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.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 700
- 试验地点
- 1
- 主要终点
- Mean Change From Baseline to the End of the 8-Week Treatment Period in Trough Forced Expiratory Volume in One Second (FEV1)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
GSK2190915 30mg and placebo
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
干预措施: Placebo montelukast (Drug)
GSK2190915 10mg and placebo
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
干预措施: GSK2190915 10mg (Drug)
GSK2190915 10mg and placebo
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
干预措施: Placebo GSK2190915 one tablet (Drug)
GSK2190915 10mg and placebo
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
干预措施: Placebo montelukast (Drug)
GSK2190915 10mg and placebo
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
干预措施: Placebo fluticasone propionate via ACCUHALER/DISKUS (Drug)
GSK2190915 30mg and placebo
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
干预措施: GSK2190915 30mg (Drug)
GSK2190915 30mg and placebo
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
干预措施: Placebo GSK2190915 one tablet (Drug)
GSK2190915 30mg and placebo
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
干预措施: Placebo fluticasone propionate via ACCUHALER/DISKUS (Drug)
GSK2190915 100mg QD and placebo
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
干预措施: GSK2190915 100mg (Drug)
GSK2190915 100mg QD and placebo
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
干预措施: Placebo GSK2190915 one tablet (Drug)
GSK2190915 100mg QD and placebo
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
干预措施: Placebo montelukast (Drug)
GSK2190915 100mg QD and placebo
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
干预措施: Placebo fluticasone propionate via ACCUHALER/DISKUS (Drug)
GSK2190915 300mg QD and placebo
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
干预措施: GSK2190915 300mg (Drug)
GSK2190915 300mg QD and placebo
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
干预措施: Placebo montelukast (Drug)
GSK2190915 300mg QD and placebo
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
干预措施: Placebo fluticasone propionate via ACCUHALER/DISKUS (Drug)
Fluticasone propionate 100mcg and placebo
Fluticasone propionate 100mcg twice daily via ACCUHALER/DISKUS and two placebo tablets in the morning and one placebo capsule in the evening
干预措施: Fluticasone Propionate 100mcg via ACCUHALER/DISKUS (Drug)
Fluticasone propionate 100mcg and placebo
Fluticasone propionate 100mcg twice daily via ACCUHALER/DISKUS and two placebo tablets in the morning and one placebo capsule in the evening
干预措施: Placebo montelukast (Drug)
Fluticasone propionate 100mcg and placebo
Fluticasone propionate 100mcg twice daily via ACCUHALER/DISKUS and two placebo tablets in the morning and one placebo capsule in the evening
干预措施: Placebo GSK2190915 two tablets (Drug)
Montelukast 10mg and placebo
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
干预措施: Montelukast 10mg (Drug)
Montelukast 10mg and placebo
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
干预措施: Placebo fluticasone propionate via ACCUHALER/DISKUS (Drug)
Montelukast 10mg and placebo
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
干预措施: Placebo GSK2190915 two tablets (Drug)
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
干预措施: Placebo montelukast (Drug)
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
干预措施: Placebo fluticasone propionate via ACCUHALER/DISKUS (Drug)
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
干预措施: Placebo GSK2190915 two tablets (Drug)
结局指标
主要结局
Mean Change From Baseline to the End of the 8-Week Treatment Period in Trough Forced Expiratory Volume in One Second (FEV1)
时间窗: 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 study medication.
次要结局
- 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)
- Mean Change From Baseline in the Percentage of Rescue-free Nights Averaged Over the 8-Week Treatment Period(Baseline up to Week 8)
- Mean Change From Baseline in Day-time Asthma Symptom Score Over the 8-Week Treatment Period(Baseline up to Week 8)
- Mean Change From Baseline in Night-time Asthma Symptom Score Over the 8-Week Treatment Period(Baseline up to Week 8)
- Mean Change From Baseline in Day-time Rescue Short Acting beta2-agonist (SABA) Usage Over the 8-Week Treatment Period(Baseline up to Week)
- Mean Change From Baseline in Night-time Rescue SABA Usage Over the 8-Week Treatment Period(Baseline up to Week 8)
- Number of Participants Who Withdrew Due to Lack of Efficacy During the 8-Week Treatment Period(Upto 8 Weeks)