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Study of Efficacy and Long-Term Safety of Mometasone Furoate in Combination With Formoterol Fumarate Versus Mometasone Furoate in Children (5 to 11 Years of Age) With Persistent Asthma (MK-0887A-087)

Primary Purpose

Asthma

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
MF MDI 100 mcg BID (Open Label)
MF/F MDI 100/10 mcg BID
MF MDI 100 mcg BID
Albuterol/Salbutamol PRN
Prednisone/Prednisolone
Sponsored by
Organon and Co
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma

Eligibility Criteria

5 Years - 11 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Has a diagnosis of asthma of ≥ 6-months duration according to the Global Initiative for Asthma (GINA) guidelines
  • Has asthma that is adequately controlled on a stable dose of inhaled corticosteroid (ICS) combined with long-acting beta-agonist (LABA) ≥ 4 weeks
  • Is able to demonstrate an FEV1 >60% and ≤90% predicted
  • Is able to demonstrate an increase in absolute FEV1 of at least 12% within 30 minutes after administration of albuterol/salbutamol.
  • Is able to use an MDI (without spacer), use a peak flow meter, and perform spirometry correctly.
  • Is willing (with consent of their parent(s)/guardian) to discontinue previously prescribed asthma medication, if there is no inherent harm in changing the participant's current asthma therapy.
  • Has laboratory tests that are clinically acceptable to the investigator.

Exclusion Criteria:

  • Requires >8 inhalations per day of albuterol (100 mcg per actuation), and/or >2 nebulized treatments per day of 2.5 mg albuterol on any 2 consecutive days
  • Has a clinical worsening of asthma that results in emergency room visit (for an asthma exacerbation), hospitalization due to asthma, or treatment with additional, excluded asthma medication (other than SABA) between the Screening and Baseline visits.
  • Is considered by the investigator to have unstable asthma at the end of the run-in period
  • Has had > 4 asthma exacerbations (defined as a worsening of asthma requiring systemic corticosteroid use and/or ≥ 24-hour stay in an emergency department, urgent care center, or hospital) within 1 year prior to visit 1
  • Has had a history of life-threatening asthma
  • Has a clinically significant condition or situation, other than the condition being studied which may interfere with trial evaluations, participant safety, or optimal participation in the trial

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    MF/F MDI 100/10 mcg BID

    MF MDI 100 mcg BID

    Arm Description

    Eligible participants will be assigned randomly to receive double-blinded MF/F MDI 100/10 mcg BID for 24 weeks.

    Eligible participants will be assigned randomly to receive double-blinded MF MDI 100 mcg BID for 24 weeks.

    Outcomes

    Primary Outcome Measures

    Change From Baseline in Morning (AM) Post-Dose % Predicted Forced Expiratory Volume in One Second (FEV1) in the Area Under the Curve (AUC)0-60
    This endpoint reflects changes in lung function data (forced expiratory volume in 1 second) measured across 0 to 60 minutes post-dose (at 0, 5, 15, 30 and 60 minutes) and averaged across study visits in the Treatment Period (Day 1, Week 1, Week 4, Week 8 and Week 12) compared to Baseline. Baseline was the average of % predicted FEV1 values at 30 min and 0 min pre-dose. At each visit, the area under the curve is calculated over the post-dose timepoints. Units are standardized to percent predicted FEV1 by dividing the AUC calculation by the duration of the observed AUC.
    Count (Percentage) of Participants Experiencing At Least One Adverse Event (AE)
    An Adverse Event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition temporally associated with the use of the Sponsor's product, is also an AE.
    Count (Percentage) of Participants Discontinuing From Study Medication Due to An AE
    An Adverse Event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition temporally associated with the use of the Sponsor's product, is also an AE.

    Secondary Outcome Measures

    Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment
    The key secondary objective was to determine the onset of action for the efficacy of MF/F MDI 100/10 mcg BID, compared with MF MDI 100 mcg BID. The post-dose AM % predicted FEV1 was averaged sequentially, and the change from baseline on Day 1 was assessed. This key secondary endpoint was controlled for multiplicity in a step-down fashion, based on trial success defined as a statistically significant improvement in the primary endpoint for MF/F vs MF. Missing data were imputed using control-based multiple imputations with the cLDA model.
    Change From Baseline AM Post-Dose % Predicted FEV1 AUC 0-4 Hours on Day 1 and Week 12 of Treatment
    This endpoint reflects changes in lung function data (forced expiratory volume in 1 second) measured across 0 to 4 hours post-dose on Day 1 and Week 12 compared to Baseline. Baseline was the average of 30 and 0 minutes pre-dose % predicted FEV1 values. The AUC was calculated over the scheduled timepoints of 0 min, 5 min, 15 min, 30 min, 60 min, 2 hr and 4 hr post-dose. Units are standardized to percent predicted FEV1 by dividing the AUC calculation by the duration of the observed AUC.
    Change From Baseline in AM Pre-Dose % Predicted FEV1 With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment
    The change from baseline in AM pre-dose % predicted FEV1 with MF/F MDI 100/10 mcg BID vs MF MDI 100 mcg BID averaged over 12 weeks treatment was assessed. This secondary analysis of the change from baseline used the cLDA method without multiple imputation. A model-based MAR approach was used for missing data.
    Mean Change From Baseline in Total Daily Use of Short-Acting Beta-Agonist (SABA) Rescue Medication With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment
    To evaluate the efficacy of MF/F MDI 100/10 mcg BID compared with MF MDI 100 mcg BID, the change from baseline in total daily short-acting beta-agonist (SABA) use (puffs per day) was averaged and assessed. All participants received SABA MDIs (albuterol 90 mcg or salbutamol 100 mcg) for as-needed relief of asthma symptoms. This secondary analysis of the change from baseline used the cLDA method without multiple imputation.A model-based MAR approach was used for missing data.
    Participants Using SABA Rescue Medication Across Weeks 1-12 of the Treatment Period
    To evaluate the efficacy of MF/F MDI 100/10 mcg BID compared with MF MDI 100 mcg BID, the number of participants using SABA rescue medication in Weeks 1-12 (individually) of the double-blind treatment period was assessed. All participants received SABA MDIs (albuterol 90 mcg or salbutamol 100 mcg) for as-needed relief of asthma symptoms.
    Participants Whose SABA Rescue Medication Use Increased Across Weeks 1-12 of the Treatment Period
    To evaluate the efficacy of MF/F MDI 100/10 mcg BID compared with MF MDI 100 mcg BID, the number of participants whose use of SABA rescue medication increased in Weeks 1-12 (individually) of the double-blind treatment period was assessed. All participants received SABA MDIs (albuterol 90 mcg or salbutamol 100 mcg) for relief of asthma symptoms.
    Area Under the Plasma Concentration-Time Curve of Mometasone Furoate From Time 0 to 12 Hours (AUC0-12)
    Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment.
    Area Under the Plasma Concentration-Time Curve of Mometasone Furoate From Time 0 to Time of Last Measurable Concentration (AUC0-last)
    Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment.
    Maximum Plasma Concentration (Cmax) of Mometsone Furoate
    Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment.
    Time to Maximum Plasma Concentration (Tmax) of Mometsone Furoate
    Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment.

    Full Information

    First Posted
    April 13, 2016
    Last Updated
    February 7, 2022
    Sponsor
    Organon and Co
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02741271
    Brief Title
    Study of Efficacy and Long-Term Safety of Mometasone Furoate in Combination With Formoterol Fumarate Versus Mometasone Furoate in Children (5 to 11 Years of Age) With Persistent Asthma (MK-0887A-087)
    Official Title
    A Phase III, Randomized, Active-Controlled, Parallel-Group Clinical Trial to Study the Efficacy and Long-Term Safety of Mometasone Furoate/Formoterol Fumarate (MF/F, MK-0887A [SCH418131]), Compared With Mometasone Furoate (MF, MK-0887 [SCH032088]), in Children With Persistent Asthma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2022
    Overall Recruitment Status
    Completed
    Study Start Date
    May 11, 2016 (Actual)
    Primary Completion Date
    December 4, 2017 (Actual)
    Study Completion Date
    December 4, 2017 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Organon and Co

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This study compares the 12-week efficacy and 24-week safety of mometasone furoate/formoterol fumarate (MF/F) 100/10 mcg and mometasone furate (MF) 100 mcg, both administered twice daily (BID) via metered-dose inhaler (MDI) in children aged 5 to 11 years with persistent asthma.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Asthma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Masking Description
    1:1 randomization to double-blinded MF/F MDI 100/10 mcg BID and MF MDI 100 mcg BID
    Allocation
    Randomized
    Enrollment
    181 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    MF/F MDI 100/10 mcg BID
    Arm Type
    Experimental
    Arm Description
    Eligible participants will be assigned randomly to receive double-blinded MF/F MDI 100/10 mcg BID for 24 weeks.
    Arm Title
    MF MDI 100 mcg BID
    Arm Type
    Active Comparator
    Arm Description
    Eligible participants will be assigned randomly to receive double-blinded MF MDI 100 mcg BID for 24 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    MF MDI 100 mcg BID (Open Label)
    Other Intervention Name(s)
    ASMANEX HFA®, SCH 032088 (MK-0887)
    Intervention Description
    Eligible participants will receive open-label MF MDI 100 mcg BID during a 2-week run-in period.
    Intervention Type
    Drug
    Intervention Name(s)
    MF/F MDI 100/10 mcg BID
    Other Intervention Name(s)
    DULERA®/ZENHALE®, SCH 418131 (MK-0887A)
    Intervention Description
    After a 2 week run-in on open-label MF MDI 100 mcg BID, eligible participants will receive double-blinded treatment with MF/F MDI 100/10 mcg BID.
    Intervention Type
    Drug
    Intervention Name(s)
    MF MDI 100 mcg BID
    Other Intervention Name(s)
    ASMANEX HFA®, SCH 032088 (MK-0887)
    Intervention Description
    After a 2 week run-in on open-label MF MDI 100 mcg BID, eligible participants will receive double-blinded treatment with MF MDI 100 mcg BID.
    Intervention Type
    Drug
    Intervention Name(s)
    Albuterol/Salbutamol PRN
    Intervention Description
    Participants may use study-provided short-acting beta agonist (SABA), albuterol/salbutamol, as needed (PRN) for the relief of asthma symptoms.
    Intervention Type
    Drug
    Intervention Name(s)
    Prednisone/Prednisolone
    Intervention Description
    Participants may use a systemic corticosteroid (prednisone/prednisolone) for acute asthma worsening per investigator discretion.
    Primary Outcome Measure Information:
    Title
    Change From Baseline in Morning (AM) Post-Dose % Predicted Forced Expiratory Volume in One Second (FEV1) in the Area Under the Curve (AUC)0-60
    Description
    This endpoint reflects changes in lung function data (forced expiratory volume in 1 second) measured across 0 to 60 minutes post-dose (at 0, 5, 15, 30 and 60 minutes) and averaged across study visits in the Treatment Period (Day 1, Week 1, Week 4, Week 8 and Week 12) compared to Baseline. Baseline was the average of % predicted FEV1 values at 30 min and 0 min pre-dose. At each visit, the area under the curve is calculated over the post-dose timepoints. Units are standardized to percent predicted FEV1 by dividing the AUC calculation by the duration of the observed AUC.
    Time Frame
    Baseline, and average of Day 1, Weeks 1, 4, 8, and 12
    Title
    Count (Percentage) of Participants Experiencing At Least One Adverse Event (AE)
    Description
    An Adverse Event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition temporally associated with the use of the Sponsor's product, is also an AE.
    Time Frame
    Up to 26 weeks
    Title
    Count (Percentage) of Participants Discontinuing From Study Medication Due to An AE
    Description
    An Adverse Event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition temporally associated with the use of the Sponsor's product, is also an AE.
    Time Frame
    Up to 24 weeks
    Secondary Outcome Measure Information:
    Title
    Change From Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment
    Description
    The key secondary objective was to determine the onset of action for the efficacy of MF/F MDI 100/10 mcg BID, compared with MF MDI 100 mcg BID. The post-dose AM % predicted FEV1 was averaged sequentially, and the change from baseline on Day 1 was assessed. This key secondary endpoint was controlled for multiplicity in a step-down fashion, based on trial success defined as a statistically significant improvement in the primary endpoint for MF/F vs MF. Missing data were imputed using control-based multiple imputations with the cLDA model.
    Time Frame
    Baseline and Day 1, measured at 4 hr, 2 hr and 60, 30, 15, and 5 min, post-dose time points
    Title
    Change From Baseline AM Post-Dose % Predicted FEV1 AUC 0-4 Hours on Day 1 and Week 12 of Treatment
    Description
    This endpoint reflects changes in lung function data (forced expiratory volume in 1 second) measured across 0 to 4 hours post-dose on Day 1 and Week 12 compared to Baseline. Baseline was the average of 30 and 0 minutes pre-dose % predicted FEV1 values. The AUC was calculated over the scheduled timepoints of 0 min, 5 min, 15 min, 30 min, 60 min, 2 hr and 4 hr post-dose. Units are standardized to percent predicted FEV1 by dividing the AUC calculation by the duration of the observed AUC.
    Time Frame
    Baseline, Day 1 and Week 12
    Title
    Change From Baseline in AM Pre-Dose % Predicted FEV1 With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment
    Description
    The change from baseline in AM pre-dose % predicted FEV1 with MF/F MDI 100/10 mcg BID vs MF MDI 100 mcg BID averaged over 12 weeks treatment was assessed. This secondary analysis of the change from baseline used the cLDA method without multiple imputation. A model-based MAR approach was used for missing data.
    Time Frame
    Baseline and Weeks 4, 8, and 12 (Averaged)
    Title
    Mean Change From Baseline in Total Daily Use of Short-Acting Beta-Agonist (SABA) Rescue Medication With MF/F MDI 100/10 mcg BID or MF MDI 100 mcg BID Over the First 12 Weeks of Treatment
    Description
    To evaluate the efficacy of MF/F MDI 100/10 mcg BID compared with MF MDI 100 mcg BID, the change from baseline in total daily short-acting beta-agonist (SABA) use (puffs per day) was averaged and assessed. All participants received SABA MDIs (albuterol 90 mcg or salbutamol 100 mcg) for as-needed relief of asthma symptoms. This secondary analysis of the change from baseline used the cLDA method without multiple imputation.A model-based MAR approach was used for missing data.
    Time Frame
    Baseline and Weeks 1-12 (Averaged)
    Title
    Participants Using SABA Rescue Medication Across Weeks 1-12 of the Treatment Period
    Description
    To evaluate the efficacy of MF/F MDI 100/10 mcg BID compared with MF MDI 100 mcg BID, the number of participants using SABA rescue medication in Weeks 1-12 (individually) of the double-blind treatment period was assessed. All participants received SABA MDIs (albuterol 90 mcg or salbutamol 100 mcg) for as-needed relief of asthma symptoms.
    Time Frame
    Baseline and Weeks 1-12 (Averaged)
    Title
    Participants Whose SABA Rescue Medication Use Increased Across Weeks 1-12 of the Treatment Period
    Description
    To evaluate the efficacy of MF/F MDI 100/10 mcg BID compared with MF MDI 100 mcg BID, the number of participants whose use of SABA rescue medication increased in Weeks 1-12 (individually) of the double-blind treatment period was assessed. All participants received SABA MDIs (albuterol 90 mcg or salbutamol 100 mcg) for relief of asthma symptoms.
    Time Frame
    Weeks 1-12 (Averaged)
    Title
    Area Under the Plasma Concentration-Time Curve of Mometasone Furoate From Time 0 to 12 Hours (AUC0-12)
    Description
    Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment.
    Time Frame
    Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12
    Title
    Area Under the Plasma Concentration-Time Curve of Mometasone Furoate From Time 0 to Time of Last Measurable Concentration (AUC0-last)
    Description
    Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment.
    Time Frame
    Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12
    Title
    Maximum Plasma Concentration (Cmax) of Mometsone Furoate
    Description
    Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment.
    Time Frame
    Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12
    Title
    Time to Maximum Plasma Concentration (Tmax) of Mometsone Furoate
    Description
    Blood samples were collected predose, and 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12 in a subset of participants who consented to take part in a PK sub-trial. Per protocol, descriptive MF pharmacokinetics were summarized without regard to treatment assignment.
    Time Frame
    Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    5 Years
    Maximum Age & Unit of Time
    11 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Has a diagnosis of asthma of ≥ 6-months duration according to the Global Initiative for Asthma (GINA) guidelines Has asthma that is adequately controlled on a stable dose of inhaled corticosteroid (ICS) combined with long-acting beta-agonist (LABA) ≥ 4 weeks Is able to demonstrate an FEV1 >60% and ≤90% predicted Is able to demonstrate an increase in absolute FEV1 of at least 12% within 30 minutes after administration of albuterol/salbutamol. Is able to use an MDI (without spacer), use a peak flow meter, and perform spirometry correctly. Is willing (with consent of their parent(s)/guardian) to discontinue previously prescribed asthma medication, if there is no inherent harm in changing the participant's current asthma therapy. Has laboratory tests that are clinically acceptable to the investigator. Exclusion Criteria: Requires >8 inhalations per day of albuterol (100 mcg per actuation), and/or >2 nebulized treatments per day of 2.5 mg albuterol on any 2 consecutive days Has a clinical worsening of asthma that results in emergency room visit (for an asthma exacerbation), hospitalization due to asthma, or treatment with additional, excluded asthma medication (other than SABA) between the Screening and Baseline visits. Is considered by the investigator to have unstable asthma at the end of the run-in period Has had > 4 asthma exacerbations (defined as a worsening of asthma requiring systemic corticosteroid use and/or ≥ 24-hour stay in an emergency department, urgent care center, or hospital) within 1 year prior to visit 1 Has had a history of life-threatening asthma Has a clinically significant condition or situation, other than the condition being studied which may interfere with trial evaluations, participant safety, or optimal participation in the trial
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    32022483
    Citation
    Weinstein CLJ, Gates D, Zhang X, Varnell T, Mok W, Vermeulen JH, Amar NJ, Jain N. A phase 3 study evaluating the safety and efficacy of a pediatric dose of mometasone furoate with and without formoterol for persistent asthma. Pediatr Pulmonol. 2020 Apr;55(4):882-889. doi: 10.1002/ppul.24667. Epub 2020 Feb 5.
    Results Reference
    result

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    Study of Efficacy and Long-Term Safety of Mometasone Furoate in Combination With Formoterol Fumarate Versus Mometasone Furoate in Children (5 to 11 Years of Age) With Persistent Asthma (MK-0887A-087)

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