NCT01431287|CompletedPhase 3Results

Tiotropium +Olodaterol Fixed Dose Combination (FDC) Versus Tiotropium and Olodaterol in Chronic Obstructive Pulmonary Disease (COPD)

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 2]

Boehringer Ingelheim ClinicalTrials.gov

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2 other identifiers

1237.62009-010669-22

Study Type

interventional

Target

2,539

Locations

23 countries

Sites

233

Timeline

RegisteredSep 2011

StartedSep 2011

CompletionNov 2013

Brief Summary

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 COPD.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

2,539

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started Sep 2011

Geographic Reach

23 countries

233 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

2.2 years study duration

Study Start

First participant enrolled

September 1, 2011

Completed

7 days until next milestone

First Submitted

Initial submission to the registry

September 8, 2011

Completed

1 day until next milestone

First Posted

Study publicly available on registry

September 9, 2011

Completed

2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2013

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2013

Completed

1.7 years until next milestone

Results Posted

Study results publicly available

July 16, 2015

Completed

Last Updated

July 16, 2015

Status Verified

June 1, 2015

Enrollment Period

2.2 years

First QC Date

September 8, 2011

Results QC Date

June 19, 2015

Last Update Submit

June 19, 2015

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (3)

Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response 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.
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
Trough FEV1 Response 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.
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
Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).
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.
Day 169

Secondary Outcomes (27)

Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
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
+22 more secondary outcomes