Clinical trial NCT01007721 (phase 2, status: completed)
Conditions: rhinitis, allergic, seasonal, asthma
ICD codes: J30.2, J45.998, J82.83, J45.909, J45.991, J45.20, J45.30, J45.40
Drugs: bi 67100 ed 25 mg, bi 671800 ed placebo, montelukast placebo tablet, montelukast placebo tablet, fluticasone propionate placebo nasal spray, fluticasone propionate placebo nasal spray, fluticasone propionate placebo nasal spray, bi 671800 ed 100 mg, bi 671800 ed placebo, bi 671800 ed placebo, bi 671800 ed placebo, bi 671800 ed 100 mg, 671800 ed placebo, montelukast placebo tablet, montelukast placebo tablet, montelukast placebo tablet, montelukast 10 mg tablet, fluticasone propionate placebo nasal spray, fluticasone propionate nasal spray placebo, fluticasonepropionate nasal spray 200 mcg
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, [H][C@@]12C[C@@H](C)[C@](OC(=O)CC)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C, [H][C@@]12C[C@@H](C)[C@](OC(=O)CC)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C, [H][C@@]12C[C@@H](C)[C@](OC(=O)CC)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C, [H][C@@]12C[C@@H](C)[C@](OC(=O)CC)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C, [H][C@@]12C[C@@H](C)[C@](OC(=O)CC)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, [H][C@@]12C[C@@H](C)[C@](OC(=O)CC)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C, [H][C@@]12C[C@@H](C)[C@](OC(=O)CC)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C, [H][C@@]12C[C@@H](C)[C@](OC(=O)CC)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C, OC(=O)CC1(CC1)CS[C@H](CCC1=CC=CC=C1C(O)(C)C)C1=CC=CC(\C=C\C2=NC3=C(C=CC(Cl)=C3)C=C2)=C1, [H][C@@]12C[C@@H](C)[C@](OC(=O)CC)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C, [H][C@@]12C[C@@H](C)[C@](OC(=O)CC)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C
Eligibility criteria:

        Inclusion Criteria:

          1. Signed informed consent consistent with ICH-GCP guidelines (International Conference
             on Harmonisation for Good Clinical Practice) and local legislations prior to any
             study-related procedures, which includes medication washout and restrictions.

          2. Male or female, with a diagnosis of seasonal allergic rhinitis by a physician with a
             positive skin prick test to Dactylis glomerata within 12 months prior to Visit 2

          3. TNSS (total nasal symptom score) of less or equal than 2 before start of challenge at
             Visit 2 and a TNSS of > 5 at least once during the 2h-baseline ECC exposure

          4. 18 to 65 years of age (age inclusive)

          5. Non-smoker or ex-smoker with a cigarette smoking history of less or equal than 10
             pack-years (and smoking cessation for at least one year prior to enrolment) with
             negative urinary cotinine at screening (Visit 1)

          6. Ability to comply with requirements, medication restrictions (see 4.2.2) and
             procedures of the study protocol including AM1® device and rescue medication use.

          7. Pre-bronchodilator FEV1 (forced expiratory volume in one second) equal or greater than
             80% of predicted value (European Community for Steel and Coal) at screening

          8. BMI between 18 and 35 (Body Mass Index)

          9. Negative breath -alcohol, urine -cotinine and -drug tests at screening (Visit 1)

        Exclusion Criteria:

          1. Significant pulmonary disease other than allergic rhinitis (or mild intermittent
             asthma managed by SABA (short acting bronchodilator) alone) or other medical
             conditions* that may, in the opinion of the investigator result in the any of the
             following:

               -  put the patient at risk because of participation in the study

               -  influence the results of the study (as determined by medical history, examination
                  and clinical investigations at screening)

               -  cause concern regarding the patient's ability to participate in the study. *e.g.
                  cardiac, gastro-intestinal, hepatic, renal, metabolic, dermatologic,
                  neurological, haematological, oncological and psychiatric. Patients with
                  malignancy for which the patient has undergone resection, radiation or
                  chemotherapy within past 5 years. Patients with treated basal cell carcinoma or
                  fully cured squamous cell carcinoma are allowed.

          2. Any other nasal and sinusoidal diseases or conditions by discretion of the
             investigator (i.e. nasal polyps, frequent nose bleeding) which may influence the study
             results

          3. Respiratory tract infection or asthma exacerbation in the 4 weeks prior to Visit 1 or
             during the screening and baseline period.

          4. Thoracotomy with pulmonary resection.

          5. Previous participation in this study (receipt of randomized treatment) or active
             participation in a current interventional study.

          6. 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. Patients will not be randomised if they have increased
             liver transaminases (AST or ALT greater than two fold the upper limit of normal at
             screening). Laboratory testing may be repeated once before randomization.

          7. Significant alcohol or drug abuse within past 2 years (see exclusion criteria No. 1)

          8. Patients with known hypersensitivity to any component of the investigational treatment
             (see section 4.1.1) or to fluticasone propionate nasal spray or montelukast or
             salbutamol or components.

          9. Patients taking CYP2C8 substrates such as -but not restricted to- amiodarone,
             amodiaquine, paclitaxel, rosiglitazone, pioglitazone, and repaglinide and CYP2C9
             substrates such as -but not restricted to- warfarin, tolbutamide, phenytoin, losartan
             and acenocoumarol.

         10. Patients who have been treated with any of the following medications in the given
             interval before the respective Visit: Before Visit 2

               -  An investigational drug within 1 month or six half lives (whichever is greater)

               -  Any immunomodulatory therapy since specific positive skin prick test.

               -  A biological based antagonist therapy including Omalizumab, or immune modulator
                  therapy within 6 months

               -  A systemic (intravenous, intramuscular or oral) corticosteroid within 3 months

               -  The following medications within 4 weeks: topical steroids, change in
                  prescription medications

               -  The following medications within 2 weeks: LABA (long acting beta agonist),
                  methylxanthines, leukotriene modifiers, any antihistamines, oral decongestants,
                  any anti-rhinitis therapies (i.e., decongestants, herbals, anticholinergics), and
                  hay-fever medications, tricyclic antidepressants, aspirin and any NSAIDs (non
                  steroidal anti inflammatory drugs) (for occasional pain relief, only paracetamol
                  may be used), oral beta 2 agonists

               -  Before Visit 1: Short acting bronchodilator within 6 hours of baseline pulmonary
                  function testing

         11. Patients with a risk for prolonged QT interval effects including:

               -  A marked baseline prolongation of the QT interval in the electrocardiogram by
                  demonstration of a QTcB interval (Bazett's correction formula) > 450 ms

               -  A history of additional risk factors for TdP (Torsades de pointes) e.g., heart
                  failure, hypokalemia, family, history of Long QT Syndrome, etc.

               -  The use of concomitant medications known to prolong the QT/QTc interval

         12. Pregnant or nursing women

         13. Women of childbearing potential not using a highly effective method of birth control.