E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic obstructive pulmonary disease (COPD) |
chronisch obstructieve longziekte |
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E.1.1.1 | Medical condition in easily understood language |
COPD includes chronic bronchitis and emphysema (= less elastic lungs, shortness of breath may occur) and is characterized by airway narrowing that is not fully reversible. |
COPD omvat chronische bronchitis en emfyseem (= longen zijn minder rekbaar waardoor kortademigheid kan voorkomen) en wordt gekenmerkt door luchtwegvernauwing die niet volledig omkeerbaar is. |
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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 | 17.1 |
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.1.3 | 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 assess the efficacy of Roflumilast in addition to long-acting muscarinic antagonist (LAMA)/ long acting β2-agonist (LABA) therapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary study objective is to obtain data about the health related quality of life, lung function tests and exercise tolerance. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patient ≥ 30 years old
2. Written informed consent obtained
3. Patient with Body mass index (BMI) ≥ 20
4. Female patient of childbearing potential who confirm that a contraception method was used at least 14 days before visit 1 and will continue to use a contraception method during the study
5. COPD patient with GOLD stages C and D
6. Patient with a Borg Fatigue score after the 6MWT on screening above 4 to indicate the susceptibility to dynamics hyperinflation
7. Patient with smoking history of at least 10 pack-years
8. Patient takes a combination therapy of LABA/ LAMA at least 6 weeks before visit 1
9. Patient must be able to understand and complete the protocol requirements, instructions, questionnaires and protocol-stated restrictions
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating females
2. Patient with severe immunological diseases and/ or severe acute infectious diseases
3. Patient with heart failure as documented in the medical history or as defined by the investigator during the physical examination performed at visit 1
4. Patient with diagnosis of cancer (except basal cell carcinoma)
5. Patient with a history of depression associated with suicidal ideation or behaviour
6. Patient with moderate or severe hepatic impairment.
7. Patient with lactose intolerance
8. Patient is unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study.
9. Patient who received inhalation corticosteroids (ICS) within the last 6 weeks prior to the screening visit
10. Patient who received any investigational new drug within the last 4 weeks prior to the screening visit or twice the duration of the biological effect of any drug (whichever is longer)
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E.5 End points |
E.5.1 | Primary end point(s) |
- Airway volume (iVaw)
- Airway resistance (iRaw)
- Lobe volumes (iVlobes)
- Air trapping
- Internal Lobar Airflow Distribution
- Low Attenuation or Emphysema Score
- Blood Vessel Density
- Airway Wall Thickness
- Aerosol deposition concentrations
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Spirometry:
• FEV1
• Peak Expiratory Flow (PEF)
• Forced Vital Capacity (FVC)
• Maximum Expiratory Flow at 50% of FVC (MEF 50)
• Maximum Expiratory Flow at 25% of FVC (MEF 25)
- Body plethysmography:
• Residual Volume (RV)
• TLC
• FRC
• Airway resistance (Raw)
- Diffusion capacity
• carbon monoxide transfer factor (TCO)
• Alveolar volume (VA)
- 6MWT:
• Exercise capacity: distance walked in 6 minutes (m), oxygen saturation measurement will be performed during the test
- PRO:
• Borg CR10 Scale: measure of the present dyspnea and leg fatigue before and after exercise
• COPD assessment test (CAT): measure of the impact of COPD on your life
• Saint George’s Respiratory Questionnaire (SGRQ): measure health related quality of life and comfort
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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) | 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 | No |
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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |