Clinical trial NCT00424008: Study of Inhaled Glucocorticosteroids/Long-Acting Bronchodilator Drugs in Subjects With Asthma That Have Been Taking Inhaled Glucocorticosteroids (Study P04705AM1)
Official title: A 52-Week Efficacy and Safety Non-Inferiority Study of Fluticasone Propionate/Salmeterol 250/50mcg BID Delivered by Dry Powder Inhaler (Diskus) Versus Mometasone Furoate/Formoterol Fumarate 200/10mcg BID Delivered by Pressurized Metered-Dose Inhaler in Persistent Asthmatics Previously Treated With Medium Doses of Inhaled Glucocorticosteroids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Glucocorticosteroids
Dry Powder Inhaler
Bronchodilator
Metered-Dose Inhaler
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2007-01-18
Enrollment: 722
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is being conducted to demonstrate the non-inferiority between two inhaled glucocorticosteroids and long-acting bronchodilator combination drugs called mometasone furoate/formoterol fumarate in a metered-dose inhaler (MDI) and fluticasone propionate/salmeterol in a dry powder inhaler (DPI) on lung function. Information on the onset of action, the overall safety, and how the drugs control asthma will also be assessed. The study is approximately 1 year in duration.


Eligibility criteria: Inclusion Criteria:

* Participants must have a diagnosis of asthma for at least 12 months' duration.
* A participant must have been using a medium daily dose of inhaled glucocorticosteroids (alone or in combination with long-acting beta 2-agonist \[LABA\]) for at least 12 weeks and must have been on a stable regimen for at least 2 weeks prior to Screening.
* If there is no inherent harm in changing the participant's current asthma therapy, the participant must be willing to discontinue his/her prescribed inhaled glucocorticosteroid (ICS) or ICS/LABA prior to initiating MF MDI run-in medication.
* The diagnosis of asthma must be documented by either demonstrating an increase in absolute forced expiratory volume in 1 second (FEV1) of at least 12% and a volume increase of at least 200 mL within approximately 15 to 20 minutes after administration of 4 inhalations of albuterol/salbutamol or of nebulized short-acting beta 2-agonist (SABA) OR peak expiratory flow (PEF) variability of more than 20% OR a diurnal variation PEF of more than 20% based on the difference between pre-bronchodilator (before taking albuterol/salbutamol) morning value and the post-bronchodilator value (after taking albuterol/salbutamol) from the evening before, expressed as a percentage of the mean daily PEF value on any day during the open-label Run-in Period.
* A participant must have a history of \>= 2 asthma-related unscheduled visits to a physician or to an emergency room within the past year AND \>= 3 asthma-related unscheduled visits within the past 2 years.
* Prior to randomization participants must have used a total of 12 or more inhalations of SABA rescue medication during the last 10 days of run-in.
* Clinical laboratory tests (complete blood counts \[CBC\], blood chemistries, including serum pregnancy for females of child-bearing potential, and urinalysis) conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor before the participant is instructed to start using open-label MF MDI run-in medication.
* An electrocardiogram (ECG) performed at the Screening Visit, using a centralized trans-telephonic technology, must be clinically acceptable to the investigator.
* A chest x-ray performed at the Screening Visit, or within 12 months prior to the Screening Visit, must be clinically acceptable to the investigator.
* A non-pregnant female participant of childbearing potential must be using a medically acceptable, adequate form of birth control. A female participant of childbearing potential must have a negative serum pregnancy test at Screening in order to be considered eligible for enrollment.

Exclusion Criteria:

* A participant who demonstrates a change in absolute FEV1 of \> 20% at any time between the Screening and Baseline Visits on any 2 consecutive days between the Screening and Baseline visits.
* A participant who requires the use of greater than 8 inhalations per day of SABA MDI or 2 or more nebulized treatments per day of 2.5 mg SABA on any 2 consecutive days between the Screening and Baseline Visits.
* A participant who experiences a decrease in AM or PM PEF below the Run-in Period stability limit on any 2 consecutive days prior to randomization. The average AM and average PM PEF respective values from the preceding 7 days are added, divided by the number of non-missing values, and multiplied by 0.70 to determine the stability limit.
* A participant who experiences a clinical asthma exacerbation: defined as a clinical deterioration of asthma as judged by the clinical investigator between the Screening and Baseline Visits, that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication (including oral or other systemic corticosteroids, but allowing SABA).

Primary outcomes:
measure: The Area Under the Curve From 0 to 12 Hours [AUC](0-12 hr) of the Change From Baseline to the Week 12 Endpoint in Forced Expiratory Volume in One Second (FEV1)
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Onset-of-action Based on Change From Baseline FEV1 at the 5 Min Pulmonary Function Test (PFT) Assessment on Day 1
timeFrame: Baseline to 5 minutes post-dose on Day 1
measure: Change From Baseline in Asthma Control Questionnaire (ACQ) Total Score at Week 12 Endpoint
timeFrame: Baseline to Week 12
measure: The Proportion of Symptom-free Days and Nights (Combined) Over the 12-week Treatment Period.
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
Study officials:
References:
citation: Bernstein DI, Hebert J, Cheema A, Murphy KR, Cherrez-Ojeda I, Matiz-Bueno CE, Kuo WL, Nolte H. Efficacy and onset of action of mometasone furoate/formoterol and fluticasone propionate/salmeterol combination treatment in subjects with persistent asthma. Allergy Asthma Clin Immunol. 2011 Dec 7;7(1):21. doi: 10.1186/1710-1492-7-21.