| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic obstructive pulmonary disease (COPD) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Chronic obstructive pulmonary disease (COPD) |
|
| 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 | 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 compare the effect of UMEC/VI (62.5/25 mcg once daily) with UMEC (62.5 mcg once daily) on lung function. |
|
| E.2.2 | Secondary objectives of the trial |
To compare UMEC/VI (62.5/25 mcg once daily), UMEC (62.5 mcg once daily) with salmeterol (50 mcg twice
daily) on patient reported outcomes (PROs). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
AGE
1. 40 years or older at date of signing informed consent at Screening Visit 1.
TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY
2. Outpatient with a diagnosis of COPD.
3. FEV1: Persistent airflow limitations as indicated by: A pre and postalbuterol/ salbutamol FEV1/FVC ratio of <0.70 and a post-albuterol/salbutamol FEV1 of ≥30% to ≤80% predicted normal values at Screening Visit 1.
4. CAT score: A CAT score of ≥10 at Screening Visit 1.
Smoking History
5. Current or former cigarette smokers with a history of cigarette smoking of ≥ 10 pack-years [number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g. 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack-years)]. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Pipe and/or cigar use cannot be used to calculate pack-year history.
SEX
6. Male and female subjects are eligible to participate in the study
A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies:
a. Non-reproductive potential defined as:
Pre-menopausal females with one of the following:
• Documented tubal ligation
• Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion
• Hysterectomy
• Documented Bilateral Oophorectomy
Postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause must be tested. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study.
Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
b. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until [at least five terminal half-lives OR until any continuing pharmacologic effect has ended, whichever is longer] after the last dose of study medication and completion of the follow-up visit.
The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
INFORMED CONSENT
7. Capable of giving signed informed consent prior to study participation, which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. |
|
| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER FUNCTION
1. Asthma
2. Alpha-antitrypsin deficiency
3. Other respiratory disorder
4. Unstable liver disease
5. Unstable or life threatening cardiac disease
6. 12 Lead ECG:
7. Antimuscarinic effects
8. Other disease abnormalities
9. Hospitalization
10. Inhaled corticosteroids (ICS)
11. Exacerbation
12. Other respiratory tract infections
13. Lung Resection
14. Oxygen
(For detailed list, please refer to pages 27-29 of the study protocol)
CONCOMITANT MEDICATIONS
1. Medications prior to Screening: Use of the following medications according to the following defined time intervals prior to Screening (Visit 1) (Please refer to table listed on page 29 of study protocol)
2. Medication prior to spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
3. Maintenance use of short-acting bronchodilators: Regular use (prescribed for daily/ regular use, not for as-needed use) of short-acting bronchodilators (e.g. albuterol/salbutamol).
RELEVANT HABITS
1. Drug or alcohol abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Screening Visit 1 that in the opinion of the investigator would prevent the subject from completing the study procedures.
CONTRAINDICATIONS
1. Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, sympathomimetic, lactose/milk protein or magnesium stearate.
DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA
1. Pulmonary Rehabilitation program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
2. Affiliation with investigator sites: Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study
3. Inability to read: In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete questionnaires on the electronic diary.
Subjects who fail to meet inclusion and exclusion criteria at the Screening Visit 1 will be considered screen failures and cannot be re-screened.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in trough Forced Expiratory Volume in One Second (FEV1) at week 24 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| To compare UMEC/VI (62.5/25 mcg once daily), UMEC (62.5 mcg once daily) with salmeterol (50 mcg twice daily) on patient reported outcomes (PROs) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| over 24 weeks of treatment |
|
| 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 | Yes |
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Salmeterol (Serevent) & Umeclidinum (UMEC) (Incruse) |
|
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 100 |
| 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 |
| Canada |
| Mexico |
| South Africa |
| United States |
|
| 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 | 7 |
| E.8.9.1 | In the Member State concerned days | 21 |
| 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 | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 21 |
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