E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chronic obstructive pulmonary disease |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic Obstructive Pulmonary Disease
N/A |
|
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 | 19.1 |
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 compare the effect of Tiotropium + Olodaterol on COPD exacerbations |
|
E.2.2 | Secondary objectives of the trial |
To compare the effect of Tiotropium + Olodaterol on hospitalisation associated with exacerbations and survival |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Spirometry substudy
An optional spirometry assessment substudy is conducted to allow
better characterization of the air flow limitation. Additional lung function
testing procedures will be added to the procedures of the main study for
approximately 854 patients at selected sites. Pulmonary function testing
will be performed at the screening visit (Visit 1) to determine patient
eligibility. At Visits 2, 3, 4, 5 and 6 pulmonary function testing will be
conducted prior to dosing and at selected time
intervals up to three hours post-dosing in the clinic. At Visit 6a,
additional pulmonaryfunction testing will be conducted up to 23 hrs 55
min post-dosing in clinic. |
|
E.3 | Principal inclusion criteria |
- Male or female patients, 40 years of age or older.
- Diagnosis of COPD with a documented post-bronchodilator Forced expiratory volume in one second (FEV1)< 60% of predicted normal and a post-bronchodilator FEV1/FVC (Forced vital capacity) <70% at Visit 1. For patients participating in the spirometry sub-study, historical data
will not be used for inclusion. These patients will perform a pre-dose
pulmonary function test which will be followed by the administration of
400 μg salbutamol / albuterol followed by a post-dose pulmonary
function test for qualification.
- Documented history of at least one moderate to severe COPD exacerbation in the previous 12 months requiring treatment with systemic corticosteroids and/or antibiotics and/or related hospitalization.
- Symptomatically stable as defined by: no evidence of COPD exacerbation requiring use of either antibiotics and/or steroids 4 weeks prior to visit 1 and no evidence of change in their usual COPD medication 4 weeks prior to visit 1.
- Current or ex-smokers with a smoking history of more than 10 pack years. |
|
E.4 | Principal exclusion criteria |
- Significant disease other than COPD.
- Clinically relevant abnormal baseline haematology, blood chemistry or creatinine > x2 ULN will be excluded regardless of clinical condition
- Current documented history of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma
- A diagnosis of thyrotoxicosis
- A history of myocardial infarction within 6 months of screening visit.
- Life-threatening cardiac arrhythmia.
- Known active tuberculosis.
- Any malignancy unless free of disease for at least 5 years (patients with treated basal cell carcinoma or squamous cell skin cancers are allowed).
- A history of cystic fibrosis.
- Clinically relevant bronchiectasis.
- Patients with severe emphysema requiring endobronchial interventions within 6 months prior to screening
- A history of significant alcohol or drug abuse in the opinion of the investigator.
- Patients who have undergone thoracotomy with pulmonary resection
- Patients being treated with oral or patch ß-adrenergics.
- Patients being treated with oral corticosteroid medication at unstable doses.
- Patients being treated with antibiotics for any reason (not limited to
exacerbation infection) within 4 weeks of screening visit.
- Patients being treated with PDE4 inhibitors within 3 months of screening visit
- Patients who have taken an investigational drug within one month or six half-lives
- Pregnant or nursing women.
- Women of childbearing potential not using a highly effective method of birth control.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
1: Primary endpoint: annualised rate of moderate to severe COPD exacerbation during the treatment period (within 1 day after the last drug administration date).
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1: 52 weeks + 1 day
2: 52 weeks+ 1 day
|
|
E.5.2 | Secondary end point(s) |
1: Key secondary endpoint: time to first moderate to severe COPD exacerbation during the treatment period (within 1 day after the last drug administration date).
2: Time to all-cause mortality (within 1 day after the last drug administration date).
3: Annualised rate of exacerbation leading to hospitalisation during the treatment period (within 1 day after the last drug administration date).
4: Time to first COPD exacerbations leading to hospitalisation during the treatment period (within 1 day after the last drug administration date).
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: 52 weeks + 1 day
2: 52 weeks + 1 day
3: 52 weeks + 1 day
4: 52 weeks + 1 day
|
|
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 | No |
E.6.4 | Safety | Yes |
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 | No |
E.8.1.4 | Double blind | Yes |
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 | No |
E.8.2.3 | Other | No |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 30 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 323 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
Colombia |
Croatia |
Czech Republic |
Denmark |
Ecuador |
Finland |
France |
Germany |
Greece |
Guatemala |
Hong Kong |
Hungary |
India |
Ireland |
Italy |
Japan |
Korea, Republic of |
Latvia |
Lithuania |
Malaysia |
Mexico |
Montenegro |
Netherlands |
New Zealand |
Norway |
Philippines |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Singapore |
Slovakia |
Slovenia |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Thailand |
Tunisia |
Turkey |
Ukraine |
United Kingdom |
United States |
Vietnam |
|
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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 20 |