A Randomised, Double-blind, Parallel Group Study to Assess the Efficacy and Safety of 52 Weeks of Once Daily Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (2.5 µg / 5 µg; 5 µg / 5 µg) (Delivered by the Respimat® Inhaler) Compared With the Individual Components (2.5 µg and 5 µg Tiotropium, 5 µg Olodaterol) (Delivered by the Respimat® Inhaler) in Patients With Chronic Obstructive Pulmonary Disease (COPD). [TOnado TM 1]
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,624
- 试验地点
- 239
- 主要终点
- Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169.
研究概览
简要总结
The overall objective of this study is to assess the efficacy and safety of 52 weeks once daily treatment with orally inhaled tiotropium + olodaterol FDC (delivered by the RESPIMAT Inhaler) compared with the individual components ( tiotropium, olodaterol) (delivered by the RESPIMAT Inhaler) in patients with Chronic Obstructive Pulmonary Disease (COPD).
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
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
tiotropium+olodaterol low dose FDC
Once daily 2 puffs solution for inhalation Respimat
干预措施: tiotropium + olodaterol (Drug)
tiotropium+olodaterol low dose FDC
Once daily 2 puffs solution for inhalation Respimat
干预措施: Respimat (Device)
tiotropium+olodaterol high dose FDC
Once daily 2 puffs solution for inhalation Respimat
干预措施: tiotropium + olodaterol (Drug)
tiotropium+olodaterol high dose FDC
Once daily 2 puffs solution for inhalation Respimat
干预措施: Respimat (Device)
olodaterol
Once daily 2 puffs solution for inhalation Respimat
干预措施: olodaterol (Drug)
olodaterol
Once daily 2 puffs solution for inhalation Respimat
干预措施: Respimat (Device)
tiotropium low dose
Once daily 2 puffs solution for inhalation Respimat
干预措施: tiotropium (Drug)
tiotropium low dose
Once daily 2 puffs solution for inhalation Respimat
干预措施: Respimat (Device)
tiotropium high dose
Once daily 2 puffs solution for inhalation Respimat
干预措施: tiotropium (Drug)
tiotropium high dose
Once daily 2 puffs solution for inhalation Respimat
干预措施: Respimat (Device)
结局指标
主要结局
Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169.
时间窗: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 169.
FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the MMRM model in each treatment group.
Trough FEV1 Response on Day 170.
时间窗: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 23 h and at 23 h 50 min after inhalation of study medication on Day 170
Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours) and was calculated as the mean of the 2 FEV1 measurements performed at 23 h and at 23 h 50 min after inhalation of study medication at the clinic visit on the previous day. Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an MMRM including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.
Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
时间窗: Day 169
The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.
次要结局
- Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)(Day 169)
- Trough FEV1 Response on Day 169(1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1 hr and 10 min pre-dose on Day 169)
- Trough FEV1 Response on Day 365(1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1 hr and 10 min pre-dose on day 365)
- FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 1(1 hour (h) and 10 minutes (min) prior to dose to 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on the first day of randomized treatment.)
- FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 85(1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 85 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 85.)
- FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 169(1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 169.)
- FEV1 AUC(0-3h) Response on Day 1(1 hour (h) and 10 minutes (min) prior to dose to 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on the first day of randomized treatment.)
- FEV1 AUC(0-3h) Response on Day 85(1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 85 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 85.)
- FEV1 AUC(0-3h) Response on Day 365(1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 365 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 365.)
- Trough FEV1 Response on Day 15.(1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 15)
- Trough FEV1 Response on Day 43(1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 43.)
- Trough FEV1 Response on Day 85(1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1 hr and 10 min pre-dose on day 85.)
- FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 365(1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 365 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 365.)
- Trough FVC Response on Day 15.(1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 15)
- Trough FVC Response on Day 43.(1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 43)
- Trough FVC Response on Day 85.(1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 85)
- Trough FVC Response on Day 170.(1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 23 h and at 23 h 50 min after inhalation of study medication on Day 170)
- Trough FVC Response on Day 365.(1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on Day 365.)
- FEV1 AUC(0-12h) Response in the Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)(1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h post-dose on Day 169.)
- FEV1 AUC(0-24h) Response in the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)(1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 23 h, 23 h and 50 min post-dose on Day 169.)
- FVC AUC(0-12h) Response in the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)(1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h post-dose on Day 169.)
- FVC AUC(0-24h) Response in Sub-set of Patients With 24-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)(1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 23 h, 23 h and 50 min post-dose on Day 169.)
- Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)(Day 85)
- Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)(Day 365)
- Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)(Day 43)
- Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)(Day 85)
- Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)(Day 365)