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 | 9.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10038738 |
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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 50 μg NVA237 compared with matching placebo 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 |
Key sec.obj.:To determine the effect of 50 μgNVA237 compared with plac.on isotime inspiratory capacity during SMETT after 3weeks of treatment. • To determine the effect of 50μg NVA237 compared with plac.on inspiratory capacity at rest and at peak during SMETT after 3 weeks of treatment.• To determine the effect of 50 μg NVA237 compared with plac.on peak and trough (i.e.24 h post dose) FEV1 after 3 weeks of treatment. • To evaluate the effects of 50 μg NVA237 compared to plac.on Slow Vital Capacity, Forced Vital Capacity, Specific Airway Conductance and Total Lung Capacity after 3 weeks of treatment.• To evaluate the effect of 50 μg NVA237 compared to placebo on exertional dyspnea during SMETT after 3weeks treatment.• To evaluate the effect of 50 μg NVA237 compared to placebo on leg discomfort during SMETT after3 weeks treatment.-To determine the effect of a single dose on treat.Day1 of 50μgNVA237 compared with plac.on exercise tolerance as measured byExer.EnduranceTime duringSMETT |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female adults aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure. 2. Patients with moderate to severe stable COPD (clinical diagnosis in compliance with GOLD Guidelines 2008). 3. Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc.). 4. Patients with a post-bronchodilator FEV1 ≥35% and < 70% of the predicted normal, and post-bronchodilator FEV1/FVC < 0.7 during screening. (Post refers to 30 min after inhalation of 80 μg ipratropium bromide). 5. Increase in FEV1 from Pre-bronchodilator to Post-bronchodilator assessment of at least 5%. |
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E.4 | Principal exclusion criteria |
- Pregnant women or nursing mothers or of child-bearing potential except for the cases listed into protocol. - Patients who have had a COPD exacerbation in the 6 weeks prior to Visit 1 or between V. 1 and V. 4.- Patients who have had a lower respiratory tract infection in the 6 weeks prior to V. 1.- Patients requiring long term oxygen therapy on a daily basis for chronic hypoxemia.- Patients with resting (5 min) oxygen SaO2 saturation on room air of < 85%.- Patients with a Wmax value <20 W at V. 2.-Patients, whose exercise endurance time at sub-maximal workload is above 25 min at baseline; - Patients with contraindications (see example into Protocol) to cardiopulmonary exercise testing ;- Patients involved in the active phase of a supervised Pulmonary Rehabilitation Program.- Patients who have a clinically relevant laboratory abnormality or a clinically significant condition such the ones described into the Protocol as example; - Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency.- Patients with concomitant pulmonary disease, e.g., pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active) or clinically significant bronchiectasis.- Patients with any history of asthma or with allergic rhinitis who use H1 antagonists or intranasal corticosteroids intermittently are to be excluded. Treatment with a stable dose is permitted (constant dose for at least 1 month prior to V. 2).- Patients with a history of long QT syndrome or whose QTc is prolonged at screening. - Patients who have a clinically significant abnormality on the screening or baseline ECG who in the judgement of the investigator would be at potential risk if enrolled into the study. - Patients contraindicated for treatment with, or having a history of reactions/hypersensitivity to any of the class drugs described into the Protocol, included, for example, anti-cholinergic agents, long- and short-acting β2-agonists, sympathomimetic amines; - Treatments for COPD and allied conditions: the medications described into the Protocol should not be used between V. 1 and V. 4 and then through the subsequent course of the study. Further to this, into the Protocol, is specified the minimum washout prior to V. 2.- Patients who need the following treatments for COPD and allied conditions (e.g. allergic rhinitis) unless they have been stabilized as follows: Inhaled corticosteroids in recommended and constant doses and dose regimens (previously given as either part of a fixed dose combination of LABA+ICS or ICS as monotherapy) for at least 1 month prior to V. 2, Intranasal corticosteroids in recommended and constant doses and dose regimens for at least 1 month prior to V. 2, H1 antagonists in recommended and constant doses and dose regimens for at least 5 days prior to V. 2;- Other excluded medications: Leukotriene antagonists (7 days prior to V. 2), Cromoglycate, nedocromil, ketotifen (7 days prior to V. 2), Intramuscular glucocorticosteroid e.g. Kenalog: unless discontinued 3 months prior to V. 2, Parenteral or oral glucocorticosteroids unless discontinued 1 month prior to V. 2;- Patients unable to use a dry powder inhaler device or pressurized rescue medication) or unable to use an electronic patient diary;- Patients who are known to be unreliable or noncompliant or with any condition or prior or present treatment rendering the patient not eligible for the study;- Use of other invest. drugs at the time of enrollment, or within 30 days or 5 halflives of V. 1, whichever is longer.- Patients whose endurance in the exercise test is limited by non–respiratory conditions. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary PD endpoint is exercise endurance at week three. |
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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 | 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 | No |
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) | No |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 | Information not present in EudraCT |
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 |
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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 | 0 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |