NCT01147744

Dose Ranging Study Evaluating the Efficacy and Safety of GSK2190915 Administered Once Daily

Completed Phase 2 Results posted Last updated 2 October 2017

What this trial tests

Phase 2 trial testing Fluticasone Propionate 100mcg via ACCUHALER/DISKUS in Asthma in 700 participants. Completed in 6 October 2011.

Timeline

28 June 2010

Primary endpoint
6 October 2011

6 October 2011

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	700
Start date	28 June 2010
Primary completion	6 October 2011
Estimated completion	6 October 2011
Sites	84 locations across Japan, Ukraine, Poland, Romania, Bulgaria, United States

Drugs / interventions tested

• Fluticasone Propionate 100mcg via ACCUHALER/DISKUS
• GSK2190915 100mg — full drug profile →
• GSK2190915 10mg — full drug profile →
• GSK2190915 300mg — full drug profile →
• GSK2190915 30mg — full drug profile →
• Montelukast 10mg
• Placebo GSK2190915 one tablet — full drug profile →
• Placebo montelukast
• Placebo fluticasone propionate via ACCUHALER/DISKUS
• Placebo GSK2190915 two tablets

Conditions studied

• Asthma — all drugs for Asthma →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

12 and older, female only, with Asthma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Change From Baseline to the End of the 8-Week Treatment Period in Trough Forced Expiratory Volume in One Second (FEV1) Primary · Baseline and Week 8

Pulmonary function was measured by forced expiratory volume in one second, defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is defined as the morning (AM) pre-dose and pre-rescue bronchodilator FEV1 at the clinic visit. Baseline was the pre-dose value obtained at Visit 3. Change from Baseline was calculated as the end of Week 8 value minus the Baseline value. Analysis of covariance (ANCOVA) model used for statistical analysis. ITT Population was comprised of all participant randomized to treatment who received at least one dose of double-blind stud

Group	Value	95% CI
Placebo	0.12	± 0.04
GSK2190915 10 mg	0.18	± 0.04
GSK2190915 30 mg	0.23	± 0.04
GSK2190915 100 mg	0.19	± 0.04
GSK2190915 300 mg	0.19	± 0.04
Fluticasone Propionate 100 mcg	0.31	± 0.04
Montelukast 10 mg	0.19	± 0.04

Mean Change From Baseline in Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the 8-Week Treatment Period Secondary · Baseline up to Week 8

Peak expiratory flow is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Change from Baseline was calculated as the value of the averaged PEF daily (pre-dose and pre-rescue bronchodilator) evening over the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the participants)

Group	Value	95% CI
Placebo	8.01	± 3.19
GSK2190915 10 mg	7.62	± 3.19
GSK2190915 30 mg	9.37	± 3.20
GSK2190915 100 mg	6.21	± 3.17
GSK2190915 300 mg	10.33	± 3.15
Fluticasone Propionate 100 mcg	10.46	± 3.16
Montelukast 10 mg	8.53	± 3.24

Mean Change From Baseline in Daily Trough AM PEF Averaged Over the 8-Week Treatment Period Secondary · Baseline up to Week 8

The PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Trough AM PEF is defined as the AM pre-dose and pre-rescue bronchodilator at the clinic visit. Change from Baseline was calculated as the value of the averaged PEF daily (pre-dose and pre-rescue bronchodilator) AM over the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the participants).

Group	Value	95% CI
Placebo	11.77	± 3.28
GSK2190915 10 mg	13.23	± 3.28
GSK2190915 30 mg	15.52	± 3.29
GSK2190915 100 mg	8.72	± 3.26
GSK2190915 300 mg	16.35	± 3.24
Fluticasone Propionate 100 mcg	15.25	± 3.26
Montelukast 10 mg	17.38	± 3.32

Mean Change From Baseline in the Percentage of Symptom-free Days Averaged Over the 8-Week Treatment Period Secondary · Baseline up to Week 8

Asthma symptoms were recorded in a daily electronic diary (eDiary) by the participants every day in the evening at bedtime and before taking any rescue or study medication and before the assessment of the PEF measurement. Participant's responses to evening assessments indicated no symptoms were considered to be symptom free. For participants, the symptom free days were assessed during the 8-Week treatment period. Change from Baseline was calculated as the averaged of symptom-free days during the 8-Week treatment period minus the Baseline value. Baseline was defined as the last 7 days prior to

Group	Value	95% CI
Placebo	13.98	± 2.84
GSK2190915 10 mg	15.15	± 2.84
GSK2190915 30 mg	18.54	± 2.84
GSK2190915 100 mg	15.31	± 2.82
GSK2190915 300 mg	14.06	± 2.81
Fluticasone Propionate 100 mcg	22.18	± 2.81
Montelukast 10 mg	16.87	± 2.87

Mean Change From Baseline in the Percentage of Symptom-free Nights Averaged Over the 8-Week Treatment Period Secondary · Baseline up to Week 8

Asthma symptoms were recorded in a daily eDairy by the participants every day in the morning upon rising and before taking any rescue or study medication and before the assessment of the PEF measurement. Participant's responses to the morning assessments indicated no symptoms were considered to be symptom free. For participants, the symptom free nights were assessed during the 8-Week treatment period. Change from Baseline was calculated as the averaged of symptom-free nights during the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the pa

Group	Value	95% CI
Placebo	13.99	± 2.90
GSK2190915 10 mg	14.83	± 2.90
GSK2190915 30 mg	16.71	± 2.90
GSK2190915 100 mg	16.12	± 2.88
GSK2190915 300 mg	12.21	± 2.86
Fluticasone Propionate 100 mcg	19.94	± 2.88
Montelukast 10 mg	19.39	± 2.93

Mean Change From Baseline in the Percentage of Rescue-free Days Averaged Over the 8-Week Treatment Period Secondary · Baseline up to Week 8

The number of inhalations of rescue salbutamol/albuterol inhalation aerosol used during the day and night was recorded by the participants in an eDiary. The time span during which the participants did not have to take any rescue medication (medication intended to relieve symptoms immediately) was considered to be a rescue-free period. For participants, the rescue-free days were assessed during the 8-Week treatment period. Change from Baseline was calculated as the averaged of rescue-free days during the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to rando

Group	Value	95% CI
Placebo	16.80	± 3.10
GSK2190915 10 mg	22.91	± 3.1
GSK2190915 30 mg	20.91	± 3.09
GSK2190915 100 mg	18.95	± 3.08
GSK2190915 300 mg	18.51	± 3.06
Fluticasone Propionate 100 mcg	26.39	± 3.06
Montelukast 10 mg	23.55	± 3.13

Mean Change From Baseline in the Percentage of Rescue-free Nights Averaged Over the 8-Week Treatment Period Secondary · Baseline up to Week 8

The number of inhalations of rescue salbutamol/albuterol inhalation aerosol used during the day and night was recorded by the participants in an eDiary. The time span during which the participants did not have to take any rescue medication (medication intended to relieve symptoms immediately) was considered to be a rescue-free period. For participants, the rescue-free nights were assessed during the 8-Week treatment period. Change from Baseline was calculated as the averaged of rescue-free nights during the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to r

Group	Value	95% CI
Placebo	16.93	± 3.04
GSK2190915 10 mg	19.28	± 3.04
GSK2190915 30 mg	17.36	± 3.03
GSK2190915 100 mg	19.63	± 3.02
GSK2190915 300 mg	15.71	± 3.00
Fluticasone Propionate 100 mcg	24.42	± 3.02
Montelukast 10 mg	20.54	± 3.07

Mean Change From Baseline in Day-time Asthma Symptom Score Over the 8-Week Treatment Period Secondary · Baseline up to Week 8

Participants recorded their day-time asthma symptom score in an eDiary each PM at bedtime and before taking any rescue or study medication and before assessing the PEF measurement during the 8-Week treatment period. Day-time asthma symptom scores, as: 0=no asthma symptoms, 1=one episode of short-time asthma symptoms, 2=two or more episodes of short-time asthma symptoms, 3=asthma symptoms occurring during most part of daytime without interference with daily life activities, 4=asthma symptoms occurring during most part of daytime with interference with daily life activities, 5=severe asthma symp

Group	Value	95% CI
Placebo	-0.34	± 0.06
GSK2190915 10mg	-0.34	± 0.06
GSK2190915 30mg	-0.50	± 0.06
GSK2190915 100mg	-0.36	± 0.06
GSK2190915 300mg	-0.34	± 0.06
Fluticasone Propionate 100 mcg	-0.43	± 0.06
Montelukast 10mg	-0.41	± 0.06

Mean Change From Baseline in Night-time Asthma Symptom Score Over the 8-Week Treatment Period Secondary · Baseline up to Week 8

Participants recorded their night-time asthma symptom score in an eDiary each AM upon rising and before taking any rescue or study medication and before assessing the PEF measurement during the 8-Week treatment period. Night-time asthma symptom scores, as: 0=no asthma symptoms, 1= one awakening or waking early due to asthma symptoms, 2= two or more awakenings due to asthma symptoms (including waking early), 3= asthma symptoms almost prevented the participant from sleeping, 4= severe asthma symptoms completely prevented from sleeping. Change from Baseline was calculated as the averaged of night

Group	Value	95% CI
Placebo	-0.23	± 0.05
GSK2190915 10mg	-0.21	± 0.05
GSK2190915 30mg	-0.33	± 0.05
GSK2190915 100mg	-0.26	± 0.05
GSK2190915 300mg	-0.22	± 0.05
Fluticasone Propionate 100 mcg	-0.29	± 0.05
Montelukast 10mg	-0.32	± 0.05

Mean Change From Baseline in Day-time Rescue Short Acting beta2-agonist (SABA) Usage Over the 8-Week Treatment Period Secondary · Baseline up to Week

The number of inhalations of rescue SABA, salbutamol/albuterol inhalation aerosol used during the day and night was recorded by the participants in an eDiary. Participants who used salbutamol/albuterol inhalation aerosol at day-time were assessed during the 8-Week treatment period. Change from Baseline was calculated as the averaged number of day-time salbutamol/albuterol inhalation aerosol used during the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the participants).

Group	Value	95% CI
Placebo	-0.42	± 0.07
GSK2190915 10mg	-0.55	± 0.07
GSK2190915 30mg	-0.68	± 0.07
GSK2190915 100mg	-0.50	± 0.07
GSK2190915 300mg	-0.47	± 0.07
Fluticasone Propionate 100 mcg	-0.67	± 0.07
Montelukast 10mg	-0.63	± 0.07

Mean Change From Baseline in Night-time Rescue SABA Usage Over the 8-Week Treatment Period Secondary · Baseline up to Week 8

The numbers of inhalations of rescue SABA, salbutamol/albuterol inhalation aerosol used during the day and night was recorded by the participants in an eDiary. Participants who used salbutamol/albuterol inhalation aerosol at night-time were assessed during the 8-Week treatment period. Change from Baseline was calculated as the averaged number of night-time salbutamol/albuterol inhalation aerosol used during the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the participants).

Group	Value	95% CI
Placebo	-0.30	± 0.07
GSK2190915 10 mg	-0.40	± 0.07
GSK2190915 30 mg	-0.44	± 0.07
GSK2190915 10 0mg	-0.42	± 0.07
GSK2190915 300 mg	-0.30	± 0.07
Fluticasone Propionate 100 mcg	-0.47	± 0.07
Montelukast 10 mg	-0.46	± 0.07

Number of Participants Who Withdrew Due to Lack of Efficacy During the 8-Week Treatment Period Secondary · Upto 8 Weeks

The participants who met any of the following withdrawal criteria were considered to be withdrawn due to lack of efficacy: 1) Clinic FEV1 below stability limit calculated at Visit 3. 2) More than three days between two consecutive visits, PEF has fallen below stability limit calculated at Visit 3. 3) Use of 12 or more inhalations of SABA per day for more than two days between consecutive visits. 4) Asthma exacerbation defined as worsening requiring any treatment other than study medication or rescue medication. This included requiring the use of systemic or inhaled corticosteroids and /or emer

Group	Value	95% CI
Placebo	11
GSK2190915 10mg	11
GSK2190915 30mg	9
GSK2190915 100mg	11
GSK2190915 300mg	13
Fluticasone Propionate 100 mcg	8
Montelukast 10mg	7

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug until the follow-up contact (up to Week 9).. Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 0/100 (0%)

Deaths: 0/100

GSK2190915 10mg

Serious: 1/99 (1%)

Deaths: 0/99

GSK2190915 30mg

Serious: 0/100 (0%)

Deaths: 0/100

GSK2190915 100mg

Serious: 1/100 (1%)

Deaths: 0/100

GSK2190915 300mg

Serious: 0/101 (0%)

Deaths: 0/101

Fluticasone Propionate 100 mcg

Serious: 1/103 (1%)

Deaths: 0/103

Montelukast 10mg

Serious: 0/97 (0%)

Deaths: 0/97

Serious adverse events (3 terms)

Reaction	System	Placebo	GSK2190915 10mg	GSK2190915 30mg	GSK2190915 100mg	GSK2190915 300mg	Fluticasone Propionate 100…	Montelukast 10mg
Cartilage injury	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Joint dislocation	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—	—

Other adverse events (3 terms — click to expand)

Reaction	System	Placebo	GSK2190915 10mg	GSK2190915 30mg	GSK2190915 100mg	GSK2190915 300mg	Fluticasone Propionate 100…	Montelukast 10mg
Headache	Nervous system disorders	—	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—
Pharyngitis	Infections and infestations	—	—	—	—	—	—	—

Most-reported serious reactions: Cartilage injury, Joint dislocation, Small intestinal obstruction.

Data from ClinicalTrials.gov NCT01147744 adverse events section.

Sponsor's own description

To evaluate the efficacy, dose response and safety of four doses of GSK2190915 in tablet form (10mg, 30mg, 100mg and 300mg) administered once daily, over 8 weeks compared with placebo in adolescent and adult subjects (12 years of age and older) with persistent asthma. These data will form the basis for the selection of the optimal daily dose of GSK2190915 to be carried forward in Phase III asthma studies. The study also includes Fluticasone Propionate Inhalation Powder (100 mcg, twice daily) and Montelukast (10mg, once daily) to allow for an exploratory analysis of the efficacy of GSK2190915 versus a low dose inhaled corticosteroid and a leukotriene receptor antagonist.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets.
   Wang B, Wu L, Chen J, Dong L, et al · · 2021 · cited 900× · PMID 33637672 · DOI 10.1038/s41392-020-00443-w
2. The role of lipoxygenases in pathophysiology; new insights and future perspectives.
   Mashima R, Okuyama T. · · 2015 · cited 290× · PMID 26298204 · DOI 10.1016/j.redox.2015.08.006
3. Efficacy, safety and tolerability of GSK2190915, a 5-lipoxygenase activating protein inhibitor, in adults and adolescents with persistent asthma: a randomised dose-ranging study.
   Follows RM, Snowise NG, Ho SY, Ambery CL, et al · · 2013 · cited 23× · PMID 23682661 · DOI 10.1186/1465-9921-14-54
4. Inflammation Drives Alzheimer's Disease: Emphasis on 5-lipoxygenase Pathways.
   Siddiqui A, Akhtar S, Shah Z, Othman I, et al · · 2021 · cited 15× · PMID 32972344 · DOI 10.2174/1570159x18666200924122732