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.1.1.2 | 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 | 10009033 |
E.1.2 | Term | Chronic obstructive pulmonary disease |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 |
Our principle objective is to investigate the effect of tiotropium (a long-acting inhaled bronchodilator), delivered from different devices, on a panel of small (IOS, MBNW, DLCO, FVC) and large airway (FEV1, PEF) responses in patients with mild-moderate COPD. We will compare equivalent doses of Titropium from Respimat (Tiotropium Respimat 5 micrograms once daily), a small particle soft mist inhaler (SMI) compared to delivering it from Handihaler (18 micrograms once daily), a standard large particle dry powder inhaler (DPI). Respimat is a novel inhaler platform that has small particles and a slow inhalation allowing deeper lung drug delivery.
We will be using easily performed non-invasive breathing tests to measure response: • Impulse Oscillometry (IOS) parameters • Multiple Nitrogen Washout parameters (MBNW) • Lung function test (LFT) parameters: We will also assess the safety and tolerability, as determined by vital signs of heart rate and blood pressure.
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E.2.2 | Secondary objectives of the trial |
Our secondary objective is to investigate the effect of Inhaler Training with Handihaler on airway function and symptoms. We will train patients in the optimal use of the Handihaler. Therefore if we train patients with the Handihaler properly can we improve (i) lung function (large and small airway) and (ii) clinical symptoms (determined by CAT score). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
COPD 1) COPD patients with FEV1/FVC <70% predicted.
2) Mild (GOLD stage I: FEV1 >80% pred.) to moderate (GOLD stage II: FEV1 50-80% pred.)
3) Aged 30 years onwards – there is no upper age limit as we do not want to exclude elderly patients as COPD is primarily a disease in the elderly population.
4) Have ongoing symptoms or exercise limitation (determined by CAT score)
5) Stable COPD (no chest infection requiring antibiotics and/or oral steroids in the past 2 months).
6) Capable of giving informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
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E.4 | Principal exclusion criteria |
COPD 1) We will not recruit subjects who lack the capacity to consent.
2) Current or past diagnosis of asthma.
3) Patients on concurrent LABAs or oral bronchodilators (theophylline, PDE4 inhibitors) will not be included.
4) History of any chronic respiratory diseases other than COPD.
5) History of another medical condition, which in the opinion of the Unit Physician, contraindicates his/her participation in the study.
6) Clinical evidence of heart failure (NYHA class III-IV).
7) Unstable respiratory disease in the last four weeks prior to the screening visit (indicated by any change in their maintenance inhaled therapy or who have had a lower respiratory tract infection in the previous four weeks).
8) Evidence of a respiratory exacerbation requiring emergency room treatment and/or hospitalisation within four weeks before screening.
9) Use of systemic (oral or intravenous) steroids 4 weeks prior to inclusion (injectable depot steroids 6 weeks) or more than 3 periods during the last 12 months.
10) Participants with a known or suspected allergy, sensitivity or intolerance to the study drugs (this will be asked directly at the screening visit) or patients with a history of another drug allergy which, in the opinion of the Unit Physician, contraindicates his/her participation in the study.
11) Patient with a contraindication to taking an inhaled long-acting beta-agonists, listed in the British National Formulary (BNF).
12) Patients treated with beta-blockers in the week preceding the screening visit and during the study period.
13) Females who are pregnant or lactating or are likely to become pregnant during the trial. Women of childbearing potential may be included in the study if, in the opinion of the investigator, they are taking adequate contraceptive precautions.
14) Patients who have evidence of alcohol or substance abuse.
15) Participation in another clinical trial with an investigational drug in the four weeks preceding the screening visit.
16) Contraindication to taking Tiotropium bromide
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure will be impulse Oscillometry (IOS) R5-R20. We will measure what effect changing the inhaler device from a Tiotropium DPI-Handihaler to a Tiotropium SMI-Respimat has on this parameter? The dose of the drug will be equivalent for each device – that is Tio 18mcg HH = Tio 5mcg Resp).
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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) |
Other IOS parameters MBNW, DLCO, FVC, FEV1, PEF, CAT score |
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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 | 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) | 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 | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 1 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |