E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
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 compare the efficacy of two doses of formoterol, 12µg and 24µg, delivered by Concept1 with corresponding doses of formoterol delivered by Aerolizer® in terms of bronchodilator efficacy in patients with persistent asthma by testing the hypotheses: •Formoterol Concept1 12µg is equivalent to formoterol Aerolizer® 12µg in terms of FEV1 AUC over 12 hours following inhalation of a single dose; •Formoterol Concept1 24µg is equivalent to formoterol Aerolizer® 24µg in terms of FEV1 AUC over 12 hours following inhalation of a single dose;
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E.2.2 | Secondary objectives of the trial |
To demonstrate that each dose of formoterol delivered by Concept1 is equivalent to the corresponding dose of formoterol delivered by the Aerolizer® in terms of serial measurements of FEV1 following inhalation of a single dose |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male and female adult and adolescent patients aged 13 years and over, who have signed an Informed Consent Form prior to initiation of any study-related procedure. In the case of patients below the legal age of consent, the Informed Consent Form should also be signed by the patient’s parent / guardian.
Patients with stable mild or moderate persistent asthma, diagnosed according to GINA guidelines [National Institutes of Health. National Heart, Lung and Blood Institute. (OCT 2005)] and who additionally meet the following criteria: •Patients receiving daily treatment with anti-inflammatory asthma medication, in a stable regimen for the month prior to Visit 1. •Patients whose FEV1 at Visit 2 is >= 60% of his/her predicted normal value. This criterion for FEV1 will have to be demonstrated after a washout period of at least 6-hours during which no shortacting β2-agonist has been inhaled, and 48 hours for a long-acting β2-agonist . •Patients who demonstrate an increase of >=15% or 200ml in FEV1 over their pre-treatment value within 30 minutes after inhalation of 400 µg (4 x 100 µg inhalations) of salbutamol (the administration of salbutamol for the reversibility test has to be within 30 minutes of pre-treatment spirometry).Reversibility will have to be demonstrated at Visit 2 only, after a washout period of at least six hours prior to the evaluation for a short-acting β2-agonist and 48 hours for a long-acting β2- agonist.
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E.4 | Principal exclusion criteria |
•Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer •History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures •History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml) •Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, hysterectomy), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable for analysis will be the 12 hour Area Under the Curve (AUC) of FEV1 following a single dose of study medication standardized with respect to length of time completed in the observation period (expressed in L) without intake of rescue medication.
The primary objective will be addressed by testing the following hypotheses: •Formoterol Concept1 12µg is equivalent to formoterol Aerolizer® 12µg in terms of FEV1 AUC over 12 hours following inhalation of a single dose; •Formoterol Concept1 24µg is equivalent to formoterol Aerolizer® 24µg in terms of FEV1 AUC over 12 hours following inhalation of a single dose;
Initially the equivalence of the 12µg doses delivered by the two devices will be tested and if established, the equivalence of the 24µg doses will be tested. However if the first hypothesis is not accepted the second will not be addressed. Treatment comparisons will be tested on the ITT population but because of the cross-over nature of the study, only patients who have received at least two different randomized treatments will contribute data to the analyses. Equivalence of the same doses of formoterol delivered by the two devices will be claimed if the two-sided 95% confidence interval of the estimated treatment difference for Concept1 12µg minus Aerolizer 12µg lies entirely within the region (-0.100L, 0.100L). No adjustment for multiplicity is required as the equivalence of the higher doses will only be tested conditional on demonstrating the equivalence of the lower doses i.e. in a hierarchical testing scheme. An analysis of covariance (ANCOVA) model will be used to estimate the treatment contrasts for the standardized FEV1 AUC fitting patient, period and treatment as fixed effects with baseline FEV1 as a covariate. No testing for carryover will be performed as it is assumed that the washout phase is adequate (at least 5 times the half life of 10 hours). Center effects will not be considered as these will be confounded with patient effects. The trapezoidal rule will be applied using planned time measurements to calculate the area under curve up to and including the last measurement recorded before intake of rescue medication. The AUC will be standardized by dividing by the length of time for which measurements of FEV1 have been included in the calculation of the AUC thereby adjusting for patients who were unable to complete the measurements during the 12 hour observation period and without inhaling rescue medication. In this way the unit of the AUC will be in L being a weighted average of the acceptable FEV1 measurements recorded over 12 hours post dose.
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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 | 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) | No |
E.8.2.2 | Placebo | Yes |
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 | 4 |
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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End of trial is last visit of last patient |
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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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |