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

Asthma Clinical Trial

Official title:

A Phase II/III, Randomised, Double-blind, Placebo-controlled, Parallel Group Trial to Evaluate Safety and Efficacy of Tiotropium Inhalation Solution (2.5 µg and 5 µg) Administered Once Daily in the Afternoon Via Respimat® Inhaler for 12 Weeks in Patients 1 to 5 Years Old With Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01634113
• Other study ID #: 205.443
• Secondary ID: 2011-005512-28
• Status: Completed
• Phase: Phase 2
• First received: April 16, 2012
• Last updated: June 3, 2015
• Start date: July 2012
• Est. completion date: December 2014

Study information

• Verified date: June 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal and Health ProductsFinland: Finnish Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthMalaysia: Ministry of HealthNetherlands: Central Committee Research Involving Human SubjectsPhilippines: Department of HealthSouth Korea: Ministry of Food and Drug Safety (MFDS)Ukraine: State Pharmacological Center - Ministry of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 5 Years

Eligibility

Inclusion criteria:

1. All patients' parents (or legal guardians) must sign and date an informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial. Where appropriate, participants should assent to enroll in the study.

2. Male or female patients between 1 and 5 years of age.

3. By a physician documented (at least 6 month) history of persistent asthma symptoms, including (but not limited to) wheezing, cough, and/or shortness of breath. (persistent = need for inhalation corticosteroid maintenance therapy to control asthma symptoms)

4. For patients aged 5 years and capable of performing technically acceptable Pulmonary Function tests (PFTs): documented impaired lung function (i.e. pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) is smaller or equal to 90% of predicted normal).

5. All patients must have been on maintenance treatment with an inhaled corticosteroid at stable dose, either as mono treatment or in combination with another controller medication, for at least 4 weeks before Visit 1.

6. All patients must be symptomatic (partly controlled) as defined by the Global Initiative for Asthma (GINA) guideline for children aged 5 years and younger in the week prior to Visit 1 (screening) and in the week prior to randomisation (Visit 2).

Further inclusion criteria apply.

Exclusion criteria:

1. Patients with a significant disease other than asthma.

2. Patients with clinically relevant abnormal screening haematology or blood chemistry will be excluded if the abnormality defines a significant disease as defined in exclusion criterion 1.

3. Patients with a history of congenital or acquired heart disease, or patients who have been hospitalised for cardiac syncope or failure during the past year.

4. Patients with any unstable or life-threatening cardiac arrhythmia, including cardiac arrhythmia requiring intervention (e.g. pacemaker implantation) or a change in drug therapy within the past year.

5. Patients with a malignancy for which the patient has undergone resection, radiation therapy or chemotherapy.

6. Patients with clinically significant lung diseases other than asthma.

7. Alternative causes (other causes than asthma) that can lead to respiratory symptoms of wheeze, cough and shortness of breath.

8. Patients with known active tuberculosis.

9. Patients who have undergone thoracotomy with pulmonary resection.

10. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit 1).

Further exclusion criteria apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• tiotropium-bromide
IMP
• tiotropium-bromide
IMP
• placebo
placebo matching tiotropium

