E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
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 |
The objective of the current study is to investigate the efficacy, safety and tolerability of BI 671800 ED (50 mg b.i.d. / 200 mg b.i.d. / 400 mg b.i.d.) compared to fluticasone propionate 110 mcg 2 puffs b.i.d. and placebo in symptomatic steroid-naïve asthma patients. An optimum dose may be selected based on efficacy, safety and pharmacokinetic evaluations of BI 671800 ED |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Signed informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial, which includes medication washout and restrictions. 2.All patients must have a diagnosis of asthma by a physician at least 3 months prior to screening. The Diagnosis of Asthma must be according to the 2008 Global Initiative for Asthma (GINA) Guidelines (P09-00393) and must meet both of the following spirometric criteria: a)Pre-bronchodilator clinic measured FEV1 ≥60% and ≤85% of predicted normal (calculated by modified NHANES [R04-1001]) measured ≥6 hours after the last use of short acting bronchodilator (see Section 5.1.1) on the day of screening and randomisation. b)FEV1 reversibility: Improvement in FEV1 ≥12% above baseline and an absolute change of at least 200 ml within 15 minutes after administration of 400 µg salbutamol. Reversibility testing must be performed during the screening / run-in period and may be repeated if reversibility is not determined in the first test. Reversibility testing must not occur on the day of randomisation. 3.The patient must not be taking asthma controller therapy for at least 3 months prior to screening Visit 2. The patient may be receiving a bronchodilator prn. 4.Diagnosis of asthma must have been made before the age of 40 years. 5.Patient must be symptomatic with an ACQ (R00-1157) value of ≥1.5 on the day of randomisation. 6.Male or female patients 18 to 65 years of age inclusive. 7.Body mass index (BMI) between 18 and 35. 8.Patients must be non-smokers or ex-smokers, having stopped smoking at least 1 year prior to Screening Visit 2 and with a smoking history of <10-pack years. Patients must have a negative urinary cotinine test at Screening Visit 2. Pack Years = Number of cigarettes / day 20x years of smoking Patients who are currently smoking cigarettes must be excluded 9.Patients must be able to perform technically acceptable pulmonary function tests and electronic PEF measurements, and must be able to maintain records (Patient Daily Diary) during the study period as required in the protocol. 10.Patients must be able to properly use or be trained in the proper use of a metered dose inhaler (MDI).
|
|
E.4 | Principal exclusion criteria |
1.Significant pulmonary disease other than asthma (or allergic rhinitis) or other medical conditions* (as determined by medical history, examination and clinical investigations at screening) that may, in the opinion of the investigator result in the any of the following: a.Put the patient at risk because of participation in the study, b.Influence the results of the study, c.Cause concern regarding the patient’s ability to participate in the study. 2.Patients with a clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis at screening, if the abnormality defines a significant disease as defined in exclusion criterion No.1. 3.Hospitalisation for asthma exacerbation within 3 months or intubation for asthma within 3 years of Screening Visit 2. 4.Respiratory tract infection or asthma exacerbation in the 4 weeks prior to Screening Visit 2 or during the run in period. 5.Thoracotomy with pulmonary resection. Thoracotomy for other reasons should be assessed under Exclusion No. 1 6.Any of the following safety net criteria are met during the run in period (from Screening Visit 2 to Randomisation Visit d.Drop in FEV1 % predicted pre-bronchodilator to below 40%e.More than 12 puffs of a short-acting 2-adrenergic agonist (SABA) per day for more than 2 consecutive days f.Exacerbation (as defined in Section 5.1) 7.Previous participation in this study (receipt of randomized treatment) or active participation in a current interventional study. 8.Significant alcohol or drug abuse within past 2 years. See exclusion criteria No.1. 9.Pregnant or nursing women. 10.Women of childbearing potential not using two effective methods of birth control (one barrier and one non-barrier). 11.Patients with known hypersensitivity to any component of the investigational treatment (see Section 4.1.1) or to the albuterol/salbutamol or fluticasone MDI components. 12.Patients who have been treated with any of the following medications in the given interval prior to Screening Visit 2: a.An investigational drug within 1 month or six half lives (whichever is greater) b.Patients who were started on immunotherapy less than one year prior to Visit 2. The patient should on the same course of immunotherapy for at least one year to be admitted into the study. A patient will be allowed an adjustment in dose within one year as long as it involves the same course of immunotherapy and they have been on that dose for at least 6 months prior to Visit 2 c.A biological based antagonist therapy including Omalizumab, or immune modulator within 6 months of Visit 2 d.A systemic (intravenous, intramuscular, or oral) corticosteroid within 3 months of Visit 2 e.A long acting anticholinergic bronchodilator within two weeks of Visit 2 f.Any of the following bronchodilators from 24 hours prior to screening Visit 2 to randomisation: short acting inhaled anticholinergic agents including fixed dose anticholinergic/ beta agonist combinations, long acting inhaled beta agonists g.The following anti-allergy medications within 2 weeks: topical nasal steroid, oral antihistamines, oral decongestants. Topical antihistamines and topical decongestants are permitted on an as needed basis for symptoms of allergic rhino-conjunctivitis h.A non-steroidal anti-inflammatory medication including aspirin and COX-2 inhibitors within 1 week i.Non-cardio-selective beta-blocker medications (e.g., propranolol) within 2 weeks. Topical beta blocker eye medications are allowed j.Any of the following asthma controller medications within 6 weeks: inhaled corticosteroids, leukotriene modifier, methyl xanthines, nedocromil or cromolyn sodium (as defined in Table 4.2.2:1) k.Mucolytics within 3 months 13.Patients receiving CYP 2C8 substrates such as amiodarone, amodiaquine, paclitaxel, rosiglitazone, pioglitazone and repaglinide or CYP2C9 such as warfarin, tolbutamide, phenytoin, losartan, acenocoumarol will be excluded. A list of prohibited drugs will be provided in their investigative site file (ISF) for the investigators and updated as necessary by the sponsor. 14.Patients at risk of prolonged QT interval effects including: a.A marked baseline prolongation of QTc interval (demonstration of a QTc interval >450 ms with confirmation on a repeat ECG); b.A history of additional risk factors for Torsade de Pointes (TdP) (e.g., heart failure, hypokalemia, family, history of Long QT Syndrome, etc) c.Patients receiving concomitant medications known to prolong the QT/QTc interval
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in this study is forced expiratory volume in one second (FEV1) % predicted trough change from baseline after six weeks of treatment. |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
Last Patient Out (last visit of the last patient entering the trial) |
|
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 | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |