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)

Organon and Co181 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

181

Conditions

Asthma

Interventions

MF MDI 100 mcg BID (Open Label)DRUG

Eligible participants will receive open-label MF MDI 100 mcg BID during a 2-week run-in period.

MF/F MDI 100/10 mcg BIDDRUG

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.

MF MDI 100 mcg BIDDRUG

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.

Eligibility

Sex: ALLMin age: 5 YearsMax age: 11 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: Baseline, and average of Day 1, Weeks 1, 4, 8, and 12

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.

Time frame: Up to 26 weeks

Count (Percentage) of Participants Discontinuing From Study Medication Due to An AE

Time frame: Up to 24 weeks

Secondary Outcomes

Data from ClinicalTrials.gov

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Participants may use study-provided short-acting beta agonist (SABA), albuterol/salbutamol, as needed (PRN) for the relief of asthma symptoms.

Prednisone/PrednisoloneDRUG

Participants may use a systemic corticosteroid (prednisone/prednisolone) for acute asthma worsening per investigator discretion.

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.

Time frame: Baseline and Day 1, measured at 4 hr, 2 hr and 60, 30, 15, and 5 min, post-dose time points

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.

Time frame: Baseline, Day 1 and Week 12

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.

Time frame: Baseline and Weeks 4, 8, and 12 (Averaged)

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.

Time frame: Baseline and Weeks 1-12 (Averaged)

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.

Time frame: Baseline and Weeks 1-12 (Averaged)

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.

Time frame: Weeks 1-12 (Averaged)

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.

Time frame: Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12

Area Under the Plasma Concentration-Time Curve of Mometasone Furoate From Time 0 to Time of Last Measurable Concentration (AUC0-last)

Time frame: Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12

Maximum Plasma Concentration (Cmax) of Mometsone Furoate

Time frame: Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12

Time to Maximum Plasma Concentration (Tmax) of Mometsone Furoate

Time frame: Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12