E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 measure the magnitude and time course of the effect of FTY720 on FEV1 and other pulmonary function tests (FVC, FEF25-75%, and FEV1/FVC) in patients with moderate asthma. • To assess the safety and tolerability of once daily dosing of FTY720 in patients with moderate asthma.
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E.2.2 | Secondary objectives of the trial |
• To assess the effect of FTY720 with once daily dosing of 0.5 mg, 1.25 mg and 2.5 mg for 10 days on the use of short-acting β2 agonists in patients with moderate asthma. • To assess the pharmacokinetics (PK) of FTY720 and FTY720-phosphate (FTY720-P) after administration of once daily doses of FTY720 in patients with moderate asthma. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female patients aged 18-65 years. 2. Moderate asthmatics; a history of asthma of at least 6 months. 3. Pre-treatment FEV1 before the start of treatment on Day 1 must be i) within 15% of the actual Screening vale (litres) and ii) ≥ 60% of normal predicted FEV1. 4. No exacerbation of asthma within 3 months. 5. Male subjects must be sterile or willing to use a clinically-approved method of contraception from the time of study entry until at least 3 months after the last dose of study medication. 6. All female patients must have a negative serum pregnancy test at Screening and Baseline and must be: a) of non-child bearing potential (i.e. physiologically incapable of becoming pregnant) b) of child bearing potential and agree to using two or more of the following acceptable methods of contraception. 7. At Screening, and Baseline (Day -2), vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed after the subject has rested for at least three (3) minutes, and again when required after three (3) minutes in the standing position. 8. Otherwise healthy having passed Screening examinations. 9. Subjects must weigh at least 50kg to participate in the study, and must have a body mass index (BMI) within the range of 18 to 33 kg/m2. 10. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent.
Please refer to the enclosed protocol for further details. |
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E.4 | Principal exclusion criteria |
1. Patients who have smoked tobacco products within the 6 month period prior to Screening, or who have a smoking history of greater than 10 packs years, (defined as the number of packs of cigarettes smoked per day (20 cigarettes/pack) multiplied by the number of years that the patient has smoked). Urine cotinine levels will be measured during screening. A CO Breath Test may be used at Baseline. Smokers will be defined as any subject who reports tobacco use and/or who has a urine cotinine ≥ 500 ng/mL. 2. Use of any inhaled corticosteroid at dose > 500 μg Fluticasone (or equivalent comparative daily dosage Budesonide-DPI 1000μg) per day or oral or injected corticosteroid, leukotriene receptor antagonist, theophylline or oral β2-agonist within 1 month prior to Screening. Changes to asthma therapy, other than the use of inhaled short-acting β2 agonists, are not allowed between Screening and Baseline (Day -1) or during the treatment phase of the study. 3. A history of pulmonary disorder other than asthma. 4. A respiratory tract infection within 1 month prior to Screening. Patients with upper respiratory tract infections during the screening period must discontinue from the trial, but can re-enter the screening period one month after the infection has resolved. Patients who develop a respiratory tract infection during the treatment period should be withdrawn and replaced. 5. History of clinically significant drug allergy, or a known hypersensitivity to the study drug, any drug similar to the study drug, or any of its excipients. 6. Participation in any clinical research trial in which the patient received investigational product within three (3) months or 5 half lives, whichever is longer, prior to initial dosing (or longer if required by local regulations, and for any other limitation of participation based on local regulations). 7. Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation. 8. Significant illness within two (2) weeks prior to dosing. 9. A past medical history of clinically significant ECG abnormalities, or a known family history (grandparents, parents, siblings) of a prolonged QT-interval syndrome 10. An abnormal ECG defined as QTcB> 470 msec females; QTcB> >450 msec males 11. History of autonomic dysfunction (e.g., recurrent episodes of fainting, orthostatic hypotension, sinus arrhythmia). 12. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study. 13. History of immunodeficiency diseases, including a positive HIV test result. 14. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. 15. History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening and/or at baseline.
Please refer to the enclosed protocol for further details. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The magnitude of the FTY720-induced bronchoconstriction will be primarily assessed by the baseline adjusted FEV1 AUC(0-6h) on Day 1.
Please refer to the enclosed protocol for further details. |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
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 | |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Time-lagged, ascending multiple-dose study. |
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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 | 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.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |