A Study of the Bronchodilator Effect of Formoterol Fumarate Used in Combination With Mometasone Furoate Metered Dose Inhaler in Children With Persistent Asthma (P06476 AM2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01258803
First received: December 9, 2010
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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 microgram (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.


Condition Intervention Phase
Asthma
Drug: Formoterol Fumarate DPI
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
Drug: Placebo MDI with spacer
Drug: Placebo MDI without spacer
Drug: Mometasone Furoate DPI
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 [ Time Frame: Up to 12 hours postdose ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 [ Time Frame: Up to 12 hours postdose ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Up to 12 hours postdose ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Baseline and 5 and 30 minutes, 1, 2, 4, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
    Baseline was defined as the average of 2 predose measurements (taken 30 minutes and immediately before dosing).

  • AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F With Spacer Compared to F DPI [ Time Frame: Up to 12 hours postdose ] [ Designated as safety issue: No ]
    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.

  • AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F Without Spacer Compared to F DPI [ Time Frame: Up to 12 hours postdose ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Up to 12 hours postdose ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Baseline and 5 and 30 minutes, 1, 2, 4, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
    Baseline was defined as the average of 2 predose FVC measurements (taken 30 minutes and immediately before dosing).


Enrollment: 92
Study Start Date: December 2010
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sequence 1
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
Drug: Formoterol Fumarate DPI
Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose
Other Names:
  • SCH 045571
  • MK-5571
  • Foradil® Aerolizer®
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
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)
Other Names:
  • SCH 418131
  • MK-0877A
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
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)
Other Names:
  • SCH 418131
  • MK-0877A
Drug: Placebo MDI with spacer
Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)
Drug: Mometasone Furoate DPI
Two inhalations of MF DPI 100 mcg administered as a single dose once daily at night. Used as maintenance therapy during screening and in between single doses of study drug.
Other Names:
  • SCH 032088
  • MK-0887
  • Asmanex® Twisthaler®
Experimental: Sequence 2
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
Drug: Formoterol Fumarate DPI
Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose
Other Names:
  • SCH 045571
  • MK-5571
  • Foradil® Aerolizer®
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
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)
Other Names:
  • SCH 418131
  • MK-0877A
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
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)
Other Names:
  • SCH 418131
  • MK-0877A
Drug: Placebo MDI with spacer
Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)
Drug: Mometasone Furoate DPI
Two inhalations of MF DPI 100 mcg administered as a single dose once daily at night. Used as maintenance therapy during screening and in between single doses of study drug.
Other Names:
  • SCH 032088
  • MK-0887
  • Asmanex® Twisthaler®
Experimental: Sequence 3
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
Drug: Formoterol Fumarate DPI
Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose
Other Names:
  • SCH 045571
  • MK-5571
  • Foradil® Aerolizer®
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
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)
Other Names:
  • SCH 418131
  • MK-0877A
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
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)
Other Names:
  • SCH 418131
  • MK-0877A
Drug: Placebo MDI with spacer
Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)
Drug: Mometasone Furoate DPI
Two inhalations of MF DPI 100 mcg administered as a single dose once daily at night. Used as maintenance therapy during screening and in between single doses of study drug.
Other Names:
  • SCH 032088
  • MK-0887
  • Asmanex® Twisthaler®
Experimental: Sequence 4
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
Drug: Formoterol Fumarate DPI
Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose
Other Names:
  • SCH 045571
  • MK-5571
  • Foradil® Aerolizer®
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
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)
Other Names:
  • SCH 418131
  • MK-0877A
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
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)
Other Names:
  • SCH 418131
  • MK-0877A
Drug: Placebo MDI without spacer
Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)
Drug: Mometasone Furoate DPI
Two inhalations of MF DPI 100 mcg administered as a single dose once daily at night. Used as maintenance therapy during screening and in between single doses of study drug.
Other Names:
  • SCH 032088
  • MK-0887
  • Asmanex® Twisthaler®
Experimental: Sequence 5
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
Drug: Formoterol Fumarate DPI
Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose
Other Names:
  • SCH 045571
  • MK-5571
  • Foradil® Aerolizer®
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
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)
Other Names:
  • SCH 418131
  • MK-0877A
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
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)
Other Names:
  • SCH 418131
  • MK-0877A
Drug: Placebo MDI without spacer
Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)
Drug: Mometasone Furoate DPI
Two inhalations of MF DPI 100 mcg administered as a single dose once daily at night. Used as maintenance therapy during screening and in between single doses of study drug.
Other Names:
  • SCH 032088
  • MK-0887
  • Asmanex® Twisthaler®
Experimental: Sequence 6
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
Drug: Formoterol Fumarate DPI
Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose
Other Names:
  • SCH 045571
  • MK-5571
  • Foradil® Aerolizer®
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
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)
Other Names:
  • SCH 418131
  • MK-0877A
Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
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)
Other Names:
  • SCH 418131
  • MK-0877A
Drug: Placebo MDI without spacer
Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)
Drug: Mometasone Furoate DPI
Two inhalations of MF DPI 100 mcg administered as a single dose once daily at night. Used as maintenance therapy during screening and in between single doses of study drug.
Other Names:
  • SCH 032088
  • MK-0887
  • Asmanex® Twisthaler®

  Eligibility

Ages Eligible for Study:   5 Years to 11 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have a diagnosis of asthma of at least 6 months duration
  • Must have taken an Inhaled Corticosteroid ([ICS]; alone or in combination with a long-acting beta-2 Agonist [LABA]) for at least 3 months prior to the Screening Visit and must have been on a stable daily dose for at least 2 weeks prior to the Screening Visit
  • FEV1 must be at least 70% predicted after all restricted medications have been withheld for the appropriate intervals
  • Must demonstrate an increase in absolute FEV1 of at least 12% within 30 minutes after administration of 360 mcg albuterol (4 inhalations x 90 mcg, ex-actuator) or of nebulized albuterol (2.5 mg), if confirmed as standard office practice

Exclusion Criteria:

  • Has been treated in the emergency room for a severe asthma exacerbation requiring systemic glucocorticosteroid treatment, or hospitalized for management of airway obstruction within 3 months prior to the Screening Visit
  • Has required ventilator support for respiratory failure secondary to asthma
  • Demonstrates a decrease in absolute FEV1 of >20% at any time from the Screening Visit up to and including the Baseline Visit
  • Requires the use of greater than 8 inhalations per day of short-acting beta-2 agonists (SABA) MDI, or 2 or more nebulized treatments per day of 2.5 mg SABA on any 2 consecutive days from the Screening Visit up to and including the Baseline Visit
  • Experiences a clinical deterioration in asthma that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication (including oral or other systemic corticosteroids, but allowing SABA) as judged by the investigator, at any time from the Screening Visit up to and including the Baseline Visit
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01258803

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Chair: Ariel Teper, MD Merck Sharp & Dohme Corp.
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01258803     History of Changes
Other Study ID Numbers: P06476, MK-0887A-178
Study First Received: December 9, 2010
Results First Received: October 1, 2012
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
asthma
children
persistent

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Bronchodilator Agents
Formoterol
Mometasone furoate
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Allergic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 28, 2014