CompletedNCT01122680Updated May 16, 2014Results posted

Efficacy and Safety of 3 Doses of Tiotropium Compared to Placebo in Adolescents (12 to 17 Yrs) With Moderate Asthma

A Phase 2 interventional study of Tiotropium bromide and tiotropium bromide in Asthma, sponsored by Boehringer Ingelheim. Completed at 19 sites in 5 countries. Open to participants aged 12 Years to 17 Years. Per ClinicalTrials.gov, last updated 2014-05-16.

Sponsored by Boehringer Ingelheim · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 105
Allocation: Randomized
Ages: 12 Years to 17 Years
Sex: All

Study summary

The primary objective of this trial is to evaluate the efficacy and safety of tiotropium 1.25 mcg (2 actuations of 0.625 mcg), tiotropium 2.5 mcg (2 actuations of 1.25 mcg) and tiotropium 5 mcg (2 actuations of 2.5 mcg) once daily in the evening delivered by the Respimat inhaler in adolescents (12 to 17 yrs) with moderate persistent asthma, compared to placebo and on top of maintenance therapy with an inhaled corticosteroid controller medication. It is a randomised, double-blind, placebo-controlled Phase II trial with incomplete cross-over design. Patients need to be still symptomatic, i. e. not fully controlled with their maintenance treatment.

Conditions studied

Asthma

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In context

Asthma

3,921 studies on the registry are indexed under Asthma; 507 are open to participants now.

This study's enrollment of 105 is above the median of 83 across 2,752 interventional studies indexed under Asthma.

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Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 12 Years to 17 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

All patients and legally accepted caregiver(s) must sign and date an Informed Consent form consistent with Good Clinical Practice (GCP) guidelines of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and local legislation prior to participation in the trial.
Male or female patients between 12 and 17 years of age.
All patients must have at least a 3 months history of asthma and fulfill the diagnostic criteria of moderate persistent asthma, according to the current Global Initiative for Asthma (GINA) guidelines at the time of enrolment into the trial.
All patients must have been on maintenance treatment with inhaled corticosteroids at a stable medium dose for at least 4 weeks before Visit 1.
All patients must be symptomatic (partly controlled) at Visit 1 (screening) and prior to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ) mean score of equal or above 1.5.
All patients must have a pre-bronchodilator FEV1 above 60% and less than or equal 90% of predicted normal at Visit 1. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%.
All patients must have an increase in FEV1 of equal or above 12% and 200 mL 15 min. after 400 mcg salbutamol (albuterol) at Visit 1. If patients in the lower age range (e.g., 12 to 14 year olds) exhibit a very small total lung volume, positive reversibility testing might be based solely on the relative (12%) post-bronchodilator response.
All patients should be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment.
Patients should be able to use the Respimat® inhaler correctly.
Patients must be able to perform all trial related procedures including technically acceptable spirometric manoeuvres, according to American Thoracic Society (ATS) standards and the use of the electronic diary/peak flow meter.

Exclusion criteria

Exclusion criteria:

Patients with a significant disease other than asthma.
Patients with a history of congenital or acquired heart disease, and/or have been hospitalised for cardiac syncope or failure during the past year.
Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention (e. g. pacemaker implantation) or a change in drug therapy within the past year.
Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.
Patients with lung diseases other than asthma, e.g. cystic fibrosis (CF). In case of ex-premature infants, a history of significant bronchopulmonary dysplasia (BPD) will be regarded as exclusion criterion
Patients with significant alcohol or drug abuse within the past two years.
Patients with known hypersensitivity to anticholinergic drugs, benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA) or any other components of the tiotropium inhalation solution.
Pregnant or nursing adolescent female patients, including female patients with a positive Beta HCG (serum pregnancy) testing at screening (visit 1).
Sexually active female patients of child-bearing potential not using a highly effective method of birth control.
Patients with a known narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated.
Patients with renal impairment, as defined by a creatinine clearance less than 50 mL/min/1.73 m2 body surface area (BSA) as calculated by Schwartz Formula.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Double
Enrollment: 105 participants (actual)

