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

NCT01147744 | Completed Phase 2 Results

• 1 other identifier: 112186
• Study Type: interventional
• Target: 700
• Locations: 6 countries
• Sites: 84

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.

Conditions

Asthma

Keywords

Efficacy; Asthma; Safety; Fluticasone Propionate; FLAP; Beta-agonists; GSK2190915; Montelukast; Placebo; FLAIR

Outcome Measures

Primary Outcomes (1)

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

  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 study medication.

  Baseline and Week 8

Secondary Outcomes (11)

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

  Baseline up to Week 8

• Mean Change From Baseline in Daily Trough AM PEF Averaged Over the 8-Week Treatment Period

  Baseline up to Week 8

• Mean Change From Baseline in the Percentage of Symptom-free Days Averaged Over the 8-Week Treatment Period

  Baseline up to Week 8

• Mean Change From Baseline in the Percentage of Symptom-free Nights Averaged Over the 8-Week Treatment Period

  Baseline up to Week 8

• Mean Change From Baseline in the Percentage of Rescue-free Days Averaged Over the 8-Week Treatment Period

  Baseline up to Week 8

Study Arms (7)

GSK2190915 10mg and placebo

EXPERIMENTAL

GSK2190915 10mg (1 x 10mg, 1 x placebo tablets) once daily in the morning and placebo caspule once daily in the evening and inhaled placebo twice daily via ACCUHALER/DISKUS

Drug: GSK2190915 10mg; Drug: Placebo GSK2190915 one tablet; Drug: Placebo montelukast; Drug: Placebo fluticasone propionate via ACCUHALER/DISKUS

GSK2190915 30mg and placebo

EXPERIMENTAL

GSK2190915 30mg (1 x 30mg, 1 x placebo tablets) once daily in the morning and placebo caspule once daily in the evening and inhaled placebo twice daily via ACCUHALER/DISKUS

Drug: GSK2190915 30mg; Drug: Placebo GSK2190915 one tablet; Drug: Placebo montelukast; Drug: Placebo fluticasone propionate via ACCUHALER/DISKUS

GSK2190915 100mg QD and placebo

EXPERIMENTAL

GSK2190915 100mg (1 x 100mg, 1 x placebo tablets) once daily in the morning and placebo caspule once daily in the evening and inhaled placebo twice daily via ACCUHALER/DISKUS

Drug: GSK2190915 100mg; Drug: Placebo GSK2190915 one tablet; Drug: Placebo montelukast; Drug: Placebo fluticasone propionate via ACCUHALER/DISKUS

GSK2190915 300mg QD and placebo

EXPERIMENTAL

GSK2190915 300mg (1 x 100mg, 1 x 200mg tablets) once daily in the morning and placebo caspule once daily in the evening and inhaled placebo twice daily via ACCUHALER/DISKUS

Drug: GSK2190915 300mg; Drug: Placebo montelukast; Drug: Placebo fluticasone propionate via ACCUHALER/DISKUS

Fluticasone propionate 100mcg and placebo

ACTIVE COMPARATOR

Fluticasone propionate 100mcg twice daily via ACCUHALER/DISKUS and two placebo tablets in the morning and one placebo capsule in the evening

Drug: Fluticasone Propionate 100mcg via ACCUHALER/DISKUS; Drug: Placebo montelukast; Drug: Placebo GSK2190915 two tablets

Montelukast 10mg and placebo

ACTIVE COMPARATOR

Montelukast 10mg (1 x 10mg capsule) once daily in the evening and two placebo tablets in the morning and inhaled placebo twice daily via ACCUHALER/DISKUS

Drug: Montelukast 10mg; Drug: Placebo fluticasone propionate via ACCUHALER/DISKUS; Drug: Placebo GSK2190915 two tablets

Placebo Comparator

PLACEBO COMPARATOR

Two GSK2190915 placebo tablets once daily in the morning, montelukast placebo capsule once daily in the evening and fluticasone propionate placebo twice daily via ACCUHALER/DISKUS

Drug: Placebo montelukast; Drug: Placebo fluticasone propionate via ACCUHALER/DISKUS; Drug: Placebo GSK2190915 two tablets

