Clinical trial NCT01634113: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2012-07-06
Enrollment: 102
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Weekly Mean Combined Daytime Asthma Symptom Score
timeFrame: Baseline and 12 weeks
measure: FEV1 Peak (0-3h) Change From Baseline
timeFrame: 10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12
Secondary outcomes:
measure: Weekly Mean Overnight Asthma Symptom Score Response
timeFrame: Baseline and 12 weeks
measure: Weekly Percentage of Days Without Asthma Symptoms
timeFrame: 12 weeks
measure: Weekly Percentage of Days With Use of Salbutamol (Albuterol) Rescue Medication
timeFrame: 12 weeks
measure: Weekly Mean Nighttime Awakenings Due to Asthma Symptoms
timeFrame: Baseline and 12 weeks
measure: Trough FEV1 Change From Baseline
timeFrame: Baseline and 12 weeks
measure: FEV1 AUC (0-3h) Change From Baseline
timeFrame: 10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12
measure: FVC Peak (0-3h) Change From Baseline
timeFrame: 10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12
measure: Trough FVC Change From Baseline
timeFrame: Baseline and 12 weeks
measure: FVC AUC (0-3h) Change From Baseline
timeFrame: 10 minutes before drug administration and 30 minutes, 1 hour (h), 2h and 3h after drug administration at baseline and week 12
measure: Individual FEV1 Measurements
timeFrame: Baseline and 12 weeks
measure: Individual FVC Measurements
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Columbia
country: United States
facility: 205.443.12003 Boehringer Ingelheim Investigational Site
state: Missouri
city: Oklahoma City
country: United States
facility: 205.443.12005 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Charleston
country: United States
facility: 205.443.12006 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Summerville
country: United States
facility: 205.443.12004 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Antwerpen
country: Belgium
facility: 205.443.01004 Boehringer Ingelheim Investigational Site
city: Brussel
country: Belgium
facility: 205.443.01002 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 205.443.01001 Boehringer Ingelheim Investigational Site
city: Helsinki
country: Finland
facility: 205.443.02002 Boehringer Ingelheim Investigational Site
city: Turku
country: Finland
facility: 205.443.02003 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 205.443.03003 Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: 205.443.03001 Boehringer Ingelheim Investigational Site
city: Ettenheim
country: Germany
facility: 205.443.03002 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 205.443.03010 Boehringer Ingelheim Investigational Site
city: Guri
country: Korea, Republic of
facility: 205.443.82003 Boehringer Ingelheim Investigational Site
city: Incheon
country: Korea, Republic of
facility: 205.443.82002 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 205.443.82001 Boehringer Ingelheim Investigational Site
city: Balvi
country: Latvia
facility: 205.443.05001 Boehringer Ingelheim Investigational Site
city: Rezekne
country: Latvia
facility: 205.443.05003 Boehringer Ingelheim Investigational Site
city: Riga
country: Latvia
facility: 205.443.05002 Boehringer Ingelheim Investigational Site
city: Vilnius
country: Lithuania
facility: 205.443.06002 Boehringer Ingelheim Investigational Site
city: Vilnius
country: Lithuania
facility: 205.443.06003 Boehringer Ingelheim Investigational Site
city: Kelantan
country: Malaysia
facility: 205.443.10002 Boehringer Ingelheim Investigational Site
city: Kuala Lumpur
country: Malaysia
facility: 205.443.10001 Boehringer Ingelheim Investigational Site
city: Pahang
country: Malaysia
facility: 205.443.10003 Boehringer Ingelheim Investigational Site
city: Breda
country: Netherlands
facility: 205.443.04003 Boehringer Ingelheim Investigational Site
city: Groningen
country: Netherlands
facility: 205.443.04001 Boehringer Ingelheim Investigational Site
city: Quezon City
country: Philippines
facility: 205.443.09001 Boehringer Ingelheim Investigational Site
city: Quezon City
country: Philippines
facility: 205.443.09002 Boehringer Ingelheim Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: 205.443.07003 Boehringer Ingelheim Investigational Site
city: Donetsk
country: Ukraine
facility: 205.443.07002 Boehringer Ingelheim Investigational Site
city: Vinnytsya
country: Ukraine
facility: 205.443.07005 Boehringer Ingelheim Investigational Site
city: Zaporizhya
country: Ukraine
facility: 205.443.07004 Boehringer Ingelheim Investigational Site
city: Zaporizhzhya
country: Ukraine
facility: 205.443.07001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Wachtel H, Nagel M, Engel M, El Azzi G, Sharma A, Suggett J. In vitro and clinical characterization of the valved holding chamber AeroChamber Plus(R) Flow-Vu(R) for administrating tiotropium Respimat(R) in 1-5-year-old children with persistent asthmatic symptoms. Respir Med. 2018 Apr;137:181-190. doi: 10.1016/j.rmed.2018.03.010. Epub 2018 Mar 7.
citation: Vrijlandt EJLE, El Azzi G, Vandewalker M, Rupp N, Harper T, Graham L, Szefler SJ, Moroni-Zentgraf P, Sharma A, Vulcu SD, Sigmund R, Chawes B, Engel M, Bisgaard H. Safety and efficacy of tiotropium in children aged 1-5 years with persistent asthmatic symptoms: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2018 Feb;6(2):127-137. doi: 10.1016/S2213-2600(18)30012-2. Epub 2018 Jan 18.