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

NCT01634113 | Completed Phase 2 Results

• 2 other identifiers: 205.4432011-005512-28
• Study Type: interventional
• Target: 102
• Locations: 11 countries
• Sites: 33

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (11)

• Weekly Mean Overnight Asthma Symptom Score Response

  Baseline and 12 weeks

• Weekly Percentage of Days Without Asthma Symptoms

  12 weeks

• Weekly Percentage of Days With Use of Salbutamol (Albuterol) Rescue Medication

  12 weeks

• Weekly Mean Nighttime Awakenings Due to Asthma Symptoms

  Baseline and 12 weeks

• Trough FEV1 Change From Baseline

  Baseline and 12 weeks

Study Arms (3)

tiotropium low dose

EXPERIMENTAL

Once daily, delivered with Respimat® inhaler

Drug: tiotropium-bromide

tiotropium high dose

EXPERIMENTAL

Once daily, delivered with Respimat® inhaler

Drug: tiotropium-bromide

placebo

PLACEBO COMPARATOR

Once daily, delivered with Respimat® inhaler

Drug: placebo

Interventions

tiotropium-bromide DRUG

IMP

tiotropium high dose

placebo DRUG

placebo matching tiotropium

placebo

Eligibility Criteria

• Age: 1 Year - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• Patients with a significant disease other than asthma.
• 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.
• 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.
• Patients with a malignancy for which the patient has undergone resection, radiation therapy or chemotherapy.
• Patients with clinically significant lung diseases other than asthma.
• Alternative causes (other causes than asthma) that can lead to respiratory symptoms of wheeze, cough and shortness of breath.
• Patients with known active tuberculosis.
• Patients who have undergone thoracotomy with pulmonary resection.
• 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).

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Pfizer: collaborator

Study Sites (33)

205.443.12003 Boehringer Ingelheim Investigational Site

Columbia, Missouri, United States

Location

205.443.12005 Boehringer Ingelheim Investigational Site

Oklahoma City, Oklahoma, United States

Location

205.443.12006 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

Location

205.443.12004 Boehringer Ingelheim Investigational Site

Summerville, South Carolina, United States

Location

205.443.01004 Boehringer Ingelheim Investigational Site

Antwerp, Belgium

Location

205.443.01002 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

205.443.01001 Boehringer Ingelheim Investigational Site

Edegem, Belgium

Location

205.443.02002 Boehringer Ingelheim Investigational Site

Helsinki, Finland

Location

205.443.02003 Boehringer Ingelheim Investigational Site

Turku, Finland

Location

205.443.03003 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

205.443.03001 Boehringer Ingelheim Investigational Site

Bochum, Germany

Location

205.443.03002 Boehringer Ingelheim Investigational Site

Ettenheim, Germany

Location

205.443.03010 Boehringer Ingelheim Investigational Site

Frankfurt, Germany

Location

205.443.05001 Boehringer Ingelheim Investigational Site

Balvi, Latvia

Location

205.443.05003 Boehringer Ingelheim Investigational Site

Rēzekne, Latvia

Location

205.443.05002 Boehringer Ingelheim Investigational Site

Riga, Latvia

Location

205.443.06002 Boehringer Ingelheim Investigational Site

Vilnius, Lithuania

Location

205.443.06003 Boehringer Ingelheim Investigational Site

Vilnius, Lithuania

Location

205.443.10002 Boehringer Ingelheim Investigational Site

Kelantan, Malaysia

Location

205.443.10001 Boehringer Ingelheim Investigational Site

Kuala Lumpur, Malaysia

Location

205.443.10003 Boehringer Ingelheim Investigational Site

Kuala Pahang, Malaysia

Location

205.443.04003 Boehringer Ingelheim Investigational Site

Breda, Netherlands

Location

205.443.04001 Boehringer Ingelheim Investigational Site

Groningen, Netherlands

Location

205.443.09001 Boehringer Ingelheim Investigational Site

Quezon City, Philippines

Location

205.443.09002 Boehringer Ingelheim Investigational Site

Quezon City, Philippines

Location

205.443.82003 Boehringer Ingelheim Investigational Site

Guri-si, South Korea

Location

205.443.82002 Boehringer Ingelheim Investigational Site

Incheon, South Korea

Location

205.443.82001 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

205.443.07003 Boehringer Ingelheim Investigational Site

Dnipropetrovsk, Ukraine

Location

205.443.07002 Boehringer Ingelheim Investigational Site

Donetsk, Ukraine

Location

205.443.07005 Boehringer Ingelheim Investigational Site

Vinnytsia, Ukraine

Location

205.443.07004 Boehringer Ingelheim Investigational Site

Zaporizhya, Ukraine

Location

205.443.07001 Boehringer Ingelheim Investigational Site

Zaporizhzhya, Ukraine

Location

Related Publications (2)

• 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.

  PMID: 29605203 DERIVED

• 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.

  PMID: 29361462 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2012
• First Posted: July 6, 2012
• Study Start: July 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 23, 2015
• Results First Posted: June 23, 2015

Record last verified: 2015-06

Locations

BE (3); KR (3); DE (4); NL (2); MY (3); PH (2); LA (3); FI (2); UA (5); US (4); LI (2)