Interventions

Fluticasone Propionate 100mcg via ACCUHALER/DISKUS DRUG

Fluticasone propionate 100mcg twice daily via ACCUHALER/DISKUS

Fluticasone propionate 100mcg and placebo

GSK2190915 100mg DRUG

GSK2190915 100mg (1 x 100mg) once daily in the morning

GSK2190915 100mg QD and placebo

GSK2190915 10mg DRUG

GSK2190915 10mg (1 x 10mg) once daily in the morning

GSK2190915 10mg and placebo

GSK2190915 300mg DRUG

GSK2190915 300mg (1 x 100mg, 1 x 200mg tablets) once daily in the morning

GSK2190915 300mg QD and placebo

GSK2190915 30mg DRUG

GSK2190915 30mg (1 x 30mg) once daily in the morning

GSK2190915 30mg and placebo

Montelukast 10mg DRUG

Montelukast 10mg (1 x 10mg capsule) once daily in the evening

Montelukast 10mg and placebo

Placebo GSK2190915 one tablet DRUG

Placebo tablet, one tablet once daily in the morning

GSK2190915 100mg QD and placebo; GSK2190915 10mg and placebo; GSK2190915 30mg and placebo

Placebo montelukast DRUG

Placebo capsule once daily in the evening

Fluticasone propionate 100mcg and placebo; GSK2190915 100mg QD and placebo; GSK2190915 10mg and placebo; GSK2190915 300mg QD and placebo; GSK2190915 30mg and placebo; Placebo Comparator

Placebo fluticasone propionate via ACCUHALER/DISKUS DRUG

Inhaled placebo twice daily via ACCUHALER/DISKUS

GSK2190915 100mg QD and placebo; GSK2190915 10mg and placebo; GSK2190915 300mg QD and placebo; GSK2190915 30mg and placebo; Montelukast 10mg and placebo; Placebo Comparator

Placebo GSK2190915 two tablets DRUG

Placebo tablet, two tablets once daily in the morning

Fluticasone propionate 100mcg and placebo; Montelukast 10mg and placebo; Placebo Comparator

Eligibility Criteria

• Age: 12 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (84)

GSK Investigational Site

Birmingham, Alabama, 35209, United States

Location

GSK Investigational Site

Huntington Beach, California, 92647, United States

Location

GSK Investigational Site

Newport Beach, California, 92663, United States

Location

GSK Investigational Site

San Diego, California, 92123, United States

Location

GSK Investigational Site

Tallahassee, Florida, 32308, United States

Location

GSK Investigational Site

Owensboro, Kentucky, 42301, United States

Location

GSK Investigational Site

Metairie, Louisiana, 70006, United States

Location

GSK Investigational Site

Bangor, Maine, 04401, United States

Location

GSK Investigational Site

Ypsilanti, Michigan, 48197, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55402, United States

Location

GSK Investigational Site

Columbia, Missouri, 65203, United States

Location

GSK Investigational Site

Rolla, Missouri, 65401, United States

Location

GSK Investigational Site

St Louis, Missouri, 63141, United States

Location

GSK Investigational Site

Ocean City, New Jersey, 07712, United States

Location

GSK Investigational Site

Raleigh, North Carolina, 27607, United States

Location

GSK Investigational Site

Canton, Ohio, 44718, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73103, United States

Location

GSK Investigational Site

Medford, Oregon, 97504, United States

Location

GSK Investigational Site

Orangeburg, South Carolina, 29118, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Waco, Texas, 76712, United States

Location

GSK Investigational Site

Bellingham, Washington, 98225, United States

Location

GSK Investigational Site

Pleven, 5800, Bulgaria

Location

GSK Investigational Site

Plovdiv, 4003, Bulgaria

Location

GSK Investigational Site

Rousse, 7000, Bulgaria

Location

GSK Investigational Site

Sofia, 1000, Bulgaria

Location

GSK Investigational Site

Sofia, 1202, Bulgaria

Location

GSK Investigational Site

Sofia, 1407, Bulgaria

Location

GSK Investigational Site

Sofia, 1431, Bulgaria

Location

GSK Investigational Site

Stara Zagora, 6000, Bulgaria

Location

GSK Investigational Site

Varna, 9010, Bulgaria

Location

GSK Investigational Site

Chiba, 292-0805, Japan

Location

GSK Investigational Site

Fukuoka, 819-0006, Japan

Location

GSK Investigational Site

Fukuoka, 819-1102, Japan

Location

GSK Investigational Site

Hokkaido, 062-0034, Japan

Location

GSK Investigational Site

Hokkaido, 064-0801, Japan

Location

GSK Investigational Site

Ibaraki, 319-1113, Japan

Location

GSK Investigational Site

Kanagawa, 210-0852, Japan

Location

GSK Investigational Site

Osaka, 530-0001, Japan

Location

GSK Investigational Site

Osaka, 565-0853, Japan

Location

GSK Investigational Site

Saitama, 343-0851, Japan

Location

GSK Investigational Site

Tokyo, 102-0083, Japan

Location

GSK Investigational Site

Tokyo, 103-0027, Japan

Location

GSK Investigational Site

Tokyo, 103-0028, Japan

Location

GSK Investigational Site

Tokyo, 130-8587, Japan

Location

GSK Investigational Site

Tokyo, 153-0051, Japan

Location

GSK Investigational Site

Tokyo, 154-0024, Japan

Location

GSK Investigational Site

Tokyo, 158-0097, Japan

Location

GSK Investigational Site

Tokyo, 171-0014, Japan

Location

GSK Investigational Site

Tokyo, 190-0013, Japan

Location

GSK Investigational Site

Bialystok, 15-084, Poland

Location

GSK Investigational Site

Katowice, 40-018, Poland

Location

GSK Investigational Site

Krakow, 31-024, Poland

Location

GSK Investigational Site

Libiąż, 32-590, Poland

Location

GSK Investigational Site

Lodz, 93-329, Poland

Location

GSK Investigational Site

Poznan, 60-693, Poland

Location

GSK Investigational Site

Tarnów, 33-100, Poland

Location

GSK Investigational Site

Brasov, 500112, Romania

Location

GSK Investigational Site

Bucharest, 020125, Romania

Location

GSK Investigational Site

Bucharest, 022102, Romania

Location

GSK Investigational Site

Bucharest, 050159, Romania

Location

GSK Investigational Site

Cluj-Napoca, 400217, Romania

Location

GSK Investigational Site

Cluj-Napoca, 400371, Romania

Location

GSK Investigational Site

Deva, 330084, Romania

Location

GSK Investigational Site

Timișoara, 300310, Romania

Location

GSK Investigational Site

Dnipropetrovsk, 49006, Ukraine

Location

GSK Investigational Site

Dnipropetrovsk, 49027, Ukraine

Location

GSK Investigational Site

Dnipropetrovsk, 49051, Ukraine

Location

GSK Investigational Site

Donetsk, 83099, Ukraine

Location

GSK Investigational Site

Ivano-Frankivsk, 76018, Ukraine

Location

GSK Investigational Site

Kharkiv, 61002, Ukraine

Location

GSK Investigational Site

Kharkiv, 61037, Ukraine

Location

GSK Investigational Site

Kharkiv, 61124, Ukraine

Location

GSK Investigational Site

Kiev, 03680, Ukraine

Location

GSK Investigational Site

Kyiv, 02232, Ukraine

Location

GSK Investigational Site

Kyiv, 03115, Ukraine

Location

GSK Investigational Site

Kyiv, 03680, Ukraine

Location

GSK Investigational Site

Kyiv, 04107, Ukraine

Location

GSK Investigational Site

Kyiv, 04201, Ukraine

Location

GSK Investigational Site

Kyiv, Ukraine

Location

GSK Investigational Site

Odesa, 65114, Ukraine

Location

GSK Investigational Site

Simferopol, 95043, Ukraine

Location

GSK Investigational Site

Yalta, 98603, Ukraine

Location

GSK Investigational Site

Zaporizhia, 69035, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 23682661 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Asthma

Interventions

Fluticasone; 3-(3-tert-butylsulfanyl-1-(4-(6-ethoxypyridin-3-yl)benzyl)-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropionic acid; montelukast

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2010
• First Posted: June 22, 2010
• Study Start: June 28, 2010
• Primary Completion: October 6, 2011
• Study Completion: October 6, 2011
• Last Updated: October 2, 2017
• Results First Posted: September 6, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will share

Locations

RO (8); US (22); JP (19); PL (7); UA (19); BU (9)