Trial Outcomes & Findings for Characterization of Lung Function Profile of Inhaled Tiotropium + Olodaterol Fixed Dose Combination Compared to Fluticasone Propionate + Salmeterol Fixed Dose Combination in COPD Patients (NCT NCT01969721)
NCT ID: NCT01969721
Last Updated: 2016-02-12
Results Overview
Change from patient baseline in Forced Expiratory Volume in one second (FEV1) Area Under the FEV1-time Curve from 0 to 12hours post-dose (AUC 0-12h) \[L\] after 6 weeks of treatment. Measured values presented are actually adjusted means. The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
229 participants
Primary outcome timeframe
Baseline and 6 weeks.
Results posted on
2016-02-12
Participant Flow
This was a randomized, double-blind, double-dummy, active-controlled, 4-treatment, 4-period, complete cross-over design.
After signing informed consent, patients entered a 4-week screening period to ensure clinical stability (i.e. no exacerbations).
Participant milestones
| Measure |
T+O 2.5/5 / T+O 5/5 / F+S 250/50 / F+S 500/50
Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled .
* Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo (T+O 2.5/5).
* Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo (T+O 5/5).
* Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo (F+S 250/50).
* Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo (F+S 500/50).
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®.
|
T+O 5/5 / F+S 500/50 / T+O 2.5/5 / F+S 250/50
Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled.
* Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
* Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
* Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
* Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®.
|
F+S 250/50 / T+O 2.5/5 / F+S 500/50 / T+O 5/5
Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled.
* Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
* Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
* Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
* Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®.
|
F+S 500/50 / F+S 250/50 / T+O 5/5 / T+O 2.5/5
Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled.
* Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
* Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
* Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
* Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
58
|
69
|
50
|
52
|
|
Overall Study
COMPLETED
|
54
|
57
|
45
|
46
|
|
Overall Study
NOT COMPLETED
|
4
|
12
|
5
|
6
|
Reasons for withdrawal
| Measure |
T+O 2.5/5 / T+O 5/5 / F+S 250/50 / F+S 500/50
Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled .
* Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo (T+O 2.5/5).
* Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo (T+O 5/5).
* Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo (F+S 250/50).
* Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo (F+S 500/50).
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®.
|
T+O 5/5 / F+S 500/50 / T+O 2.5/5 / F+S 250/50
Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled.
* Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
* Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
* Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
* Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®.
|
F+S 250/50 / T+O 2.5/5 / F+S 500/50 / T+O 5/5
Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled.
* Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
* Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
* Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
* Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®.
|
F+S 500/50 / F+S 250/50 / T+O 5/5 / T+O 2.5/5
Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled.
* Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
* Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
* Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
* Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
8
|
3
|
2
|
|
Overall Study
Lack of Efficacy
|
0
|
0
|
1
|
0
|
|
Overall Study
Non compliant with protocol
|
1
|
1
|
0
|
2
|
|
Overall Study
Other not defined above
|
0
|
2
|
0
|
0
|
|
Overall Study
Discontinued during washout periods.
|
0
|
1
|
1
|
2
|
Baseline Characteristics
Characterization of Lung Function Profile of Inhaled Tiotropium + Olodaterol Fixed Dose Combination Compared to Fluticasone Propionate + Salmeterol Fixed Dose Combination in COPD Patients
Baseline characteristics by cohort
| Measure |
Overall Study
n=229 Participants
Patients received a total of four treatments. Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days. The treatments were orally inhaled.
* Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
* Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg plus Fluticasone propionate+Salmeterol placebo.
* Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
* Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg plus Tiotropium+Olodaterol placebo.
Tiotropium+Olodaterol FDC inhalation solutions were administered via the Respimat® inhaler once daily, Fluticasone propionate+Salmeterol FDC inhalation powders were administered orally twice daily via Accuhaler®.
|
|---|---|
|
Age, Continuous
|
63.6 Years
STANDARD_DEVIATION 7.6 • n=99 Participants
|
|
Sex: Female, Male
Female
|
81 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
148 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Baseline and 6 weeks.Population: FAS (Full Analysis Set): Included all randomised patients who were documented to have had received any dose of trial medication and who had both baseline and any evaluable post-baseline measurement for the primary efficacy endpoint.
Change from patient baseline in Forced Expiratory Volume in one second (FEV1) Area Under the FEV1-time Curve from 0 to 12hours post-dose (AUC 0-12h) \[L\] after 6 weeks of treatment. Measured values presented are actually adjusted means. The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient.
Outcome measures
| Measure |
T+O 2.5/5 / F+S Placebo
n=214 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg (T+O 2.5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
T+O 5/5 / F+S Placebo
n=216 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg (T+O 5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
F+S 250/50 / T+O Placebo
n=211 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg (F+S 250/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
F+S 500/50 / T+O Placebo
n=217 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg (F+S 500/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
|---|---|---|---|---|
|
FEV1 AUC (0-12h) Change From Patient Baseline After 6 Weeks of Treatment
|
0.295 Litres
Standard Error 0.014
|
0.317 Litres
Standard Error 0.014
|
0.192 Litres
Standard Error 0.015
|
0.188 Litres
Standard Error 0.014
|
SECONDARY outcome
Timeframe: Baseline and 6 weeks.Population: FAS (Full Analysis Set): Included all randomised patients who were documented to have had received any dose of trial medication and who had both baseline and any evaluable post-baseline measurement for the primary efficacy endpoint.
Change from patient baseline in Forced Expiratory Volume in one second (FEV1) Area Under the FEV1-time Curve from 0 to 24 hours post-dose (AUC 0-24h) \[L\] after 6 weeks of treatment. Measured values presented are actually adjusted means. The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient.
Outcome measures
| Measure |
T+O 2.5/5 / F+S Placebo
n=214 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg (T+O 2.5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
T+O 5/5 / F+S Placebo
n=216 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg (T+O 5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
F+S 250/50 / T+O Placebo
n=211 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg (F+S 250/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
F+S 500/50 / T+O Placebo
n=217 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg (F+S 500/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
|---|---|---|---|---|
|
FEV1 AUC (0-24h) Change From Patient Baseline After 6 Weeks of Treatment
|
0.228 Litres
Standard Error 0.014
|
0.244 Litres
Standard Error 0.014
|
0.162 Litres
Standard Error 0.014
|
0.159 Litres
Standard Error 0.014
|
SECONDARY outcome
Timeframe: Baseline and 6 weeks.Population: FAS (Full Analysis Set): Included all randomised patients who were documented to have had received any dose of trial medication and who had both baseline and any evaluable post-baseline measurement for the primary efficacy endpoint.
Change from patient baseline in Trough Forced Expiratory Volume in one second (FEV1) after 6 weeks of treatment. Trough FEV1 was defined as the mean of the 23h and 23h 50min (minutes) post-dose FEV1 measurements. Measured values presented are actually adjusted means. The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient.
Outcome measures
| Measure |
T+O 2.5/5 / F+S Placebo
n=214 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg (T+O 2.5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
T+O 5/5 / F+S Placebo
n=216 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg (T+O 5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
F+S 250/50 / T+O Placebo
n=211 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg (F+S 250/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
F+S 500/50 / T+O Placebo
n=217 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg (F+S 500/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
|---|---|---|---|---|
|
Trough FEV1 Change From Patient Baseline After 6 Weeks of Treatment
|
0.192 Litres
Standard Error 0.014
|
0.197 Litres
Standard Error 0.014
|
0.150 Litres
Standard Error 0.014
|
0.139 Litres
Standard Error 0.014
|
SECONDARY outcome
Timeframe: Baseline and 6 weeks.Population: FAS (Full Analysis Set): Included all randomised patients who were documented to have had received any dose of trial medication and who had both baseline and any evaluable post-baseline measurement for the primary efficacy endpoint.
Change from patient baseline in Forced Expiratory Volume in one second (FEV1) Area Under the FEV1-time Curve from 12 to 24 hours post-dose (AUC 12-24h) \[L\] after 6 weeks of treatment. Measured values presented are actually adjusted means. The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient.
Outcome measures
| Measure |
T+O 2.5/5 / F+S Placebo
n=214 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg (T+O 2.5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
T+O 5/5 / F+S Placebo
n=216 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg (T+O 5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
F+S 250/50 / T+O Placebo
n=211 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg (F+S 250/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
F+S 500/50 / T+O Placebo
n=217 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg (F+S 500/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
|---|---|---|---|---|
|
FEV1 AUC (12-24h) Change From Patient Baseline After 6 Weeks of Treatment
|
0.160 Litres
Standard Error 0.014
|
0.172 Litres
Standard Error 0.014
|
0.132 Litres
Standard Error 0.014
|
0.129 Litres
Standard Error 0.014
|
SECONDARY outcome
Timeframe: Baseline and 6 weeks.Population: FAS (Full Analysis Set): Included all randomised patients who were documented to have had received any dose of trial medication and who had both baseline and any evaluable post-baseline measurement for the primary efficacy endpoint.
Change from patient baseline in Forced Expiratory Volume in one second (FEV1) peak (0-3 hours) after 6 weeks of treatment. FEV1 peak (0-3 hours) was defined as the maximum FEV1 value measured within the first three hours post dosing. Measured values presented are actually adjusted means.
Outcome measures
| Measure |
T+O 2.5/5 / F+S Placebo
n=214 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg (T+O 2.5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
T+O 5/5 / F+S Placebo
n=216 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg (T+O 5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
F+S 250/50 / T+O Placebo
n=211 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg (F+S 250/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
F+S 500/50 / T+O Placebo
n=217 Participants
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg (F+S 500/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
|---|---|---|---|---|
|
FEV1 Peak (0-3h) Change From Patient Baseline After 6 Weeks of Treatment
|
0.401 Litres
Standard Error 0.016
|
0.432 Litres
Standard Error 0.016
|
0.291 Litres
Standard Error 0.016
|
0.285 Litres
Standard Error 0.015
|
Adverse Events
T+O 2.5/5 / F+S Placebo
Serious events: 6 serious events
Other events: 21 other events
Deaths: 0 deaths
T+O 5/5 / F+S Placebo
Serious events: 7 serious events
Other events: 28 other events
Deaths: 0 deaths
F+S 250/50 / T+O Placebo
Serious events: 4 serious events
Other events: 19 other events
Deaths: 0 deaths
F+S 500/50 / T+O Placebo
Serious events: 9 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
T+O 2.5/5 / F+S Placebo
n=215 participants at risk
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg (T+O 2.5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
T+O 5/5 / F+S Placebo
n=221 participants at risk
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg (T+O 5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
F+S 250/50 / T+O Placebo
n=212 participants at risk
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg (F+S 250/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
F+S 500/50 / T+O Placebo
n=219 participants at risk
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg (F+S 500/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
|---|---|---|---|---|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.46%
1/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Cardiac disorders
Atrial flutter
|
0.47%
1/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Cardiac disorders
Cardiac failure
|
0.47%
1/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.46%
1/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.45%
1/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.45%
1/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
General disorders
Death
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.45%
1/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.47%
1/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Immune system disorders
Drug hypersensitivity
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.46%
1/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.45%
1/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Infections and infestations
Lobar pneumonia
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.47%
1/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Infections and infestations
Osteomyelitis
|
0.47%
1/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Infections and infestations
Pneumonia
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.47%
1/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.46%
1/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Infections and infestations
Sialoadenitis
|
0.47%
1/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.47%
1/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.47%
1/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.47%
1/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Injury, poisoning and procedural complications
Vascular graft occlusion
|
0.47%
1/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.46%
1/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.45%
1/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.46%
1/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.45%
1/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.47%
1/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.45%
1/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.45%
1/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.00%
0/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.93%
2/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.90%
2/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
0.94%
2/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
1.8%
4/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
Other adverse events
| Measure |
T+O 2.5/5 / F+S Placebo
n=215 participants at risk
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed Dose Combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg (T+O 2.5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
T+O 5/5 / F+S Placebo
n=221 participants at risk
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Tiotropium 5 μg and Olodaterol 5 μg (T+O 5/5) administered orally via the Respimat® inhaler once daily plus Fluticasone propionate+Salmeterol (F+S) placebo treatment administered orally twice daily via Accuhaler®.
|
F+S 250/50 / T+O Placebo
n=212 participants at risk
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 250 μg and Salmeterol 50 μg (F+S 250/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
F+S 500/50 / T+O Placebo
n=219 participants at risk
Treatments were taken for 6 weeks and each treatment period was separated by a washout period of at least 21 days.
• Fixed dose combination (FDC) of Fluticasone propionate 500 μg and Salmeterol 50 μg (F+S 500/50) administered orally twice daily via Accuhaler® plus Tiotropium+Olodaterol (T+O) placebo treatment administered orally once daily via the Respimat® inhaler.
|
|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
5.6%
12/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
5.4%
12/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
6.1%
13/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
5.0%
11/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
4.7%
10/215 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
8.1%
18/221 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
3.3%
7/212 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
6.8%
15/219 • From first drug intake until 21 days after last drug intake, up to 88 days.
AEs are displayed by treatment, however in total patients were in the study for up to 223 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER