E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to Very Severe COPD |
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
E.1.2 | System Organ Class | 100000004855 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010953 |
E.1.2 | Term | COPD exacerbation |
E.1.2 | System Organ Class | 100000004855 |
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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 |
The primary objective of this study is to compare the efficacy of treatment with GFF MDI, FF MDI, and GP MDI to Placebo MDI and to compare the efficacy of GFF MDI to its components on lung function using trough forced expiratory volume in 1 second (FEV1) in subjects with moderate to very severe COPD. |
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E.2.2 | Secondary objectives of the trial |
•To compare the effects of GFF MDI, FF MDI, GP MDI, and Placebo MDI on dyspnea using the Transition Dyspnea Index (TDI) focal score. •To compare the effects of GFF MDI, FF MDI, GP MDI and Placebo MDI on quality of life using the change in St. George Respiratory Questionnaire (SGRQ) score. •To compare the effects of GFF MDI, FF MDI, GP MDI, and Placebo MDI on symptoms using the change in rescue Ventolin (albuterol sulfate) HFA use as an indirect measure of COPD symptom control. •To determine the time to onset of action on Visit 4 (Day 1). Please see the protocol for Other Objectives and Safety Objectives. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Non-child bearing potential (ie, physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal); or Child bearing potential, has a negative serum pregnancy test at Visit 1, and agrees to acceptable contraceptive methods used consistently and correctly for the duration of the study. • Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS). • Current or former smokers with a history of at least 10 pack-years of cigarette smoking. • Forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of <0.70. • FEV1 must be <80% predicted normal value calculated using the Third National Health and Nutrition Examination Survey (NHANES III) reference equations. (Or reference norms applicable to other regions).
Please refer to the study protocol for the complete inclusion criteria list.
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E.4 | Principal exclusion criteria |
• Significant diseases other than COPD, ie, disease or condition which, in the opinion of the Investigator, may put the subject at risk because of participation in the study or may influence either the results of the study or the subject's ability to participate in the study. • Women who are pregnant or lactating or women of childbearing potential who are not using an acceptable method of contraception. • Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma. • Subjects who have been hospitalized due to poorly controlled COPD within 3 months prior to Visit 1 (Screening) or during the Screening Period (Visit 1 to Visit 4). • Subjects who have poorly controlled COPD, defined as acute worsening of COPD that requires treatment with oral corticosteroids or antibiotics within 6 weeks prior to Visit 1 (Screening) or during the Screening Period (Visit 1 to Visit 4). • Subjects with a diagnosis of angle closure glaucoma will be excluded, regardless of whether or not they have been treated. Subjects with a diagnosis of open angle glaucoma who have intraocular pressure controlled with medication(s) are eligible. • Subjects who have a history of hypersensitivity to β2-agonists, glycopyrronium or other muscarinic anticholinergics, or any component of the MDI.
Please refer to the study protocol for the complete exclusion criteria list. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to confirm the efficacy of GFF MDI compared to its individual components and Placebo MDI as well as the efficacy of FF MDI and GP MDI compared to Placebo MDI.
Co-Primary Endpoints in the European approach • For the EU approach, the primary endpoint will be the change from baseline in morning pre-dose trough FEV1 over 24 weeks of treatment. • TDI score over 24 weeks |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoint is listed with the endpoints. |
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E.5.2 | Secondary end point(s) |
For European approach
•Peak change from baseline in FEV1 within 2 hours post-dosing over 24 weeks •Change from baseline in SGRQ total score over 24 weeks •Change from baseline in average daily rescue Ventolin (albuterol sulfate) HFA use over 24 weeks •Time to onset of action on Day 1 Please see the protocol for Other Endpoints and Safety Endpoints. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints are listed with the endpoints. |
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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 | Yes |
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 | Yes |
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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
China |
Czech Republic |
Germany |
Hungary |
Japan |
Korea, Republic of |
Poland |
Russian Federation |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 24 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 14 |