Trial Outcomes & Findings for A Randomised, Double- Blind, Placebo Controlled, Cross-over Efficacy and Safety Comparison of Tiotropium 5 µg Once Daily and Tiotropium 2.5 µg Twice Daily for Four Weeks in Patients With Moderate Persistent Asthma (NCT NCT01152450)
NCT ID: NCT01152450
Last Updated: 2024-12-19
Results Overview
Mixed Model Repeated Measure (MMRM) results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measurements performed in relation to evening dosing. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
94 participants
Primary outcome timeframe
10 minutes (min) prior to first dose (baseline) and -10 min, 30 min, 60 min, 2 hours (h) , 3 h, 4 h , 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose at week 4
Results posted on
2024-12-19
Participant Flow
A total of 94 patients entered the study and was treated whilst 89 patients completed the trial.
Randomised, double-blind, placebo controlled, cross-over design without washout phase between the three periods. Patients were randomized equally to one of the six sequences (ABC, ACB, BAC, BCA, CAB, CBA).
Participant milestones
| Measure |
Tio R2.5 Twice Daily (Bid) /Tio R5 Once Daily (qd) /Placebo
Patients treated with Tiotropium 2.5 mcg in period 1 (morning and evening), with a matching placebo in the morning and Tiotropium 5 mcg in the evening in period 2 and with a matching Placebo in period 3 (morning and evening). All products were delivered by the Respimat inhaler, on top on maintenance therapy with inhaled corticosteroid (iCS). No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
|
Tio R2.5 Bid/Placebo/Tio R5 qd
Patients treated with Tiotropium 2.5 mcg in period 1 (morning and evening), with a matching Placebo in period 2 (morning and evening) and with a matching placebo in the morning and Tiotropium 5 mcg in the evening in period 3. All products were delivered by the Respimat inhaler, on top on maintenance therapy with iCS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
|
Tio R5 qd/Tio R2.5 Bid/Placebo
Patients treated with a matching placebo in the morning and Tiotropium 5 mcg in the evening in period 1, with Tiotropium 2.5 mcg in period 2 (morning and evening) and with matching Placebo in period 3 (morning and evening) . All products were delivered by the Respimat inhaler, on top on maintenance therapy with iCS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
|
Tio R5 qd/Placebo/Tio R2.5 Bid
Patients treated with a matching placebo in the morning and Tiotropium 5 mcg in the evening in period 1, with matching Placebo in period 2 (morning and evening) and with Tiotropium 2.5 mcg in period 3 (morning and evening) . All products were delivered by the Respimat inhaler, on top on maintenance therapy with iCS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
|
Placebo/Tio R2.5 Bid/Tio R5 qd
Patients treated with matching Placebo in period 1 (morning and evening), with Tiotropium 2.5 mcg in period 2 (morning and evening) and with a matching placebo in the morning and Tiotropium 5 mcg in the evening in period 3. All products were delivered by the Respimat inhaler, on top on maintenance therapy with iCS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
|
Placebo/Tio R5 qd/Tio R2.5 Bid
Patients treated with a matching Placebo in period 1 (morning and evening), with a matching placebo in the morning and Tiotropium 5 mcg in the evening in period 2 and with Tiotropium 2.5 mcg in period 3 (morning and evening) . All products were delivered by the Respimat inhaler, on top on maintenance therapy with iCS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
|
|---|---|---|---|---|---|---|
|
Period 1 (4 Weeks)
STARTED
|
15
|
16
|
17
|
15
|
18
|
13
|
|
Period 1 (4 Weeks)
COMPLETED
|
15
|
15
|
16
|
15
|
16
|
12
|
|
Period 1 (4 Weeks)
NOT COMPLETED
|
0
|
1
|
1
|
0
|
2
|
1
|
|
Period 2 (4 Weeks)
STARTED
|
15
|
15
|
16
|
15
|
16
|
12
|
|
Period 2 (4 Weeks)
COMPLETED
|
15
|
15
|
16
|
15
|
16
|
12
|
|
Period 2 (4 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 3 (4 Weeks)
STARTED
|
15
|
15
|
16
|
15
|
16
|
12
|
|
Period 3 (4 Weeks)
COMPLETED
|
15
|
15
|
16
|
15
|
16
|
12
|
|
Period 3 (4 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Tio R2.5 Twice Daily (Bid) /Tio R5 Once Daily (qd) /Placebo
Patients treated with Tiotropium 2.5 mcg in period 1 (morning and evening), with a matching placebo in the morning and Tiotropium 5 mcg in the evening in period 2 and with a matching Placebo in period 3 (morning and evening). All products were delivered by the Respimat inhaler, on top on maintenance therapy with inhaled corticosteroid (iCS). No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
|
Tio R2.5 Bid/Placebo/Tio R5 qd
Patients treated with Tiotropium 2.5 mcg in period 1 (morning and evening), with a matching Placebo in period 2 (morning and evening) and with a matching placebo in the morning and Tiotropium 5 mcg in the evening in period 3. All products were delivered by the Respimat inhaler, on top on maintenance therapy with iCS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
|
Tio R5 qd/Tio R2.5 Bid/Placebo
Patients treated with a matching placebo in the morning and Tiotropium 5 mcg in the evening in period 1, with Tiotropium 2.5 mcg in period 2 (morning and evening) and with matching Placebo in period 3 (morning and evening) . All products were delivered by the Respimat inhaler, on top on maintenance therapy with iCS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
|
Tio R5 qd/Placebo/Tio R2.5 Bid
Patients treated with a matching placebo in the morning and Tiotropium 5 mcg in the evening in period 1, with matching Placebo in period 2 (morning and evening) and with Tiotropium 2.5 mcg in period 3 (morning and evening) . All products were delivered by the Respimat inhaler, on top on maintenance therapy with iCS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
|
Placebo/Tio R2.5 Bid/Tio R5 qd
Patients treated with matching Placebo in period 1 (morning and evening), with Tiotropium 2.5 mcg in period 2 (morning and evening) and with a matching placebo in the morning and Tiotropium 5 mcg in the evening in period 3. All products were delivered by the Respimat inhaler, on top on maintenance therapy with iCS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
|
Placebo/Tio R5 qd/Tio R2.5 Bid
Patients treated with a matching Placebo in period 1 (morning and evening), with a matching placebo in the morning and Tiotropium 5 mcg in the evening in period 2 and with Tiotropium 2.5 mcg in period 3 (morning and evening) . All products were delivered by the Respimat inhaler, on top on maintenance therapy with iCS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
|
|---|---|---|---|---|---|---|
|
Period 1 (4 Weeks)
Adverse Event
|
0
|
0
|
0
|
0
|
1
|
1
|
|
Period 1 (4 Weeks)
Protocol Violation
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Period 1 (4 Weeks)
Lost to Follow-up
|
0
|
1
|
1
|
0
|
0
|
0
|
Baseline Characteristics
A Randomised, Double- Blind, Placebo Controlled, Cross-over Efficacy and Safety Comparison of Tiotropium 5 µg Once Daily and Tiotropium 2.5 µg Twice Daily for Four Weeks in Patients With Moderate Persistent Asthma
Baseline characteristics by cohort
| Measure |
Baseline Total
n=94 Participants
Total number of patients randomised and treated in the study.
|
|---|---|
|
Age, Continuous
|
44.3 Years
STANDARD_DEVIATION 13.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
55 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 10 minutes (min) prior to first dose (baseline) and -10 min, 30 min, 60 min, 2 hours (h) , 3 h, 4 h , 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose at week 4Population: Full Analysis Set (FAS) defined as all treated patients who had baseline data and at least 1 on-treatment efficacy measurement after 4 weeks on treatment within a period.
Mixed Model Repeated Measure (MMRM) results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measurements performed in relation to evening dosing. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Forced Expiratory Volume in One Second (FEV1) Area Under the Curve 0-24 Hours (AUC0-24h) Response
|
0.091 L
Standard Error 0.043
|
0.241 L
Standard Error 0.044
|
0.250 L
Standard Error 0.044
|
SECONDARY outcome
Timeframe: Baseline and during week 4 of each treatment periodPopulation: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured by patients at home using the AM2+ device.
Outcome measures
| Measure |
Placebo
n=91 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=88 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Mean Pre-dose Morning Peak Expiratory Flow (PEF a.m.) Response During the Last Week on Treatment
|
1.953 L/min
Standard Error 5.864
|
23.281 L/min
Standard Error 5.907
|
24.310 L/min
Standard Error 5.924
|
SECONDARY outcome
Timeframe: Baseline and during week 4 of each treatment periodPopulation: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured by patients at home using the AM2+ device.
Outcome measures
| Measure |
Placebo
n=91 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=89 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Mean Pre-dose Evening Peak Expiratory Flow (PEF p.m.) Response During the Last Week on Treatment
|
-1.560 L/min
Standard Error 5.891
|
28.360 L/min
Standard Error 5.932
|
27.096 L/min
Standard Error 5.931
|
SECONDARY outcome
Timeframe: 10 min prior to first dose (baseline) and -10 min, 30 min, 60 min, 2 h, 3 h, 4 h and 11 h 50 min related to evening dose at week 4Population: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-12h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
FEV1 Area Under the Curve 0-12 Hours (AUC0-12h) Response
|
0.048 L
Standard Error 0.044
|
0.217 L
Standard Error 0.044
|
0.233 L
Standard Error 0.044
|
SECONDARY outcome
Timeframe: 10 min prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose at week 4Population: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC12-24h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
FEV1 Area Under the Curve 12-24 Hours (AUC12-24h) Response
|
0.135 L
Standard Error 0.044
|
0.264 L
Standard Error 0.045
|
0.266 L
Standard Error 0.044
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the evening trial-drug inhalation at the end of each 4 week period of randomised treatment.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Peak FEV1 Within 24 Hours Post-dose Response
|
0.337 L
Standard Error 0.045
|
0.469 L
Standard Error 0.045
|
0.468 L
Standard Error 0.045
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Trough FEV1 is defined as FEV1 value (performed at 10 minutes prior to the evening trial-drug inhalation) at the end of each 4 week period of randomised treatment.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Trough FEV1 Response
|
0.143 L
Standard Error 0.044
|
0.254 L
Standard Error 0.044
|
0.275 L
Standard Error 0.044
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Trough FVC is defined as FVC value (performed at 10 minutes prior to the evening trial-drug inhalation) at the end of each 4 week period of randomised treatment.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Trough Forced Vital Capacity (FVC) Response
|
0.112 L
Standard Error 0.046
|
0.179 L
Standard Error 0.046
|
0.168 L
Standard Error 0.046
|
SECONDARY outcome
Timeframe: 10 min prior to first dose (baseline) and -10 min, 30 min, 60 min, 2 h, 3 h, 4 h and 11 h 50 min related to evening dose at week 4Population: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following each dosing determined at the end of each 4 week treatment period. AUC0-12h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
FVC Area Under the Curve 0-12 Hours (AUC0-12h) Response
|
-0.026 L
Standard Error 0.046
|
0.099 L
Standard Error 0.046
|
0.074 L
Standard Error 0.046
|
SECONDARY outcome
Timeframe: 10 min prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose at week 4Population: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following each dosing determined at the end of each 4 week treatment period. AUC12-24h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
FVC Area Under the Curve 12-24 Hours (AUC12-24h) Response
|
0.032 L
Standard Error 0.045
|
0.108 L
Standard Error 0.045
|
0.100 L
Standard Error 0.045
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following each dosing determined at the end of each 4 week treatment period.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Peak FVC Within 24 Hours Post-dose Response
|
0.302 L
Standard Error 0.045
|
0.380 L
Standard Error 0.045
|
0.350 L
Standard Error 0.045
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint -0:10 (hours:minutes)
|
0.143 L
Standard Error 0.044
|
0.254 L
Standard Error 0.044
|
0.275 L
Standard Error 0.044
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 0:30 (hours:minutes)
|
0.132 L
Standard Error 0.044
|
0.281 L
Standard Error 0.044
|
0.304 L
Standard Error 0.044
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 1:00 (hours:minutes)
|
0.123 L
Standard Error 0.044
|
0.274 L
Standard Error 0.044
|
0.289 L
Standard Error 0.044
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 2:00 (hours:minutes)
|
0.103 L
Standard Error 0.044
|
0.270 L
Standard Error 0.044
|
0.297 L
Standard Error 0.044
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 3:00 (hours:minutes)
|
0.082 L
Standard Error 0.044
|
0.264 L
Standard Error 0.044
|
0.268 L
Standard Error 0.044
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 4:00 (hours:minutes)
|
0.062 L
Standard Error 0.045
|
0.248 L
Standard Error 0.045
|
0.263 L
Standard Error 0.045
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 11:50 (hours:minutes)
|
-0.021 L
Standard Error 0.049
|
0.134 L
Standard Error 0.049
|
0.150 L
Standard Error 0.049
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 12:30 (hours:minutes)
|
0.075 L
Standard Error 0.047
|
0.198 L
Standard Error 0.047
|
0.217 L
Standard Error 0.047
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 13:00 (hours:minutes)
|
0.101 L
Standard Error 0.047
|
0.250 L
Standard Error 0.047
|
0.237 L
Standard Error 0.047
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 14:00 (hours:minutes)
|
0.138 L
Standard Error 0.045
|
0.288 L
Standard Error 0.045
|
0.282 L
Standard Error 0.045
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 15:00 (hours:minutes)
|
0.163 L
Standard Error 0.046
|
0.299 L
Standard Error 0.046
|
0.308 L
Standard Error 0.046
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 16:00 (hours:minutes)
|
0.161 L
Standard Error 0.046
|
0.306 L
Standard Error 0.046
|
0.313 L
Standard Error 0.046
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 18:00 (hours:minutes)
|
0.177 L
Standard Error 0.047
|
0.300 L
Standard Error 0.047
|
0.308 L
Standard Error 0.047
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 20:00 (hours:minutes)
|
0.127 L
Standard Error 0.045
|
0.256 L
Standard Error 0.046
|
0.245 L
Standard Error 0.045
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 22:00 (hours:minutes)
|
0.117 L
Standard Error 0.047
|
0.221 L
Standard Error 0.047
|
0.244 L
Standard Error 0.047
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 23:00 (hours:minutes)
|
0.124 L
Standard Error 0.045
|
0.243 L
Standard Error 0.045
|
0.223 L
Standard Error 0.045
|
|
Individual FEV1 Over Time (at Each Timepoint at Visits) Response
Timepoint 23:50 (hours:minutes)
|
0.125 L
Standard Error 0.047
|
0.232 L
Standard Error 0.047
|
0.224 L
Standard Error 0.047
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint -0:10 (hours:minutes)
|
0.112 L
Standard Error 0.046
|
0.179 L
Standard Error 0.046
|
0.168 L
Standard Error 0.046
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 0:30 (hours:minutes)
|
0.053 L
Standard Error 0.047
|
0.158 L
Standard Error 0.048
|
0.130 L
Standard Error 0.047
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 1:00 (hours:minutes)
|
0.055 L
Standard Error 0.047
|
0.152 L
Standard Error 0.047
|
0.124 L
Standard Error 0.047
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 2:00 (hours:minutes)
|
0.033 L
Standard Error 0.047
|
0.131 L
Standard Error 0.047
|
0.093 L
Standard Error 0.047
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 3:00 (hours:minutes)
|
-0.003 L
Standard Error 0.047
|
0.100 L
Standard Error 0.047
|
0.057 L
Standard Error 0.047
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 4:00 (hours:minutes)
|
-0.040 L
Standard Error 0.049
|
0.096 L
Standard Error 0.049
|
0.065 L
Standard Error 0.049
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 11:50 (hours:minutes)
|
-0.064 L
Standard Error 0.049
|
0.070 L
Standard Error 0.049
|
0.060 L
Standard Error 0.049
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 12:30 (hours:minutes)
|
0.004 L
Standard Error 0.046
|
0.133 L
Standard Error 0.046
|
0.103 L
Standard Error 0.046
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 13:00 (hours:minutes)
|
0.010 L
Standard Error 0.047
|
0.114 L
Standard Error 0.047
|
0.102 L
Standard Error 0.047
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 14:00 (hours:minutes)
|
0.038 L
Standard Error 0.047
|
0.106 L
Standard Error 0.047
|
0.120 L
Standard Error 0.047
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 15:00 (hours:minutes)
|
0.034 L
Standard Error 0.047
|
0.109 L
Standard Error 0.047
|
0.124 L
Standard Error 0.047
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 16:00 (hours:minutes)
|
0.050 L
Standard Error 0.047
|
0.111 L
Standard Error 0.047
|
0.116 L
Standard Error 0.047
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 18:00 (hours:minutes)
|
0.062 L
Standard Error 0.046
|
0.123 L
Standard Error 0.046
|
0.113 L
Standard Error 0.046
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 20:00 (hours:minutes)
|
0.036 L
Standard Error 0.047
|
0.125 L
Standard Error 0.047
|
0.088 L
Standard Error 0.047
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 22:00 (hours:minutes)
|
0.028 L
Standard Error 0.048
|
0.077 L
Standard Error 0.048
|
0.096 L
Standard Error 0.048
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 23:00 (hours:minutes)
|
0.018 L
Standard Error 0.048
|
0.094 L
Standard Error 0.048
|
0.062 L
Standard Error 0.048
|
|
Individual FVC Over Time (at Each Timepoint at Visits) Response
Timepoint 23:50 (hours:minutes)
|
-0.015 L
Standard Error 0.049
|
0.078 L
Standard Error 0.049
|
0.052 L
Standard Error 0.049
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint -0:10 (hours:minutes)
|
19.770 L/min
Standard Error 7.357
|
42.428 L/min
Standard Error 7.378
|
57.897 L/min
Standard Error 7.359
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 0:30 (hours:minutes)
|
12.994 L/min
Standard Error 7.275
|
46.272 L/min
Standard Error 7.295
|
58.436 L/min
Standard Error 7.277
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 1:00 (hours:minutes)
|
13.783 L/min
Standard Error 7.027
|
43.049 L/min
Standard Error 7.043
|
53.138 L/min
Standard Error 7.028
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 2:00 (hours:minutes)
|
11.366 L/min
Standard Error 7.246
|
48.328 L/min
Standard Error 7.263
|
55.826 L/min
Standard Error 7.248
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 3:00 (hours:minutes)
|
9.769 L/min
Standard Error 7.457
|
48.723 L/min
Standard Error 7.474
|
50.747 L/min
Standard Error 7.458
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 4:00 (hours:minutes)
|
7.499 L/min
Standard Error 7.242
|
42.599 L/min
Standard Error 7.260
|
50.077 L/min
Standard Error 7.244
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 11:50 (hours:minutes)
|
-11.219 L/min
Standard Error 7.747
|
20.011 L/min
Standard Error 7.765
|
26.201 L/min
Standard Error 7.749
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 12:30 (hours:minutes)
|
4.345 L/min
Standard Error 7.314
|
27.436 L/min
Standard Error 7.335
|
33.887 L/min
Standard Error 7.316
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 13:00 (hours:minutes)
|
6.820 L/min
Standard Error 7.479
|
33.810 L/min
Standard Error 7.499
|
34.582 L/min
Standard Error 7.481
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 14:00 (hours:minutes)
|
13.879 L/min
Standard Error 7.323
|
44.786 L/min
Standard Error 7.348
|
43.371 L/min
Standard Error 7.325
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 15:00 (hours:minutes)
|
16.125 L/min
Standard Error 6.992
|
47.991 L/min
Standard Error 7.012
|
45.699 L/min
Standard Error 6.994
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 16:00 (hours:minutes)
|
19.616 L/min
Standard Error 7.304
|
47.697 L/min
Standard Error 7.330
|
46.441 L/min
Standard Error 7.306
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 18:00 (hours:minutes)
|
20.084 L/min
Standard Error 7.303
|
47.795 L/min
Standard Error 7.326
|
48.790 L/min
Standard Error 7.306
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 20:00 (hours:minutes)
|
13.348 L/min
Standard Error 7.213
|
42.240 L/min
Standard Error 7.232
|
40.888 L/min
Standard Error 7.215
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 22:00 (hours:minutes)
|
14.275 L/min
Standard Error 7.317
|
33.567 L/min
Standard Error 7.339
|
41.635 L/min
Standard Error 7.319
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 23:00 (hours:minutes)
|
13.590 L/min
Standard Error 7.360
|
36.712 L/min
Standard Error 7.384
|
38.384 L/min
Standard Error 7.362
|
|
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response
Timepoint 23:50 (hours:minutes)
|
15.169 L/min
Standard Error 7.670
|
36.837 L/min
Standard Error 7.697
|
37.595 L/min
Standard Error 7.673
|
SECONDARY outcome
Timeframe: 10 min prior to first dose (baseline) and -10 min, 30 min, 60 min, 2 h, 3 h, 4 h , 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose at week 4Population: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
FVC Area Under the Curve 0-24 Hours (AUC0-24h) Response
|
0.003 L
Standard Error 0.044
|
0.104 L
Standard Error 0.044
|
0.087 L
Standard Error 0.044
|
SECONDARY outcome
Timeframe: 10 min prior to first dose (baseline) and -10 min, 30 min, 60 min, 2 h, 3 h, 4 h , 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose at week 4Population: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres/min.
Outcome measures
| Measure |
Placebo
n=90 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
PEF Area Under the Curve 0-24 Hours (AUC0-24h) Response
|
8.589 L/min
Standard Error 6.870
|
38.831 L/min
Standard Error 6.883
|
42.899 L/min
Standard Error 6.871
|
SECONDARY outcome
Timeframe: Baseline and during week 4Population: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. PEF variability is the absolute difference between morning and evening PEF value divided by the mean of these two values, expressed as a percent (weekly means obtained during the last week of each period of randomised treatment will be compared).
Outcome measures
| Measure |
Placebo
n=91 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=88 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
PEF Variability Response (Last Week on Treatment)
|
0.296 Percent
Standard Error 0.711
|
0.619 Percent
Standard Error 0.718
|
0.685 Percent
Standard Error 0.721
|
SECONDARY outcome
Timeframe: Baseline and during week 4Population: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared.
Outcome measures
| Measure |
Placebo
n=91 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=89 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Mean Number of Puffs of Rescue Medication During the Whole Day (Last Week on Treatment, Response Values)
|
-0.841 Puffs
Standard Error 0.189
|
-0.917 Puffs
Standard Error 0.190
|
-1.016 Puffs
Standard Error 0.190
|
SECONDARY outcome
Timeframe: Baseline and during week 4Population: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared.
Outcome measures
| Measure |
Placebo
n=91 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=89 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Mean Number of Puffs of Rescue Medication During Daytime (Last Week on Treatment, Response Values)
|
-0.562 Puffs
Standard Error 0.106
|
-0.564 Puffs
Standard Error 0.106
|
-0.624 Puffs
Standard Error 0.106
|
SECONDARY outcome
Timeframe: Baseline and during week 4Population: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared.
Outcome measures
| Measure |
Placebo
n=91 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=88 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Mean Number of Puffs of Rescue Medication During Nighttime (Last Week on Treatment, Response Values)
|
-0.358 Puffs
Standard Error 0.092
|
-0.419 Puffs
Standard Error 0.093
|
-0.432 Puffs
Standard Error 0.093
|
SECONDARY outcome
Timeframe: Baseline and during week 4Population: FAS
MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Assessed by the patient's electronic diary (eDiary incorporated in the AM2+ device), obtained during the last week of each period of randomised treatment.
Outcome measures
| Measure |
Placebo
n=91 Participants
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5 Bid
n=89 Participants
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=88 Participants
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Mean Number of Night Awakenings During the Last Week on Treatment (Score, Response Values)
|
-0.106 Night awakenings
Standard Error 0.028
|
-0.104 Night awakenings
Standard Error 0.029
|
-0.102 Night awakenings
Standard Error 0.029
|
Adverse Events
Placebo
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Tio R2.5
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Tio R5 qd
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=92 participants at risk
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5
n=90 participants at risk
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 participants at risk
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Vascular disorders
Haemorrhage
|
0.00%
0/92 • 4 weeks + 30 days if in last period
|
0.00%
0/90 • 4 weeks + 30 days if in last period
|
1.1%
1/90 • 4 weeks + 30 days if in last period
|
|
Vascular disorders
Hypertensive crisis
|
1.1%
1/92 • 4 weeks + 30 days if in last period
|
0.00%
0/90 • 4 weeks + 30 days if in last period
|
0.00%
0/90 • 4 weeks + 30 days if in last period
|
|
Vascular disorders
Venous thrombosis limb
|
0.00%
0/92 • 4 weeks + 30 days if in last period
|
0.00%
0/90 • 4 weeks + 30 days if in last period
|
1.1%
1/90 • 4 weeks + 30 days if in last period
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/92 • 4 weeks + 30 days if in last period
|
0.00%
0/90 • 4 weeks + 30 days if in last period
|
1.1%
1/90 • 4 weeks + 30 days if in last period
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/92 • 4 weeks + 30 days if in last period
|
0.00%
0/90 • 4 weeks + 30 days if in last period
|
1.1%
1/90 • 4 weeks + 30 days if in last period
|
Other adverse events
| Measure |
Placebo
n=92 participants at risk
Matching Placebo bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R2.5
n=90 participants at risk
Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
Tio R5 qd
n=90 participants at risk
Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top on maintenance therapy with iCS.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
4.3%
4/92 • 4 weeks + 30 days if in last period
|
7.8%
7/90 • 4 weeks + 30 days if in last period
|
5.6%
5/90 • 4 weeks + 30 days if in last period
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER