E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease (COPD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
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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 determine the effect of QVA149 110/50 µg compared with placebo to QVA149 inhaled once daily on exercise tolerance as measured by exercise endurance time during a sub-maximal constant-load cycle ergometry test (SMETT) after three weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
• Determine effect of QVA149 vs placebo on isotime inspiratory capacity during SMETT after 3 weeks of treatment. • Determine effect of QVA149 vs tiotropium o.d. in patients with moderate to severe COPD with respect to exercise endurance time during SMETT after 3 weeks of treatment. •Determine effect of QVA149 vs placebo on trough (ie. 24 h post dose) inspiratory capacity after 3 weeks of treatment. •Determine effect of QVA149 vs placebo on trough (i.e. 24 h post dose) FEV1 after 3 weeks of treatment. •Determine effect of QVA149 vs placebo on pulmonary function tests on Day 1 and Day 21, at 5 min and 15 min post dose as determined by body plethysmography. •Evaluate effects of QVA149 vs placebo on spirometry after 3 weeks of treatment •Evaluate effect of QVA149 vs placebo on exertional dyspnea (Borg CR10 Scale®) during exercise after 3 weeks treatment •Evaluate effect of QVA149 vs placebo on leg discomfort (Borg CR10 Scale®) during SMETT after 3 weeks treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female adults aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure • Patients with moderate to severe stable COPD (Stage II or Stage III) according to the GOLD Guidelines 2009 • Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten pack-years is defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc.) • Patients with a post-bronchodilator FEV1 ≥40% and <70% of the predicted normal, and post-bronchodilator FEV1/FVC < 0.7 at Visit 2 • [Post refers to 1 h after sequential inhalation of the equivalent of 84 µg (ex valve) or 17 µg (ex-mouthpiece) of ipratropium bromide and 400 µg of salbutamol base)] |
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E.4 | Principal exclusion criteria |
• Pregnant women (confirmed by positive urine pregnancy test) or nursing mothers. • Women of child-bearing potential [further defined in protocol], unless specific • Patients contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs, drugs of a similar class or any component thereof: • anticholinergic agents • long and short acting beta-2 agonists • sympathomimetic amines. • lactose or any of the other excipients • Patients with a history of long QT syndrome or whose QTc measured at screening (Fridericia method) is prolonged (>450 ms for males and females) as confirmed by the central ECG assessor. • Patients who have a clinically significant abnormality on the screening ECG who in the judgment of the investigator would be at potential risk if enrolled into the study. (These patients should not be re-screened). • Patients who have not achieved an acceptable spirometry result at Visit 2 in accordance with ATS/ERS criteria for acceptability and repeatability • Patients with a Wmax value < 20 W (as determined by the incremental cycle endurance test) at Visit 2. • Patients with contraindications to cardiopulmonary exercise testing • Patients with resting (5 min) oxygen SaO2 saturation on room air of <85% • Patients who do not maintain regular day/night, waking/sleeping cycles (e.g. night shift workers). • Patients whose endurance in the exercise test is limited by non-respiratory conditions e.g. by neurologic, orthopedic, or other disorders • Patients who, in the judgment of the investigator, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to): • unstable ischemic heart disease, left ventricular failure history of myocardial infarction, arrhythmia (excluding chronic stable AF). history of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. • uncontrolled hypo-or hyperthyroidism, hypokalemia or hyperadrenergic state • narrow-angle glaucoma • symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. Patients with a transurethral resection of prostate (TURP) are excluded from the study. Patients who have undergone full re-section of the prostate may be considered for the study, as well as patients who are asymptomatic and stable on pharmacological treatment for the condition. • Patients requiring long term oxygen therapy (> 15 h a day) on a daily basis for chronic hypoxemia or who experience oxygen desaturation <80% during cycle exercise on room air. • Patients who have had a COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the 6 weeks prior to Visit 1 or between Visit 1 and Visit 4.
[other exclusion criteria are defined in the protocol] |
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the effect of QVA149 110/50 µg compared with placebo to QVA149 inhaled once daily on exercise tolerance as measured by exercise endurance time during a sub-maximal constant-load cycle ergometry test (SMETT) after three weeks of treatment. |
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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 | 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 | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
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.8.3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 3 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 3 |