Locations

Country	Name	City	State
Belgium	205.443.01004 Boehringer Ingelheim Investigational Site	Antwerpen
Belgium	205.443.01002 Boehringer Ingelheim Investigational Site	Brussel
Belgium	205.443.01001 Boehringer Ingelheim Investigational Site	Edegem
Finland	205.443.02002 Boehringer Ingelheim Investigational Site	Helsinki
Finland	205.443.02003 Boehringer Ingelheim Investigational Site	Turku
Germany	205.443.03003 Boehringer Ingelheim Investigational Site	Berlin
Germany	205.443.03001 Boehringer Ingelheim Investigational Site	Bochum
Germany	205.443.03002 Boehringer Ingelheim Investigational Site	Ettenheim
Germany	205.443.03010 Boehringer Ingelheim Investigational Site	Frankfurt
Korea, Republic of	205.443.82003 Boehringer Ingelheim Investigational Site	Guri
Korea, Republic of	205.443.82002 Boehringer Ingelheim Investigational Site	Incheon
Korea, Republic of	205.443.82001 Boehringer Ingelheim Investigational Site	Seoul
Latvia	205.443.05001 Boehringer Ingelheim Investigational Site	Balvi
Latvia	205.443.05003 Boehringer Ingelheim Investigational Site	Rezekne
Latvia	205.443.05002 Boehringer Ingelheim Investigational Site	Riga
Lithuania	205.443.06002 Boehringer Ingelheim Investigational Site	Vilnius
Lithuania	205.443.06003 Boehringer Ingelheim Investigational Site	Vilnius
Malaysia	205.443.10002 Boehringer Ingelheim Investigational Site	Kelantan
Malaysia	205.443.10001 Boehringer Ingelheim Investigational Site	Kuala Lumpur
Malaysia	205.443.10003 Boehringer Ingelheim Investigational Site	Pahang
Netherlands	205.443.04003 Boehringer Ingelheim Investigational Site	Breda
Netherlands	205.443.04001 Boehringer Ingelheim Investigational Site	Groningen
Philippines	205.443.09001 Boehringer Ingelheim Investigational Site	Quezon City
Philippines	205.443.09002 Boehringer Ingelheim Investigational Site	Quezon City
Ukraine	205.443.07003 Boehringer Ingelheim Investigational Site	Dnipropetrovsk
Ukraine	205.443.07002 Boehringer Ingelheim Investigational Site	Donetsk
Ukraine	205.443.07005 Boehringer Ingelheim Investigational Site	Vinnytsya
Ukraine	205.443.07004 Boehringer Ingelheim Investigational Site	Zaporizhya
Ukraine	205.443.07001 Boehringer Ingelheim Investigational Site	Zaporizhzhya
United States	205.443.12006 Boehringer Ingelheim Investigational Site	Charleston	South Carolina
United States	205.443.12003 Boehringer Ingelheim Investigational Site	Columbia	Missouri
United States	205.443.12005 Boehringer Ingelheim Investigational Site	Oklahoma City	Oklahoma
United States	205.443.12004 Boehringer Ingelheim Investigational Site	Summerville	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Pfizer

Countries where clinical trial is conducted

United States,  Belgium,  Finland,  Germany,  Korea, Republic of,  Latvia,  Lithuania,  Malaysia,  Netherlands,  Philippines,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weekly Mean Combined Daytime Asthma Symptom Score	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.	Baseline and 12 weeks	No
Primary	FEV1 Peak (0-3h) Change From Baseline	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	10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12	No
Secondary	Weekly Mean Overnight Asthma Symptom Score Response	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 ß-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	Baseline and 12 weeks	No
Secondary	Weekly Percentage of Days Without Asthma Symptoms	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	12 weeks	No
Secondary	Weekly Percentage of Days With Use of Salbutamol (Albuterol) Rescue Medication	Weekly percentage of days with use of salbutamol (albuterol) rescue medication at week 12. A week was defined as 7 days.	12 weeks	No
Secondary	Weekly Mean Nighttime Awakenings Due to Asthma Symptoms	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	Baseline and 12 weeks	No
Secondary	Trough FEV1 Change From Baseline	Change from baseline in Trough (pre-dose) Forced expiratory volume in 1 second (FEV1) measured at week 12.	Baseline and 12 weeks	No
Secondary	FEV1 AUC (0-3h) Change From Baseline	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).	10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12	No
Secondary	FVC Peak (0-3h) Change From Baseline	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.	10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12	No
Secondary	Trough FVC Change From Baseline	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.	Baseline and 12 weeks	No
Secondary	FVC AUC (0-3h) Change From Baseline	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).	10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12	No
Secondary	Individual FEV1 Measurements	Change from baseline in individual FEV1 measurements at each timepoint after 12 weeks	Baseline and 12 weeks	No
Secondary	Individual FVC Measurements	Change from baseline in individual FVC measurements at each timepoint after 12 weeks	Baseline and 12 weeks	No

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