clinical study to evaluate the efficacy and safety of vr506 using a new inhaler for the treatment of asthma

Conditions: Asthma

Summary: to evaluate the clinical efficacy, safety, tolerability and dose-response relationship, using oral corticosteroid (ocs) modulation, of 3 different doses of vr506 using a twice daily regimen from a new dry powder inhaler (ndpi) for 16 weeks in subjects with severe persistent asthma requiring ocs therapy, i.e. step 5 treatment as defined by modified global initiative for asthma (gina) guidelines 2011.


Eligibility criteria:
inclusion: * written informed consent * adolescents aged 12-17 years \& adults aged 18-65 years (both inclusive) * documented clinical history of severe asthma requiring prednisone/prednisolone therapy, high-intensity treatment ics, ocs, laba * stable ocs dose for ≥7 days before screening visit \& during screening period. * at least 80% compliant w/regular asthma medication per investigator at end of screening period * documented asthma reversibility within 5 yrs prior to/during screening period, or diagnosis of asthma that is incontrovertible per investigator * ability to use ndpi correctly, per investigator's review of completed inhaler operation checklist * ability to use ediary correctly, assessed by investigator at end of screening period * ability to comply w/study procedures, including blood sampling * ability to perform technically satisfactory pulmonary function tests * available to complete all study visits before 12 noon * bmi of 16-26 kg/m2 in adolescents and 18-32 kg/m2 in adults * oral pif ≥40 l/min, using an appropriate device set to match resistance of inhaler * good health, except for presence of asthma, per medical history/physical examination * negative drug/alcohol/urine cotinine screen. subjects must test negative for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine, ethanol \& opiates (unless given as prescription medicine) * non-smokers or ex-smokers with a smoking history of less than 10 pack-yrs (e.g. \<20 cigarettes per day for 10 years or \<40 cigarettes per day for 5 years) \& stopped smoking for at least 1 year prior to screening visit. smoking will not be permitted throughout study * female subjects of child-bearing potential must be using medically acceptable forms of contraception \[abstinence, hormonal (oral/implant/transdermal/injection), in use for ≥3 consecutive months before first dose of study medication, double barrier (condom w/spermicide, or diaphragm w/spermicide), iud, or vasectomised partner (≥6 months since vasectomy)\]. exclusion: * regular use (≥3 times/wk) of topical steroids to treat dermatitis/rhinitis/allergic conjunctivitis, within 28 days of screening visit * subjects who have/who have had, an upper/lower respiratory tract infection within 28 days of screening visit * subjects w/"brittle asthma * subjects w/asthma that required admission to an icu and/or ventilation within previous 12 months * subjects whose comorbidities, per investigator's opinion, are major contributors to their respiratory symptoms (e.g. copd, bronchiectasis, dysfunctional breathlessness, vocal cord dysfunction, gastro-oesophageal reflux) * previously/currently diagnosed as having churg-strauss syndrome * previously/currently diagnosed as having pulmonary eosinophilia * history of lung cancer * subjects w/current diagnosis of hiv infection * active chronic hepatitis b or c infection * subjects who have clinically significant abnormality/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 arterial hypotension, with average sbp readings of ≤95 mmhg * persistent elevation of blood pressure, with average sbp readings of ≥160 mmhg or average dbp readings of ≥100 mmhg * pregnant or lactating females * participation in another clinical study in 28 days prior to screening visit * evidence of clinically significant renal, hepatic, cardiac, pulmonary (apart from asthma) or metabolic dysfunction, e.g. diabetes mellitus, thyrotoxicosis, uncorrectable hypokalaemia, or predisposition to low levels of serum potassium * current/history of drug/alcohol abuse/dependence per who criteria * inability to communicate well w/investigator * donation of ≥450 ml of blood/blood products within previous 3 months prior to screening * history of allergy/intolerance/contraindications to corticosteroids/lactose, or severe allergy to milk proteins * consumption of alcohol- or caffeine-containing foods/beverages from midnight before or during screening visit * history of medically diagnosed chronic respiratory diseases other than asthma (e.g. chronic obstructive pulmonary disease, abpa in the absence of asthma)