An Exploratory, Multi-centre, Double-blind, Placebocontrolled Crossover Study, to Investigate the Bronchodilatory Efficacy of a Single Dose of Indacaterol in Fixed Combination With Mometasone Furoate Delivered Via a MDDPI (Twisthaler®) in Adult Patients With Persistent Asthma Using Open Label Seretide® Accuhaler® (50/250 Mcg b.i.d.) as an Active Control
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Change From Period Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)
研究概览
简要总结
This study is designed to evaluate the bronchodilatory efficacy of indacaterol maleate 500 μg/mometasone furoate 400 μg via the Twisthaler® device in adult patients with persistent asthma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female adult patients aged 18-75 years with persistent asthma
- •Patients with persistent asthma, diagnosed according to the Global Initiative for Asthma guidelines (GINA) and who additionally met the following criteria:
- •Patients receiving daily treatment with inhaled corticosteroid up to the maximum dose per day indicated in the package leaflet, in a stable regimen for the month prior to Visit
- •Patients with a forced expiratory volume in 1 second (FEV1) at Visit 1 of ≥ 50% of the predicted normal value. This criterion for FEV1 had to be demonstrated after a washout period of at least 6 hours during which no short acting β2-agonist had been inhaled, and a minimum of 48 hours for a long acting β2-agonist.
- •Patients who demonstrated an increase of ≥12% and ≥200 mL in FEV1 over their pre-bronchodilator value 30 minutes after inhaling a total of 200 μg of salbutamol (or albuterol) via metered dose inhaler (MDI) (the reversibility test). Reversibility had to be demonstrated after an appropriate washout period of at least 6 hrs prior to the evaluation for a shortacting β2-agonist. The administration of salbutamol (or albuterol) for the reversibility test was to be within 30 minutes after pre-bronchodilator spirometry. Reversibility had to be demonstrated at Visit 1 or between Visits 1 and 2, in order for patients to be included in the trial.
- •For each patient, the smaller value of the Visit 1 FEV1 or the Visit 2 FEV1 pre-dose value had to be at least 85% of the larger value.
- •Body mass index (BMI) between 18 and 32 kg/m^2 and weight >50 kg.
- •patients using local contraception
排除标准
- •Pregnant or nursing women
- •Recent use of tobacco or history of smoking > 10 pack years
- •Patients diagnosed with chronic obstructive pulmonary disease (COPD)
- •Patients with recent experience of severe asthma attack/exacerbation within 6-months of study start
- •Patients with frequent rescue medication (>8 puffs/day for two consecutive days)
- •Clinically relevant laboratory abnormality or a clinically significant condition
- •Active cancer or a history of cancer with less than 5 years disease free survival time
- •History of long QT syndrome or with long QTc interval prior to dosing
- •History of hypersensitivity to the study drugs or to drugs with similar chemical structures
- •Use of certain medications
- •Use of other investigational drugs
- •A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result
- •History of immunodeficiency diseases, including a positive human immumodeficiency virus (HIV) test result.
- •History of drug or alcohol abuse or evidence of such abuse
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Indacaterol/mometasone - Placebo
In Treatment Period 1 (Day 1) participants received 2 inhalations of indacaterol maleate 250 μg / mometasone furoate 200 μg once a day in the morning via the Twisthaler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of placebo via the Twisthaler device once a day in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg / salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.
干预措施: indacaterol maleate/mometasone furoate (Drug)
Indacaterol/mometasone - Placebo
In Treatment Period 1 (Day 1) participants received 2 inhalations of indacaterol maleate 250 μg / mometasone furoate 200 μg once a day in the morning via the Twisthaler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of placebo via the Twisthaler device once a day in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg / salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.
干预措施: placebo to indacaterol maleate/mometasone furoate (Drug)
Indacaterol/mometasone - Placebo
In Treatment Period 1 (Day 1) participants received 2 inhalations of indacaterol maleate 250 μg / mometasone furoate 200 μg once a day in the morning via the Twisthaler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of placebo via the Twisthaler device once a day in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg / salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.
干预措施: fluticasone proprionate / salmeterol xinafoate (Drug)
Placebo - indacaterol/mometasone
In Treatment Period 1 (Day 1) participants received 2 inhalations of placebo in the morning via the Twistheler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of indacaterol maleate 250 μg / mometasone furoate 200 μg via the Twisthaler device in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg / salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.
干预措施: indacaterol maleate/mometasone furoate (Drug)
Placebo - indacaterol/mometasone
In Treatment Period 1 (Day 1) participants received 2 inhalations of placebo in the morning via the Twistheler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of indacaterol maleate 250 μg / mometasone furoate 200 μg via the Twisthaler device in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg / salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.
干预措施: placebo to indacaterol maleate/mometasone furoate (Drug)
Placebo - indacaterol/mometasone
In Treatment Period 1 (Day 1) participants received 2 inhalations of placebo in the morning via the Twistheler device. In Treatment Period 2 (Day 8) participants received 2 inhalations of indacaterol maleate 250 μg / mometasone furoate 200 μg via the Twisthaler device in the morning. In Treatment Period 3 (Day 15) participants received fluticasone proprionate 250 μg / salmeterol xinafoate 50 μg twice a day delivered via dry-powder inhaler. Each treatment period was separated by a minimum washout period of 7 days.
干预措施: fluticasone proprionate / salmeterol xinafoate (Drug)
结局指标
主要结局
Change From Period Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)
时间窗: Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16).
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from the period baseline to 24 hour post dose trough FEV1 after 1 day of treatment was modeled using a linear mixed effect model fitting treatment, sequence and period as fixed factors, patient within sequence as a random factor and pre-dose FEV1 as covariate.
次要结局
- Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)(Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose.)
- Change From Period Baseline in Trough Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)(Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16).)
- Change From Period Baseline in Peak Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)(Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose.)
- Change From Period Baseline in Trough Forced Vital Capacity (FVC)(Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16).)
- Change From Period Baseline in Peak Forced Vital Capacity (FVC)(Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose.)
- Change From Period Baseline in Trough FEV1/FVC Ratio(Pre-dose for each Treatment Period (Days 1, 8 and 15) and 24-hours post-dose for each Treatment Period (Days 2, 9 and 16).)
- Change From Period Baseline in Peak FEV1/FVC Ratio(Days 1, 8 and 15, pre-dose (Baseline) and 5, 15, and 30 minutes, 1, 2, 3, and 4 hours post-dose.)
- Area Under the Concentration-time Curve From Time 0 to 12 Hours Post-dose for Mometasone Furoate(Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, and 12 hours post-dose.)
- Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose for Mometasone Furoate(Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.)
- Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose for Indacaterol(Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.)
- Maximum (Peak) Plasma Concentration (Cmax) of Mometasone Furoate(Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.)
- Maximum (Peak) Plasma Concentration (Cmax) of Indacaterol(Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.)
- Time to Reach Peak or Maximum Concentration Following Drug Administration for Mometasone Furoate(Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.)
- Time to Reach Peak or Maximum Concentration Following Drug Administration for Indacaterol(Samples were taken pre-dose and at 15 and 30 minutes and 1, 2, 4, 12 and 24 hours post-dose.)