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

A Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel Group, 6-Week Study to Evaluate the Effect of Multiple Doses of FlutiForm™ 250/10 Microgram HFA pMDI Twice Daily, FlutiForm™ 100/10 Microgram HFA pMDI Twice Daily, Prednisone and Placebo on the Hypothalmic-Pituitary-Adrenal Axis in Adult Subjects With Mild to Moderate Asthma.

The medications being used in this study are individually approved by the Food and Drug Administration (FDA). The medication under investigation is a combination of the two medications in one inhaler. The purpose of the study is to determine how the medication affects the amount, if any, of cortisol produced by the adrenal glands.

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.

Inclusion Criteria:

• Age 18-65 at the Screening Visit;
• History of asthma for at least 6 months prior to Screening Visit
• Well controlled asthma with rescue short acting beta agonist (albuterol) and or stable doses of other medications for at least 4 weeks prior to Screening Visit
• Female subjects that are not pregnant or lactating
• Otherwise healthy as determined by the Investigator.

Exclusion Criteria:

• Life-threatening asthma within the past year or visit to emergency room for asthma in the past 3 months prior to the Screening Visit;
• Significant,nonreversible pulmonary disease (e.g. chronic obstructive pulmonary disease, cystic fibrosis or bronchiectasis)
• Use of any steroid medications, topical or inhaled steroids within 4 weeks or systemic (oral or injectable) steroids within 3 months of dosing
• An upper or lower respiratory tract infection within the last 4 weeks pior to Screening Visit or acute illness or infection within 6 weeks prior to dosing
• Any significant disease or major disorder that may jeopardize subject safety
• History of tabacco use within 6 months prior to dosing and/or smoking history > 10 pack-years
• Female subjects on hormone replacement therapy or using birth control involving hormones in the past 6 months
• Additional inclusion and exclusion criteria will evaluated by the investigator.