Trial Outcomes & Findings for A Study to Test the Combination of Tiotropium and Olodaterol Using the Respimat® Inhaler in People With Chronic Obstructive Pulmonary Disease (COPD) Who Have Different Abilities to Inhale (NCT NCT04223843)
NCT ID: NCT04223843
Last Updated: 2021-11-18
Results Overview
FEV1 AUC0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in liters. Mean is adjusted mean. A hierarchical testing procedure was used to test the primary endpoint. Each of the tests were considered confirmatory only if all previous tests were successful.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
213 participants
Primary outcome timeframe
At baseline and at week 4: 10 minutes (min) prior and 5 min, 15 min, 30 min and 1 hour (h), 2h and 3h after drug administration, respectively.
Results posted on
2021-11-18
Participant Flow
A randomised, double-blind, placebo-controlled trial to demonstrate the efficacy of 5µg/5µg inhaled tiotropium + olodaterol (Tio+Olo) via Respimat® on lung function in patients with moderate to severe chronic obstructive pulmonary disease (COPD) with optimal and sub-optimal peak inspiratory flow rate (PIFR).
Only patients that met all inclusion and none of the exclusion criteria were included in this trial. Prior to the initiation of any trial-related procedure, all patients were informed about the trial verbally and in writing by the investigator. Each patient signed and dated an Informed Consent Form (ICF) according to the local regulatory and legal requirements.
Participant milestones
| Measure |
Tio+Olo (5μg/5μg) - Sub-optimal PIFR
A fixed dose combination of 5 microgram (μg)/5μg (two times 2.5µg/2.5µg) tiotropium + olodaterol (Tio+Olo) inhalation solution was administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with sub-optimal peak inspiratory flow rate (PIFR) (\<60 Liter(L)/minute (min)) over a 4-week treatment period.
|
Matching Placebo - Sub-optimal PIFR
2 inhalation solutions of matching placebo were administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with sub-optimal peak inspiratory flow rate (PIFR) (\<60 L/min) over a 4-week treatment period.
|
Tio+Olo (5μg/5μg ) - Optimal PIFR
A fixed dose combination of 5μg/5μg (two times 2.5µg/2.5µg) tiotropium + olodaterol (Tio+Olo) inhalation solution was administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with sub-optimal peak inspiratory flow rate (PIFR) (≥60 L/min) over a 4-week treatment period.
|
Matching Placebo - Optimal PIFR
2 inhalation solutions of matching placebo were administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with optimal peak inspiratory flow rate (PIFR) (≥60 L/min) over a 4-week treatment period.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
55
|
55
|
51
|
52
|
|
Overall Study
COMPLETED
|
55
|
55
|
51
|
52
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Full Analysis Set (FAS): This patient set was nested within the TS and included all patients who had a baseline and at least 1 post-baseline measurement for at least 1 efficacy endpoint. Only patients with availble data for this endpoint were included.
Baseline characteristics by cohort
| Measure |
Tio+Olo (5μg/5μg) - Sub-optimal PIFR
n=55 Participants
A fixed dose combination of 5 microgram (μg)/5μg (two times 2.5µg/2.5µg) tiotropium + olodaterol (Tio+Olo) inhalation solution was administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with sub-optimal peak inspiratory flow rate (PIFR) (\<60 Liter(L)/minute (min)) over a 4-week treatment period.
|
Matching Placebo - Sub-optimal PIFR
n=55 Participants
2 inhalation solutions of matching placebo were administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with sub-optimal peak inspiratory flow rate (PIFR) (\<60 L/min) over a 4-week treatment period.
|
Tio+Olo (5μg/5μg ) - Optimal PIFR
n=51 Participants
A fixed dose combination of 5μg/5μg (two times 2.5µg/2.5µg) tiotropium + olodaterol (Tio+Olo) inhalation solution was administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with sub-optimal peak inspiratory flow rate (PIFR) (≥60 L/min) over a 4-week treatment period.
|
Matching Placebo - Optimal PIFR
n=52 Participants
2 inhalation solutions of matching placebo were administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with optimal peak inspiratory flow rate (PIFR) (≥60 L/min) over a 4-week treatment period.
|
Total
n=213 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
64 Years
STANDARD_DEVIATION 9.79 • n=55 Participants
|
67.05 Years
STANDARD_DEVIATION 7.54 • n=55 Participants
|
62.80 Years
STANDARD_DEVIATION 7.48 • n=51 Participants
|
65.88 Years
STANDARD_DEVIATION 7.43 • n=52 Participants
|
64.96 Years
STANDARD_DEVIATION 8.25 • n=213 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=55 Participants
|
37 Participants
n=55 Participants
|
24 Participants
n=51 Participants
|
20 Participants
n=52 Participants
|
109 Participants
n=213 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=55 Participants
|
18 Participants
n=55 Participants
|
27 Participants
n=51 Participants
|
32 Participants
n=52 Participants
|
104 Participants
n=213 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=55 Participants
|
1 Participants
n=55 Participants
|
0 Participants
n=51 Participants
|
0 Participants
n=52 Participants
|
3 Participants
n=213 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=55 Participants
|
0 Participants
n=55 Participants
|
0 Participants
n=51 Participants
|
0 Participants
n=52 Participants
|
0 Participants
n=213 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=55 Participants
|
0 Participants
n=55 Participants
|
0 Participants
n=51 Participants
|
0 Participants
n=52 Participants
|
0 Participants
n=213 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=55 Participants
|
3 Participants
n=55 Participants
|
1 Participants
n=51 Participants
|
0 Participants
n=52 Participants
|
6 Participants
n=213 Participants
|
|
Race (NIH/OMB)
White
|
51 Participants
n=55 Participants
|
51 Participants
n=55 Participants
|
50 Participants
n=51 Participants
|
51 Participants
n=52 Participants
|
203 Participants
n=213 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=55 Participants
|
0 Participants
n=55 Participants
|
0 Participants
n=51 Participants
|
1 Participants
n=52 Participants
|
1 Participants
n=213 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=55 Participants
|
0 Participants
n=55 Participants
|
0 Participants
n=51 Participants
|
0 Participants
n=52 Participants
|
0 Participants
n=213 Participants
|
|
Forced Expiratory Volume in one second (FEV1) area under the curve from 0 to 3 hours (AUC0-3h)
|
1.224 Liter (L)
STANDARD_DEVIATION 0.060 • n=43 Participants • Full Analysis Set (FAS): This patient set was nested within the TS and included all patients who had a baseline and at least 1 post-baseline measurement for at least 1 efficacy endpoint. Only patients with availble data for this endpoint were included.
|
1.277 Liter (L)
STANDARD_DEVIATION 0.079 • n=47 Participants • Full Analysis Set (FAS): This patient set was nested within the TS and included all patients who had a baseline and at least 1 post-baseline measurement for at least 1 efficacy endpoint. Only patients with availble data for this endpoint were included.
|
1.388 Liter (L)
STANDARD_DEVIATION 0.070 • n=44 Participants • Full Analysis Set (FAS): This patient set was nested within the TS and included all patients who had a baseline and at least 1 post-baseline measurement for at least 1 efficacy endpoint. Only patients with availble data for this endpoint were included.
|
1.523 Liter (L)
STANDARD_DEVIATION 0.074 • n=47 Participants • Full Analysis Set (FAS): This patient set was nested within the TS and included all patients who had a baseline and at least 1 post-baseline measurement for at least 1 efficacy endpoint. Only patients with availble data for this endpoint were included.
|
1.324 Liter (L)
STANDARD_DEVIATION 0.467 • n=181 Participants • Full Analysis Set (FAS): This patient set was nested within the TS and included all patients who had a baseline and at least 1 post-baseline measurement for at least 1 efficacy endpoint. Only patients with availble data for this endpoint were included.
|
PRIMARY outcome
Timeframe: At baseline and at week 4: 10 minutes (min) prior and 5 min, 15 min, 30 min and 1 hour (h), 2h and 3h after drug administration, respectively.Population: Full Analysis Set (FAS): This patient set was nested within the TS and included all patients who had a baseline and at least 1 post-baseline measurement for at least 1 efficacy endpoint. Only patients with non-missing endpoint results were included.
