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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: GSK2190915 30mg; Drug: Placebo GSK2190915 two tablets; Drug: Montelukast 10mg; Drug: GSK2190915 100mg; Drug: Placebo fluticasone propionate via ACCUHALER/DISKUS; Drug: Fluticasone Propionate 100mcg via ACCUHALER/DISKUS; Drug: Placebo GSK2190915 one tablet; Drug: GSK2190915 10mg; Drug: Placebo montelukast; Drug: GSK2190915 300mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01147744

112186

Details and patient eligibility

About

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.

Enrollment: 700 patients

Sex: Female

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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700 participants in 7 patient groups, including a placebo group

GSK2190915 10mg and placebo

Experimental group

Description:

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

Treatment:

Drug: Placebo fluticasone propionate via ACCUHALER/DISKUS

Drug: GSK2190915 10mg

Drug: Placebo GSK2190915 one tablet

Drug: Placebo montelukast

GSK2190915 30mg and placebo

Experimental group

Description:

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

Treatment:

Drug: Placebo fluticasone propionate via ACCUHALER/DISKUS

Drug: Placebo GSK2190915 one tablet

Drug: GSK2190915 30mg

Drug: Placebo montelukast

GSK2190915 100mg QD and placebo

Experimental group

Description:

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

Treatment:

Drug: Placebo fluticasone propionate via ACCUHALER/DISKUS

Drug: GSK2190915 100mg

Drug: Placebo GSK2190915 one tablet

Drug: Placebo montelukast

GSK2190915 300mg QD and placebo

Experimental group

Description:

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

Treatment:

Drug: Placebo fluticasone propionate via ACCUHALER/DISKUS

Drug: GSK2190915 300mg

Drug: Placebo montelukast

Fluticasone propionate 100mcg and placebo

Active Comparator group

Description:

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

Treatment:

Drug: Placebo GSK2190915 two tablets

Drug: Fluticasone Propionate 100mcg via ACCUHALER/DISKUS

Drug: Placebo montelukast

Montelukast 10mg and placebo

Active Comparator group

Description:

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

Treatment:

Drug: Montelukast 10mg

Drug: Placebo fluticasone propionate via ACCUHALER/DISKUS

Drug: Placebo GSK2190915 two tablets

Placebo Comparator

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo fluticasone propionate via ACCUHALER/DISKUS

Drug: Placebo GSK2190915 two tablets

Drug: Placebo montelukast