Trial Outcomes & Findings for A Study to Evaluate Efficacy and Safety of Tiotropium in Children 6 to 11 Years Old With Moderate Asthma (NCT NCT01383499)

NCT ID: NCT01383499

Last Updated: 2015-04-15

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 101 participants
• Primary outcome timeframe: Baseline and 4 weeks
• Results posted on: 2015-04-15

Participant Flow

Participant milestones

Measure	Tio R5/Placebo/Tio R1.25 Patients treated with Tiotropium 5 mcg in Period 1, with Placebo in Period 2 and with Tiotropium 1.25 mcg in Period 3. All products were administered once daily (QD) in the evening, delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. No washouts (off treatment periods) between treatments.	Tio R1.25/Tio R5/Tio R2.5 Patients treated with Tiotropium 1.25 mcg in Period 1, with Tiotropium 5 mcg in Period 2 and with Tiotropium 2.5 mcg in Period 3. All products were administered once daily (QD) in the evening, delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. No washouts (off treatment periods) between treatments.	Placebo/Tio R2.5/Tio R5 Patients treated with Placebo in Period 1, with Tiotropium 2.5 mcg in Period 2 and with Tiotropium 5 mcg in Period 3. All products were administered once daily (QD) in the evening, delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. No washouts (off treatment periods) between treatments.	Tio R2.5/Tio R1.25/Placebo Patients treated with Tiotropium 2.5 mcg in Period 1, with Tiotropium 1.25 mcg in Period 2 and with Placebo in Period 3. All products were administered once daily (QD) in the evening, delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. No washouts (off treatment periods) between treatments.
Period 1 (4 Weeks) STARTED	27	24	25	25
Period 1 (4 Weeks) COMPLETED	26	24	25	25
Period 1 (4 Weeks) NOT COMPLETED	1	0	0	0
Period 2 (4 Weeks) STARTED	26	24	25	25
Period 2 (4 Weeks) COMPLETED	26	24	25	25
Period 2 (4 Weeks) NOT COMPLETED	0	0	0	0
Period 3 (4 Weeks) STARTED	26	24	25	25
Period 3 (4 Weeks) COMPLETED	26	24	25	25
Period 3 (4 Weeks) NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Measure	Tio R5/Placebo/Tio R1.25 Patients treated with Tiotropium 5 mcg in Period 1, with Placebo in Period 2 and with Tiotropium 1.25 mcg in Period 3. All products were administered once daily (QD) in the evening, delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. No washouts (off treatment periods) between treatments.	Tio R1.25/Tio R5/Tio R2.5 Patients treated with Tiotropium 1.25 mcg in Period 1, with Tiotropium 5 mcg in Period 2 and with Tiotropium 2.5 mcg in Period 3. All products were administered once daily (QD) in the evening, delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. No washouts (off treatment periods) between treatments.	Placebo/Tio R2.5/Tio R5 Patients treated with Placebo in Period 1, with Tiotropium 2.5 mcg in Period 2 and with Tiotropium 5 mcg in Period 3. All products were administered once daily (QD) in the evening, delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. No washouts (off treatment periods) between treatments.	Tio R2.5/Tio R1.25/Placebo Patients treated with Tiotropium 2.5 mcg in Period 1, with Tiotropium 1.25 mcg in Period 2 and with Placebo in Period 3. All products were administered once daily (QD) in the evening, delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication. No washouts (off treatment periods) between treatments.
Period 1 (4 Weeks) Withdrawal by Subject	1	0	0	0

Baseline Characteristics

A Study to Evaluate Efficacy and Safety of Tiotropium in Children 6 to 11 Years Old With Moderate Asthma

Baseline characteristics by cohort

Measure	Total. n=101 Participants Total number of patients randomised and treated at all in the study.
Age, Continuous	8.8 years STANDARD_DEVIATION 1.7 • n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants
Sex: Female, Male Male	69 Participants n=5 Participants
Forced expiratory volume in 1s (FEV1)	1.640 Litre STANDARD_DEVIATION 0.386 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 4 weeks

Population: The Full analysis set (FAS) is defined as patients randomised, treated, with baseline data and at least one on-treatment efficacy measurement after 4 weeks on treatment within a period.

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.

Outcome measures

Measure	Placebo n=76 Participants Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R1.25 n=75 Participants Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R2.5 n=74 Participants Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R5 n=75 Participants Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Forced Expiratory Volume (FEV1) Peak (0-3h) Response	0.185 Litre Standard Error 0.025	0.261 Litre Standard Error 0.026	0.290 Litre Standard Error 0.026	0.272 Litre Standard Error 0.026

SECONDARY outcome

Timeframe: Baseline and 4 weeks

Population: FAS with at least one on-treatment value.

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.

Outcome measures

Measure	Placebo n=76 Participants Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R1.25 n=75 Participants Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R2.5 n=74 Participants Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R5 n=75 Participants Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Trough FEV1 Response	0.085 Litre Standard Error 0.026	0.160 Litre Standard Error 0.026	0.190 Litre Standard Error 0.026	0.183 Litre Standard Error 0.026

SECONDARY outcome

Timeframe: Baseline and 4 weeks

Population: FAS with at least one on-treatment value.

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.

Outcome measures

Measure	Placebo n=76 Participants Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R1.25 n=75 Participants Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R2.5 n=74 Participants Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R5 n=75 Participants Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Forced Vital Capacity (FVC) Peak (0-3h) Response	0.202 Litre Standard Error 0.029	0.208 Litre Standard Error 0.029	0.253 Litre Standard Error 0.029	0.239 Litre Standard Error 0.029

SECONDARY outcome

Timeframe: Baseline and 4 weeks

Population: FAS with at least one on-treatment value.

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.

Outcome measures

Measure	Placebo n=76 Participants Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R1.25 n=75 Participants Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R2.5 n=74 Participants Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R5 n=75 Participants Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
FVC Trough Response	0.060 Litre Standard Error 0.030	0.109 Litre Standard Error 0.030	0.107 Litre Standard Error 0.030	0.113 Litre Standard Error 0.030

SECONDARY outcome

Timeframe: Baseline and 4 weeks

Population: FAS with at least one on-treatment value.

FEV1 (AUC0-3h) will be calculated as the area under the curve from 0 to 3 hours 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.

Outcome measures

Measure	Placebo n=76 Participants Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R1.25 n=75 Participants Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R2.5 n=74 Participants Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R5 n=75 Participants Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
FEV1 Area Under the Curve From 0 to 3 h (AUC0-3h) Response	0.110 Litre Standard Error 0.025	0.178 Litre Standard Error 0.025	0.208 Litre Standard Error 0.025	0.201 Litre Standard Error 0.025

SECONDARY outcome

Timeframe: Baseline and 4 weeks

Population: FAS with at least one on-treatment value.

FVC (AUC0-3h) will be calculated as the area under the curve from 0 to 3 hours 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.

Outcome measures

Measure	Placebo n=76 Participants Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R1.25 n=75 Participants Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R2.5 n=74 Participants Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R5 n=75 Participants Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
FVC Area Under the Curve From 0 to 3 h (AUC0-3h) Response	0.087 Litre Standard Error 0.027	0.097 Litre Standard Error 0.027	0.134 Litre Standard Error 0.027	0.110 Litre Standard Error 0.027

SECONDARY outcome

Timeframe: Baseline and 4 weeks

Population: FAS with at least one on-treatment value. For outcome measures obtained by AM3 device one patient in the "TioR2.5" group had no on-treatment data.

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.

Outcome measures

Measure	Placebo n=76 Participants Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R1.25 n=75 Participants Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R2.5 n=73 Participants Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R5 n=75 Participants Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Mean Morning Peak Expiratory Flow (PEF) Response	-0.928 Litre/min Standard Error 5.103	14.474 Litre/min Standard Error 5.127	12.045 Litre/min Standard Error 5.177	15.439 Litre/min Standard Error 5.127

SECONDARY outcome

Timeframe: Baseline and 4 weeks

Population: FAS with at least one on-treatment value. For outcome measures obtained by AM3 device one patient in the "TioR2.5" group had no on-treatment data.

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.

Outcome measures

Measure	Placebo n=76 Participants Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R1.25 n=75 Participants Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R2.5 n=73 Participants Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R5 n=75 Participants Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Mean Evening PEF Response	-0.568 Litre/min Standard Error 5.081	9.910 Litre/min Standard Error 5.103	6.991 Litre/min Standard Error 5.150	15.910 Litre/min Standard Error 5.103

SECONDARY outcome

Timeframe: Baseline and 4 weeks

Population: FAS with at least one on-treatment value. For outcome measures obtained by AM3 device one patient in the "TioR2.5" group had no on-treatment data.

Mean number of inhalations (puffs) of unscheduled rescue salbutamol therapy during whole day (24 h, daytime and night-time use). Analysis adjusted for treatment, period, patient and baseline using a mixed model.

Outcome measures

Measure	Placebo n=76 Participants Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R1.25 n=75 Participants Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R2.5 n=73 Participants Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R5 n=75 Participants Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Change From Baseline in the Number of Puffs of Rescue Medication Per Period (24 h, Daytime and Night-time Use) 24 h	-0.664 Puffs Standard Error 0.105	-0.691 Puffs Standard Error 0.105	-0.314 Puffs Standard Error 0.106	-0.550 Puffs Standard Error 0.105
Change From Baseline in the Number of Puffs of Rescue Medication Per Period (24 h, Daytime and Night-time Use) Daytime	-0.338 Puffs Standard Error 0.061	-0.348 Puffs Standard Error 0.062	-0.130 Puffs Standard Error 0.062	-0.258 Puffs Standard Error 0.062
Change From Baseline in the Number of Puffs of Rescue Medication Per Period (24 h, Daytime and Night-time Use) Night-time	-0.354 Puffs Standard Error 0.060	-0.355 Puffs Standard Error 0.060	-0.180 Puffs Standard Error 0.060	-0.272 Puffs Standard Error 0.060

SECONDARY outcome

Timeframe: 4 weeks

Population: FAS with at least one on-treatment value.

ACQ is a questionnaire consisting of 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.

Outcome measures

Measure	Placebo n=76 Participants Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R1.25 n=75 Participants Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R2.5 n=74 Participants Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R5 n=75 Participants Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Control of Asthma as Assessed by Asthma Control Questionnaire (ACQ)	0.966 Score Standard Error 0.066	0.909 Score Standard Error 0.066	0.846 Score Standard Error 0.066	0.879 Score Standard Error 0.066

SECONDARY outcome

Timeframe: Baseline and last week of treatment (week 4)

Population: FAS with at least one on-treatment value. For outcome measures obtained by AM3 device one patient in the "TioR2.5" group had no on-treatment data.

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. The scores for this question used the following scale where: 1='Did not wake up', 2='Woke up once', 3='Woke up 2-5 times', 4='Woke up more than 5 times' and 5='Was awake all night'.

Outcome measures

Measure	Placebo n=76 Participants Placebo once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R1.25 n=75 Participants Tiotropium 1.25 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R2.5 n=73 Participants Tiotropium 2.5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.	Tio R5 n=75 Participants Tiotropium 5 microgram once daily (QD) in the evening delivered by the Respimat® inhaler, on top on maintenance therapy with an inhaled corticosteroid controller medication.
Change From Baseline in Mean Number of Nighttime Awakenings	-0.135 scores on a scale Standard Error 0.034	-0.104 scores on a scale Standard Error 0.034	-0.080 scores on a scale Standard Error 0.034	-0.099 scores on a scale Standard Error 0.034

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Tio R1.25

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Tio R2.5

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Tio R5

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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