E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Symptomatic asthmatic patients on inhaled corticosteroids |
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E.1.1.1 | Medical condition in easily understood language |
Symptomatic asthmatic patients on inhaled corticosteroids |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 investigate the efficacy, safety and tolerability of BI 671800 ED 400 mg b.i.d. compared to placebo or montelukast 10 mg q.d., given for 6 weeks as add-on therapy to fluticasone propionate MDI (50 μg 2 puffs b.i.d.) in symptomatic asthmatic
patients. |
|
E.2.2 | Secondary objectives of the trial |
- Efficacy: Morning trough forced expiratory volume in one second (FEV1) % predicted, FEV1, forced vital capacity, Forced expiratory flow (FEF) 25-75%, Peak FEV1, Peak FVC, FEV1 area under the curve (AUC)0-3h, FVC AUC0-3h, asthma control
questionnaire (ACQ) and sub-scores, standardised asthma quality of life questionnaire (AQLQ(S)), daily symptom scores (a.m. and p.m.), weekly means of daily puffs of rescue medication usage, peak expiratory flow (PEF) and FEV1, asthma symptom-free days, asthma controlled weeks, asthma exacerbations, fractional exhaled Nitric Oxide (FeNO), total IgE and eosinophilic cationic protein (ECP).
- PK: Population PK from plasma concentrations of BI 671800 sampled
during the treatment period (total of 2 samples)
- Pharmacogenomics: Unspecified pharmacogenomic (PGx) testing
- Safety: AEs, routine laboratory, |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent prior to any study procedures, which includes medication washout and restrictions. 2. Diagnosis of asthma by a physician at least 3 months prior to Visit2. The diagnosis must be according to the 2008 GINA Guidelines and must meet the following spirometric criteria: a) Pre-bronchodilator clinic measured FEV1≥60% and ≤85% predicted normal (modified NHANES measured ≥6hours after the last use of salbutamol/albuterol rescue medication on the day of randomisation.b) FEV1 reversibility: Improvement in FEV1≥12% above baseline and an absolute change of at least 200ml within 15-30 minutes after 400μg salbutamol HFA MDI. Reversibility testing must be performed during the run-in at Visit2 and may be repeated once at Visit3. It must not occur on the day of randomisation.
3. Patient must be on at least iCS at a stable dose for at least 3 months and at a stable dose for at least 6 weeks prior to screening Visit2. 4. Diagnosis of asthma made before the age of 40 years. 5. Patient must be symptomatic with an ACQ≥1.5 on the day of randomisation. 6. Male or female patients 18 to 65 yrs of age inclusive. 7. BMI between 18≥and≤35. 8. Non-smokers or ex-smokers with cigarette smoking history of ≤ 10 pack-years (and smoking cessation for at least one year prior to enrolment). Patients must have a negative urinary cotinine at visit 2. 9. Able to perform technically acceptable pulmonary function tests and electronic PEF measurements, and must be able to maintain records (AM2+®). |
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E.4 | Principal exclusion criteria |
1. Significant pulmonary disease other than asthma or other medical conditions that may put the patient at risk, influence the results of the study, cause concern regarding the patient’s ability to participate in the study. Patients with malignancy for which patient has undergone resection/radiation/chemotherapy within past 5yrs. Patients with treated basal cell carcinoma or fully cured squamous cell carcinoma are allowed. 2. Clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis at screening, if the abnormality defines a significant disease. Patients with AST, ALT, γGT, TBIL or INR>1.5 ULN at Visit2. 3. Hospitalisation for asthma exacerb. within 3mths or intubation for asthma within 3yrs of Visit2. 4. Partially controlled (ACQ6>1.5) on iCS plus any other asthma controller at Visit2. 5. Respiratory tract infection or asthma exacerb. in the 4wks prior to Visit2 or during the run-in. In case of URTI (without asthma exacerb.) during run-in, patients can be pre-screened again 4wks after resolution. 6. Thoracotomy with pulmonary resection. Thoracotomy for other reasons should be assessed (excl.1). 7. Any safety net criteria are met during the run-in period a) In clinic FEV1 %predicted pre-bronchodilator <40%, b) >12 puffs rescue salbutamol HFA MDI per day for>2 consecutive days, c) Exacerbation of asthma. If AM2+ indicates a drop in absolute PEF of 30% from average absolute PEF of the last pre-screening week or last week prior to Visit4, for>2 consecutive days, an alert is generated, the patient should contact the study site for immediate assessment. 8. Previous participation in this study or participation in a current interventional study. 9. Significant alcohol or drug abuse within past 2yrs of Visit2. 10. Pregnant or nursing women. 11. Women of childbearing potential not using two effective methods of birth control (one barrier and one non-barrier). Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least 2yrs. Effective methods of birth control include established use of oral, injected or implanted hormonal methods of contraception, placement of an IUD or IUS, barrier method of contraception: condom or occlusive cap with spermicidal foam/gel/film/ cream/suppository or male sterilization (with appropriate post-vasectomy document of the absence of sperm in the ejaculate). 12. Known hypersensitivity to any component of the investigat. treatment, salbutamol, fluticasone or montelukast components. 13. Patients who have been treated with any of the following medications in the given interval prior to Visit2: a) An investigational drug within 1mth or 6 1/2 lives (whichever is greater). b) Started on immunotherapy <1yr prior to Visit2. Patient should on the same course of immunotherapy for at least 1yr to be admitted into the study. Adjustment in dose within 1yr is allowed, as long as it involves the same course of immunotherapy and they have been on that dose for at least 6mths prior to Visit2. c)A biological based antagonist therapy including Omalizumab or immune modulator within 6mths. d)A systemic (i.v., i.m. or oral)corticosteroid within 3mths. e) A long acting anticholinergic bronchodilator within 2wks. f) Any of the following bronchodilators within 24hrs: inhaled anticholinergic agents, including fixed dose anticholinergic/ß2adrenergics, LABA including combination iCS/LABA, methylxanthines and oral β2agonists. g) Leukotriene modifiers, orally inhaled or oral nedocromil sodium/ sodium cromoglycate, mucolytics from morning of Visit2. h) The following anti-allergy medications within 2wks: topical nasal steroid (ocular steroids allowed) and cromolyn (nasal and oral cromones allowed),oral antihistamines, oral decongestants. Topical antihistamines and topical decongestants are permitted on an as needed basis for symptoms of allergic rhino-conjunctivitis. i) Non-steroidal anti-inflammatory medication including COX-2 inhibitors and aspirin (except ocular formulations) within 1wk. j) Non-cardio-selective β-blocker medications (e.g., propranolol) within 2wks. Topical β-blocker eye medications are allowed. 14) Patients taking specific CYP2C8 and CYP2C9 substrates and potent or moderate CYP3A4 inhibitors at Screening Visit2 or within 5 1/2 lives from Visit4, whichever is longer, will be excluded. A list of the specifically prohibited drugs is provided in the ISF at each site and updated as necessary by the sponsor. Any specific query should be directed to the sponsor prior to enrolment. 15) Patients with a risk for 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 TdP (e.g. heart failure, hypokalemia, family, history of Long QT Syndrome, etc); c)Patients on concomitant medications known to prolong the QT/QTc interval. |
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E.5 End points |
E.5.1 | Primary end point(s) |
FEV1 % predicted trough change from baseline after 6 weeks of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 4 will be used for baseline.
Visit 7 after 6 weeks of treatment. |
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E.5.2 | Secondary end point(s) |
ACQ total score change from baseline after 6 weeks of treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visit 4 will be used for baseline.
Visit 7 after 6 weeks of treatment. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | 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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 18 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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 | No |
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 |
Austria |
Germany |
Italy |
Korea, Republic of |
New Zealand |
Sweden |
Turkey |
United Kingdom |
United States |
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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
|
Last patient out (last visit of the last subject entering 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 | 1 |
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 | 1 |
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 |