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    Clinical Trial Results:
    A Randomized, Evaluator-Blind, Crossover, Single Dose Study of the Bronchodilator Effect of Formoterol Fumarate in Combination With Mometasone Furoate Metered Dose Inhaler Delivered With and Without a Spacer Versus Placebo and Foradil® Aerolizer® in Children With Persistent Asthma (Protocol No. P06476)

    Summary
    EudraCT number
    2014-004582-24
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    15 Oct 2011

    Results information
    Results version number
    v1(current)
    This version publication date
    16 Feb 2016
    First version publication date
    30 Jul 2015
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    P06476
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01258803
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Merck protocol number: MK-0887A-178
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    15 Oct 2011
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Oct 2011
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Oct 2011
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    A study to compare the bronchodilatory effect of a single dose of Mometasone Furoate/Formoterol Fumarate (MF/F) pressurized metered dose inhaler (MDI) delivered with and without an AeroChamber Plus® with Flow-Vu® Anti-Static Valved Holding Chamber (spacer) versus Placebo MDI (combined with and without spacer) and formoterol fumarate (F) dry powder inhaler (DPI). Participants were randomly assigned to 1 of 6 treatment sequences and each participant was to receive a single dose of each of 4 treatments in each period. Each treatment period was separated by a 5 to 7 day washout period. It assumed that a single dose MF/F MDI 100/10 mcg delivered with a spacer would produce bronchodilation, defined as a significant increase in forced expiratory volume in one second (FEV1) area under the curve from 0 to 12 hours (AUC[0-12 hr]) when compared to placebo.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    08 Dec 2010
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 92
    Worldwide total number of subjects
    92
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    92
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Participants were recruited from 28 study sites in the United States. Primary Therapy Period: December 2010 to October 2011.

    Pre-assignment
    Screening details
    The study included a 4-week Run-In Period during which participants were treated with Mometasone Furoate (MF) Dry Powdered Inhaler (DPI) 100 mcg.

    Period 1
    Period 1 title
    Treatment Period 1 (1 dose)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Single blind
    Roles blinded
    Investigator [1]

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Treatment Sequence 1
    Arm description
    Treatment Period 1: Placebo Metered Dose Inhaler (MDI) with spacer, Treatment Period 2: Mometasone Furoate/Formoterol Fumarate (MF/F) MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: F Dry Powder Inhaler (DPI)
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI with spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 2
    Arm description
    Treatment Period 1: F DPI, Treatment Period 2: MF/F MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI with spacer
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI with spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 3
    Arm description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: Placebo MDI with spacer, Treatment Period 4: MF/F MDI with spacer
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI with spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 4
    Arm description
    Treatment Period 1: Placebo MDI without spacer, Treatment Period 2: MF/F MDI with spacer, Treatment Period 3: F DPI, Treatment Period 4: MF/F MDI without spacer
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI without spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 5
    Arm description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI without spacer
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI without spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 6
    Arm description
    Treatment Period 1: MF/F MDI with spacer, Treatment Period 2: Placebo MDI without spacer, Treatment Period 3: MF/F MDI without spacer, Treatment Period 4: F DPI
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI without spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Notes
    [1] - The roles blinded appear inconsistent with a simple blinded trial.
    Justification: This was an evaluator-blind study. The investigator, clinical study staff and personnel performing the assessments and data analysis were to remain blinded to the identity of the study medication and treatment sequence. The Third-Party Dispenser was the only one at the site who knew the treatment assignment of each subject.
    Number of subjects in period 1
    Treatment Sequence 1 Treatment Sequence 2 Treatment Sequence 3 Treatment Sequence 4 Treatment Sequence 5 Treatment Sequence 6
    Started
    15
    16
    15
    15
    15
    16
    Completed
    15
    16
    15
    15
    15
    16
    Period 2
    Period 2 title
    Treatment Period 2 (1 dose)
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Single blind
    Roles blinded
    Investigator [2]

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Treatment Sequence 1
    Arm description
    Treatment Period 1: Placebo MDI with spacer, Treatment Period 2: MF/F MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: F DPI
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI with spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 2
    Arm description
    Treatment Period 1: F DPI, Treatment Period 2: MF/F MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI with spacer
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI with spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 3
    Arm description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: Placebo MDI with spacer, Treatment Period 4: MF/F MDI with spacer
    Arm type
    Treatment Sequence

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI with spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 4
    Arm description
    Treatment Period 1: Placebo MDI without spacer, Treatment Period 2: MF/F MDI with spacer, Treatment Period 3: F DPI, Treatment Period 4: MF/F MDI without spacer
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI without spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 5
    Arm description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI without spacer
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI without spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 6
    Arm description
    Treatment Period 1: MF/F MDI with spacer, Treatment Period 2: Placebo MDI without spacer, Treatment Period 3: MF/F MDI without spacer, Treatment Period 4: F DPI
    Arm type
    Treatment Sequence

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI without spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Notes
    [2] - The roles blinded appear inconsistent with a simple blinded trial.
    Justification: This was an evaluator-blind study. The investigator, clinical study staff and personnel performing the assessments and data analysis were to remain blinded to the identity of the study medication and treatment sequence. The Third-Party Dispenser was the only one at the site who knew the treatment assignment of each subject.
    Number of subjects in period 2
    Treatment Sequence 1 Treatment Sequence 2 Treatment Sequence 3 Treatment Sequence 4 Treatment Sequence 5 Treatment Sequence 6
    Started
    15
    16
    15
    15
    15
    16
    Completed
    14
    14
    15
    15
    15
    15
    Not completed
    1
    2
    0
    0
    0
    1
         Protocol deviation
    1
    1
    -
    -
    -
    1
         Consent withdrawn by subject
    -
    1
    -
    -
    -
    -
    Period 3
    Period 3 title
    Treatment Period 3 (1 dose)
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Single blind
    Roles blinded
    Investigator [3]

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Treatment Sequence 1
    Arm description
    Treatment Period 1: Placebo Metered Dose Inhaler (MDI) with spacer, Treatment Period 2: Mometasone Furoate/Formoterol Fumarate (MF/F) MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: F Dry Powder Inhaler (DPI)
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI with spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 2
    Arm description
    Treatment Period 1: F DPI, Treatment Period 2: MF/F MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI with spacer
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI with spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 3
    Arm description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: Placebo MDI with spacer, Treatment Period 4: MF/F MDI with spacer
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI with spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 4
    Arm description
    Treatment Period 1: Placebo MDI without spacer, Treatment Period 2: MF/F MDI with spacer, Treatment Period 3: F DPI, Treatment Period 4: MF/F MDI without spacer
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI without spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 5
    Arm description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI without spacer
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI without spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 6
    Arm description
    Treatment Period 1: MF/F MDI with spacer, Treatment Period 2: Placebo MDI without spacer, Treatment Period 3: MF/F MDI without spacer, Treatment Period 4: F DPI
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI without spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Notes
    [3] - The roles blinded appear inconsistent with a simple blinded trial.
    Justification: This was an evaluator-blind study. The investigator, clinical study staff and personnel performing the assessments and data analysis were to remain blinded to the identity of the study medication and treatment sequence. The Third-Party Dispenser was the only one at the site who knew the treatment assignment of each subject.
    Number of subjects in period 3
    Treatment Sequence 1 Treatment Sequence 2 Treatment Sequence 3 Treatment Sequence 4 Treatment Sequence 5 Treatment Sequence 6
    Started
    14
    14
    15
    15
    15
    15
    Completed
    14
    14
    14
    15
    15
    15
    Not completed
    0
    0
    1
    0
    0
    0
         Protocol deviation
    -
    -
    1
    -
    -
    -
    Period 4
    Period 4 title
    Treatment Period 4 (1 dose)
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Single blind
    Roles blinded
    Investigator [4]

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Treatment Sequence 1
    Arm description
    Treatment Period 1: Placebo MDI with spacer, Treatment Period 2: MF/F MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: F DPI
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI with spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 2
    Arm description
    Treatment Period 1: F DPI, Treatment Period 2: MF/F MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI with spacer
    Arm type
    Treatment Sequence

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI with spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 3
    Arm description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: Placebo MDI with spacer, Treatment Period 4: MF/F MDI with spacer
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI with spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 4
    Arm description
    Treatment Period 1: Placebo MDI without spacer, Treatment Period 2: MF/F MDI with spacer, Treatment Period 3: F DPI, Treatment Period 4: MF/F MDI without spacer
    Arm type
    Treatment Sequence

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI without spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 5
    Arm description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI without spacer
    Arm type
    Treatment Sequence

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI without spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Arm title
    Treatment Sequence 6
    Arm description
    Treatment Period 1: MF/F MDI with spacer, Treatment Period 2: Placebo MDI without spacer, Treatment Period 3: MF/F MDI without spacer, Treatment Period 4: F DPI
    Arm type
    Experimental

    Investigational medicinal product name
    Formoterol Fumarate DPI
    Investigational medicinal product code
    Other name
    SCH 045571, MK-5571, Foradil® Aerolizer®
    Pharmaceutical forms
    Inhalation powder
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
    Investigational medicinal product code
    Other name
    SCH 418131, MK-0877A
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Investigational medicinal product name
    Placebo MDI without spacer
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)

    Notes
    [4] - The roles blinded appear inconsistent with a simple blinded trial.
    Justification: This was an evaluator-blind study. The investigator, clinical study staff and personnel performing the assessments and data analysis were to remain blinded to the identity of the study medication and treatment sequence. The Third-Party Dispenser was the only one at the site who knew the treatment assignment of each subject.
    Number of subjects in period 4
    Treatment Sequence 1 Treatment Sequence 2 Treatment Sequence 3 Treatment Sequence 4 Treatment Sequence 5 Treatment Sequence 6
    Started
    14
    14
    14
    15
    15
    15
    Completed
    14
    14
    14
    15
    15
    15

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Treatment Period 1 (1 dose)
    Reporting group description
    All Randomized Participants

    Reporting group values
    Treatment Period 1 (1 dose) Total
    Number of subjects
    92 92
    Age, Customized
    Units: participants
        5-7 years
    17 17
        8-11 years
    75 75
    Age continuous
    Units:
        
    9.1 ± 1.7 -
    Gender, Male/Female
    Units: participants
        Female
    35 35
        Male
    57 57

    End points

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    End points reporting groups
    Reporting group title
    Treatment Sequence 1
    Reporting group description
    Treatment Period 1: Placebo Metered Dose Inhaler (MDI) with spacer, Treatment Period 2: Mometasone Furoate/Formoterol Fumarate (MF/F) MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: F Dry Powder Inhaler (DPI)

    Reporting group title
    Treatment Sequence 2
    Reporting group description
    Treatment Period 1: F DPI, Treatment Period 2: MF/F MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI with spacer

    Reporting group title
    Treatment Sequence 3
    Reporting group description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: Placebo MDI with spacer, Treatment Period 4: MF/F MDI with spacer

    Reporting group title
    Treatment Sequence 4
    Reporting group description
    Treatment Period 1: Placebo MDI without spacer, Treatment Period 2: MF/F MDI with spacer, Treatment Period 3: F DPI, Treatment Period 4: MF/F MDI without spacer

    Reporting group title
    Treatment Sequence 5
    Reporting group description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI without spacer

    Reporting group title
    Treatment Sequence 6
    Reporting group description
    Treatment Period 1: MF/F MDI with spacer, Treatment Period 2: Placebo MDI without spacer, Treatment Period 3: MF/F MDI without spacer, Treatment Period 4: F DPI
    Reporting group title
    Treatment Sequence 1
    Reporting group description
    Treatment Period 1: Placebo MDI with spacer, Treatment Period 2: MF/F MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: F DPI

    Reporting group title
    Treatment Sequence 2
    Reporting group description
    Treatment Period 1: F DPI, Treatment Period 2: MF/F MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI with spacer

    Reporting group title
    Treatment Sequence 3
    Reporting group description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: Placebo MDI with spacer, Treatment Period 4: MF/F MDI with spacer

    Reporting group title
    Treatment Sequence 4
    Reporting group description
    Treatment Period 1: Placebo MDI without spacer, Treatment Period 2: MF/F MDI with spacer, Treatment Period 3: F DPI, Treatment Period 4: MF/F MDI without spacer

    Reporting group title
    Treatment Sequence 5
    Reporting group description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI without spacer

    Reporting group title
    Treatment Sequence 6
    Reporting group description
    Treatment Period 1: MF/F MDI with spacer, Treatment Period 2: Placebo MDI without spacer, Treatment Period 3: MF/F MDI without spacer, Treatment Period 4: F DPI
    Reporting group title
    Treatment Sequence 1
    Reporting group description
    Treatment Period 1: Placebo Metered Dose Inhaler (MDI) with spacer, Treatment Period 2: Mometasone Furoate/Formoterol Fumarate (MF/F) MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: F Dry Powder Inhaler (DPI)

    Reporting group title
    Treatment Sequence 2
    Reporting group description
    Treatment Period 1: F DPI, Treatment Period 2: MF/F MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI with spacer

    Reporting group title
    Treatment Sequence 3
    Reporting group description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: Placebo MDI with spacer, Treatment Period 4: MF/F MDI with spacer

    Reporting group title
    Treatment Sequence 4
    Reporting group description
    Treatment Period 1: Placebo MDI without spacer, Treatment Period 2: MF/F MDI with spacer, Treatment Period 3: F DPI, Treatment Period 4: MF/F MDI without spacer

    Reporting group title
    Treatment Sequence 5
    Reporting group description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI without spacer

    Reporting group title
    Treatment Sequence 6
    Reporting group description
    Treatment Period 1: MF/F MDI with spacer, Treatment Period 2: Placebo MDI without spacer, Treatment Period 3: MF/F MDI without spacer, Treatment Period 4: F DPI
    Reporting group title
    Treatment Sequence 1
    Reporting group description
    Treatment Period 1: Placebo MDI with spacer, Treatment Period 2: MF/F MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: F DPI

    Reporting group title
    Treatment Sequence 2
    Reporting group description
    Treatment Period 1: F DPI, Treatment Period 2: MF/F MDI without spacer, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI with spacer

    Reporting group title
    Treatment Sequence 3
    Reporting group description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: Placebo MDI with spacer, Treatment Period 4: MF/F MDI with spacer

    Reporting group title
    Treatment Sequence 4
    Reporting group description
    Treatment Period 1: Placebo MDI without spacer, Treatment Period 2: MF/F MDI with spacer, Treatment Period 3: F DPI, Treatment Period 4: MF/F MDI without spacer

    Reporting group title
    Treatment Sequence 5
    Reporting group description
    Treatment Period 1: MF/F MDI without spacer, Treatment Period 2: F DPI, Treatment Period 3: MF/F MDI with spacer, Treatment Period 4: Placebo MDI without spacer

    Reporting group title
    Treatment Sequence 6
    Reporting group description
    Treatment Period 1: MF/F MDI with spacer, Treatment Period 2: Placebo MDI without spacer, Treatment Period 3: MF/F MDI without spacer, Treatment Period 4: F DPI

    Subject analysis set title
    MF/F MDI with spacer
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants receiving a single dose of MF/F MDI 100/10 mcg with a spacer

    Subject analysis set title
    MF/F MDI without spacer
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants receiving a single dose of MF/F MDI 100/10 mcg without a spacer

    Subject analysis set title
    F DPI
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants receiving a single dose of F DPI 20 mcg

    Subject analysis set title
    Placebo MDI with or without spacer
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants receiving a single dose of Placebo MDI with or without a spacer

    Primary: Area Under the Curve From 0-12 hours (AUC[0-12h]) of the Change From baseline in Forced Expiratory Volume in 1 Second (FEV1) After a Single Dose of MF/F MDI With Spacer Compared to Placebo MDI Combined With or Without Spacer

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    End point title
    Area Under the Curve From 0-12 hours (AUC[0-12h]) of the Change From baseline in Forced Expiratory Volume in 1 Second (FEV1) After a Single Dose of MF/F MDI With Spacer Compared to Placebo MDI Combined With or Without Spacer
    End point description
    The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. The analysis population for this endpoint included all participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, spacer and spirometry maneuvers; and used >80% of prescribed MF DPI across the entire study treatment.
    End point type
    Primary
    End point timeframe
    Up to 12 hours postdose
    End point values
    MF/F MDI with spacer Placebo MDI with or without spacer
    Number of subjects analysed
    79
    79
    Units: Liters
        least squares mean (standard error)
    0.115 ± 0.016
    -0.009 ± 0.016
    Statistical analysis title
    AUC(0-12h) chg from BL in FEV1 after single dose
    Statistical analysis description
    Pairwise Treatment Comparison of MF/F MDI with spacer and Placebo MDI combined with or without spacer. Analysis was performed using an analysis of covariance (ANCOVA) model extracting the effects due to treatment, sequence, subject (random effect nested within sequence), period, age groups (5 to 7 years and 8 to 11 years) and Baseline FEV1 as a covariate.
    Comparison groups
    MF/F MDI with spacer v Placebo MDI with or without spacer
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.124
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.094
         upper limit
    0.154

    Secondary: AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose MF/F MDI Without Spacer Compared to Placebo MDI Combined With or Without Spacer

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    End point title
    AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose MF/F MDI Without Spacer Compared to Placebo MDI Combined With or Without Spacer
    End point description
    The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. The analysis population for this endpoint included all participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, spacer and spirometry maneuvers; and used >80% of prescribed MF DPI across the entire study treatment.
    End point type
    Secondary
    End point timeframe
    Up to 12 hours postdose
    End point values
    Placebo MDI with or without spacer MF/F MDI without spacer
    Number of subjects analysed
    79
    79
    Units: Liters
        least squares mean (standard error)
    -0.009 ± 0.016
    0.093 ± 0.016
    Statistical analysis title
    AUC(0-12h) chg from BL in FEV1 after single dose
    Statistical analysis description
    Pairwise Treatment Comparison of MF/F MDI without spacer and Placebo MDI combined with or without spacer. Analysis was performed using an ANCOVA model extracting the effects due to treatment, sequence, subject (random effect nested within sequence), period, age groups (5 to 7 years and 8 to 11 years) and Baseline FEV1 as a covariate.
    Comparison groups
    MF/F MDI without spacer v Placebo MDI with or without spacer
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.102
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.073
         upper limit
    0.131

    Secondary: AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer Compared to MF/F MDI Without Spacer

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    End point title
    AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer Compared to MF/F MDI Without Spacer
    End point description
    The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. The analysis population for this endpoint included all participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, spacer and spirometry maneuvers; and used >80% of prescribed MF DPI across the entire study treatment.
    End point type
    Secondary
    End point timeframe
    Up to 12 hours postdose
    End point values
    MF/F MDI with spacer MF/F MDI without spacer
    Number of subjects analysed
    79
    79
    Units: Liters
        least squares mean (standard error)
    0.115 ± 0.016
    0.093 ± 0.016
    Statistical analysis title
    AUC(0-12h) chg from BL in FEV1 after single dose
    Statistical analysis description
    Pairwise Treatment Comparison of MF/F MDI with spacer and MF/F MDI without spacer. Analysis was performed using an ANCOVA model extracting the effects due to treatment, sequence, subject (random effect nested within sequence), period, age groups (5 to 7 years and 8 to 11 years) and Baseline FEV1 as a covariate.
    Comparison groups
    MF/F MDI with spacer v MF/F MDI without spacer
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.144
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.022
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.008
         upper limit
    0.052

    Secondary: AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F With Spacer Compared to F DPI

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    End point title
    AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F With Spacer Compared to F DPI
    End point description
    The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. The analysis population for this endpoint included all participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, space and spirometry maneuvers; and used >80% of prescribed MF DPI across the entire study treatment.
    End point type
    Secondary
    End point timeframe
    Up to 12 hours postdose
    End point values
    MF/F MDI with spacer F DPI
    Number of subjects analysed
    79
    79
    Units: Liters
        least squares mean (standard error)
    0.115 ± 0.016
    0.097 ± 0.016
    Statistical analysis title
    AUC(0-12h) chg from BL in FEV1 after single dose
    Statistical analysis description
    Pairwise Treatment Comparison of MF/F MDI with spacer and F DPI. Analysis was performed using an ANCOVA model extracting the effects due to treatment, sequence, subject (random effect nested within sequence), period, age groups (5 to 7 years and 8 to 11 years) and Baseline FEV1 as a covariate.
    Comparison groups
    MF/F MDI with spacer v F DPI
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.229
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.018
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.012
         upper limit
    0.048

    Secondary: AUC (0-12h) of the Change from Baseline in FEV1 After a Single Dose of MF/F Without Spacer Compared to F DPI

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    End point title
    AUC (0-12h) of the Change from Baseline in FEV1 After a Single Dose of MF/F Without Spacer Compared to F DPI
    End point description
    The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. The analysis population for this endpoint included all participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, space and spirometry maneuvers; and used >80% of prescribed MF DPI across the entire study treatment.
    End point type
    Secondary
    End point timeframe
    Up to 12 hours postdose
    End point values
    MF/F MDI without spacer F DPI
    Number of subjects analysed
    79
    79
    Units: Liters
        least squares mean (standard error)
    0.093 ± 0.016
    0.097 ± 0.016
    Statistical analysis title
    AUC(0-12h) chg from BL in FEV1 after single dose
    Statistical analysis description
    Pairwise Treatment Comparison of MF/F MDI without spacer and F DPI. Analysis was performed using an ANCOVA model extracting the effects due to treatment, sequence, subject (random effect nested within sequence), period, age groups (5 to 7 years and 8 to 11 years) and Baseline FEV1 as a covariate.
    Comparison groups
    MF/F MDI without spacer v F DPI
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.79
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.004
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.033
         upper limit
    0.025

    Secondary: AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of F DPI Compared to Placebo MDI Combined With or Without Spacer

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    End point title
    AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of F DPI Compared to Placebo MDI Combined With or Without Spacer
    End point description
    The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. The analysis population for this endpoint included all participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, space and spirometry maneuvers; and used >80% of prescribed MF DPI across the entire study treatment.
    End point type
    Secondary
    End point timeframe
    Up to 12 hours postdose
    End point values
    Placebo MDI with or without spacer F DPI
    Number of subjects analysed
    79
    79
    Units: Liters
        least squares mean (standard error)
    -0.009 ± 0.016
    0.097 ± 0.016
    Statistical analysis title
    AUC(0-12h) chg from BL in FEV1 after single dose
    Statistical analysis description
    Pairwise Treatment Comparison of F DPI and Placebo MDI combined with or without spacer. Analysis was performed using an ANCOVA model extracting the effects due to treatment, sequence, subject (random effect nested within sequence), period, age groups (5 to 7 years and 8 to 11 years) and Baseline FEV1 as a covariate.
    Comparison groups
    F DPI v Placebo MDI with or without spacer
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.106
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.077
         upper limit
    0.135

    Secondary: Change from Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose

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    End point title
    Change from Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose
    End point description
    Baseline was defined as the average of 2 predose FVC measurements (taken 30 minutes and immediately before dosing). The analysis population for this endpoint included all participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, spacer and spirometry maneuvers; and used >80% of prescribed MF DPI across the entire study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline and 5 and 30 minutes, 1, 2, 4, 8 and 12 hours postdose
    End point values
    MF/F MDI with spacer Placebo MDI with or without spacer MF/F MDI without spacer F DPI
    Number of subjects analysed
    79
    79
    79
    79
    Units: Liters
    least squares mean (standard error)
        Baseline (n=79,79,79,79)
    1.914 ± 0.061
    1.913 ± 0.061
    1.931 ± 0.061
    1.928 ± 0.061
        5 minutes postdose (n=79,79,79,79)
    0.028 ± 0.012
    0.018 ± 0.012
    0.005 ± 0.012
    0.032 ± 0.012
        30 minutes postdose (n=79,79,79,79)
    0.037 ± 0.013
    0.009 ± 0.013
    0.02 ± 0.013
    0.017 ± 0.013
        1 hour postdose (n=79,79,79,79)
    0.048 ± 0.015
    -0.003 ± 0.014
    0.027 ± 0.014
    0.022 ± 0.014
        2 hours postdose (n=79,79,79,79)
    0.023 ± 0.015
    0.015 ± 0.015
    0.026 ± 0.015
    0.047 ± 0.015
        4 hours postdose (n=79,79,79,79)
    0.031 ± 0.015
    -0.006 ± 0.015
    0.018 ± 0.015
    0.008 ± 0.015
        8 hours postdose (n=79,79,79,79)
    -0.001 ± 0.016
    -0.006 ± 0.015
    0.007 ± 0.015
    -0.013 ± 0.015
        12 hours postdose (n=78,79,78,79)
    -0.001 ± 0.017
    -0.012 ± 0.016
    -0.022 ± 0.016
    -0.014 ± 0.016
    No statistical analyses for this end point

    Secondary: Change from Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose

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    End point title
    Change from Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose
    End point description
    Baseline was defined as the average of 2 predose measurements (taken 30 minutes and immediately before dosing). The analysis population for this endpoint included all participants who received each assigned single-dose treatment, performed at least the 0- and 2-hour spirometry evaluations and met the following criteria: did not use any prohibited concomitant medications; demonstrated satisfactory use of inhaler, spacer and spirometry maneuvers; and used >80% of prescribed MF DPI across the entire study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline and 5 and 30 minutes, 1, 2, 4, 8 and 12 hours postdose
    End point values
    MF/F MDI with spacer Placebo MDI with or without spacer MF/F MDI without spacer F DPI
    Number of subjects analysed
    79
    79
    79
    79
    Units: Liters
    least squares mean (standard error)
        Baseline (n=79,79,79,79)
    1.554 ± 0.049
    1.547 ± 0.049
    1.563 ± 0.049
    1.57 ± 0.049
        5 minutes postdose (n=79,79,79,79)
    0.111 ± 0.014
    -0.001 ± 0.014
    0.068 ± 0.013
    0.105 ± 0.013
        30 minutes postdose (n=79,79,79,79)
    0.131 ± 0.017
    0.006 ± 0.016
    0.099 ± 0.016
    0.117 ± 0.016
        1 hour postdose (n=79,79,79,79)
    0.159 ± 0.017
    0.007 ± 0.016
    0.131 ± 0.016
    0.136 ± 0.016
        2 hours postdose (n=79,79,79,79)
    0.136 ± 0.018
    0.019 ± 0.018
    0.126 ± 0.018
    0.135 ± 0.018
        4 hours postdose (n=79,79,79,79)
    0.136 ± 0.018
    0.005 ± 0.018
    0.115 ± 0.018
    0.118 ± 0.018
        8 hours postdose (n=79,79,79,79)
    0.108 ± 0.018
    -0.012 ± 0.018
    0.093 ± 0.018
    0.087 ± 0.017
        12 hours postdose (n=78,79,78,79)
    0.092 ± 0.019
    -0.033 ± 0.019
    0.046 ± 0.018
    0.059 ± 0.018
    No statistical analyses for this end point

    Adverse events

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    Adverse events information [1]
    Timeframe for reporting adverse events
    Adverse event data were collected for up to 30 days after last dose of study drug (up to a total of 90 days)
    Adverse event reporting additional description
    The Safety Population consisted of all randomized participants who received at least one dose of the study drug.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    14.1
    Reporting groups
    Reporting group title
    MF/F MDI with spacer
    Reporting group description
    Participants receiving a single dose of MF/F MDI 100/10 mcg with a spacer

    Reporting group title
    F DPI
    Reporting group description
    Participants receiving a single dose of F DPI 20 mcg

    Reporting group title
    Placebo MDI with or without spacer
    Reporting group description
    Participants receiving a single dose of Placebo MDI with or without a spacer

    Reporting group title
    MF/F MDI without spacer
    Reporting group description
    Participants receiving a single dose of MF/F MDI 100/10 mcg without a spacer

    Serious adverse events
    MF/F MDI with spacer F DPI Placebo MDI with or without spacer MF/F MDI without spacer
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 88 (0.00%)
    0 / 90 (0.00%)
    0 / 90 (0.00%)
    0 / 91 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    MF/F MDI with spacer F DPI Placebo MDI with or without spacer MF/F MDI without spacer
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 88 (0.00%)
    0 / 90 (0.00%)
    0 / 90 (0.00%)
    0 / 91 (0.00%)
    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: In this study, no non-serious adverse events reached the 5% frequency threshold for reporting.

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Oct 2010
    Amendment 1: Changes to Inclusion Criterion 14: text added to be consistent with other references in protocol: Subject must be able to demonstrate his/her ability to perform reproducible expiratory maneuvers (including PEF), following the principles of the ATS/ERS guidelines. Text also modified in following procedures: 7.Review of prior medications, including washout times, with subject. Record of prior medication taken by subject within 30 days, or longer, if applicable as per washout requirements, before starting trial to be obtained; 14.Venous blood and urine samples specified in Table 8 (protocol) to be analyzed and reported by central laboratory using standard procedures. Urine pregnancy test for female subjects of childbearing potential to be taken at Screening Visit and Visit 5 or Discontinuation Visit; must be negative for subject to be considered for eligibility. If subject is menstruating at time of urine collection, it should be noted in the source and eCRF comment module. Female subjects who begin menses after Screening Visit will have urine pregnancy test at next scheduled visit. Subjects with positive test will be discontinued; 16.Subjects to refrain from using SABA for 6 hours prior to start of spirometry unless FEV1 falls below stability limit. Spirometry to be performed following principles of ATS/ERS guidelines; should be performed with subject sitting, using a chair with arms and without wheels; if necessary, undertake testing with subject standing or in another position and note on spirometry report; position should be consistent throughout study. Use of nose clips required; 17.Reversibility should be demonstrated within 30 minutes of bronchodilator administration. If subject does not meet reversibility at Visit 1, three repeat assessments can be performed during Run-in Period, prior to Baseline Visit; 18.e-Diary/PEF meter will collect and save relevant expiratory flow-volume parameters, use of rescue medication, and dosing information.
    17 Dec 2010
    Amendment 2: The only change the protocol was reinserting missing pages in Appendix 8.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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