

7. Secondary Outcome

Title	Number of Participants With Clinical Chemistry Values of PCC
Description	The clinical chemistry parameters evaluated were albumin, calcium, creatinine, glucose, magnesium, phosphorus, potassium, sodium, urea, gamma glutamyl transferase, and bicarbonate. The number of participants with values outside the PCC values were reported. The PCC value observed for bicarbonate was reported.
Time Frame	Visit 2 (Day 1) to Upto follow-up (Day 28)

Outcome Measure Data

Analysis Population Description

All subject population.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days
Measure Participants	3	4
Count of Participants [Participants]	0 0%	1 25%

8. Secondary Outcome

Title	Number of Participants With Hematology Values of PCC
Description	The hematology parameters evaluated were white blood cells, neutrophils, hemoglobin, hematocrit, platelets and lymphocytes. The number of participants with values outside the PCC values were reported. The PCC value observed for lymphocyte was reported.
Time Frame	Visit 2 (Day 1) to Upto follow-up (Day 28)

Outcome Measure Data

Analysis Population Description

All subject population.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, once daily for 12-days.	The eligible participants in this arm received 100 mg GSK2190915, once daily for 12-days.
Measure Participants	3	4
Count of Participants [Participants]	0 0%	1 25%

9. Secondary Outcome

Title	Plasma Concentration of GSK2190915
Description	The blood samples for analysis of pharmacokinetic parameters were collected at pre-dose and 2 hours post dose on Day 1 and pre-dose trough and 2 hour post dose on Day 12, to evaluate the concentration of the drug GSK2190915 in plasma.
Time Frame	At Day 1, pre-dose; Day 1, 2 hour; Day 12, pre-dose; and Day 12, 2 hour

Outcome Measure Data

Analysis Population Description

All Subject Population.

Arm/Group Title	GSK2190915
Arm/Group Description	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days
Measure Participants	4
Day 1, pre-dose	0.000 (NA)
Day 1, 2 hour	1609.303 (958.4609)
Day 12, pre-dose	1073.623 (627.7852)
Day 12, 2 hour	2334.238 (1252.5057)

10. Secondary Outcome

Title	Percentage Change From Baseline Urine LTE4 Biomarker
Description	The urine spot samples were collected from the participants at pre-dose on day 1 and trough day 12 for evaluation of LTE4 biomarker. This evaluated the level of inflammation in the airways of the asthma participants. The percentage change from baseline was calculated by dividing the post randomization change by the baseline value from the individual and multiplying by a 100. If either the baseline or post-randomization value is missing, the change from baseline is set to missing. Baseline was defined as Day 1(pre-dose).
Time Frame	Day 1 and Day 12

Outcome Measure Data

Analysis Population Description

All subject population.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days
Measure Participants	3	4
Mean (Standard Deviation) [Percent change]	26.22 (89.173)	-89.62 (4.996)

11. Secondary Outcome

Title	Percentage Change From Baseline of LTB4 Biomarker in Plasma
Description	The plasma samples were evaluated for presence of LTB4 biomarkers. The percentage change from baseline was calculated by dividing the post-randomization change by the baseline value from the individual and multiplying by a 100. If either the baseline or post-randomization value is missing, the change from baseline is set to missing. Baseline was defined as Day 1(pre-dose).
Time Frame	Day 1 and Day 12

Outcome Measure Data

Analysis Population Description

All subject population.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days
Measure Participants	3	4
Day 1, 2 hour	-24.72 (53.130)	-95.24 (6.711)
Day 12, pre-dose	282.81 (452.763)	-95.29 (7.326)
Day 12, 2 hour	-22.05 (58.391)	-99.23 (1.010)

12. Secondary Outcome

Title	Concentration of LTB4 in Sputum
Description	The concentration of LTB4 levels in sputum were evaluated. However due to early termination of the study, the data was not collected.
Time Frame	Day 1 and Day 12

Outcome Measure Data

Analysis Population Description

All Subject Population. Data not collected.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days
Measure Participants	0	0

13. Secondary Outcome

Title	Concentration of Interleukin (IL)-17 and High-sensitivity C-reactive Protein (hsCRP) in Blood
Description	The blood samples were collected to evaluate the concentration of IL-17 and hsCRP in blood. However due to early termination of the study, the data was not collected.
Time Frame	Day 1 and Day 12

Outcome Measure Data

Analysis Population Description

All Subject Population. Data not summarized for this parameter.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days
Measure Participants	0	0

14. Secondary Outcome

Title	Assessment of Established Markers of Anti-inflammatory Activity in Sputum: the Measurements Will Include IL-17, Neutrophil Elastase, Myeloperoxidase and IL-8
Description	During the study conduct it was observed that the levels of IL-17, measured in both blood and sputum were below limit of quantification; for neutrophil elastase, in sputum no inference could be made as most levels were above the limit of quantification. Thus due to limited amount of data the analysis was not summarized.
Time Frame	Day 1 and Day 12

Outcome Measure Data

Analysis Population Description

All Subjects Population. Collected data were below the limit of quantification, so data could not be summarized

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days
Measure Participants	0	0

15. Secondary Outcome

Title	Asthma Control Questionnaire (ACQ) Assessment
Description	ACQ measures the adequacy of asthma control. It includes 5 questions about symptoms of asthma, 1 question about the rescue medication used and 1 about lung function (FEV1% predicted). This is a 7-item scale where the items are equally weighted and the ACQ score is the mean of 7 items which ranges from 0 to 6. 0= Well controlled and 6=extremely poorly controlled. Mean scores of =<0.75 indicate well-controlled asthma, scores between 0.76 and < 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma. Thus for ACQ a higher score indicates severe disease and a low score indicative of less severe disease.
Time Frame	At Day 1, Day 5 to 7 and Day 12

Outcome Measure Data

Analysis Population Description

All Subject Population.

Arm/Group Title	Placebo	GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days	The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days
Measure Participants	3	4
Day 1	1.19 (0.218)	1.57 (0.857)
Day 5 to 7	1.29 (0.286)	1.50 (0.474)
Day 12	1.14 (0.429)	1.54 (0.811)

Adverse Events

Time Frame	From visit 1 (Day -7) to upto follow-up (upto Day 28)
Adverse Event Reporting Description	All subject population was used to record the AEs.
Arm/Group Title	Placebo		GSK2190915
Arm/Group Description	The eligible participants in this arm were administered with matching placebo, orally, once daily for 12-days.		The eligible participants in this arm received GSK2190915 as 100 mg, orally once daily for 12-days.
All Cause Mortality
	Placebo		GSK2190915
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/4 (0%)
Serious Adverse Events
	Placebo		GSK2190915
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		GSK2190915
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		3/4 (75%)
Cardiac disorders
Palpitations	0/3 (0%)		1/4 (25%)
Supraventricular extrasystoles	0/3 (0%)		1/4 (25%)
Gastrointestinal disorders
Abdominal pain	0/3 (0%)		1/4 (25%)
Constipation	0/3 (0%)		1/4 (25%)
General disorders
Chills	1/3 (33.3%)		0/4 (0%)
Infections and infestations
Nasopharyngitis	0/3 (0%)		1/4 (25%)
Investigations
Bacterial test positive	0/3 (0%)		1/4 (25%)
Metabolism and nutrition disorders
Decreased appetite	0/3 (0%)		1/4 (25%)
Nervous system disorders
Headache	1/3 (33.3%)		2/4 (50%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/3 (0%)		1/4 (25%)
Productive cough	0/3 (0%)		1/4 (25%)

Limitations/Caveats

The study was terminated early due to difficulties in recruiting the required participants.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.