Clinical trial NCT01472757 (phase 2/phase 3, status: completed)
Conditions: asthma
ICD codes: J45.998, J82.83, J45.909, J45.991, J45.20, J45.30, J45.40
Drugs: vr506, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent

          -  Adolescents aged 12 to 17 years (inclusive) and adults aged 18 to 65 years (inclusive)

          -  Documented clinical history of asthma (i.e. made by a physician) for at least 6 months
             before the Screening Visit

          -  Documented asthma reversibility in the 5 years prior to or during Screening, or if the
             asthma reversibility criterion is not met at Screening, then a repeat test may be
             carried out at the end of the Run-In Period

          -  Subjects with asthma who, in the opinion of the investigator, require maintenance
             therapy with inhaled corticosteroids (ICS), are believed to have been regularly
             compliant with this therapy, and are therefore likely to deteriorate within 6 weeks
             following withdrawal of their usual ICS treatment

          -  Mild or moderate asthma, defined as:

               -  Mild - good asthma control achieved by low-dose inhaled corticosteroid (daily
                  dose 200-500 μg beclomethasone dipropionate or equivalent) with or without other
                  low-intensity treatment (e.g. leukotriene modifiers or cromones) for at least 28
                  days before the Screening Visit

               -  Moderate - good asthma control achieved by low- to moderate-dose ICS (daily dose
                  200-1000 μg beclomethasone dipropionate or equivalent), and long acting
                  β2-agonist (LABA) or other extra treatment, for at least 28 days before the
                  Screening Visit

          -  Ability to use the new inhaler correctly, based on investigator's review of the
             completed inhaler operation checklist

          -  Ability to use the eDiary correctly, assessed by the investigator during the Screening
             Period

          -  Ability to perform technically satisfactory pulmonary function tests

          -  Ability to comply with study procedures, including blood sampling

          -  Body mass index (BMI) of 16.0 to 26.0 kg/m2 in adolescents, and in adult subjects
             recruited in the Philippines, and 18.0 to 32.0 kg/m2 in adults recruited in other
             countries

          -  Available to complete all study visits

          -  Oral peak inspiratory flow (PIF) of at least 60 L/min; using an appropriate device set
             to match the resistance of the new dry powder inhaler (nDPI)

          -  Good health, except for the presence of asthma, according to medical history and
             physical examination

          -  Normal (i.e. non-clinically significant abnormality) 12-lead electrocardiogram (ECG)

          -  Negative drug, alcohol, and urine cotinine screen; subjects must test negative for
             amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine (unless
             related to nicotine-containing therapies), ethanol, and opiates (unless given as a
             prescription medicine)

          -  Non-smokers or ex-smokers with a smoking history of less than 10 pack-years (e.g. <20
             cigarettes per day for 10 years or 40 cigarettes per day for 5 years) and stopped
             smoking for at least one year prior to the Screening Visit. Smoking will not be
             permitted throughout the study

          -  Female subjects of child-bearing potential must be using medically acceptable forms of
             contraception; approved forms of contraception are abstinence, hormonal (oral,
             implant, transdermal, or injection, in use for ≥3 consecutive months before the start
             of the Run-In Period), double barrier (condom with spermicide, diaphragm with
             spermicide), intrauterine device, or vasectomised partner (≥6 months since vasectomy)

        Exclusion Criteria:

          -  Regular use (≥3 times per week) of topical steroids taken to treat dermatitis,
             rhinitis or allergic conjunctivitis, within 28 days of the Screening Visit

          -  Subjects who have or who have had an upper or lower respiratory tract infection within
             28 days of the Screening Visit

          -  Subjects with asthma that required admission to an intensive care unit and/or
             ventilation within the previous 12 months

          -  History of lung cancer

          -  Subjects with "brittle asthma", defined as patients with asthma who either maintain
             over many months a wide variation (>40%) in peak expiratory flow (PEF) between morning
             and evening measurements despite moderate to high doses of ICS, or are prone to acute,
             severe and often unpredictable attacks of asthma that may be fatal, on a background of
             apparently good asthma control

          -  History or current diagnosis of human immunodeficiency virus (HIV) infection

          -  Active chronic hepatitis B or C infection. If the patient's screening test is positive
             for hepatitis B surface antigen, the patient should be excluded unless the
             investigator, after a careful review of the patient's medical history and current
             laboratory tests of liver function, can exclude the possibility of recent or current
             infection

          -  Persistent arterial hypotension, with average systolic blood pressure (SBP) readings
             of ≤95 mmHg

          -  Subjects who have any clinically significant abnormality or finding from examination,
             tests, or history that may compromise subject safety, specifically any history of
             cardiac, renal or hepatic impairment

          -  Subjects with an abnormal ECG

          -  Persistent elevation of blood pressure, with average SBP readings of ≥160 mmHg or
             average diastolic blood pressure (DBP) readings of ≥100 mmHg

          -  Pregnant or lactating females

          -  Participation in another clinical study in the 28 days prior to the Screening Visit

          -  Current or a history of drug or alcohol abuse or dependence according to World Health
             Organization criteria in the 12 months prior to the Screening Visit or evidence of
             such abuse as indicated by laboratory assays conducted during the screening evaluation

          -  Evidence of clinically significant renal, hepatic, cardiac, pulmonary (apart from
             asthma) or metabolic dysfunction, e.g. diabetes mellitus, thyrotoxicosis, uncorrected
             hypokalaemia, or predisposition to low levels of serum potassium

          -  Inability to communicate well with the investigator

          -  Evidence of clinically significant renal, hepatic, cardiac, pulmonary (apart from
             asthma) or metabolic dysfunction, e.g. diabetes mellitus, thyrotoxicosis, uncorrected
             hypokalaemia, or predisposition to low levels of serum potassium

          -  Donation of ≥450 mL of blood or blood products within the previous 12 weeks prior to
             the Screening Visit

          -  History of allergy, intolerance or contraindications to corticosteroids, lactose, or
             severe allergy to milk proteins

          -  Consumption of alcohol- or caffeine-containing foods or beverages from midnight before
             or during the Screening Visit. The visit can be rescheduled once before the subject is
             excluded

          -  History of medically diagnosed chronic respiratory diseases (other than asthma) e.g.
             chronic obstructive pulmonary disease

          -  Subjects with previously clinically or radiologically diagnosed osteoporosis and/or
             those receiving regular treatment (more than 1 month duration) with oral or parenteral
             corticosteroids in the last year prior to the Screening Visit