Study to assess the efficacy and safety of tiotropium+olodaterol fixed dose combination in patients with COPD

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2009-010668-40-PT
• Date of registration: 07/07/2011
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim Lda.
• Public title: Study to assess the efficacy and safety of tiotropium+olodaterol fixed dose combination in patients with COPD
• Scientific title: A randomised, double-blind, parallel group study to assess the efficacy and safety of 52 weeks of once daily treatment of orally inhaled tiotropium + olodaterol fixed dose combination (2.5 µg / 5 µg; 5 µg / 5 µg) (delivered by the Respimat® Inhaler) compared with the individual components (2.5 µg and 5 µg tiotropium, 5 µg olodaterol) (delivered by the Respimat® Inhaler) in patients with Chronic Obstructive Pulmonary Disease (COPD) - TOnado 1
• Date of first enrolment: 02/09/2011
• Target sample size: 2500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-010668-40
• 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: no Other: no Number of treatment arms in the trial: 5

Countries of recruitment

Argentina, Australia, Bulgaria, Canada, China, Czech Republic, Denmark, Estonia, Finland, France, Germany, Guatemala, Hungary, India, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Portugal, Réunion, Russian Federation, Slovenia, Turkey, United States

Contacts

• Name: Manuel Quaresma
• Affiliation: Boehringer Ingelheim Lda.

• Name: Manuel Quaresma
• Affiliation: Boehringer Ingelheim Lda.

Key inclusion & exclusion criteria

Inclusion criteria:
1. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions.
2. All patients must have a diagnosis of chronic obstructive pulmonary diseaseand must meet the following spirometric criteria:
Patients must have relatively stable airway obstruction with a post-bronchodilator FEV1< 80% of predicted normal and a post-bronchodilator FEV1/FVC <70% at Visit 1
3. Male or female patients, 40 years of age or older.
4.Patients must be current or ex-smokers with a smoking history of more 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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Patients with a significant disease other than COPD;
2.Patients with a, in the opinion of the investigator, clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis;
3.Patients with a history of asthma.
Patients with any of the following conditions:
4.A diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2- agonists).
5.A diagnosis of (>100 beats per minute) (due to the known class side effect profile of ß2-agonists).
6.A history of myocardial infarction within 1 year of screening visit (Visit 1).
7.Unstable or life-threatening cardiac arrhythmia.
8.Hospitalization for heart failure within the past year.
9.Known active tuberculosis.
10.A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed).
11.A history of life-threatening pulmonary obstruction.
12.A history of cystic fibrosis.
13.Clinically evident bronchiectasis.
14.A history of significant alcohol or drug abuse.
15.Patients who have undergone thoracotomy with pulmonary resection
16.Patients being treated with oral or patch ß-adrenergics.
17.Patients being treated with oral corticosteroid medication at unstable doses
18.Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator’s opinion will be unable to abstain from the use of oxygen therapy during clinic visits.
19.Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program.
20.Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit (Visit 1).
21.Patients with known hypersensitivity to ß-adrenergic drugs, BAC, EDTA, or any other component of the RESPIMAT inhalation solution
22.Pregnant or nursing women.
23.Women of childbearing potential not using a highly effective method of birth control.
24.Patients who have previously been randomized in this study or are currently participating in another study.
25.Patients who are unable to comply with pulmonary medication restrictions prior to randomization.



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

Health Condition(s) or Problem(s) studied

Patients with Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 14.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

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

Intervention(s)

Product Name: Tiotropium 1.25µg/Olodaterol 2.5µg
Pharmaceutical Form: Inhalation vapour, solution
INN or Proposed INN: tiotropium
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 1.25-
INN or Proposed INN: olodaterol
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.5-

Product Name: Tiotropium 2.5µg/Olodaterol 2.5µg
Pharmaceutical Form: Inhalation vapour, solution
INN or Proposed INN: tiotropium
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.5-
INN or Proposed INN: olodaterol
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.5-

Trade Name: Spiriva Respimat 2.5 µg
Pharmaceutical Form: Inhalation vapour, solution
INN or Proposed INN: tiotropium
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.5-

Product Name: Tiotropium 1.25µg
Pharmaceutical Form: Inhalation vapour, solution
INN or Proposed INN: tiotropium
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 1.25-

Product Name: Olodaterol 2.5µg
Pharmaceutical Form: Inhalation vapour, solution
INN or Proposed INN: olodaterol
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2.5-

Primary Outcome(s)

Primary end point(s): There are three primary endpoints in this study: FEV1 AUC0-3h response, trough FEV1 response, and the SGRQ total score. The third primary endpoint, SGRQ total score will be evaluated after combining the data from this and the replicate study 1237.6.

Main Objective: The primary objective of this study is to assess the efficacy and safety of 52 weeks once daily treatment with orally inhaled tiotropium + olodaterol fixed dose combination ((2.5 µg / 5 µg; 5 µg / 5 µg) (delivered by the Respimat® Inhaler) compared with the individual components (2.5 and 5 µg tiotropium, 5 µg olodaterol) (delivered by the Respimat® Inhaler) in patients with Chronic Obstructive Pulmonary Disease (COPD).

Secondary Objective:

Timepoint(s) of evaluation of this end point: The three endpoints will be evaluated after 24 weeks of treatment

Secondary Outcome(s)

Secondary end point(s): TDI focal score will be considered as a key secondary endpoint.

Other secondary endpoints:

•FVC (forced vital capacity) AUC0-3h response [L]
•Trough FVC response [L]
•FEV1 AUC0-12h response [L] in the subset of patients with 12-hour PFTs
•FVC AUC0-12h response [L] in the subset of patients with 12-hour PFTs
•FEV1 peak0-3h response [L]
•FVC peak0-3h response [L]
•FEV1 response [L] at 5, 15 and 30 minutes, and at 1, 2 and 3 hours after inhalation of study medication,
•FVC response [L] at 5, 15 and 30 minutes, and at 1, 2 and 3 hours after inhalation of study medication

Timepoint(s) of evaluation of this end point: The secondary endpoints will be evaluated after 24 weeks of treatment

Secondary ID(s)

1237.5

2009-010668-40-NL

Source(s) of Monetary Support

Boehringer Ingelheim