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Evaluation of Tiotropium 2.5 and 5 mcg Once Daily Delivered Via the Respimat® Inhaler Compared to Placebo in 1 to 5 Year Old Patients With Persistent Asthma

Phase 2
Completed
Conditions
Asthma
Interventions
Drug: tiotropium-bromide
Drug: placebo
Registration Number
NCT01634113
Lead Sponsor
Boehringer Ingelheim
Brief Summary

The primary objective of this trial is to evaluate the safety and efficacy of two doses of tiotropium inhalation solution delivered via the Respimat® inhaler once daily in the afternoon in patients (1 to 5 years old) with persistent asthma on top of inhaled corticosteroid (ICS) treatment.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
102
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
tiotropium low dosetiotropium-bromideOnce daily, delivered with Respimat® inhaler
placeboplaceboOnce daily, delivered with Respimat® inhaler
tiotropium high dosetiotropium-bromideOnce daily, delivered with Respimat® inhaler
Primary Outcome Measures
NameTimeMethod
FEV1 Peak (0-3h) Change From Baseline10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12

Change from baseline in peak Forced expiratory volume in 1 second within the first 3 hours post dosing (FEV1 peak (0-3h)) measured at week 12

Weekly Mean Combined Daytime Asthma Symptom ScoreBaseline and 12 weeks

Change from baseline in the weekly mean combined daytime asthma symptom score as assessed by the Paediatric Asthma Caregivers Diary (PACD) in the last week of the 12 week treatment period.

The PACD is a diary designed to evaluate daily asthma symptoms in children aged 2-5 years. The diary consists of three questions to be answered each morning, when the child wakes up, and seven questions to be answered each evening, right after the child goes to bed for the night. A week was defined as 7 days.

The combined daytime score is the average of scores from questions 4 - 7 in the diary which are questions regarding severity of cough, wheezing, trouble breathing and interference with activities, scores for each question range from 0 (best) to 5 (worst). The week 12 weekly mean is the mean of the responses for each day averaged over the 7 days in week 12, so combined daytime asthma symptom scores also range from 0 (best) to 5 (worst).

The measured values presented are adjusted means.

Secondary Outcome Measures
NameTimeMethod
Trough FEV1 Change From BaselineBaseline and 12 weeks

Change from baseline in Trough (pre-dose) Forced expiratory volume in 1 second (FEV1) measured at week 12.

Individual FEV1 MeasurementsBaseline and 12 weeks

Change from baseline in individual FEV1 measurements at each timepoint after 12 weeks

Individual FVC MeasurementsBaseline and 12 weeks

Change from baseline in individual FVC measurements at each timepoint after 12 weeks

Weekly Mean Overnight Asthma Symptom Score ResponseBaseline and 12 weeks

Change from baseline in the weekly mean overnight asthma symptom score response as assessed by the PACD in the last week of the 12 week treatment period.

The overnight score is the score from the following question in the PACD, "How much did your child cough last night after your child was put to bed for the night until he/she awoke this morning?". This endpoint was determined only for patients with 2 or more nights with symptoms per week during the baseline period. In this case, the baseline period is the 7 days used to derive the baseline value. A patient has a night with symptoms if the question was answered with scores 1, 2, 3, 4 or 5 or the patient received β-Agonist at least one time since he/she went to bed. A week was defined as 7 days.

Scores range from 0 (best) to 4 (worst), a value of 5 indicates severity of symptoms is unknown.

The measured values presented are adjusted means

Weekly Mean Nighttime Awakenings Due to Asthma SymptomsBaseline and 12 weeks

Change from baseline in the weekly mean nighttime awakenings due to asthma symptoms as assessed by the PACD, in the last week of the 12 week treatment period.

The weekly mean was calculated as the average of the weekly scores for the question "Did your child wake up during the night due to his/her asthma?" The question was answered on a 5-point verbal rating scale, with scores ranging from 1 (did not wake up) to 5 (was awake all night). A week was defined as 7 days.

The measured values presented are adjusted means

FEV1 AUC (0-3h) Change From Baseline10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12

Change from baseline of area under the curve (AUC) from 0 to 3 h for FEV1 (FEV1 AUC 0-3h) after 12 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h).

Trough FVC Change From BaselineBaseline and 12 weeks

Change from baseline of trough (pre-dose) forced vital capacity (FVC) measured 10 min before the administration of trial medication after 12 weeks of treatment.

FVC AUC (0-3h) Change From Baseline10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12

Change from baseline of area under the curve (AUC) from 0 to 3 h for FVC (FVC AUC0-3h) after 12 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h).

Weekly Percentage of Days Without Asthma Symptoms12 weeks

Weekly Percentage of days without asthma symptoms at week 12.

A day without asthma symptoms was defined as a day during which the patient experienced no asthma symptoms, did not use rescue medication (salbutamol/albuterol) and had no asthma exacerbation/worsening requiring systemic corticosteroids, or unscheduled visits to a doctor's office, emergency department, or hospital. A week was defined as 7 days.

The measured values presented are adjusted means

Weekly Percentage of Days With Use of Salbutamol (Albuterol) Rescue Medication12 weeks

Weekly percentage of days with use of salbutamol (albuterol) rescue medication at week 12. A week was defined as 7 days.

FVC Peak (0-3h) Change From Baseline10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12

Change from baseline in maximum forced vital capacity (FVC) measured within the first 3 hours after administration of trial medication (FVC peak (0-3h)) after 12 weeks of treatment.

Trial Locations

Locations (33)

205.443.12003 Boehringer Ingelheim Investigational Site

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Columbia, Missouri, United States

205.443.05001 Boehringer Ingelheim Investigational Site

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Balvi, Latvia

205.443.01002 Boehringer Ingelheim Investigational Site

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Brussel, Belgium

205.443.10001 Boehringer Ingelheim Investigational Site

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Kuala Lumpur, Malaysia

205.443.01001 Boehringer Ingelheim Investigational Site

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Edegem, Belgium

205.443.10002 Boehringer Ingelheim Investigational Site

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Kelantan, Malaysia

205.443.07001 Boehringer Ingelheim Investigational Site

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Zaporizhzhya, Ukraine

205.443.06003 Boehringer Ingelheim Investigational Site

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Vilnius, Lithuania

205.443.09001 Boehringer Ingelheim Investigational Site

🇵🇭

Quezon City, Philippines

205.443.12004 Boehringer Ingelheim Investigational Site

🇺🇸

Summerville, South Carolina, United States

205.443.01004 Boehringer Ingelheim Investigational Site

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Antwerpen, Belgium

205.443.02002 Boehringer Ingelheim Investigational Site

🇫🇮

Helsinki, Finland

205.443.03003 Boehringer Ingelheim Investigational Site

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Berlin, Germany

205.443.02003 Boehringer Ingelheim Investigational Site

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Turku, Finland

205.443.03001 Boehringer Ingelheim Investigational Site

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Bochum, Germany

205.443.03010 Boehringer Ingelheim Investigational Site

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Frankfurt, Germany

205.443.03002 Boehringer Ingelheim Investigational Site

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Ettenheim, Germany

205.443.82003 Boehringer Ingelheim Investigational Site

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Guri, Korea, Republic of

205.443.82002 Boehringer Ingelheim Investigational Site

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Incheon, Korea, Republic of

205.443.82001 Boehringer Ingelheim Investigational Site

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Seoul, Korea, Republic of

205.443.05003 Boehringer Ingelheim Investigational Site

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Rezekne, Latvia

205.443.05002 Boehringer Ingelheim Investigational Site

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Riga, Latvia

205.443.06002 Boehringer Ingelheim Investigational Site

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Vilnius, Lithuania

205.443.04003 Boehringer Ingelheim Investigational Site

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Breda, Netherlands

205.443.10003 Boehringer Ingelheim Investigational Site

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Pahang, Malaysia

205.443.04001 Boehringer Ingelheim Investigational Site

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Groningen, Netherlands

205.443.09002 Boehringer Ingelheim Investigational Site

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Quezon City, Philippines

205.443.07003 Boehringer Ingelheim Investigational Site

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Dnipropetrovsk, Ukraine

205.443.07004 Boehringer Ingelheim Investigational Site

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Zaporizhya, Ukraine

205.443.07002 Boehringer Ingelheim Investigational Site

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Donetsk, Ukraine

205.443.07005 Boehringer Ingelheim Investigational Site

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Vinnytsya, Ukraine

205.443.12006 Boehringer Ingelheim Investigational Site

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Charleston, South Carolina, United States

205.443.12005 Boehringer Ingelheim Investigational Site

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Oklahoma City, Oklahoma, United States

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