Study arms

Experimental
Treatment A
patients inhale 2 puffs (dose of 1.25 mcg) once daily in the evening via Respimat inhaler
Drug: Tiotropium bromide
Experimental
Treatment C
patients inhale 2 puffs (dose of 5 mcg) once daily in the evening via Respimat inhaler
Drug: tiotropium bromide
Placebo comparator
Placebo
patients inhale 2 puffs of placebo matching tiotropium once daily in the evening via Respimat inhaler
Drug: Placebo
Experimental
Treatment B
patients inhale 2 puffs (dose of 2.5 mcg) once daily in the evening via Respimat inhaler
Drug: tiotropium bromide

Interventions

DrugTiotropium bromide
inhalation solution, dose of 1.25 mcg (2 puffs of 0.625 mcg)
Drugtiotropium bromide
inhalation solution, dose of 2.5 mcg (2 puffs of 1.25 mcg)
Drugtiotropium bromide
inhalation solution, dose of 5 mcg (2 puffs of 2.5 mcg)
DrugPlacebo
placebo inhalation solution

What researchers measure

Primary outcomes

Forced Expiratory Volume (FEV1) Peak (0-3h) Response
The FEV1 peak (0-3h) response is determined at the end of the 4 week treatment period. This is the difference between the maximum FEV1 measured within the first 3 hours post dosing and the FEV1 baseline measurement. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: Baseline and 4 weeks

Secondary outcomes

Trough FEV1 Response
The trough FEV1 is defined as the pre-dose FEV1 measured just prior to the last administration of randomised treatment. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: Baseline and 4 weeks
FEV1 Area Under the Curve From 0 to 3 h (AUC0-3h) Response
FEV1 (AUC0-3h) will be calculated as the area under the curve from 0 to 3hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: Baseline and 4 weeks
FEV1 Individual Measurements Response at Each Time-point
Individual FEV1 measurements at each time-point ("personal best"). Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
Forced Vital Capacity (FVC) Peak (0-3h) Response
The FVC peak (0-3h) response is determined at the end of the 4 week treatment period. This is the difference between the maximum FVC measured within the first 3 hours post dosing and the FVC baseline measurement. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: Baseline and 4 weeks
FVC Trough Response
The trough FVC response is defined as the pre-dose FVC measured just prior to the last administration of randomised treatment. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: Baseline and 4 weeks
FVC Area Under the Curve From 0 to 3 h (AUC0-3h) Response
FVC (AUC0-3h) will be calculated as the area under the curve from 0 to 3hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: Baseline and 4 weeks
FVC Individual Measurements at Each Time-point
Individual FVC measurements at each time-point ("personal best"). Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
Forced Expiratory Flow (FEF) 25-75% Individual Measurements Response at Each Time Point
FEF 25-75% is the mean forced expiratory flow between 25% and 75% of the FVC determined at the end of the 4-week treatment period. This is often referred to as the maximum midexpiratory flow. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
Mean Morning Peak Expiratory Flow (PEF) Response
Mean morning PEF assessed by patients at home. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: Baseline and 4 weeks
Mean Evening PEF Response
Mean evening PEF assessed by patients at home. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: Baseline and 4 weeks
Change From Baseline in the Number of Puffs of Rescue Medication Per Day
Mean number of inhalations (puffs) of unscheduled rescue salbutamol therapy during whole day. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: Baseline and 4 weeks
Control of Asthma as Assessed by Asthma Control Questionnaire (ACQ)
ACQ is a questionnaire consisting of a seven point Likert scale ranging from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The scale describes the frequency and severity of asthma symptoms. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: 4 weeks
Change From Baseline in Mean Number of Nighttime Awakenings
Mean number of nighttime awakenings due to asthma symptoms as assessed by patients eDiary incorporated in the AM3® device. Analysis adjusted for treatment, period, patient and baseline using a mixed model.
Time frame: Baseline and last week of treatment (week 4)

Results

Posted Jun 27, 2012

Participant flow

In this incomplete crossover design, 105 patients were randomised to one of four sequences (in general terms, ABC, BDA, CAD or DCB). Whilst there were 4 possible treatments, A, B, C and D, each patient would receive a maximum of 3 different treatments. Hence, approximately 75 patients would receive each of A, B, C and D at any timepoint.

Period 1 (4 Weeks)

Participant flow — Period 1 (4 Weeks)
Milestone	Tio R5/Placebo/Tio R1.25	Tio R1.25/Tio R5/Tio R2.5	Placebo/Tio R2.5/Tio R5	Tio R2.5/Tio R1.25/Placebo
Started	29	26	26	24
Completed	26	25	26	24
Not completed	3	1	0	0
Withdrew: Adverse event	1	0	0	0
Withdrew: Protocol violation	1	0	0	0
Withdrew: Other	1	1	0	0

Period 2 (4 Weeks)

Participant flow — Period 2 (4 Weeks)
Milestone	Tio R5/Placebo/Tio R1.25	Tio R1.25/Tio R5/Tio R2.5	Placebo/Tio R2.5/Tio R5	Tio R2.5/Tio R1.25/Placebo
Started	26	25	26	24
Completed	25	25	26	23
Not completed	1	0	0	1
Withdrew: Protocol violation	0	0	0	1
Withdrew: Other	1	0	0	0

Period 3 (4 Weeks)

Participant flow — Period 3 (4 Weeks)
Milestone	Tio R5/Placebo/Tio R1.25	Tio R1.25/Tio R5/Tio R2.5	Placebo/Tio R2.5/Tio R5	Tio R2.5/Tio R1.25/Placebo
Started	25	25	26	23
Completed	24	24	26	23
Not completed	1	1	0	0
Withdrew: Adverse event	1	0	0	0
Withdrew: Withdrawal by subject	0	1	0	0

Outcome measures

PrimaryForced Expiratory Volume (FEV1) Peak (0-3h) Response

The FEV1 peak (0-3h) response is determined at the end of the 4 week treatment period. This is the difference between the maximum FEV1 measured within the first 3 hours post dosing and the FEV1 baseline measurement. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: Baseline and 4 weeks
Reported as:: Least squares mean · Litre

Forced Expiratory Volume (FEV1) Peak (0-3h) Response
Litre	Placebo	Tio R1.25	Tio R2.5	Tio R5
Forced Expiratory Volume (FEV1) Peak (0-3h) Response	0.489 ± 0.047	0.556 ± 0.047	0.546 ± 0.047	0.602 ± 0.046

Statistical analysis

Placebo vs Tio R5 · Mixed model repeated measures (MMRM) · p = 0.0043 (First step of closed testing procedure, where the active treatments are compared to placebo. If this statisical test significant at the 0.05 alpha level then proceed to comparison of the next lower dose to placebo.) · Mean difference (final values): 0.113 · 95% CI 0.036 to 0.190This MMRM model includes treatment, period and baseline as fixed effects, and patient as a random effect.
Placebo vs Tio R2.5 · Mixed effect repeated measures (MMRM) · p = 0.1484 (Second step of closed testing procedure. If this statisical test significant at the 0.05 alpha level then proceed to comparison of the next lower dose to placebo.) · Mean difference (final values): 0.057 · 95% CI -0.021 to 0.135This MMRM model includes treatment, period and baseline as fixed effects, and patient as a random effect.
Placebo vs Tio R1.25 · Mixed effect repeated measures (MMRM) · p = 0.0664 (This test is considered as descriptive.) · Mean difference (final values): 0.067 · 95% CI -0.005 to 0.138This MMRM model includes treatment, period and baseline as fixed effects, and patient as a random effect.
Tio R1.25 vs Tio R5 · Mixed effect repeated measures (MMRM) · Mean difference (final values): 0.046 · 95% CI -0.031 to 0.124This MMRM model includes treatment, period and baseline as fixed effects, and patient as a random effect.
Tio R2.5 vs Tio R5 · Mixed effect repeated measures (MMRM) · Mean difference (final values): 0.056 · 95% CI -0.014 to 0.126This MMRM model includes treatment, period and baseline as fixed effects, and patient as a random effect.
Tio R1.25 vs Tio R2.5 · Mixed effect repeated measures (MMRM) · Mean difference (final values): -0.010 · 95% CI -0.088 to 0.069This MMRM model includes treatment, period and baseline as fixed effects, and patient as a random effect.

SecondaryTrough FEV1 Response

The trough FEV1 is defined as the pre-dose FEV1 measured just prior to the last administration of randomised treatment. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: Baseline and 4 weeks
Reported as:: Least squares mean · Litre

Trough FEV1 Response
Litre	Placebo	Tio R1.25	Tio R2.5	Tio R5
Trough FEV1 Response	0.292 ± 0.045	0.384 ± 0.045	0.353 ± 0.045	0.442 ± 0.045

SecondaryFEV1 Area Under the Curve From 0 to 3 h (AUC0-3h) Response

FEV1 (AUC0-3h) will be calculated as the area under the curve from 0 to 3hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: Baseline and 4 weeks
Reported as:: Least squares mean · Litre

FEV1 Area Under the Curve From 0 to 3 h (AUC0-3h) Response
Litre	Placebo	Tio R1.25	Tio R2.5	Tio R5
FEV1 Area Under the Curve From 0 to 3 h (AUC0-3h) Response	0.363 ± 0.045	0.455 ± 0.045	0.434 ± 0.045	0.497 ± 0.045

SecondaryFEV1 Individual Measurements Response at Each Time-point

Individual FEV1 measurements at each time-point ("personal best"). Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
Reported as:: Least squares mean · Litre

FEV1 Individual Measurements Response at Each Time-point
Litre	Placebo	Tio R1.25	Tio R2.5	Tio R5
Timepoint -0:10 hr response	0.292 ± 0.045	0.384 ± 0.045	0.353 ± 0.045	0.442 ± 0.045
Timepoint 0:30 hr response	0.337 ± 0.047	0.456 ± 0.047	0.407 ± 0.047	0.486 ± 0.047
Timepoint 1:00 hr response	0.353 ± 0.048	0.456 ± 0.048	0.416 ± 0.048	0.505 ± 0.047
Timepoint 2:00 hr response	0.394 ± 0.047	0.467 ± 0.048	0.453 ± 0.047	0.501 ± 0.047
Timepoint 3:00 hr response	0.396 ± 0.048	0.467 ± 0.048	0.489 ± 0.048	0.497 ± 0.047

SecondaryForced Vital Capacity (FVC) Peak (0-3h) Response

The FVC peak (0-3h) response is determined at the end of the 4 week treatment period. This is the difference between the maximum FVC measured within the first 3 hours post dosing and the FVC baseline measurement. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: Baseline and 4 weeks
Reported as:: Least squares mean · Litre

Forced Vital Capacity (FVC) Peak (0-3h) Response
Litre	Placebo	Tio R1.25	Tio R2.5	Tio R5
Forced Vital Capacity (FVC) Peak (0-3h) Response	0.546 ± 0.049	0.554 ± 0.049	0.554 ± 0.048	0.548 ± 0.048

SecondaryFVC Trough Response

The trough FVC response is defined as the pre-dose FVC measured just prior to the last administration of randomised treatment. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: Baseline and 4 weeks
Reported as:: Least squares mean · Litre

FVC Trough Response
Litre	Placebo	Tio R1.25	Tio R2.5	Tio R5
FVC Trough Response	0.357 ± 0.047	0.375 ± 0.047	0.381 ± 0.047	0.400 ± 0.047

SecondaryFVC Area Under the Curve From 0 to 3 h (AUC0-3h) Response

FVC (AUC0-3h) will be calculated as the area under the curve from 0 to 3hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: Baseline and 4 weeks
Reported as:: Least squares mean · Litre

FVC Area Under the Curve From 0 to 3 h (AUC0-3h) Response
Litre	Placebo	Tio R1.25	Tio R2.5	Tio R5
FVC Area Under the Curve From 0 to 3 h (AUC0-3h) Response	0.413 ± 0.046	0.441 ± 0.046	0.417 ± 0.045	0.429 ± 0.045

SecondaryFVC Individual Measurements at Each Time-point

Individual FVC measurements at each time-point ("personal best"). Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
Reported as:: Least squares mean · Litre

FVC Individual Measurements at Each Time-point
Litre	Placebo	Tio R1.25	Tio R2.5	Tio R5
Timepoint -0:10 hr response	0.357 ± 0.047	0.375 ± 0.047	0.381 ± 0.047	0.400 ± 0.047
Timepoint 0:30 hr response	0.397 ± 0.049	0.434 ± 0.049	0.394 ± 0.049	0.409 ± 0.049
Timepoint 1:00 hr response	0.417 ± 0.049	0.443 ± 0.050	0.387 ± 0.049	0.448 ± 0.049
Timepoint 2:00 hr response	0.429 ± 0.048	0.438 ± 0.048	0.444 ± 0.048	0.423 ± 0.048
Timepoint 3:00 hr response	0.430 ± 0.048	0.461 ± 0.048	0.454 ± 0.048	0.456 ± 0.048

SecondaryForced Expiratory Flow (FEF) 25-75% Individual Measurements Response at Each Time Point

FEF 25-75% is the mean forced expiratory flow between 25% and 75% of the FVC determined at the end of the 4-week treatment period. This is often referred to as the maximum midexpiratory flow. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: Baseline and 4 weeks (10 min pre-dose, 30 min, 1,2,3 hours post-dose)
Reported as:: Least squares mean · Litre

Forced Expiratory Flow (FEF) 25-75% Individual Measurements Response at Each Time Point
Litre	Placebo	Tio R1.25	Tio R2.5	Tio R5
Timepoint -0:10 hr response	0.242 ± 0.081	0.533 ± 0.082	0.380 ± 0.082	0.566 ± 0.080
Timepoint 0:30 hr response	0.268 ± 0.083	0.643 ± 0.084	0.513 ± 0.084	0.647 ± 0.082
Timepoint 1:00 hr response	0.321 ± 0.087	0.655 ± 0.087	0.569 ± 0.087	0.641 ± 0.086
Timepoint 2:00 hr response	0.357 ± 0.088	0.678 ± 0.089	0.607 ± 0.089	0.622 ± 0.087
Timepoint 3:00 hr response	0.329 ± 0.083	0.662 ± 0.084	0.616 ± 0.084	0.620 ± 0.083

SecondaryMean Morning Peak Expiratory Flow (PEF) Response

Mean morning PEF assessed by patients at home. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: Baseline and 4 weeks
Reported as:: Least squares mean · Litre/min

Mean Morning Peak Expiratory Flow (PEF) Response
Litre/min	Placebo	Tio R1.25	Tio R2.5	Tio R5
Mean Morning Peak Expiratory Flow (PEF) Response	7.267 ± 6.152	18.613 ± 6.118	23.185 ± 6.146	20.491 ± 6.031

SecondaryMean Evening PEF Response

Mean evening PEF assessed by patients at home. Response was defined as the change from baseline. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: Baseline and 4 weeks
Reported as:: Least squares mean · Litre/min

Mean Evening PEF Response
Litre/min	Placebo	Tio R1.25	Tio R2.5	Tio R5
Mean Evening PEF Response	-0.552 ± 6.098	5.985 ± 6.089	18.971 ± 6.043	16.565 ± 5.970

SecondaryChange From Baseline in the Number of Puffs of Rescue Medication Per Day

Mean number of inhalations (puffs) of unscheduled rescue salbutamol therapy during whole day. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: Baseline and 4 weeks
Reported as:: Least squares mean · Puffs/day

Change From Baseline in the Number of Puffs of Rescue Medication Per Day
Puffs/day	Placebo	Tio R1.25	Tio R2.5	Tio R5
Change From Baseline in the Number of Puffs of Rescue Medication Per Day	-0.412 ± 0.155	-0.635 ± 0.156	-0.521 ± 0.154	-0.528 ± 0.151

SecondaryControl of Asthma as Assessed by Asthma Control Questionnaire (ACQ)

ACQ is a questionnaire consisting of a seven point Likert scale ranging from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The scale describes the frequency and severity of asthma symptoms. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: 4 weeks
Reported as:: Least squares mean · Units on a scale

Control of Asthma as Assessed by Asthma Control Questionnaire (ACQ)
Units on a scale	Placebo	Tio R1.25	Tio R2.5	Tio R5
Control of Asthma as Assessed by Asthma Control Questionnaire (ACQ)	1.371 ± 0.078	1.189 ± 0.079	1.366 ± 0.078	1.287 ± 0.078

SecondaryChange From Baseline in Mean Number of Nighttime Awakenings

Mean number of nighttime awakenings due to asthma symptoms as assessed by patients eDiary incorporated in the AM3® device. Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Time frame:: Baseline and last week of treatment (week 4)
Reported as:: Least squares mean · Night awakenings per week

Change From Baseline in Mean Number of Nighttime Awakenings
Night awakenings per week	Placebo	Tio R1.25	Tio R2.5	Tio R5
Change From Baseline in Mean Number of Nighttime Awakenings	-0.086 ± 0.030	-0.027 ± 0.030	-0.074 ± 0.030	-0.066 ± 0.029

Adverse events

Collected over 4 weeks + 30 days if in last period. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Placebo	—	0/75 (0%)	0/75 (0%)
Tio R1.25	—	1/75 (1.3%)	0/75 (0%)
Tio R2.5	—	0/75 (0%)	0/75 (0%)
Tio R5	—	1/80 (1.3%)	0/80 (0%)

Most frequent serious events

Most frequent serious events
Event	Placebo	Tio R1.25	Tio R2.5	Tio R5
H1N1 influenzaInfections and infestations	0/75	1/75	0/75	0/80
Pneumonia mycoplasmalInfections and infestations	0/75	1/75	0/75	0/80
AsthmaRespiratory, thoracic and mediastinal disorders	0/75	1/75	0/75	0/80
PresyncopeNervous system disorders	0/75	0/75	0/75	1/80

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	Total.
Mean	14.0 ± 1.5

Sex: Female, Male
Sex: Female, Male(Participants)	Total.
Female	38
Male	67

Forced expiratory volume in 1s (FEV1)
Forced expiratory volume in 1s (FEV1)(Litre)	Total.
Mean	2.742 ± 0.697

Study locations

19 sites

205.424.01002 Boehringer Ingelheim Investigational Site
Denver, Colorado, United States
205.424.01006 Boehringer Ingelheim Investigational Site
Columbia, Missouri, United States
205.424.01007 Boehringer Ingelheim Investigational Site
Warrensburg, Missouri, United States
205.424.01004 Boehringer Ingelheim Investigational Site
Boys Town, Nebraska, United States
205.424.01001 Boehringer Ingelheim Investigational Site
Canton, Ohio, United States
205.424.49007 Boehringer Ingelheim Investigational Site
Koblenz, Germany
205.424.49004 Boehringer Ingelheim Investigational Site
Rosenheim, Germany
205.424.49002 Boehringer Ingelheim Investigational Site
Wesel, Germany
205.424.37104 Boehringer Ingelheim Investigational Site
Balvi, Latvia
205.424.37103 Boehringer Ingelheim Investigational Site
Daugavpils, Latvia
205.424.37105 Boehringer Ingelheim Investigational Site
Rezekne, Latvia
205.424.37101 Boehringer Ingelheim Investigational Site
Riga, Latvia
205.424.37102 Boehringer Ingelheim Investigational Site
Riga, Latvia
205.424.37001 Boehringer Ingelheim Investigational Site
Vilnius, Lithuania
205.424.37003 Boehringer Ingelheim Investigational Site
Vilnius, Lithuania
205.424.37004 Boehringer Ingelheim Investigational Site
Vilnius, Lithuania
205.424.38604 Boehringer Ingelheim Investigational Site
Kamnik, Slovenia
205.424.38605 Boehringer Ingelheim Investigational Site
Ljubljana, Slovenia
205.424.38602 Boehringer Ingelheim Investigational Site
Maribor, Slovenia

References and documents

Publications

Vogelberg C, Engel M, Moroni-Zentgraf P, Leonaviciute-Klimantaviciene M, Sigmund R, Downie J, Nething K, Vevere V, Vandewalker M. Tiotropium in asthmatic adolescents symptomatic despite inhaled corticosteroids: a randomised dose-ranging study. Respir Med. 2014 Sep;108(9):1268-76. doi: 10.1016/j.rmed.2014.06.011. Epub 2014 Jul 17. PubMed 25081651 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 16, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01122680
Lead sponsor: Boehringer Ingelheim
Collaborators: Pfizer
Responsible party: Sponsor
First posted: May 13, 2010
Start date: May 2010
Primary completion: Apr 2011
Results posted: Jun 27, 2012
Last update: May 16, 2014

Study contacts

Boehringer Ingelheim

study chair · Boehringer Ingelheim

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Not currently enrolling

This study is completed, as verified in Jul 2012. You cannot join it, but the record below documents what was studied.

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