E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease (COPD) |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic lung disease with obstruction of the airways |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
E.1.2 | System Organ Class | 100000004855 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To explore the effect of treatment with orally inhaled tiotropium and olodaterol in fixed dose combination with and without exercise training, and tiotropium comparing to placebo, on top of behavioural modification in improving exercise capacity in patients with COPD |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effect of interventions (pharmacological intervention +/- exercise training, with a comprehensive behavioral modification program) on two domains of physical activity (i) amount of physical activity (as measured with the activity monitor) (ii) perceived difficulties associated with physical activity (as measured by the FPI questionnaire) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions.
- All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:
Patients must have relatively stable airway obstruction with a post-bronchodilator 30% = forced expiratory volume in one second <80% of predicted normal; Global Initiative for Chronic Obstructive Lung DiseaseGlobal stage II - III, and a post-bronchodilator Tiffeneau index <70% at Visit 1.
- Male or female patients, aged = 40 years and = 75 years.
- Patients must be current or ex-smokers with a smoking history of more than 10 pack years (see Appendix 10.3 for calculations). Patients who have never smoked cigarettes must be excluded. |
|
E.4 | Principal exclusion criteria |
- Patients with a significant disease other than chronic obstructive pulmonary disease.
- Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis.
- Patients with a history of asthma.
- A diagnosis of thyrotoxicosis.
- A diagnosis of paroxysmal tachycardia (>100 beats per minute).
- A history of myocardial infarction within 1 year of screening visit.
- Unstable or life-threatening cardiac arrhythmia.
- Hospitalized for heart failure within the past year.
- Known active tuberculosis.
- A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years.
- A history of life-threatening pulmonary obstruction and patients with chronic respiratory failure.
- A history of cystic fibrosis.
- Clinically evident bronchiectasis.
- A history of significant alcohol or drug abuse.
- Any contraindications for exercise testing.
- Patients who have undergone thoracotomy with pulmonary resection.
- Patients being treated with any oral ß-adrenergics.
- Patients being treated with oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.
- Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigators opinion will be unable to abstain from the use of oxygen therapy during clinic visits.
- Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit or patients who are currently in a pulmonary rehabilitation program.
- Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea, such as arthritis in the leg, angina pectoris or claudication or morbid obesity.
- Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit.
- Patients with known hypersensitivity to ß-adrenergics drugs, anticholinergic drugs, benzalkonium chloride, disodium edentat, or any other component of the Respimat® inhalation solution delivery system.
- Pregnant or nursing women.
- Women of childbearing potential not using highly effective methods of birth control.
- Patients who have previously been randomized in this study or are currently participating in another study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1: Endurance time [sec] during Endurance Shuttle Walk Test to symptom limitation at walking speed corresponding to 85% of predicted maximum oxygen consumption after 8 weeks of treatment
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1: Average daily walking time measured by the activity monitor in the week prior to 12 weeks of treatment
2: Average daily walking intensity measured by the activity monitor in the week prior to 12 weeks of treatment
3: Functional Performance Inventory-Short Form score at Week 12
4: Endurance time [sec] during Endurance Shuttle Walk Test to symptom limitation at walking speed corresponding to 85% of predicted maximum oxygen consumption after 12 weeks of treatment
5: One hour post-dose forced expiratory volume in one second after 8 weeks of treatment
6: One hour post-dose forced vital capacity after 8 weeks of treatment
7: Resting inspiratory capacity measured at 1.5 hours post dose after 8 weeks of treatment
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: 12 weeks
2: 12 weeks
3: 12 weeks
4: 12 weeks
5: 8 weeks
6: 8 weeks
7: 8 weeks
6: 8 weeks
7: 8 weeks
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
New Zealand |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 10 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 10 |