| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic obstructive pulmonary disease (COPD) |
|
| 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 |
|
| 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 evaluate the relationship of incremental doses of NVA237 q.d. and b.i.d. and their effect on trough FEV1 after 28 days of treatment, as defined by the percentage of the maximal effect that each dose achieves in relation to the maximal effect of NVA237. (Trough is defined as the mean of FEV1 measurements at 23 h 15 min and 23 h 45 min post morning dose). |
|
| E.2.2 | Secondary objectives of the trial |
Key secondary objective
To evaluate the magnitude of any difference of effect on trough FEV1 after 28 days of treatment between the same total daily doses of NVA237 by comparing once daily and twice daily dosing regimens.
Important secondary objectives
• To evaluate the relationship of incremental doses of NVA237 q.d. and b.i.d. and their effect on AUC5 min-24 h FEV1 after 28 days of treatment, as defined by the percentage of the maximal effect that each dose achieves in relation to the maximal effect of NVA237.
• To evaluate the magnitude of any difference of effect on AUC5 min-24 h FEV1 after 28 days of treatment between the same total daily doses of NVA237 by comparing once daily and twice daily dosing regimens.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study have to fulfill all of the following 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 2008.
• Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten packyears are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc.)
• Patients with a post-bronchodilator FEV1 ≥30% and < 80% of the predicted normal, and post-bronchodilator FEV1/FVC < 0.7 at Visit 2 (Day -8). (Post refers to 45 mins after inhalation of 84 μg ipratropium bromide)
• Symptomatic patients, according to daily electronic diary data between Visit 2 (Day -8) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to Visit 3. |
|
| E.4 | Principal exclusion criteria |
General exclusion
1. Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test).
2. Women of child-bearing potential (WOCBP)as defined in the protocol
3. Patients who have a clinically significant abnormality on the screening or baseline ECG who in the judgment of the investigator would be at potential risk if enrolled into the study.
4. Patients with a history of long QT syndrome or whose QTc measured at Visit 2 (Day -8) is prolonged as confirmed by a central ECG assessor.
5. Patients with Type I or uncontrolled Type II Diabetes.
6. Patients who, in the judgment of the investigator or the responsible Novartis personnel, 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). Patients with such events not considered clinically significant by the investigator may be considered for inclusion in the study.
• 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.
• 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).
• uncontrolled hypo- or hyperthyroidism, hypokalemia, or hyperadrenergic state
• any condition which might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study
7. 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.
COPD specific exclusion
1. Patients with any history of asthma indicated by (but not limited to) a blood eosinophil count > 600/mm3 (at Visit 2), or onset of symptoms prior to age 40 years. 2. Patients with eczema (atopic), known high IgE levels or a known positive skin prick test in the last 5 years.
3. Patients with concomitant pulmonary disease
4. Patients with lung lobectomy or lung volume reduction or lung transplantation
5. Patients with a known history and diagnosis of alpha-1 anti-trypsin defiency.
6. Patients with allergic rhinitis who use a H1 antagonist or intra-nasal corticosteroids intermittently (treatment with a stable dose is permitted).
7. Patients requiring long term oxygen therapy on a daily basis for chronic hypoxemia.
9. Patients who have had a COPD exacerbation that required treatment with antibiotics or oral glucocorticosteroids or hospitalization in the 6 weeks prior to Visit 1 or between Visit 1 (Day -15) and Visit 3 (Day 1).
• Patients who develop a COPD exacerbation between pre-screening (Visit 1) and randomization (Visit 3) will not be eligible but will be permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation
10. Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1 (Day -15).
• Patients who develop an upper or lower respiratory tract infection during the screening period (between Visit 1 (Day -15) and Visit 3 (Day 1)) will not be eligible, but will be permitted to be re-screened 4 weeks after the resolution of the lower respiratory tract infection
Medication exclusion
1. Patients receiving any prohibited medications in the classes or groups listed in Table 5-3
2. Patients receiving any prohibited COPD related medications in the classes or groups listed in Table 5-4 must undergo the required washout period prior to screening (Visit 2) and follow the adjustment to treatment programme.
• Patients receiving any medications belonging to the classes or groups listed in Table 5- 5 should only be enrolled if the treatment has been stabilized.
3. Patients who have had live attenuated vaccinations within 30 days prior to the screening visit or during the run-in period. Inactivated influenza vaccination, pneumococcal vaccination or any other inactivated vaccine is acceptable provided it is not administered within 48 hours prior to the screening and/or randomizationa study visit.
4. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives of Visit 1 (Day -15), whichever is longer.
Please report to the protocol for Study conduct exclusion criteria |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| To evaluate the relationship of incremental doses of NVA237 q.d. and b.i.d. and their effect on trough FEV1 after 28 days of treatment, as defined by the percentage of the maximal effect that each dose achieves in relation to the maximal effect of NVA237. (Trough is defined as the mean of FEV1 measurements at 23 h 15 min and 23 h 45 min post morning dose). |
|
| 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 | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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) | 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 31 |
| 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 |
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 26 |
| 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 | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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