Clinical trial NCT01772368: Dose Ranging Study of the Salmeterol Component of Fluticasone /Salmeterol Spiromax Compared to Fluticasone Spiromax and Advair Diskus in Asthma Subjects
Official title: A Six-Period Crossover, Dose-Ranging Study to Evaluate the Efficacy and Safety of Four Doses of FS Spiromax (Fluticasone Propionate/Salmeterol Xinafoate Inhalation Powder) Administered as Single Doses Compared With Single Doses of Fluticasone Propionate Spiromax and Open Label Advair Diskus in Adult and Adolescent Subjects With Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
dry powder inhaler
long-acting beta2-agonist
bronchodilation
bronchodilator
metered dose inhaler
inhaled corticosteroid
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2013-01-21
Enrollment: 72
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the dose response, efficacy, and safety of 4 different doses of salmeterol Spiromax (6.25, 12.5, 25, and 50 mcg) each combined with a fixed dose of fluticasone propionate (100 mcg) delivered as Fluticasone/Salmeterol Spiromax® Inhalation Powder (FS Spiromax) when administered as a single dose in subjects 12 years of age and older with persistent asthma.

Detailed description: This was a multicenter, randomized, double-blind and open-label active-controlled, single-dose, 6 period crossover, dose-ranging study conducted in male and female subjects ages 12 years and older with persistent asthma.

Fluticasone propionate multidose dry powder inhaler (Fp MDPI) 50 mcg was provided (to replace the subject's current inhaled corticosteroid (ICS)) throughout the 14 day run-in period and each of the washout periods between treatments. Subjects were instructed to administer 2 inhalations of Fp MDPI 50 mcg (100 mcg total dose) twice daily during the run-in and washout periods. All other medications for the treatment of asthma were discontinued at or prior to the screening visit.

A short-acting β2-adrenergic agonist (SABA), salbuterol HFA, MDI, was provided (to replace the subject's current rescue medication) for symptomatic relief of asthma symptoms in each the run-in, treatment, and washout periods.

Treatment period lasted 5 weeks with a 5 to 7 day washout between each of the six single dose treatments:

* fluticasone propionate/salmeterol xinafoate multidose dry powder inhaler (FS MDPI) given in doses of 6.25, 12.5, 25, or 50 mcg of salmeterol xinafoate in blinded fashion.
* fluticasone propionate multidose dry powder inhaler (Fp MDPI) 100 mcg in blinded fashion
* ADVAIR DISKUS, 100/50 mcg in open-label fashion

Eligibility criteria: Inclusion Criteria:

* Written informed consent/assent
* General good health
* Diagnosis of asthma as defined by the National Institutes of Health (NIH)
* A best FEV1 of 40%-85% of the predicted normal value during the screening visit (SV)
* Subjects need to demonstrate a ≥ 15% reversibility of FEV1 within 30 minutes following 4 inhalations of albuterol inhalation aerosol (if required, spacers are permitted for reversibility testing) at the SV.
* Other inclusion criteria apply

Exclusion Criteria:

* History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation.
* Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that is not resolved within 2 weeks prior to the SV.
* Any asthma exacerbation requiring oral corticosteroids within 3 months of the SV. A subject must not have had any hospitalization for asthma within 6 months prior to the SV.
* Taking long-acting β-agonists within 2 weeks of the SV
* Other exclusion criteria apply.

Primary outcomes:
measure: Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12)
timeFrame: Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours
Secondary outcomes:
measure: Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment
timeFrame: Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 12 hours
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t) of Salmeterol
timeFrame: Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose
measure: Maximum Observed Plasma Concentration (Cmax) of Salmeterol
timeFrame: Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose
measure: Time of Maximum Observed Plasma Concentration (Tmax) of Salmeterol
timeFrame: Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose
measure: Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period
timeFrame: Day 1 up to Day 35
Other outcomes:
Locations:
city: Denver
country: United States
facility: Teva Investigational Site 10453
state: Colorado
city: North Dartmouth
country: United States
facility: Teva Investigational Site 10452
state: Massachusetts
city: Saint Louis
country: United States
facility: Teva Investigational Site 10455
state: Missouri
city: Skillman
country: United States
facility: Teva Investigational Site 10454
state: New Jersey
city: Raleigh
country: United States
facility: Teva Investigational Site 10448
state: North Carolina
city: Medford
country: United States
facility: Teva Investigational Site 10451
state: Oregon
city: Portland
country: United States
facility: Teva Investigational Site 10449
state: Oregon
city: El Paso
country: United States
facility: Teva Investigational Site 10457
state: Texas
city: New Braunfels
country: United States
facility: Teva Investigational Site 10450
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 10456
state: Texas
Study officials:
References: