A Phase I Study in Asthma Patients Evaluating the Effect of Doses of FlutiForm™ on the Amount, if Any, of Cortisol Produced by the Adrenal Glands

• Investigate effect of SKP FlutiForm 250/10 ug HFA pMDI BID for 6 weeks, FlutiForm 100/10 ug HFA pMDI BID, 10 mg prednisone for 7 days, compared to Placebo on the hypothalamic-pituitary-adrenal (HPA) axis using measurement of 24-hours UFC [ Time Frame: Baseline and Study days 42-43 ] [ Designated as safety issue: Yes ]
  

• To assess the safety profile of SKP FlutiForm HFA pMDI using incidence of adverse events (AEs) and changes in electrocardiograms (ECGs), vital signs and clinical laboratory tests. [ Time Frame: From Baseline up to 2 weeks after last dosing ] [ Designated as safety issue: Yes ]
  

This is a Phase-1 randomized, double-blind, placebo- and active-controlled, parallel group 6 week study to evaluate the effect on the HPA axis of treatment with SKP FlutiForm 250/10 mg HFA pMDI twice daily administered over 6 weeks, FlutiForm 100/10 mg HFA pMDI twice daily administered over 6 weeks and 10 mg prednisone administered over 7 days compared to placebo. All subjects will undergo a Screening Visit to determine eligibility for the study and training on pMDI use. Eligible subjects will meet all of the following criteria: at least 6 month history of asthma, demonstrate an FEV1 of at least ≥ 60 % of predicted normal values at both Screening and Baseline visits, and stable asthma without the use of inhaled steroids for the past month or oral or parenteral corticosteroids for the past three months. All subjects will be admitted to the study site on the morning of Study Day -1 to begin a 24-hour urine collection and undergo Baseline trough PK sampling. On the morning of Study Day 1, subjects will be randomized to one of four treatment groups: SKP FlutiForm 250/10 mg twice daily + placebo capsule for six weeks, SKP FlutiForm 100/10 mg twice daily + placebo capsule for six weeks, Placebo inhaler + placebo capsule for six weeks or Placebo inhaler for six weeks + placebo capsule for 5 weeks followed by one week of 10 mg prednisone QD. After the first dose, subjects will be discharged from the study site to continue dosing at home for 6 weeks. Subjects will be required to record their compliance with their twice daily inhaler dosing and once daily oral medication dosing in a diary. Subjects will also record their predose morning and evening Peak Expiratory Flow Rate (PEFR) in a diary. Clinic visits will occur at Study Days 7, 14 and 35 during which safety assessments (AEs and vital signs) will be made, trough PK samples will be obtained and pMDI training will be continued. Also, subjects will return to the study site in the morning on Study Days 40 to 41 for observed dosing of prednisone or placebo. Subjects will be readmitted to the study site in the morning on Study Day 42 for trough PK sampling, observed dosing of prednisone or placebo and to begin a 24-hour urine collection. A safety follow-up phone call will occur 7 days later.