Clinical trial NCT01147744: Dose Ranging Study Evaluating the Efficacy and Safety of GSK2190915 Administered Once Daily
Official title: A Randomised Double-Blind, Double-Dummy, Placebo-Controlled, Stratified, Parallel-Group, Multicentre, Dose Ranging Study to Evaluate the Efficacy and Safety of GSK2190915 Tablets Administered Once Daily, Fluticasone Propionate Inhalation Powder 100mcg Twice Daily and Montelukast 10mg Once Daily Compared With Placebo for 8 Weeks in Adolescent and Adult Subjects With Persistent Asthma While Treated With Short Acting Beta2-agonist.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Efficacy
Asthma
Safety
Fluticasone Propionate
FLAP
Beta-agonists
GSK2190915
Montelukast
Placebo
FLAIR
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-06-22
Enrollment: 700
Sex: FEMALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Type of Subject: Outpatient
* Age: ≥12 years of age
* Gender: Eligible Female (females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control)
* Asthma Diagnosis: As defined by NIH
* Severity of Disease: FEV1 50-85% predicted AND in current and former smokers a post salbutamol/albuterol ratio \>0.70
* Reversibility: ≥12% and ≥200mL in FEV1 within 30 ±15 minutes following salbutamol/albuterol
* Current anti-asthma therapy: Using short-acting beta-agonist (SABA) for ≥3 months
* Tobacco use: Non-smoker /former smoker with ≤10 pack years or current smoker with ≤10 pack years
* QTC: QTc(F)\<450msec or QTc(F)\<480 for subjects with Bundle Branch Block
* Liver function: Normal liver function
* Informed Consent

Exclusion Criteria:

* History of Life-threatening asthma: Within previous 5 years
* Asthma Exacerbation: Requiring OCS within 3 months or hospitalisation within 6 months
* Respiratory Infection: Not resolved within the 4 weeks before V1 AND led to a change in asthma management OR treatment with antibiotics OR is expected to affect the subject's asthma status or ability to participate
* Corticosteroid Use: ICS used within 6 weeks or OCS/depot corticosteroids within 12 weeks
* OATP1B1 substrates: OATP1B1 substrates (e.g. statins, rifampicin, bromosulphophthalein, benzylpenicillin, methotrexate) within 4 weeks
* Immunosuppressive medications: Either using or required during the study
* Liver disease: Current or chronic history
* Concurrent disease/abnormalities: Clinically significant uncontrolled disease
* Investigational medications: Participation in a study or used investigational drug within 30 days
* Drug allergy: β-agonists, corticosteroids, constituents of inhalers
* Milk Protein Allergy: History of severe milk protein allergy
* Compliance: Factors likely to impair compliance either with regards to study medication, procedures or attendance
* Unable or unwilling to follow instructions: Procedures, dosing directions, e-diaries or pMDIs
* History of alcohol or drug abuse: Likely to interfere with the study
* Affiliation with Investigator's Site: Relative or employee

Primary outcomes:
measure: Mean Change From Baseline to the End of the 8-Week Treatment Period in Trough Forced Expiratory Volume in One Second (FEV1)
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Mean Change From Baseline in Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the 8-Week Treatment Period
timeFrame: Baseline up to Week 8
measure: Mean Change From Baseline in Daily Trough AM PEF Averaged Over the 8-Week Treatment Period
timeFrame: Baseline up to Week 8
measure: Mean Change From Baseline in the Percentage of Symptom-free Days Averaged Over the 8-Week Treatment Period
timeFrame: Baseline up to Week 8
measure: Mean Change From Baseline in the Percentage of Symptom-free Nights Averaged Over the 8-Week Treatment Period
timeFrame: Baseline up to Week 8
measure: Mean Change From Baseline in the Percentage of Rescue-free Days Averaged Over the 8-Week Treatment Period
timeFrame: Baseline up to Week 8
measure: Mean Change From Baseline in the Percentage of Rescue-free Nights Averaged Over the 8-Week Treatment Period
timeFrame: Baseline up to Week 8
measure: Mean Change From Baseline in Day-time Asthma Symptom Score Over the 8-Week Treatment Period
timeFrame: Baseline up to Week 8
measure: Mean Change From Baseline in Night-time Asthma Symptom Score Over the 8-Week Treatment Period
timeFrame: Baseline up to Week 8
measure: Mean Change From Baseline in Day-time Rescue Short Acting beta2-agonist (SABA) Usage Over the 8-Week Treatment Period
timeFrame: Baseline up to Week
measure: Mean Change From Baseline in Night-time Rescue SABA Usage Over the 8-Week Treatment Period
timeFrame: Baseline up to Week 8
measure: Number of Participants Who Withdrew Due to Lack of Efficacy During the 8-Week Treatment Period
timeFrame: Upto 8 Weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Huntington Beach
country: United States
facility: GSK Investigational Site
state: California
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Tallahassee
country: United States
facility: GSK Investigational Site
state: Florida
city: Owensboro
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Metairie
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Bangor
country: United States
facility: GSK Investigational Site
state: Maine
city: Ypsilanti
country: United States
facility: GSK Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Columbia
country: United States
facility: GSK Investigational Site
state: Missouri
city: Rolla
country: United States
facility: GSK Investigational Site
state: Missouri
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Ocean City
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Canton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Orangeburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Waco
country: United States
facility: GSK Investigational Site
state: Texas
city: Bellingham
country: United States
facility: GSK Investigational Site
state: Washington
city: Pleven
country: Bulgaria
facility: GSK Investigational Site
city: Plovdiv
country: Bulgaria
facility: GSK Investigational Site
city: Ruse
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Stara Zagora
country: Bulgaria
facility: GSK Investigational Site
city: Varna
country: Bulgaria
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Libiaz
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Tarnow
country: Poland
facility: GSK Investigational Site
city: Brasov
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Cluj-Napoca
country: Romania
facility: GSK Investigational Site
city: Cluj-Napoca
country: Romania
facility: GSK Investigational Site
city: Deva
country: Romania
facility: GSK Investigational Site
city: Timisoara
country: Romania
facility: GSK Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: GSK Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: GSK Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: GSK Investigational Site
city: Donetsk
country: Ukraine
facility: GSK Investigational Site
city: Ivano-Frankivsk
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kiev
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Odesa
country: Ukraine
facility: GSK Investigational Site
city: Simferopol
country: Ukraine
facility: GSK Investigational Site
city: Yalta
country: Ukraine
facility: GSK Investigational Site
city: Zaporizhia
country: Ukraine
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Follows RM, Snowise NG, Ho SY, Ambery CL, Smart K, McQuade BA. Efficacy, safety and tolerability of GSK2190915, a 5-lipoxygenase activating protein inhibitor, in adults and adolescents with persistent asthma: a randomised dose-ranging study. Respir Res. 2013 May 17;14(1):54. doi: 10.1186/1465-9921-14-54.