GSK2190915 Moderate to Severe Asthma Study | NCT00850642

ID	Type	Description	Link
2008-007244-33	EudraCT Number

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	12 day repeat dosing with placebo	Drug: Placebo
GSK2190915 100mg	Experimental	12 day repeat dosing treatment phase with 100mg GSK2190915.	Drug: GSK2190195 100mg

Name	Type	Description	Arm Group Labels	Other Names
GSK2190195 100mg	Drug	GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor.	GSK2190915 100mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
The Numbers of Neutrophils in Induced Sputum-Absolute Neutrophil Count	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.	Day -9 to -7, Day 1, Day 12 and follow-up (Day 24-28)
Percentage of Neutrophils in Induced Sputum	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.	Day -9 to -7, Day 1, Day 12 and follow-up (Day 24-28)

Secondary Outcomes

Measure	Description	Time Frame
Assessment of FEV1 on Visit 2, 3 and Visit 4	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.	Visit 2 (Day 1), visit 3 (Day 5 to 7) and visit 4 (Day 12)
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Hamilton	Ontario	L8N 4A6	Canada
GSK Investigational Site

ID	Title	Description
FG000	Placebo	The eligible participants in this arm were administered with matching placebo, orally, once daily for 12-days.
FG001	GSK2190915	The eligible participants in this arm received GSK2190915 as 100 milligram (mg), orally once daily for 12-days.

ID	Title	Description
BG000	Placebo	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days.
BG001	GSK2190915	The eligible participants in this arm received GSK2190915 as 100 mg, orally, once daily for 12-days.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

The Numbers of Neutrophils in Induced Sputum-Absolute Neutrophil Count

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.

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

Posted

Mean

Standard Deviation

Giga cells per g

Day -9 to -7, Day 1, Day 12 and follow-up (Day 24-28)

ID	Title	Description
OG000	Placebo	The eligible participants in this arm were administered with matching placebo, orally once daily for 12-days

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases