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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
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

P06476

ISRCTN number

US NCT number

NCT01258803

WHO universal trial number (UTN)

Other trial identifiers

Merck protocol number: MK-0887A-178

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

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

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?

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

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 92

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Participants were recruited from 28 study sites in the United States. Primary Therapy Period: December 2010 to October 2011.

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 title

Treatment Period 1 (1 dose)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Investigator ^[1]

Are arms mutually exclusive

Yes

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)

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)

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)

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)

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)

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 title

Treatment Period 2 (1 dose)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Investigator ^[2]

Are arms mutually exclusive

Yes

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)

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)

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)

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)

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)

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
Consent withdrawn by subject	-	1	-	-	-	-
Protocol deviation	1	1	-	-	-	1

Period 3 title

Treatment Period 3 (1 dose)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Investigator ^[3]

Are arms mutually exclusive

Yes

Treatment Sequence 1

Arm description

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)

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)

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)

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)

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)

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 title

Treatment Period 4 (1 dose)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Investigator ^[4]

Are arms mutually exclusive

Yes

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)

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)

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)

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)

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)

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

Top of page

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

Top of page

Reporting group title

Treatment Sequence 1

Reporting group description

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

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 )

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

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 )

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

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 )

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 )

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 )

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 )

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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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 name

MedDRA

Dictionary version

14.1

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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Were there any global substantial amendments to the protocol? Yes

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.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA