200699: A Clinical Study to Evaluate Four Doses of Umeclidinium Bromide in Combination With Fluticasone Furoate in COPD Subjects With an Asthmatic Component
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 338
- 试验地点
- 1
- 主要终点
- Change From Baseline in Clinic Trough Forced Expiratory Volume in One Second (FEV1) at the End of Treatment Phase A (Visit 6/Day 29)
研究概览
简要总结
The purpose of this study is to evaluate the dose-response of 4 doses of umeclidinium bromide in combination with fluticasone furoate compared with fluticasone furoate monotherapy in chronic obstructive pulmonary disease participants with an asthmatic component. The fluticasone furoate/umeclidinium bromide treatments will also be compared to the once-daily inhaled corticosteroid/long-acting beta agonist combination fluticasone furoate/vilanterol.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years of age or older
- •COPD with evidence of an asthmatic component as demonstrated by spirometry, reversibility and current therapy at screening as follows:
- •Post-bronchodilator morning (AM) FEV1 >=50% and <=80% of the predicted normal value at Visit 1
- •Pre- and post-bronchodilator FEV1/FVC ratio <0.
- •Demonstrated reversibility by >=12% and >=200 mL increase in FEV1 following albuterol at Visit
- •A need for regular controller therapy (i.e., inhaled corticosteroids alone or in combination with a long-acting beta-agonist or leukotriene modifier, etc.) for a minimum of 12 weeks prior to Visit
- •Outpatient subjects who are smokers or non-smokers.
排除标准
- •History of life-threatening respiratory event within the last 5 years.
- •Unresolved respiratory infection
- •Recent Severe COPD or Asthma Exacerbation
- •Risk factors for pneumonia
- •Hospitalization for pneumonia within 3 months
- •Concurrent respiratory disease other than chronic obstructive pulmonary disease or asthma.
- •Other uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
- •Viral hepatitis or HIV
- •Current or chronic history of liver disease, known hepatic or biliary abnormalities
- •Drug or milk protein allergy
- •Administration of prescription or over-the-counter medication that would significantly affect the course of COPD or asthma, or interact with study drug
- •Subjects with lung volume reduction surgery within 12 months prior to screening.
- •Use of long-term oxygen therapy (LTOT)
- •Requirement for nebulized therapy
- •Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks
- •Unstable or life-threatening cardiac disease
- •Abnormal and clinically significant 12-Lead Electrocardiogram (ECG) finding
- •Diseases preventing the use of anticholinergics
研究组 & 干预措施
Treatment Phase A
Eligible subjects will enter a 4-week run-in period and will receive fluticasone propionate/salmeterol. Subjects will then be randomized to receive fluticasone furoate 100 mcg, fluticasone furoate/umeclidinium bromide 100/15.6 mcg, fluticasone furoate/umeclidinium bromide 100/62.5 mcg, fluticasone furoate/umeclidinium bromide 100/125 mcg, fluticasone furoate/umeclidinium bromide 100/250 mcg, or fluticasone furoate/vilanterol 100/25 mcg, respectively for 4 weeks
干预措施: FF (Drug)
Treatment Phase A
Eligible subjects will enter a 4-week run-in period and will receive fluticasone propionate/salmeterol. Subjects will then be randomized to receive fluticasone furoate 100 mcg, fluticasone furoate/umeclidinium bromide 100/15.6 mcg, fluticasone furoate/umeclidinium bromide 100/62.5 mcg, fluticasone furoate/umeclidinium bromide 100/125 mcg, fluticasone furoate/umeclidinium bromide 100/250 mcg, or fluticasone furoate/vilanterol 100/25 mcg, respectively for 4 weeks
干预措施: UMEC (Drug)
Treatment Phase A
Eligible subjects will enter a 4-week run-in period and will receive fluticasone propionate/salmeterol. Subjects will then be randomized to receive fluticasone furoate 100 mcg, fluticasone furoate/umeclidinium bromide 100/15.6 mcg, fluticasone furoate/umeclidinium bromide 100/62.5 mcg, fluticasone furoate/umeclidinium bromide 100/125 mcg, fluticasone furoate/umeclidinium bromide 100/250 mcg, or fluticasone furoate/vilanterol 100/25 mcg, respectively for 4 weeks
干预措施: VI (Drug)
Treatment Phase B
Subjects completing Treatment Phase A will be randomized to receive either fluticasone furoate/umeclidinium bromide100/250 mcg or fluticasone furoate/umeclidinium bromide/vilanterol 100/250/25 mcg for 1 week.
干预措施: FF (Drug)
Treatment Phase B
Subjects completing Treatment Phase A will be randomized to receive either fluticasone furoate/umeclidinium bromide100/250 mcg or fluticasone furoate/umeclidinium bromide/vilanterol 100/250/25 mcg for 1 week.
干预措施: UMEC (Drug)
Treatment Phase B
Subjects completing Treatment Phase A will be randomized to receive either fluticasone furoate/umeclidinium bromide100/250 mcg or fluticasone furoate/umeclidinium bromide/vilanterol 100/250/25 mcg for 1 week.
干预措施: VI (Drug)
Treatment Phase C
Subjects completing Treatment Phase B will be randomized to receive either the same treatment as in Treatment Phase B, or the same treatment minus the umeclidinium bromide component, for 1 week.
干预措施: FF (Drug)
Treatment Phase C
Subjects completing Treatment Phase B will be randomized to receive either the same treatment as in Treatment Phase B, or the same treatment minus the umeclidinium bromide component, for 1 week.
干预措施: UMEC (Drug)
Treatment Phase C
Subjects completing Treatment Phase B will be randomized to receive either the same treatment as in Treatment Phase B, or the same treatment minus the umeclidinium bromide component, for 1 week.
干预措施: VI (Drug)
结局指标
主要结局
Change From Baseline in Clinic Trough Forced Expiratory Volume in One Second (FEV1) at the End of Treatment Phase A (Visit 6/Day 29)
时间窗: Baseline and Day 29
FEV1 is defined as forced expiratory volume in one second and measured in the morning at Visits 1 through 8 between 6:00 and 11:00 electronically by spirometry. Change from Baseline in trough FEV1 is defined as the difference in the value obtained at Visit 6 (24 hours post-dose on Visit 5) and the last acceptable/borderline acceptable value obtained prior to randomization (from Visit 2 pre-bronchodilator or Visit 3 pre-dose). Trough FEV1 is defined as the acceptable/borderline acceptable FEV1 value obtained at Visit 6, approximately 24 hours after morning dosing on Visit 5. ITT population is comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period. All comparisons for statistical purposes are with the FF 100 µg arm.
次要结局
- Change From Trough in Clinic Forced Expiratory Volume (FEV1) at 3 Hours Post-study Treatment at Visit 5/Day 28(Baseline and Day 28)
- Mean Change From Baseline in E-RS Total Scores at the End of Treatment Phase A(Baseline and End of Treatment Phase A (The end of Treatment Phase A was defined as the last 7 days of Treatment Phase A, including the AM assessments on the date of Visit 6))
- Mean Change From Baseline in Rescue Medication Use at the End of Treatment Phase A(Baseline and End of Treatment Phase A (The end of Treatment Phase A was defined as the last 7 days of Treatment Phase A, including the AM assessments on the date of Visit 6))
- Change From Baseline in Daily Morning (AM) PEF (Pre-dose and Pre-rescue Bronchodilator) Measured at Home and Averaged Over the Last 21 Days of Treatment Phase A(Baseline and from Day 8 through Day 29)
- Change in Clinic FEV1 Following 2 Puffs of Albuterol/Salbutamol Given 3 Hours Post-study Treatment Dose at Visit 5/Day 28(Baseline and Day 28)