Evaluation of tiotropium 2.5 and 5 mcg once daily delivered via the Respimat® inhaler compared to placebo and salmeterol HydroFluoroAlkane (HFA) Metered Dose Inhaler (MDI) (50 mcg twice daily) in patient with moderate persistent asthma I

• Register: EUCTR
• Last refreshed on: 18 February 2013
• Main ID: EUCTR2009-018004-18-LV
• Date of registration: 16/07/2010
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim RCV GmbH&Co KG
• Public title: Evaluation of tiotropium 2.5 and 5 mcg once daily delivered via the Respimat® inhaler compared to placebo and salmeterol HydroFluoroAlkane (HFA) Metered Dose Inhaler (MDI) (50 mcg twice daily) in patient with moderate persistent asthma I
• Scientific title: A Phase III randomised, double-blind, placebo-controlled, parallel-group trial to evaluate efficacy and safety of tiotropium inhalation solution delivered via Respimat® inhaler (2.5 and 5 µg once daily) compared with placebo and salmeterol HFA MDI (50 µg twice daily) over 24 weeks in patients with moderate persistent asthma
• Date of first enrolment: 20/09/2010
• Target sample size: 1000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-018004-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Brazil, China, Guatemala, India, Japan, Latvia, Mexico, Peru, Poland, Russian Federation, United States

Contacts

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG

Key inclusion & exclusion criteria

Inclusion criteria:
Outpatients of either sex, aged 18-75 years
Diagnosis of moderate persistent asthma.
Asthma diagnosis made before age of 40.
At leaset a 3 month history of asthma.
Pre-bronchodilator FEV1 = 60% and = 90% of predicted at Visit 1.
Increase in FEV1 of = 12% and = 200 mL 15 to 30 min after 400 µg salbutamol (albuterol) at Visit 1.
Maintenance treatment with medium dose of inhaled corticosteroids for at least 4 weeks before Visit 1.
Symptomatic despite their current maintenance treatment with ICS (ACQ = 1.5).
Variation in absolute pre-BD FEV1 values Visit 1 compared to Visit 2 within ± 30%.
Never-smokers or ex-smokers (stopped at least one year prior to enrolment + smoking history of less than 10 pack years).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 900
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion criteria:
Patients with a significant disease other than asthma.
Patients with a clinically relevant abnormal screening haematology or blood chemistry if the abnormalitiy defines a significant disease.
Patients with a recent history (i.e. six months or less) of myocardial infarction.
Patients who have been hospitalised for cardiac failure during the past year.
Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year.
Patients with lung diseases other than asthma (e.g. COPD).
Patients with known active tuberculosis.
Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years. Patients with treated basal cell carcinoma are allowed.
Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion no. 1.
Patients with significant alcohol or drug abuse within the past two years.
Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to Visit 1 (screening).
Pregnant or nursing woman.
Women of childbearing potential not using a highly effective method of birth control.
Patients with any asthma exacerbation or any respiratory tract infection in the four weeks prior to Visit 1 or during the screening period.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Moderate persistent asthma
MedDRA version: 13.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Trade Name: Spiriva Respimat 2.5 microgram, solution for inhalation
Product Name: Spiriva Respimat 2.5 mcg
Product Code: Tiotropium Respimat
Pharmaceutical Form: Inhalation vapour, solution
Current Sponsor code: Ba 679 Br
Other descriptive name: TIOTROPIUM BROMIDE MONOHYDRATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 3.124-
Pharmaceutical form of the placebo: Inhalation vapour
Route of administration of the placebo: Inhalation use

Product Name: Tiotropium Respimat 1.25 mcg
Product Code: Tiotropium Respimat 1.25 mcg
Pharmaceutical Form: Inhalation vapour, solution
Current Sponsor code: Ba 679 Br
Other descriptive name: TIOTROPIUM BROMIDE MONOHYDRATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 1.562-
Pharmaceutical form of the placebo: Inhalation vapour
Route of administration of the placebo: Inhalation use

Trade Name: Serevent Evohaler
(according to UK SPC)
Product Name: Salmeterol pressurised inhalation suspension
Pharmaceutical Form: Pressurised inhalation, suspension
INN or Proposed INN: SALMETEROL
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Pressurised inhalation
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Secondary Objective: Evaluate the long term (24 weeks) safety of two doses (2.5 µg and 5 µg) of tiotropium inhalation solution (administered once daily) compared to placebo and to salmeterol (50 µg; administered twice daily) on top of maintenance therapy with inhaled corticosteroid controller medication in patients with moderate persistent asthma.

Primary end point(s): The co-primary endpoints are
1. Peak forced expiratory volume in one second (FEV1) response (within 3 hours post dosing) determined at the end of the 24-week treatment period.
2. Trough forced expiratory volume in one second (FEV1) response determined at the end of the 24-week treatment period.

Primary endpoint Meta-Analysis (combined data 205.418 and 205.419 trial):
1. The responder rate as assessed by the Asthma Control Questionnaire (ACQ) determined at the end of the 24-week treatment period on combined data from the two twin trials 205.418 and 205.419.

Timepoint(s) of evaluation of this end point: At 24 weeks of treatment

Main Objective: Evaluate the long term (24 weeks) efficacy of two doses (2.5 µg and 5 µg) of tiotropium inhalation solution (administered once daily) compared to placebo and to salmeterol (50 µg; administered twice daily) on top of maintenance therapy with inhaled corticosteroid controller medication in patients with moderate persistent asthma.

Secondary Outcome(s)

Secondary end point(s): 1. Peak (within 3 hours post dosing) and trough forced vital capacity
(FVC) determined at the end of the 24-week treatment period.
2. FEV1 (AUC0-3h) and FVC (AUC0-3h) at the end of the 24-week
treatment period.
3. Individual in-clinic FEV1, FVC and PEF measurements at all time
points including peak, trough and AUC0-3h during the 24-week treatment period.
4. Quality of Life as assessed by standardised Asthma Quality of Life
Questionnaire (AQLQ (S)) at all clinic visits during the 24-week
treatment period.
5. PEF am/pm: change from baseline in mean weekly pre-dose morning
and evening PEF measured by patients at home in the last week of the
24-week treatment period.
6. Use of PRN salbutamol (albuterol) rescue medication during the 24-
week treatment period.
7. Asthma symptoms as assessed by the patient's electronic diary during the 24-week treatment period.
8. Asthma symptom free days as assessed by the patient's electronic
diary during the 24-week treatment period.
9. The responder rate as assessed by the ACQ determined at the end of the 24-week treatment period for each trial separately.

Additionally in a subset of patients:
10. FEV1 (AUC0-12h), FEV1 (AUC12-24h), FEV1 (AUC0-24h), FVC (AUC0-12h), FVC (AUC12-24h), FVC (AUC0-24h) after 24-week treatment
11. Individual FEV1 and FVC measurements at 5 and 15 minutes post
dose including peak and AUC0-3h.

Timepoint(s) of evaluation of this end point: During or at the end of the 24 week treatment period

Secondary ID(s)

NCT01172808

205.418

Source(s) of Monetary Support

Boehringer Ingelheim RCV GmbH&Co KG