| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| This study has been initianed to assess the bronchodilating properties of a new generic dry powder formoterol formulation given from a novel dry powder inhaler compared to the reference Foradil Aerolizer in moderate to severe adult asthmatic subjects. |
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| MedDRA Classification |
| 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 therapeutic equivalence of the Liconsa 12 µg dry powder formoterol inhalation product compared to a reference formoterol product (Foradil Aerolizer) given in a crossover, single-dose design. |
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| E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of the Liconsa 12 µg dry powder formoterol inhalation product compared to a reference formoterol product (Foradil Aerolizer)
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
At study entry:
1. Subjects who are willing to give written informed consent to participate in the study.
2. Male and female asthmatic subjects, legally aged 18 - 75 years, inclusive.
3. Documented asthma for at least 6 months before screening as per the current GINA guidelines, treated with or without the use of inhaled corticosteroids. Patients on inhaled corticosteroids must have followed a stable treatment regimen for at least the previous 4 weeks prior to the Screening Visit
4. Subjects with a baseline FEV1 40% - 70% of the predicted normal value for age, height and gender after withholding short acting beta2-agonists/anticholinergics for at least 8 hours and methylxanthines, long acting 2-agonists/ anticholinergics for at least 32 hours. Qualifying lung function parameters will be measured using standardized equipment for all participating centres. Appropriate standard formulae from the European Community for Coal and Steel (Quanjer et al., 1993) will be used for the calculation of the predicted FEV1 values. The reference (ECCS) values will be generated by the specific spirometer provided by the Sponsor to the investigator.
5. Subjects who demonstrate a reversibility in airway obstruction (increase in FEV1 of 15% and an increase of at least 250 ml over pre-salbutamol values) 30 minutes after the inhalation of a dose of 200g salbutamol from a standard pMDI.
6. Subjects who are able to handle dry powder inhalers correctly.
7. Subjects who are able to perform lung function tests properly.
On study days:
1. A pre-dose baseline FEV1 within ±10% of the value obtained at the Screening Visit.
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| E.4 | Principal exclusion criteria |
Subjects will be excluded from participation if any of the following apply:
1. Subjects currently receiving oral, intravenous or intramuscular corticosteroid therapy or who have received such corticosteroid therapy in the 3 months preceding the screening or who have received more than 3 short courses of such therapy in the last year.
2. Subjects currently receiving therapy for an upper respiratory tract infection or who have received such a therapy in the month prior to the start of the study. Subjects who require such a treatment during the run-in or washout periods will be discontinued from the trial.
3. Subjects who have been hospitalized or have received emergency treatment for an exacerbation of asthma in the 3 months prior to the start of the study. Subjects who require such a treatment during the run-in or washout periods will be discontinued from the trial.
4. Subjects with a known or suspected hypersensitivity to formoterol or other β2-receptor agonists or any other ingredients of the study medications.
5. Subject who show signs of paradoxical bronchospasm after salbutamol inhalation (defined as having the lowest FEV1 within 30 minutes after inhalation smaller or equal to the lowest pre-dose baseline FEV1).
6. Subjects with any of the following concurrent conditions:
• Uncontrolled diabetes mellitus defined as fasting plasma glucose 10 mmol/L
• Evidence of current neoplastic disease other than basal cell carcinoma
• Evidence or history of tuberculosis
• Evidence or history of significant cardiovascular disease
• Respiratory disorders other than asthma or allergic rhinitis
• Clinically significant hepatic or renal disease
• Evidence or history of alcohol or drug abuse
• Evidence or history of low potassium levels (i.e., potassium values below the lower limit of normal, as per the central laboratory results at the Screening Visit) or concomitant use of non-potassium sparing diuretics.
7. Subjects currently receiving or who intend to receive during the study any of the following medications, except what is specifically permitted during the run-in and/or washout periods:
• Mono-amine-oxidase inhibitors or tricyclic anti-depressants
• Leukotriene-antagonists, either currently or during the last week preceding the screening visit
• Non-selective beta-receptor blocking agents
• Use of anticholinergics, other inhaled 2-agonists or methylxanthines:
These medications are permitted during the run-in and washout periods, provided that a washout period of at least 8 hours prior to screening and both treatment days is adhered to for short acting anticholinergics/short acting 2-agonists and a washout period of 32 hours prior to screening and both treatment days is adhered to for methylxanthines/long acting beta2-agonists/ long acting anticholinergics.
• Oral beta2-agonists. A washout period of 72 hours is required prior to the screening visit.
• Use of any other medications that contain products known to have β2-agonistic activity (i.e. ephedrine):
A washout period of 72 hours prior to screening is required.
8. Heavy smokers defined as smoking at least 10 cigarettes per day or ex-smokers who smoked more than 10 pack years.
Pack-years are calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes in a pack) and multiplying this figure by the number of years a person has smoked. For example, a person who smokes 40 cigarettes a day and has smoked for 10 years would have a 20 pack-year smoking history (40 cigarettes per day /20 cigarettes per pack = 2; 2 x 10 years of smoking = 20 pack-year history).
9. Subjects currently receiving other investigational medication or who have received investigational medication in the month prior to the screening of the study.
10. Subjects who are unlikely to be compliant, take their medication as directed or attend scheduled clinic visits as required.
11. Employees of the Sponsor or the CRO responsible for the execution of the study.
12. Women who are pregnant, lactating or likely to become pregnant during the course of the study. Women of child bearing potential will be eligible to enter the study if using adequate contraception (i.e. contraceptive pill or barrier methods).
On study days:
1. Use of short-acting beta2-agonists/short-acting anticholinergics in the 8 hours preceding the visit (or at any time on study days), or methylxanthines/long-acting beta2-agonists/long acting anticholinergics in the 32 hours preceding the visit.
2. Signs of paradoxical bronchospasm (defined as having the lowest FEV1 within 30 minutes after the inhalation of the study drug smaller or equal to the lowest pre-dose baseline FEV1 for the given study day) in the spirometries.
3. Any clinically significant abnormality following the investigator’s review of the clinical laboratory tests or ECGs done at the previous visit.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary aim of the study is to assess therapeutic equivalence of the Liconsa 12 µg dry powder formoterol inhalation product compared to a reference formoterol product (Foradil Aerolizer) given in a crossover, single-dose design
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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 | Yes |
| 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 | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
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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 | 7 |
| 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 | 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 | 8 |
| 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 | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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