FEV1 AUC0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in liters. Mean is adjusted mean. A hierarchical testing procedure was used to test the primary endpoint. Each of the tests were considered confirmatory only if all previous tests were successful.
Outcome measures
| Measure |
Tio+Olo (5μg/5μg) - Sub-optimal PIFR
n=43 Participants
A fixed dose combination of 5 microgram (μg)/5μg (two times 2.5µg/2.5µg) tiotropium + olodaterol (Tio+Olo) inhalation solution was administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with sub-optimal peak inspiratory flow rate (PIFR) (\<60 Liter(L)/minute (min)) over a 4-week treatment period.
|
Matching Placebo - Sub-optimal PIFR
n=47 Participants
2 inhalation solutions of matching placebo were administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with sub-optimal peak inspiratory flow rate (PIFR) (\<60 L/min) over a 4-week treatment period.
|
Tio+Olo (5μg/5μg ) - Optimal PIFR
n=44 Participants
A fixed dose combination of 5μg/5μg (two times 2.5µg/2.5µg) tiotropium + olodaterol (Tio+Olo) inhalation solution was administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with sub-optimal peak inspiratory flow rate (PIFR) (≥60 L/min) over a 4-week treatment period.
|
Matching Placebo - Optimal PIFR
n=47 Participants
2 inhalation solutions of matching placebo were administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with optimal peak inspiratory flow rate (PIFR) (≥60 L/min) over a 4-week treatment period.
|
|---|---|---|---|---|
|
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 3 Hours (AUC0-3h) After 4 Weeks of Treatment.
|
0.250 Liter (L)
Standard Error 0.033
|
-0.086 Liter (L)
Standard Error 0.031
|
0.333 Liter (L)
Standard Error 0.032
|
0.012 Liter (L)
Standard Error 0.031
|
SECONDARY outcome
Timeframe: At baseline and at week 4.Population: FAS: This patient set was nested within the TS and included all patients who had a baseline and at least 1 post-baseline measurement for at least 1 efficacy endpoint. Only patients with non-missing endpoint results were included.
Change from baseline in trough Forced Expiratory Volume in one second (FEV1) after 4 weeks of treatment.
Outcome measures
| Measure |
Tio+Olo (5μg/5μg) - Sub-optimal PIFR
n=50 Participants
A fixed dose combination of 5 microgram (μg)/5μg (two times 2.5µg/2.5µg) tiotropium + olodaterol (Tio+Olo) inhalation solution was administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with sub-optimal peak inspiratory flow rate (PIFR) (\<60 Liter(L)/minute (min)) over a 4-week treatment period.
|
Matching Placebo - Sub-optimal PIFR
n=52 Participants
2 inhalation solutions of matching placebo were administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with sub-optimal peak inspiratory flow rate (PIFR) (\<60 L/min) over a 4-week treatment period.
|
Tio+Olo (5μg/5μg ) - Optimal PIFR
n=47 Participants
A fixed dose combination of 5μg/5μg (two times 2.5µg/2.5µg) tiotropium + olodaterol (Tio+Olo) inhalation solution was administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with sub-optimal peak inspiratory flow rate (PIFR) (≥60 L/min) over a 4-week treatment period.
|
Matching Placebo - Optimal PIFR
n=50 Participants
2 inhalation solutions of matching placebo were administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and with optimal peak inspiratory flow rate (PIFR) (≥60 L/min) over a 4-week treatment period.
|
|---|---|---|---|---|
|
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) After 4 Weeks of Treatment
|
0.095 Liter
Standard Error 0.031
|
-0.106 Liter
Standard Error 0.030
|
0.177 Liter
Standard Error 0.030
|
-0.040 Liter
Standard Error 0.029
|
Adverse Events
5μg/5μg Tio+Olo - Overall
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
Matching Placebo - Overall
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
5μg/5μg Tio+Olo - Overall
n=106 participants at risk
A fixed dose combination (FDC) of 5μg/5μg (two times 2.5µg/2.5µg) tiotropium + olodaterol (Tio+Olo) inhalation solution was administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) over a 4-week treatment period. Overall group included patients with both, sub-optimal (\<60 L/min) peak inspiratory flow rate (PIFR) and optimal (≥60 L/min) peak inspiratory flow rate (PIFR).
|
Matching Placebo - Overall
n=107 participants at risk
2 inhalation solutions of matching placebo were administered orally once daily via Respimat inhaler in patients with moderate to severe chronic obstructive pulmonary disease (COPD) over a 4-week treatment period. Overall group included patients with both, sub-optimal (\<60 L/min) peak inspiratory flow rate (PIFR) and optimal (≥60 L/min) peak inspiratory flow rate (PIFR).
|
|---|---|---|
|
Infections and infestations
Gastroenteritis
|
0.94%
1/106 • From first intake of trial medication until last trial medication intake plus 21 days (residual effect period), up to 50 days.
Treated Set: This patient set included all randomised patients who were dispensed trial medication and were documented to have taken any dose of trial medication. Adverse events were summarized by treatment group (Tio/Olo vs. Placebo), as defined in the statistical analysis plan.
|
0.00%
0/107 • From first intake of trial medication until last trial medication intake plus 21 days (residual effect period), up to 50 days.
Treated Set: This patient set included all randomised patients who were dispensed trial medication and were documented to have taken any dose of trial medication. Adverse events were summarized by treatment group (Tio/Olo vs. Placebo), as defined in the statistical analysis plan.
|
|
Infections and infestations
Necrotising fasciitis
|
0.00%
0/106 • From first intake of trial medication until last trial medication intake plus 21 days (residual effect period), up to 50 days.
Treated Set: This patient set included all randomised patients who were dispensed trial medication and were documented to have taken any dose of trial medication. Adverse events were summarized by treatment group (Tio/Olo vs. Placebo), as defined in the statistical analysis plan.
|
0.93%
1/107 • From first intake of trial medication until last trial medication intake plus 21 days (residual effect period), up to 50 days.
Treated Set: This patient set included all randomised patients who were dispensed trial medication and were documented to have taken any dose of trial medication. Adverse events were summarized by treatment group (Tio/Olo vs. Placebo), as defined in the statistical analysis plan.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.94%
1/106 • From first intake of trial medication until last trial medication intake plus 21 days (residual effect period), up to 50 days.
Treated Set: This patient set included all randomised patients who were dispensed trial medication and were documented to have taken any dose of trial medication. Adverse events were summarized by treatment group (Tio/Olo vs. Placebo), as defined in the statistical analysis plan.
|
0.00%
0/107 • From first intake of trial medication until last trial medication intake plus 21 days (residual effect period), up to 50 days.
Treated Set: This patient set included all randomised patients who were dispensed trial medication and were documented to have taken any dose of trial medication. Adverse events were summarized by treatment group (Tio/Olo vs. Placebo), as defined in the statistical analysis plan.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/106 • From first intake of trial medication until last trial medication intake plus 21 days (residual effect period), up to 50 days.
Treated Set: This patient set included all randomised patients who were dispensed trial medication and were documented to have taken any dose of trial medication. Adverse events were summarized by treatment group (Tio/Olo vs. Placebo), as defined in the statistical analysis plan.
|
0.93%
1/107 • From first intake of trial medication until last trial medication intake plus 21 days (residual effect period), up to 50 days.
Treated Set: This patient set included all randomised patients who were dispensed trial medication and were documented to have taken any dose of trial medication. Adverse events were summarized by treatment group (Tio/Olo vs. Placebo), as defined in the statistical analysis plan.
|
Other adverse events
Adverse event data not reported
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
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