New Combination Inhaler (FlutiForm HFA MDI 100/10 µg and 250/10 µg) Versus Fluticasone and Formoterol Administered Alone, and Placebo in Patients With Moderate to Severe Asthma

Official Title: “A Randomized, Double-blind, Placebo-controlled, Parallel Group, Stratified, Multi-center, 12-Week Study Comparing the Safety and Efficacy of Fluticasone and Formoterol Combination (FlutiForm(tm) 100/10 µg or 250/10 µg Twice Daily) in a Single Inhaler (SkyePharma HFA pMDI) With the Administration of Placebo or Fluticasone (250 µg Twice Daily) and Formoterol (10 µg Twice Daily) Alone in Adolescent and Adult Patients With Moderate to Severe Asthma”

The purpose of this study is to compare the efficacy and safety of the fixed combination asthma drug FlutiForm with its two components administered alone, fluticasone propionate and formoterol fumarate, and with placebo in adult and adolescent patients with moderate to severe asthma.

Intervention(s) in this Clinical Trial

• Drug: Fluticasone propionate/Formoterol fumarate 250/10
  • FlutiForm 250/10ug is a HFA pMDI that delivers 125ug of Fluticasone propionate per actuation and 5ug of Formoterol fumarate per actuation. Patients will take 2 actuations BID for 12 weeks.
• Drug: Placebo
  • Placebo is a HFA pMDI that delivers placebo aerosol. Patients will take 2 actuations BID for 12 weeks.
• Drug: Fluticasone propionate/Formoterol fumarate 100/10
  • FlutiForm 100/10ug is a HFA pMDI that delivers 50ug of Fluticasone propionate per actuation and 5ug of Formoterol fumarate per actuation. Patients will take 2 actuations BID for 12 weeks.
• Drug: Fluticasone propionate 250
  • Fluticasone 250 is a HFA pMDI that delivers 125ug of Fluticasone propionate per actuation. Patients will take 2 actuations BID for 12 weeks.
• Drug: Formoterol fumarate 10
  • Formoterol 10ug is a HFA pMDI that delivers 5ug of Formoterol fumarate per actuation. Patients will take 2 actuations BID for 12 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • FlutiForm 250/10
• Active Comparator: 2
  • FlutiForm 100/10
• Active Comparator: 3
  • Fluticasone 250
• Active Comparator: 4
  • Formoterol 10
• Placebo Comparator: 5
  • Placebo

Primary Measures

• Change in Forced Expiratory Volume in 1 s(FEV-1) from Baseline (Week 0) to Week 12.
  • Time Frame: Week 0 and 12 visits
    Safety Issue?: No
• Discontinuation due to lack of efficacy.
  • Time Frame: Whole duration of study
    Safety Issue?: No

Secondary Measures

• Other pulmonary function tests including forced vial capacity (FVC) and peak expiratory flow rate (PEFR).
  • Time Frame: Whole duration of study
    Safety Issue?: No
• Clinical endpoints (frequency of asthma exacerbations and patient data captured in diary including daily morning and evening PEFR).
  • Time Frame: Whole duration of study
    Safety Issue?: No
• Serial 12-hour FEV-1 area under the curve (AUC).
  • Time Frame: Week 0, 2 and 12 visits
    Safety Issue?: No
• Safety variables including adverse events, ECGs clinical laboratory tests and vital signs.
  • Time Frame: Whole duration of study
    Safety Issue?: Yes

• Ages eligible for study: 12 years and above; genders eligible for study: both; prior steroid use: steroid-requiring

Inclusion Criteria:

• History of asthma for at least 12 months.
• Documented use of inhaled corticosteroid for at least 4 weeks prior to Screening Visit Demonstrate FEV-1 of 40-80% of predicted normal values at Screening and Baseline Visit.
• Documented reversibility of 15% within 12 months of Screening visit or at Screening Visit (15% increase from pre-FEV-1 levels following albuterol inhalation or nebulized albuterol administration).
• Symptoms of Asthma during Run-in.
• Females of childbearing potential must have a negative urine pregnancy test at
• Screening and Baseline Visits. Females are eligible only if they are not pregnant or lactating, and are either sterile or using acceptable methods of contraception
• Must otherwise be healthy.
• Provide written informed consent. Wishes of minors must be respected.

Exclusion Criteria:

• Life-threatening asthma within past year or during Run-In Period.
• History of systemic corticosteroid medication within 3 months before Screening Visit.
• History of omalizumab use within past 6 months.
• History of leukotriene receptor antagonist use, e.g. montelukast, within past week.
• Current evidence or history of any clinically significant disease or abnormality including uncontrolled hypertension, uncontrolled coronary artery disease, congestive heart failure, myocardial infarction, or cardiac dysrhythmia.
• Upper or lower respiratory infection within 4 weeks prior to Screening visit or during Run-In Period
• Significant, non-reversible, pulmonary disease (e.g., chronic obstructive pulmonary disease [COPD], cystic fibrosis, bronchiectasis).
• Known Human Immunodeficiency Virus (HIV)-positive status.
• Smoking history equivalent to "10 pack years".
• Current smoking history within 12 months prior to Screening Visit.
• Current evidence or history of alcohol and/or substance abuse within 12 months prior to Screening visit.
• Patients who are confined in institution.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 12 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: SkyePharma AG Industry

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00393952

Study ID Number: SKY2028-3-004

ClinicalTrials.gov Identifier: NCT00393952

Health Authority: United States: Food and Drug Administration