Clinical Study to Evaluate the Efficacy and Safety of VR506 Using a New Inhaler for the Treatment of Asthma

A Randomised Double-blind, Parallel Group, Dose-ranging Study to Evaluate the Efficacy and Safety of VR506 From a New Dry Powder Inhaler in Subjects With Severe Persistent Asthma Requiring Oral Corticosteroid Therapy.

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.

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)