E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease (COPD) |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Obstructive Pulmonary Disease (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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052996 |
E.1.2 | Term | Inhalation therapy |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
Q1. What is the lung deposition behaviour of inhaled bronchodilator (salbutamol)aerosols of different particle size within the airways of patients with chronic obstructive pulmonary disease (COPD)? How does this distribution compare to that observed in healthy subjects with no lung disease?
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E.2.2 | Secondary objectives of the trial |
Q2. What is the effect of different patient inhalation flows on the lung deposition of different sized bronchodilator (salbutamol) particles? Is there a specific particle size and inhalation flow to achieve optimal lung deposition in COPD patients?
Q3. Does the regional deposition and distribution of inhaled bronchodilator (salbutamol) aerosols influence the clinical (physiological pharmacodynamic) and systemic (urinary pharmacokinetic) responses in COPD patients?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
COPD patients, either male or female, over the age of 40 with a clincal diagnosis of COPD with airflow obstruction (FEV1/FVC<0.7) and post-bronchodilator FEV1>50% predicted, gas trapping (on lung volume testing), and decreased carbon monoxide transfer factor.
Healthy subjects will be non-smokers (or ex-smokers stopped 5 years ago), will have no respiratory disease, normal spirometry and be age-matched to the COPD patients.
Asthmatic subjects, either male or female, over the age of 18 with a clincal diagnosis of Asthma with airflow obstruction (FEV1/FVC<0.7).
Capable of giving informed consent. |
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E.4 | Principal exclusion criteria |
1) Oral corticosteroids taken within last month.
2)Current involvement (or involvement in the last 4 weeks)in clinical trials assessing investigational medicinal products.
3)Previous adverse reaction to short or long acting β2 agonist.
4) Any subject with a contraindication to taking inhaled beta-2 adrenoceptor agonists (especially salbutamol) as listed in the British National Formulary will not be entered into this study.
5) Those who have experienced an acute respiratory exacerbation requiring emergency room treatment and/ or hospitalisation within four weeks of visit 1 (screening visit).
6) Pregnant or breast-feeding women.
7) Subjects unable to give Informed Consent. |
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E.5 End points |
E.5.1 | Primary end point(s) |
LUNG DEPOSITION study: The primary endpoint for aerosol deposition is penetration index (PI) calculated from planar-images, which will indicate differences in regional lung deposition as a function of particle size.
Lung PHYSIOLOGY study: The primary endpoints are multi-breath nitrgen washout (UNGW) indices of acinar airways (Sacin) and conducting airways (Scond), which will indicate differences in small (and large) airway physiology as a function of particle size. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
LUNG DEPOSITION study: The timepoint of evaluation will be 5 minutes after drug inhalation.
LUNG PHYSIOLOGY study: The timepoint of evaluation will be 30 minutes after drug inhalation. |
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E.5.2 | Secondary end point(s) |
The secondary outcome measures for both LUNG DEPOSITION and LUNG PHYSIOLOGY studies are: Analysis of the lung physiology (Multi-breath Nitrogen Washout(MBNW), Impulse oscillometry (IOS), Spirometry, Body plethysmography, Oral Pharngometry) and Urine pharmacokinetics |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
MBNW, IOS and Spiromtery: The timepoint(s) of evaluation are 30, 60, 120 minutes Body Plethysmography: The timepoint(s) of evaluation are 60, 120 minutes Oral Pharyngometry: The timepoint(s) of evaluation are 30, 120 minutes Urine Pharmacokinetics: The timepoints of evaluation are 0-30minutes, 0-24 hours, 30mins -24 hours) |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 |
Study of inhaled drug deposition and pharmokinetics of salbutamol absorbtion from the lung. |
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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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Salbutamol of differing inhaled particle size |
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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 | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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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Last visit of last subject |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |