Clinical trial NCT00649025: A Study Comparing the Safety and Efficacy of Fluticasone and Formoterol Combination (FlutiForm™) With Fluticasone or Flovent to Treat Moderate to Severe Asthma in Adolescents and Adults
Official title: A Randomized, Double-blind, Active-controlled, Parallel Group, Stratified, Multi-center, 12-Week Study Comparing the Safety and Efficacy of Fluticasone and Formoterol Combination (FlutiForm™ 250/10ug Twice Daily) in a Single Inhaler (SkyePharma HFA pMDI) With the Administration of Fluticasone (250ug Twice Daily) Alone in SkyePharma HFA pMDI and Flovent® HFA pMDI in Adolescent and Adult Patients With Moderate to Severe Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Asthma Moderate to Severe
Lead sponsor: SkyePharma AG
Sponsor class: INDUSTRY
Collaborators: name: Abbott
name: MDS Pharma Services
First posted: 2008-04-01
Enrollment: 438
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 two medications in one inhaler. The purpose of this study is to determine how well your asthma is controlled when taking one of the three treatment.

Detailed description: This Phase 3 randomized, double-blind, active-controlled, parallel group, stratified, multi-center study will evaluate the safety and efficacy of FlutiForm (250/10ug) after twice daily dosing over 12 weeks delivered by SKP HFA pMDI compared with Fluticasone propionate (250ug of twice daily) delivered by SKP HFA pMDI and Flovent® Fluticasone 250ug HFA pMDI in adolescent and adult patients with moderate to severe asthma. Only steroid-requiring patients (inhaled steroid regimen stable for at least 4 weeks prior to the Screening Visit at a dose not greater than 500ug/day Fluticasone propionate or equivalent) will be eligible. All patients will undergo a Run-In Period of 14 ± 3 days during which they will receive asthma maintenance therapy using Fluticasone HFA pMDI (Flovent® HFA 50 ug/actuation: 100µg/day (one inhalation twice daily) if they were using less than or equal to 250mg/day Fluticasone propionate or equivalent inhaled steroid, or 200ug/day (two inhalations twice daily) if they were using greater than 250ug/day Fluticasone propionate or equivalent inhaled steroid prior to the Screening Visit.). The use of rescue Salbutamol (Albuterol) pMDI will be permitted for all patients as needed for the control of worsening asthma symptoms during the Run-In Period. At the Baseline Visit (Week 0) following the Run-In period, eligible patients will be randomized to the treatment groups. Treatment assignment will be stratified according to their Baseline FEV1 % predicted (40-60% or \>60-80%).Study drug will be administered twice daily over a 12-week period. Patient visits will occur at Weeks 2, 4, 8, and 12 during which assessments (including serial PFTs up to 4 hours) will be made. In a subset of at least 66 patients (22 patients per treatment group) from selected centers, post-dose 12-hour serial PFTs will be performed at Baseline, Weeks 2 and 12. During the Treatment Period, patients may only take their blinded study medication; all other asthma medications will be withheld for the duration of the Treatment Period. However, the use of rescue Salbutamol (Albuterol) pMDI will be permitted in all patients as needed during the Treatment Period for the control of worsening asthma symptoms.

Eligibility criteria: Main Inclusion Criteria:

* ≥ Age 12 years at the Screening Visit.
* History of asthma for 12 months prior to the Screening Visit.
* Documented use of an inhaled corticosteroid for at least 4 weeks prior to the Screening Visit.
* Steroid-requiring patient
* patients must demonstrate (1) an FEV1 of 40% to 80% (inclusive) of predicted normal values at both the Screening and Baseline Visits and (2) documented reversibility within 12 months of the Screening Visit, defined as a ≥ 15%

Main Exclusion Criteria:

* Life-threatening asthma within the past year or during the Run-In Period.
* History of systemic (oral or injectable) corticosteroid medication within 3 months before the Screening Visit.
* An upper or lower respiratory infection within 4 weeks prior to the Screening Visit or during the Run-In Period.
* Significant, non-reversible, pulmonary disease (e.g., chronic obstructive pulmonary disease \[COPD\], cystic fibrosis, bronchiectasis).
* A smoking history equivalent to "10 pack years" (i.e., at least 1 pack of 20 cigarettes /day for 10 years or 10 packs/day for 1 year, etc.).
* Current smoking history within 12 months prior to the Screening Visit.
* Previous exposure to FlutiForm

Primary outcomes:
measure: To demonstrate the efficacy in terms of the Formoterol fumarate component of SKP FlutiForm HFA pMDI (250/10ug) compared to SKP Fluticasone HFA pMDI (250ug), on the change in FEV1 from morning pre-dose at Baseline (Week 0) to 2 hours post-dose at Week 12.
timeFrame: Week 0 and 12 visits
Secondary outcomes:
measure: Demonstrate the efficacy of SKP FLUTIFORM HFA pMDI (250/10ug) compared to FLOVENT® Fluticasone pMDI (250ug) on the change in FEV1 from morning pre-dose at Baseline (Week 0) to 2 hours post-dose at Week 12.
timeFrame: Week 0 and 12 visits
measure: Demonstrate the efficacy of SKP FLUTIFORM HFA pMDI (250/10ug) using other pulmonary function tests (PFTs), and clinical endpoints.
timeFrame: Whole duration of study
measure: Assess the safety profile of SKP FLUTIFORM HFA pMDI (250/10ug twice daily) using incidence of adverse events, and changes in electrocardiograms, clinical laboratory tests and vital signs.
timeFrame: Whole duration of study
measure: To assess the 12-hour serial FEV1 area under the curve (AUC) in a subset population (in a minimum of 66 patients).
timeFrame: Week 0; 2 and 12 visits
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Investigational site
state: Arizona
city: Tempe
country: United States
facility: Investigational Site
state: Arizona
city: Encinitas
country: United States
facility: Investigational Site
state: California
city: Long Beach
country: United States
facility: Investigational site
state: California
city: Orange
country: United States
facility: Investigational site
state: California
city: Oldsmar
country: United States
facility: Investigational Site
state: Florida
city: Indianapolis
country: United States
facility: Investigational Site
state: Indiana
city: Crestview Hills
country: United States
facility: Investigational site
state: Kentucky
city: Metarie
country: United States
facility: Investigational Site
state: Louisiana
city: North Dartmouth
country: United States
facility: Investigational site
state: Massachusetts
city: Wellesley Hills
country: United States
facility: Investigational Site
state: Massachusetts
city: Elizabeth City
country: United States
facility: Investigational site
state: North Carolina
city: Akron
country: United States
facility: Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Investigational site
state: Ohio
city: Portland
country: United States
facility: Investigational Site
state: Oregon
city: East Providence
country: United States
facility: Investigational Site
state: Rhode Island
city: Providence
country: United States
facility: Investigational site
state: Rhode Island
city: Austin
country: United States
facility: Investigational Site
state: Texas
city: El Paso
country: United States
facility: Investigational site
state: Texas
city: Richmond
country: United States
facility: Investigational site
state: Virginia
city: West Allis
country: United States
facility: Investigational Site
state: Wisconsin
city: Bahia Blanca
country: Argentina
facility: Investigational Site
city: Buenos Aires
country: Argentina
facility: Investigational Site
city: Buenos Aires
country: Argentina
facility: Investigational Site
city: Buenos Aires
country: Argentina
facility: Investigational Site
city: Caba
country: Argentina
facility: Investigational Site
city: Caba
country: Argentina
facility: Investigational Site
city: Caba
country: Argentina
facility: Investigational Site
city: Caba
country: Argentina
facility: Investigational Site
city: Caba
country: Argentina
facility: Investigational Site
city: Caba
country: Argentina
facility: Investigational Site
city: Provincia de Buenos Aires
country: Argentina
facility: Investigational Site
city: Salta
country: Argentina
facility: Investigational Site
city: Santa Fe
country: Argentina
facility: Investigational Site
city: Santa Fe
country: Argentina
facility: Investigational Site
city: Tucuman
country: Argentina
facility: Investigational Site
city: Concepcion
country: Chile
facility: Investigational Site
city: Rancagua
country: Chile
facility: Investigational Site
city: Santiago
country: Chile
facility: Investigational Site
city: Budapest
country: Hungary
facility: Investigational Site
city: Budapest
country: Hungary
facility: Investigational Site
city: Deszk
country: Hungary
facility: Investigational Site
city: Miskolc
country: Hungary
facility: Investigational Site
city: Miskolc
country: Hungary
facility: Investigational Site
city: Pecs
country: Hungary
facility: Investigational Site
city: Chihuahua
country: Mexico
facility: Investigational Site
city: Guerrero
country: Mexico
facility: Investigational Site
city: Jalisco
country: Mexico
facility: Investigational Site
city: Jalisco
country: Mexico
facility: Investigational Site
city: Luis Encinas S/N
country: Mexico
facility: Investigational Site
city: Mexico City
country: Mexico
facility: Investigational Site
city: Mexico City
country: Mexico
facility: Investigational Site
city: Michoacán
country: Mexico
facility: Investigational Site
city: Nuevo León
country: Mexico
facility: Investigational Site
city: Puebla
country: Mexico
facility: Investigational Site
city: San Bernardino
country: Mexico
facility: Investigational Site
city: Tabasco
country: Mexico
facility: Investigational Site
city: Cercado de Lima
country: Peru
facility: Investigational Site
city: Cusco
country: Peru
facility: Investigational Site
city: Jesus Maria
country: Peru
facility: Investigational Site
city: Lima
country: Peru
facility: Investigational Site
city: Lima
country: Peru
facility: Investigational Site
city: Lima
country: Peru
facility: Investigational Site
city: Lima
country: Peru
facility: Investigational Site
city: Lima
country: Peru
facility: Investigational Site
city: Lima
country: Peru
facility: Investigational Site
city: Lima
country: Peru
facility: Investigational Site
city: Gdansk
country: Poland
facility: Investigational Site
city: Krakow
country: Poland
facility: Investigational Site
city: Lodz
country: Poland
facility: Investigational Site
city: Rzeszow
country: Poland
facility: Investigational Site
city: Wroclaw
country: Poland
facility: Investigational Site
city: Brasov
country: Romania
facility: Investigational Site
city: Bucharest
country: Romania
facility: Investigational Site
city: Bucharest
country: Romania
facility: Investigational Site
city: Bucharest
country: Romania
facility: Investigational Site
city: Bucharest
country: Romania
facility: Investigational Site
city: Bucharest
country: Romania
facility: Investigational Site
city: Bucuresti
country: Romania
facility: Investigational Site
city: Craiova
country: Romania
facility: Investigational Site
city: Palazu Mare
country: Romania
facility: Investigational Site
city: Timisoara
country: Romania
facility: Investigational Site
city: Bloemfontein
country: South Africa
facility: Investigational Site
city: Cape Town
country: South Africa
facility: Investigational Site
city: Cape Town
country: South Africa
facility: Investigational Site
city: Durban
country: South Africa
facility: Investigational Site
city: Pretoria
country: South Africa
facility: Investigational Site
city: Pretoria
country: South Africa
facility: Investigational Site
city: Somerset West
country: South Africa
facility: Investigational Site
city: Tygerberg
country: South Africa
facility: Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: Investigational Site
city: Donetsk
country: Ukraine
facility: Investigational Site
city: Donetsk
country: Ukraine
facility: Investigational Site
city: Kharkiv
country: Ukraine
facility: Investigational Site
city: Kiev
country: Ukraine
facility: Investigational Site
city: Kiev
country: Ukraine
facility: Investigational Site
city: Kiev
country: Ukraine
facility: Investigational Site
city: Lviv
country: Ukraine
facility: Investigational Site
city: Vinnytsya
country: Ukraine
facility: Investigational Site
city: Zaporizhzhya
country: Ukraine
facility: Investigational Site
city: Zaporizhzhya
country: Ukraine
facility: Investigational Site
Study officials:
References:
citation: Pertseva T, Dissanayake S, Kaiser K. Superiority of fluticasone propionate/formoterol fumarate versus fluticasone propionate alone in patients with moderate-to-severe asthma: a randomised controlled trial. Curr Med Res Opin. 2013 Oct;29(10):1357-69. doi: 10.1185/03007995.2013.825592. Epub 2013 Aug 20.