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)
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MF/F MDI 100/10 mcg BID Eligible participants will be assigned randomly to receive double-blinded MF/F MDI 100/10 mcg BID for 24 weeks. |
Drug: MF MDI 100 mcg BID (Open Label)
Eligible participants will receive open-label MF MDI 100 mcg BID during a 2-week run-in period.
Other Names:
Drug: MF/F MDI 100/10 mcg BID
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.
Other Names:
Drug: Albuterol/Salbutamol PRN
Participants may use study-provided short-acting beta agonist (SABA), albuterol/salbutamol, as needed (PRN) for the relief of asthma symptoms.
Drug: Prednisone/Prednisolone
Participants may use a systemic corticosteroid (prednisone/prednisolone) for acute asthma worsening per investigator discretion.
|
| Active Comparator: MF MDI 100 mcg BID Eligible participants will be assigned randomly to receive double-blinded MF MDI 100 mcg BID for 24 weeks. |
Drug: MF MDI 100 mcg BID (Open Label)
Eligible participants will receive open-label MF MDI 100 mcg BID during a 2-week run-in period.
Other Names:
Drug: MF MDI 100 mcg BID
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.
Other Names:
Drug: Albuterol/Salbutamol PRN
Participants may use study-provided short-acting beta agonist (SABA), albuterol/salbutamol, as needed (PRN) for the relief of asthma symptoms.
Drug: Prednisone/Prednisolone
Participants may use a systemic corticosteroid (prednisone/prednisolone) for acute asthma worsening per investigator discretion.
|
Outcome Measures
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 [Baseline, and average of Day 1, Weeks 1, 4, 8, and 12]
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) [Up to 26 weeks]
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 [Up to 24 weeks]
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 [Baseline and Day 1, measured at 4 hr, 2 hr and 60, 30, 15, and 5 min, post-dose time points]
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 [Baseline, Day 1 and Week 12]
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 [Baseline and Weeks 4, 8, and 12 (Averaged)]
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 [Baseline and Weeks 1-12 (Averaged)]
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 [Baseline and Weeks 1-12 (Averaged)]
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 [Weeks 1-12 (Averaged)]
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) [Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 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) [Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 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.
- Maximum Plasma Concentration (Cmax) of Mometsone Furoate [Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 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 to Maximum Plasma Concentration (Tmax) of Mometsone Furoate [Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 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.
Eligibility Criteria
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Organon and Co
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
More Information
Publications
None provided.- 0887A-087
- MK-0887A-087
- 2009-010110-30
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID |
|---|---|---|
| Arm/Group Description | MF/F administered by MDI, given as 100/10 mcg BID | MF administered by MDI, given as 100 mcg BID |
| Period Title: Overall Study | ||
| STARTED | 91 | 90 |
| COMPLETED | 89 | 88 |
| NOT COMPLETED | 2 | 2 |
Baseline Characteristics
| Arm/Group Title | MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID | Total |
|---|---|---|---|
| Arm/Group Description | MF/F administered by MDI, given as 100/10 mcg BID | MF administered by MDI, given as 100 mcg BID | Total of all reporting groups |
| Overall Participants | 91 | 90 | 181 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
9.1
(1.7)
|
9.1
(1.7)
|
9.1
(1.7)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
46
50.5%
|
43
47.8%
|
89
49.2%
|
| Male |
45
49.5%
|
47
52.2%
|
92
50.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
40
44%
|
38
42.2%
|
78
43.1%
|
| Not Hispanic or Latino |
51
56%
|
52
57.8%
|
103
56.9%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
5
5.5%
|
2
2.2%
|
7
3.9%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
10
11%
|
10
11.1%
|
20
11%
|
| White |
43
47.3%
|
41
45.6%
|
84
46.4%
|
| More than one race |
33
36.3%
|
37
41.1%
|
70
38.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of randomized trial medication with at least one primary efficacy evaluation. |
| Arm/Group Title | MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID |
|---|---|---|
| Arm/Group Description | MF/F administered by MDI, given as 100/10 mcg BID | MF administered by MDI, given as 100 mcg BID |
| Measure Participants | 91 | 90 |
| Baseline |
79.21
(11.44)
|
78.48
(12.79)
|
| Change from Baseline |
8.99
(8.29)
|
3.96
(5.92)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MF/F MDI 100/10 mcg BID, MF MDI 100 mcg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | cLDA with multiple imputation | |
| Comments | Primary Analysis Method, using the constrained Longitudinal Data Analysis (cLDA) model for missing data | |
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 5.21 | |
| Confidence Interval |
(2-Sided) 95% 3.21 to 7.20 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Between-Treatment Difference | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of trial medication. |
| Arm/Group Title | MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID | Total |
|---|---|---|---|
| Arm/Group Description | MF/F administered by MDI, given as 100/10 mcg BID | MF administered by MDI, given as 100 mcg BID | All treated participants |
| Measure Participants | 91 | 90 | 181 |
| Count of Participants [Participants] |
37
40.7%
|
52
57.8%
|
89
49.2%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of trial medication |
| Arm/Group Title | MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID | Total |
|---|---|---|---|
| Arm/Group Description | MF/F administered by MDI, given as 100/10 mcg BID | MF administered by MDI, given as 100 mcg BID | All treated participants |
| Measure Participants | 91 | 90 | 181 |
| Count of Participants [Participants] |
0
0%
|
3
3.3%
|
3
1.7%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of randomized trial medication with at least one efficacy evaluation |
| Arm/Group Title | MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID |
|---|---|---|
| Arm/Group Description | MF/F administered by MDI, given as 100/10 mcg BID | MF administered by MDI, given as 100 mcg BID |
| Measure Participants | 91 | 90 |
| Baseline |
79.21
(11.44)
|
78.48
(12.79)
|
| Change from Baseline (4 hr post-dose on Day 1) |
11.61
(10.31)
|
5.68
(7.38)
|
| Change from Baseline (2 hr post-dose on Day 1) |
12.71
(9.53)
|
5.87
(6.52)
|
| Change from Baseline (60 min post-dose on Day 1) |
11.05
(8.51)
|
4.92
(6.06)
|
| Change from Baseline (30 min post-dose on Day 1) |
9.56
(7.02)
|
3.05
(4.99)
|
| Change from Baseline (15 min post-dose on Day 1) |
8.00
(7.12)
|
1.38
(4.42)
|
| Change from Baseline (5 min post-dose on Day 1) |
5.20
(6.93)
|
0.95
(4.33)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MF/F MDI 100/10 mcg BID, MF MDI 100 mcg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | cLDA with multiple imputation | |
| Comments | Primary Analysis Method | |
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 6.05 | |
| Confidence Interval |
(2-Sided) 95% 3.53 to 8.56 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Between-Treatment Difference at 4 hr Post-Dose | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MF/F MDI 100/10 mcg BID, MF MDI 100 mcg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | cLDA with multiple imputation | |
| Comments | Primary Analysis Method | |
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 7.04 | |
| Confidence Interval |
(2-Sided) 95% 4.74 to 9.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Between-Treatment Difference at 2 hr Post-Dose | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | MF/F MDI 100/10 mcg BID, MF MDI 100 mcg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | cLDA with multiple imputation | |
| Comments | Primary Analysis Method | |
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 6.19 | |
| Confidence Interval |
(2-Sided) 95% 4.09 to 8.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Between-Treatment Difference at 60 min Post-Dose | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | MF/F MDI 100/10 mcg BID, MF MDI 100 mcg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | cLDA with multiple imputation | |
| Comments | Primary Analysis Method | |
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 6.89 | |
| Confidence Interval |
(2-Sided) 95% 5.10 to 8.67 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Between-Treatment Difference at 30 min Post-Dose | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | MF/F MDI 100/10 mcg BID, MF MDI 100 mcg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | cLDA with multiple imputation | |
| Comments | Primary Analysis Method | |
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 6.64 | |
| Confidence Interval |
(2-Sided) 95% 4.89 to 8.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Between-Treatment Difference at 15 min Post-Dose | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | MF/F MDI 100/10 mcg BID, MF MDI 100 mcg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | cLDA with multiple imputation | |
| Comments | Primary Analysis Method | |
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 4.20 | |
| Confidence Interval |
(2-Sided) 95% 2.50 to 5.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Between-Treatment Difference at 5 min Post-Dose | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of randomized trial medication with at least one efficacy evaluation. |
| Arm/Group Title | MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID |
|---|---|---|
| Arm/Group Description | MF/F administered by MDI, given as 100/10 mcg BID | MF administered by MDI, given as 100 mcg BID |
| Measure Participants | 91 | 89 |
| Baseline |
79.21
(11.44)
|
78.48
(12.79)
|
| Change from Baseline on Day 1 |
7.13
(5.35)
|
2.70
(3.09)
|
| Change from Baseline at Week 12 |
7.56
(11.20)
|
4.87
(7.72)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MF/F MDI 100/10 mcg BID, MF MDI 100 mcg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | cLDA | |
| Comments | Secondary Outcome Measure on Day 1 | |
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 6.32 | |
| Confidence Interval |
(2-Sided) 95% 4.36 to 8.27 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Between-Treatment Difference at 4 hr Post-Dose | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MF/F MDI 100/10 mcg BID, MF MDI 100 mcg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.026 |
| Comments | ||
| Method | cLDA | |
| Comments | Secondary Outcome Measure at Week 12 | |
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 3.33 | |
| Confidence Interval |
(2-Sided) 95% 0.41 to 6.26 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Between-Treatment Difference at 4 hr Post-Dose | |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of randomized trial medication with at least one efficacy evaluation across the treatment period. |
| Arm/Group Title | MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID |
|---|---|---|
| Arm/Group Description | MF/F administered by MDI, given as 100/10 mcg BID | MF administered by MDI, given as 100 mcg BID |
| Measure Participants | 91 | 90 |
| Baseline |
79.21
(11.44)
|
78.22
(12.93)
|
| Change from Baseline (Weeks 4, 8, and 12) |
1.51
(7.15)
|
0.44
(5.49)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MF/F MDI 100/10 mcg BID, MF MDI 100 mcg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.197 |
| Comments | ||
| Method | cLDA | |
| Comments | Secondary Outcome Measure | |
| Method of Estimation | Estimation Parameter | LSM Difference |
| Estimated Value | 1.63 | |
| Confidence Interval |
(2-Sided) 95% -0.85 to 4.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Between-Treatment Difference | |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of randomized trial medication with at least one efficacy evaluation |
| Arm/Group Title | MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID |
|---|---|---|
| Arm/Group Description | MF/F administered by MDI, given as 100/10 mcg BID | MF administered by MDI, given as 100 mcg BID |
| Measure Participants | 91 | 90 |
| Baseline |
0.25
(0.66)
|
0.13
(0.50)
|
| Change from Baseline Over Weeks 1-12 (Average) |
-0.12
(0.58)
|
-0.02
(0.52)
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were provided for all participants who received at least one dose of randomized trial medication and had at least one efficacy evaluation. |
| Arm/Group Title | MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID |
|---|---|---|
| Arm/Group Description | MF/F administered by MDI, given as 100/10 mcg BID | MF administered by MDI, given as 100 mcg BID |
| Measure Participants | 91 | 90 |
| Baseline |
23
25.3%
|
17
18.9%
|
| Weeks 1-12 |
41
45.1%
|
45
50%
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were provided for all participants who received at least one dose of randomized trial medication and had at least one efficacy evaluation. |
| Arm/Group Title | MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID |
|---|---|---|
| Arm/Group Description | MF/F administered by MDI, given as 100/10 mcg BID | MF administered by MDI, given as 100 mcg BID |
| Measure Participants | 91 | 90 |
| Number [Participants] |
24
26.4%
|
34
37.8%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who consented to take part in the PK sub-trial and had evaluable data for AUC(0-12). |
| Arm/Group Title | Pooled MF/F 100/10 mcg and MF 100 mcg |
|---|---|
| Arm/Group Description | MF/F 100/10 mcg BID or MF 100 mcg BID, administered by MDI |
| Measure Participants | 10 |
| Geometric Mean (Geometric Coefficient of Variation) [hr*pg/mL] |
109
(55.8)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who consented to take part in the PK sub-trial and had evaluable data for AUC(0-last). |
| Arm/Group Title | Pooled MF/F 100/10 mcg and MF 100 mcg |
|---|---|
| Arm/Group Description | MF/F 100/10 mcg BID or MF 100 mcg BID, administered by MDI |
| Measure Participants | 11 |
| Geometric Mean (Geometric Coefficient of Variation) [hr*pg/mL] |
106
(53.5)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who consented to take part in the PK sub-trial and had evaluable data for Cmax. |
| Arm/Group Title | Pooled MF/F 100/10 mcg and MF 100 mcg |
|---|---|
| Arm/Group Description | MF/F 100/10 mcg BID or MF 100 mcg BID, administered by MDI |
| Measure Participants | 11 |
| Geometric Mean (Geometric Coefficient of Variation) [pg/mL] |
16
(68.2)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who consented to take part in the PK sub-trial and had evaluable data for Tmax. |
| Arm/Group Title | Pooled MF/F 100/10 mcg and MF 100 mcg |
|---|---|
| Arm/Group Description | MF/F 100/10 mcg BID or MF 100 mcg BID, administered by MDI |
| Measure Participants | 11 |
| Median (Full Range) [hr] |
1.47
|
Adverse Events
| Time Frame | Up to 26 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All participants who received double-blind treatment | |||
| Arm/Group Title | MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID | ||
| Arm/Group Description | MF/F administered by MDI, given as 100/10 mcg BID | MF administered by MDI, given as 100 mcg BID | ||
All Cause Mortality |
||||
| MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/91 (0%) | 0/90 (0%) | ||
Serious Adverse Events |
||||
| MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/91 (1.1%) | 2/90 (2.2%) | ||
| Infections and infestations | ||||
| Epididymitis | 0/91 (0%) | 1/90 (1.1%) | 1 | |
| Injury, poisoning and procedural complications | ||||
| Concussion | 1/91 (1.1%) | 1 | 0/90 (0%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 1/91 (1.1%) | 1 | 1/90 (1.1%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Urticaria | 1/91 (1.1%) | 1 | 0/90 (0%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| MF/F MDI 100/10 mcg BID | MF MDI 100 mcg BID | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/91 (24.2%) | 32/90 (35.6%) | ||
| Infections and infestations | ||||
| Influenza | 5/91 (5.5%) | 5 | 3/90 (3.3%) | 4 |
| Nasopharyngitis | 2/91 (2.2%) | 3 | 8/90 (8.9%) | 9 |
| Pharyngitis | 1/91 (1.1%) | 1 | 6/90 (6.7%) | 6 |
| Rhinitis | 0/91 (0%) | 5/90 (5.6%) | 5 | |
| Upper respiratory tract infection | 9/91 (9.9%) | 12 | 3/90 (3.3%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 10/91 (11%) | 13 | 14/90 (15.6%) | 19 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
- 0887A-087
- MK-0887A-087
- 2009-010110-30