E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Caucasian males between 18 and 65 years of age (both inclusive) with the diagnose of persistent asthma for at least 6 months prior to screening, who are otherwise in good general physical health |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
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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 |
To assess the activity of single doses of LAS100977 administered by inhalation to patients with persistent asthma.
To evaluate the safety, tolerability and pharmacokinetics of single doses of LAS100977 after single administration to patients with persistent asthma
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult male subjects aged 18-65 years (both included).
Clinical diagnosis of persistent asthma (according to GINA guidelines 2002) for at least 6 months prior to screening.
Maintenance on a stable dose of inhaled corticosteroids over the previous 6 weeks prior to screening, either together with a short-or long-acting beta-2-agonist.
Screening FEV1 value of 60 < FEV1 <= 85% of the predicted normal value after a washout of at least 6 hours for short-acting ß2-agonists and 72 hours for long-acting beta-2-agonists, if applicable.
FEV1 reversibility of 12% and an absolute increase of at least 200 ml over baseline value within 30 minutes after inhalation of 400 µg (four inhalations) of salbutamol via a metered dose inhaler.
Ability to communicate adequately with the investigator and comply with the protocol requirements, instructions and protocol-stated restrictions.
Ability to use an inhaler device and perform spirometries.
Eligibility and ability to participate in the trial and consent to do so in writing after the purpose and nature of the investigation have been explained.
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E.4 | Principal exclusion criteria |
Smoking history during the last 12 months or history of smoking more than 10 pack-yrs.
Presence of clinically significant diseases other than asthma (cardiovascular, renal, hepatic, gastrointestinal, haematological, neurological, genitourinary, autoimmune, endocrine, metabolic, etc), which, in the opinion of the investigator, may either put the patient at risk because of participation in the trial, or diseases which may influence the results of the study or the patient’s ability to take part in it.
Presence of relevant pulmonary diseases or history of thoracic surgery, such as: • Known active tuberculosis. • History of interstitial lung or pulmonary thromboembolic disease. • Pulmonary resection during the past 12 months. • History of status asthmaticus. • History of bronchiectasis secondary to respiratory diseases (e.g., cystic fibrosis, Kartagener’s syndrome, etc). • History of chronic bronchitis, emphysema, allergic bronchopulmonary aspergillosis or respiratory infection within the 4 preceding weeks of the first morning IMP administration.
Hospitalisation or emergency room treatment for acute asthma in the 6 weeks prior to screening, between screening and the start of the first treatment period, or between treatment periods.
Intubation (ever) or hospitalization for longer than 24 hours for the management of an asthma exacerbation within the preceding 6 weeks of the screening visit.
Positive laboratory test for urine illicit drug screening.
Positive test Hepatitis B surface antigen or HBc, HIV and Hepatitis C antibodies. Patients vaccinated for Hepatitis B and not infected from the disease can take part in the trial.
History of severe allergy (anaphylaxis, angioneurotic oedema) or drug hypersensitivity reactions or hypersensitivity to drugs chemically related IMP.
Intention to use any concomitant medication not permitted by this protocol or insufficient washout period for a particular prohibited medication (see section 10.3).
Treatment with β2-antagonists (including eye drops).
Treatment with drugs that may modify QT interval (non-potassium sparing diuretics, MAOIs, TCAs, SSRIs, antipsychotic agents, serotonin receptor agonists, macrolide antibiotics, fluoroquinolone antibiotics, anti-protozoal antibiotics and antihypertensive agents).
Excessive coffee, tea or chocolate consumption (more than 6 cups/day on average) or cola / caffeine containing drinks (more than 6 glasses/day).
Loss of more than 400 mL of blood within the previous 3 months, or more than 250 mL within the month before entering the trial.
History of drug and/or alcohol abuse during the last 2 years, that may interfere with the trial activities compliance.
Treatment with any Investigational Medicinal Product (IMP) within 6 weeks prior to screening or the equivalent time to 6 half-lives of the IMP, whichever is longer.
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E.5 End points |
E.5.1 | Primary end point(s) |
Spirometry Change from pre-dose in the trough FEV1
Trough FEV1, FVC, PEF and FEF25-75 (The trough value will be the mean of the 23h and 24h FEV1, FVC, PEF and FEF25-75 values)
Normalised FEV1, FVC, PEF and FEF25-75 area under the curve over the 6-hour (AUC 0-6), 12-hour (AUC 0-12), 24-hour (AUC 0-24), 36-hour (AUC 0-36) post-dosing interval.
Normalised FEV1, FVC, PEF and FEF25-75 area under the curve between 12 and 24 hours (AUC 12-24) post-dosing interval.
Change from pre-dose in normalised FEV1 / FVC / PEF / FEF25-75 AUC 0-6, AUC 0-12, AUC 0-24, AUC 0-36, AUC 12-24.
Change from pre-dose in the trough FVC, PEF and FEF25-75.
Change from pre-dose in FEV1, FVC, PEF and FEF25-75 at each time point.
Peak FEV1, FVC, PEF and FEF25-75: the maximum FEV1, FVC, PEF and FEF25-75 value over the first 3 hours after the morning IMP administration.
Change from pre-dose in the peak FEV1, FVC, PEF and FEF25-75 .
Time to peak FEV1.
Number and percentage of patients achieving the peak FEV1 at each timepoint during the 3-h period after the morning IMP administration.
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability in asthmatic patients |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 2 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |