Clinical trial NCT01400906 (phase 2, status: completed)
Conditions: asthma
ICD codes: J45.998, J82.83, J45.909, J45.991, J45.20, J45.30, J45.40
Drugs: 100 micrograms fluticasone propionate, 500 micrograms fluticasone propionate, lactose powder
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Eligibility criteria:

        Inclusion Criteria:

          -  males and females between 18 and 55 years of age inclusive

          -  female subject of child-bearing potential and agrees to use one of the contraception
             methods; or of non-childbearing potential including pre-menopausal females with
             documented (medical report verification) hysterectomy or double oophorectomy or
             postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of
             spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 40 pg/ml
             (<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without
             hysterectomy.

          -  male subjects with female partners of child-bearing potential must agree to use a
             contraception method

          -  body weight ≥50 kg and BMI within the range (18.5-35) kg/m2 (inclusive)

          -  documented history of bronchial asthma, first diagnosed at least 6 months prior to the
             first screening visit (according to the BTS guideline 2009), and currently being
             treated only with prn short-acting inhaled β2-agonist therapy

          -  current smokers or non-smokers or ex-smokers

          -  pre-bronchodilator FEV1 >70% of predicted at screening

          -  sensitivity to methacholine with a provocative concentration of methacholine resulting
             in a 20 % fall in FEV1 of < 8 mg/ml at screening

          -  able to produce acceptable induced sputum samples

          -  positive wheal and/or flare reaction (≥ 3 mm relative to negative control) to at least
             one allergen on skin prick testing at screening or within 12 months of the study start

          -  screening allergen challenge must demonstrate that the subject experiences both an
             early and late asthmatic response.

          -  AST, ALT, alkaline phosphatase and bilirubin <=1.5xULN

          -  written informed consent

          -  able to understand and comply with the study procedures, planned treatment period and
             other protocol requirements and stated restrictions

        Exclusion Criteria:

          -  past or present disease (other than asthma)

          -  respiratory tract infection and / or exacerbation of asthma within 4 weeks prior the
             first dose of study drug

          -  history of life-threatening asthma

          -  symptomatic with hay fever at screening or predicted to have symptomatic hay fever
             during the time of the study

          -  administration of oral or injectable steroids within 5 weeks of the screening visit or
             intranasal and / or inhaled steroids within 4 weeks of the screening visit

          -  unable to abstain from other medication, including non-steroidal anti-inflammatory
             drugs, anti-depressants, anti-histamines, anti-asthma and anti-rhinitis or hay fever
             medication, other than short acting β2-agonists and paracetamol (up to 4 gram per day)
             for the treatment of minor ailments (such as headache) from 14 days before screening
             until the follow-up visit

          -  unable to abstain from short acting β2-agonists as described in the restriction
             section of the protocol

          -  if, after two consecutive administrations of saline, during the allergen challenge at
             screening, the subject still has a fall of FEV1 of 10%

          -  a positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
             result

          -  clinical significant abnormalities in safety laboratory analysis at screening

          -  significant abnormality on 12-lead ECG at screening

          -  the subject is undergoing an allergen desensitisation therapy. Subjects with a
             positive pre-study drug/alcohol screen

          -  a history of regular alcohol consumption within 6 months of the screening visit

          -  a positive test for HIV antibody

          -  the subject has participated in a clinical trial and has received an investigational
             product within the following time period prior to the first dosing day in the current
             study: 30 days, 5 half-lives or twice the duration of the biological effect of the
             investigational product (whichever is longer)

          -  history of being unable to tolerate or complete methacholine and / or allergen
             challenge test

          -  use of prescription or non-prescription drugs, including vitamins, herbal and dietary
             supplements (including St John's Wort) within 7 days (or 14 days if the drug is a
             potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first
             dose of study medication

          -  unable to abstain from medication or supplements that significantly inhibit the
             cytochrome P450 subfamily enzyme CYP3A4, including but not limited to antiretrovirals
             (protease inhibitors - e.g. ritonavir indinavir, nelfinavir, ritonavir, saquinavir);
             imidazole and triazole anti-fungals (e.g. ketoconazole, itraconazole) and macrolide
             antibiotics (e.g. clarithromycin, telithromycin) from screening and throughout the
             study

          -  consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days
             prior to the first dose of study medication

          -  history of sensitivity to any of the study medications, or components thereof or a
             history of drug or other allergy that contraindicates their participation

          -  donation of blood or blood products in excess of 500 mL within a 56 day period

          -  pregnant females at screening or prior to dosing

          -  lactating females

          -  unwillingness or inability to follow the procedures outlined in the protocol

          -  subject is mentally or legally incapacitated

          -  urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
             nicotine-containing products within 6 months prior to screening (for subjects taking
             part in the non-smokers group of the study)