Study of Inhaled Glucocorticosteroids/Long-Acting Bronchodilator Drugs in Subjects With Asthma That Have Been Taking Inhaled Glucocorticosteroids (Study P04705AM1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00424008
Recruitment Status : Completed
First Posted : January 18, 2007
Results First Posted : November 1, 2010
Last Update Posted : April 12, 2017
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Asthma Drug: Mometasone furoate/formoterol (MF/F) MDI Drug: Fluticasone propionate/salmeterol (F/SC) DPI Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 722 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
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 Start Date : April 2007
Actual Primary Completion Date : November 2008
Actual Study Completion Date : November 2008

Arm Intervention/treatment
Experimental: MF/F MDI 200/10 mcg BID
Mometasone furoate 200 mcg and formoterol 10 mcg fixed dose combination taken twice daily.
Drug: Mometasone furoate/formoterol (MF/F) MDI
MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 52 weeks.
Other Name: SCH 418131
Active Comparator: F/SC DPI 250/50 mcg BID
Fluticasone propionate/salmeterol (F/SC) 250/50 mcg BID
Drug: Fluticasone propionate/salmeterol (F/SC) DPI
Fluticasone propionate 250 mcg and salmeterol 50 mcg fixed dose combination dry powder inhaler taken twice daily for 52 weeks.
Other Name: Advair Diskus in the US/Seretide Diskus outside the US

Primary Outcome Measures :
  1. 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) [ Time Frame: Baseline to Week 12 ]

Secondary Outcome Measures :
  1. Onset-of-action Based on Change From Baseline FEV1 at the 5 Min Pulmonary Function Test (PFT) Assessment on Day 1 [ Time Frame: Baseline to 5 minutes post-dose on Day 1 ]
    PFTs, including FEV1, were done on Day 1. Evaluations included 30 min before and immediately before the first dose, the mean of which was Baseline, and at intervals from 5 min to 12 hrs postdose. Onset of action was defined as statistically significant improvement of MF/F over F/SC in Change from Baseline FEV1 at the 5-min postdose evaluation on Day 1. The same series of PFTs were done at Week 12. Change from Baseline to Week 12 evaluations were calculated using the same Day 1 predose scores for Baseline. The Week-12 evaluation consisted of AUC FEV1 scores across the 12-hour postdose interval.

  2. Change From Baseline in Asthma Control Questionnaire (ACQ) Total Score at Week 12 Endpoint [ Time Frame: Baseline to Week 12 ]
    The Asthma Control Questionnaire (ACQ) by Juniper et al. is a mean of 7 equally weighted composite scores; each scaled from 0=best case scenario to 6=worst case scenario on an integer scale. Composites include the following: How Often Woken by Asthma, How Bad Were Asthma Symptoms When You Woke, Activity Limitations, Shortness of Breath, Wheezing, Average Daily Short-Acting Beta 2-Agonist (SABA) Puffs, and physician-evaluated lung function. With the exception of physician-evaluated lung function collected at the visit, evaluations were over the last week recall period.

  3. The Proportion of Symptom-free Days and Nights (Combined) Over the 12-week Treatment Period. [ Time Frame: Baseline to Week 12 ]
    For each day of the evaluation period, symptoms were collected in the morning for the night's evaluation, and in the evening for the day's evaluation. Symptoms included coughing, wheezing, and difficulty breathing, each integer-scaled from 0=none to 3=severe. A symptom-free Day/Night is defined as a combined score of 0 across the morning and evening evaluations. The proportion of 0 scores across the Baseline period, and across the 12-week treatment period, is calculated to determine the overall proportion of symptom-free Days/Nights for each of these periods.

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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).

Publications of Results:
Responsible Party: Merck Sharp & Dohme Corp. Identifier: NCT00424008     History of Changes
Other Study ID Numbers: P04705
SCH 418131
First Posted: January 18, 2007    Key Record Dates
Results First Posted: November 1, 2010
Last Update Posted: April 12, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Keywords provided by Merck Sharp & Dohme Corp.:
Dry Powder Inhaler
Metered-Dose Inhaler

Additional relevant MeSH terms:
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Mometasone Furoate
Formoterol Fumarate
Salmeterol Xinafoate
Bronchodilator Agents
Fluticasone Propionate, Salmeterol Xinafoate Drug Combination
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action