E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease |
|
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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009033 |
E.1.2 | Term | Chronic obstructive pulmonary disease |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
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 demonstrate that QVA149 110/50 µg q.d. is superior to placebo in terms of improvement of patient reported dyspnea as assessed by BDI/TDI (SAC version) after 6 weeks of treatment. |
|
E.2.2 | Secondary objectives of the trial |
To demonstrate that QVA149 110/50 µg q.d. is superior to tiotropium 18 µg q.d. in terms of improvement of patient reported dyspnea as assessed by BDI/TDI (SAC version) after 6 weeks of treatment.
Secondary objectives:
To evaluate QVA149 110/50 µg q.d. as compared to placebo and tiotropium 18 µg q.d. after 6 weeks of treatment in terms of;
•Standardized FEV1 AUC 0-4 hrs
•Standardized FVC AUC 0-4 hrs
•The mean change from baseline in morning activities using The Capacity of Daily Living during the Morning (CDLM) Questionnaire
•The mean change from baseline in number of puffs of rescue medication
•Safety and tolerability (adverse events, laboratory tests, ECGs, and vital signs).
To assess the correlation of improvement in CDLM to the improvement in FEV1 AUC0-4 hrs after 6 weeks of treatment. |
|
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 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 -14).
- mMRC grade of at least 2 at Visit 2.
- Patients with ability to use the computer mouse and navigate the computer display. |
|
E.4 | Principal exclusion criteria |
- Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy
test).
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use effective contraception during the study. UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea, OR 6 weeks after surgical bilateral oophorectomy (with or without hysterectomy).
- Patients with a history of long QT syndrome or whose QTc measured at Visit 2 (Day -14) (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 ECG at Visit 2, who in the judgment of the investigator would be at potential risk if enrolled into the study.
- Patients with Type I or uncontrolled Type II diabetes
- Patients who have not achieved spirometry result at Visit 2 in accordance with ATS/ERS criteria for acceptability and repeatability.
- Patients with narrow-angle glaucoma, symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention.
-Patients with a history of malignancy of any organ system
-Patients requiring long term oxygen therapy (> 15 h a day) on a daily basis for chronic
hypoxemia.
-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 screening (Visit 1 or between Visit 1 and Visit 3).
-Patients who develop a COPD exacerbation between the pre-screening and the randomization visit (Visits 1 and 3) will not be eligible but will be permitted to be rescreened after a minimum of 6 weeks after the resolution of the COPD exacerbation.
-Patients who have had a respiratory tract infection within 6 weeks prior to pre-screening
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
To demonstrate that QVA149 110/50 μg q.d. is superior to tiotropium 18 μg q.d. in terms of improvement of patient reported dyspnea as assessed by BDI/TDI (SAC version) after 6 weeks of treatment. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
To evaluate QVA149 110/50 μg q.d. as compared to placebo and tiotropium 18 μg q.d. after 6
weeks of treatment in terms of;
• Standardized FEV1 AUC 0-4 hrs
• Standardized FVC AUC 0-4 hrs
• The mean change from baseline in morning activities using The Capacity of Daily Living
during the Morning (CDLM) Questionnaire
• The mean change from baseline in number of puffs of rescue medication
• Safety and tolerability (adverse events, laboratory tests, ECGs, and vital signs). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 |
|
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |