Clinical Trial Results:
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
|
Summary
|
|
EudraCT number |
2009-010110-30 |
Trial protocol |
LV HU DK Outside EU/EEA |
Global end of trial date |
04 Dec 2017
|
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
04 Oct 2019
|
First version publication date |
07 Apr 2019
|
Other versions |
v1 |
Version creation reason |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
MK-0887A-087
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02741271 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
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., ClinicalTrialsDiclosure@merck.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
04 Dec 2017
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
04 Dec 2017
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
04 Dec 2017
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To demonstrate the efficacy of mometasone furoate/formoterol (MF/F) 100/10 mcg twice daily (BID), compared with mometasone furoate (MF) 100 mcg BID, by evaluating lung function during the first 12 weeks of double-blind treatment in children ages 5–11 years with persistent asthma.
|
||
Protection of trial subjects |
This study was conducted in conformance with the ethical principles originating from the Declaration of Helsinki, Good Clinical Practice (GCP) requirements and applicable country and/or local statutes and regulations regarding Independent Ethics Committee (IEC) review, informed consent/assent, and the protection of human participants in biomedical research as stated in the Sponsor’s Code of Conduct for Interventional Clinical Trials. The Code of Conduct includes a description of how the study was monitored to ensure compliance with GCP.
|
||
Background therapy |
- | ||
Evidence for comparator |
To assess the efficacy of MF/F combination therapy, mometasone furoate (MF) monotherapy is the comparator chosen, allowing the trial to demonstrate the contribution of the formoterol (F) component to the clinical benefits of the fixed-dose combination of MF/F in children. The safety and effectiveness of MF monotherapy and F monotherapy has already been established from controlled clinical trials in adults and adolescents, and most recently has been evaluated in children 5-11 years of age (P086 and P178, respectively). The MF comparator product has the same formulation as the MF/F combination product, with the exception that the drug substance F has been removed. | ||
Actual start date of recruitment |
11 May 2016
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Colombia: 11
|
||
Country: Number of subjects enrolled |
Guatemala: 35
|
||
Country: Number of subjects enrolled |
Hungary: 18
|
||
Country: Number of subjects enrolled |
Latvia: 9
|
||
Country: Number of subjects enrolled |
Mexico: 28
|
||
Country: Number of subjects enrolled |
Romania: 14
|
||
Country: Number of subjects enrolled |
Russian Federation: 15
|
||
Country: Number of subjects enrolled |
South Africa: 13
|
||
Country: Number of subjects enrolled |
United States: 38
|
||
Worldwide total number of subjects |
181
|
||
EEA total number of subjects |
41
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
181
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||
Recruitment details |
- | ||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||
Screening details |
Eligible participants had been adequately controlled on a stable dose of an inhaled corticosteroid (ICS)/LABA for at least 4 weeks prior to Visit 1. There were 182 randomized participants, of whom 181 received at least one dose of blinded study medication as reflected in the enrollment data. | ||||||||||||||||||
|
Period 1
|
|||||||||||||||||||
Period 1 title |
Treatment (overall period)
|
||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||
Blinding implementation details |
A double-blind/masking technique was used during the double-blind treatment Period. MF/F 50/5 mcg and MF 50 mcg, both given by metered-dose inhaler (MDI), were packaged identically so that blind/masking was maintained. The randomized dosages of MF/F 100/10 mcg or MF 100 mcg were obtained after inhalation of two puffs of MF/F 50/5 mcg or MF 50 mcg, respectively. The Run-in Period was open-label MF monotherapy, taken as 2 puffs of MF 50 mcg BID.
|
||||||||||||||||||
|
Arms
|
|||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||
|
Arm title
|
MF/F MDI 100/10 mcg BID | ||||||||||||||||||
Arm description |
Eligible participants were assigned randomly to receive double-blinded mometasone furoate/formoterol fumarate (MF/F; MK-0887A) administered as 2 puffs of MF/F 50/5 mcg BID for 24 weeks. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
mometasone furoate/formoterol
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
MK-0887A SCH418131
|
||||||||||||||||||
Pharmaceutical forms |
Pressurised inhalation, suspension
|
||||||||||||||||||
Routes of administration |
Inhalation use
|
||||||||||||||||||
Dosage and administration details |
Administered BID via MDI
|
||||||||||||||||||
|
Arm title
|
MF MDI 100 mcg BID | ||||||||||||||||||
Arm description |
Eligible participants were assigned randomly to receive double-blinded mometasone furoate (MF; MK-0887) administered as 2 puffs of MF 50 mcg BID for 24 weeks. | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
mometasone furoate
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
MK-0887 SCH032088
|
||||||||||||||||||
Pharmaceutical forms |
Pressurised inhalation, suspension
|
||||||||||||||||||
Routes of administration |
Inhalation use
|
||||||||||||||||||
Dosage and administration details |
Administered BID via MDI
|
||||||||||||||||||
|
|||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MF/F MDI 100/10 mcg BID
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Eligible participants were assigned randomly to receive double-blinded mometasone furoate/formoterol fumarate (MF/F; MK-0887A) administered as 2 puffs of MF/F 50/5 mcg BID for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MF MDI 100 mcg BID
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Eligible participants were assigned randomly to receive double-blinded mometasone furoate (MF; MK-0887) administered as 2 puffs of MF 50 mcg BID for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
MF/F MDI 100/10 mcg BID
|
||
Reporting group description |
Eligible participants were assigned randomly to receive double-blinded mometasone furoate/formoterol fumarate (MF/F; MK-0887A) administered as 2 puffs of MF/F 50/5 mcg BID for 24 weeks. | ||
Reporting group title |
MF MDI 100 mcg BID
|
||
Reporting group description |
Eligible participants were assigned randomly to receive double-blinded mometasone furoate (MF; MK-0887) administered as 2 puffs of MF 50 mcg BID for 24 weeks. | ||
Subject analysis set title |
Total
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All treated participants
|
||
Subject analysis set title |
Pooled MF/F 100/10 mcg and MF 100 mcg (PK Sub-trial)
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
MF/F 100/10 mcg and MF 100 mcg
|
||
|
|||||||||||||||||||
End point 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 | ||||||||||||||||||
End point 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 postdose timepoints. Units are standardized to percent predicted FEV1 by dividing the AUC calculation by the duration of the observed AUC. The analysed population included participants who received at least one dose of randomised trial medication with at least one primary efficacy evaluation.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Baseline, and average of Day 1, Weeks 1, 4, 8, and 12
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
MF/F 100/10 mcg MDI BID vs MF 100 mcg MDI BID | ||||||||||||||||||
Statistical analysis description |
Comparative analysis of MF/F vs MF for the change from baseline in % predicted FEV1 as measured across 0 to 60 minutes post-dose
|
||||||||||||||||||
Comparison groups |
MF/F MDI 100/10 mcg BID v MF MDI 100 mcg BID
|
||||||||||||||||||
Number of subjects included in analysis |
181
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||
Method |
cLDA with multiple imputation | ||||||||||||||||||
Parameter type |
LSM Difference | ||||||||||||||||||
Point estimate |
5.21
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
3.21 | ||||||||||||||||||
upper limit |
7.2 | ||||||||||||||||||
|
|||||||||||||||||||||||||||||
End point title |
Participants Experiencing At Least One Adverse Event (AE) [1] | ||||||||||||||||||||||||||||
End point description |
An Adverse Event (AE) is defined as any unfavourable 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. Safety summaries, including the number and percentage of participants, were provided for AEs, serious AEs (SAEs), and drug-related AEs. The analysed population was all randomised participants who received at least one dose of trial medication.
|
||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||
End point timeframe |
Up to 26 weeks
|
||||||||||||||||||||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Safety summaries were provided for AEs in accordance with the statistical analysis plan |
|||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||
|
|||||||||||||||||
End point title |
Participants Discontinuing From Study Medication Due to an AE [2] | ||||||||||||||||
End point description |
An Adverse Event (AE) is defined as any unfavourable 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. The analysed population was all randomised participants who received at least one dose of trial medication.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Up to 24 weeks
|
||||||||||||||||
| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Safety summaries were provided for AEs in accordance with the statistical analysis plan |
|||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline AM Post-Dose Percent Predicted FEV1 on Day 1 of Treatment | |||||||||||||||||||||||||||||||||
End point 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. The analysed population was all participants who received at least one dose of randomised trial medication with at least one efficacy evaluation.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and Day 1, assessed at 4 h, 2 h and 60, 30, 15 and 5 min post-dose time points
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
Statistical analysis title |
MF/F 100/10 MDI BID vs MF 100 mcg MDI BID | |||||||||||||||||||||||||||||||||
Statistical analysis description |
Comparative analysis of MF/F vs MF for the change from baseline in % predicted FEV1 at 5 minutes post-dose on Day 1. This endpoint was multiplicity controlled.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
MF/F MDI 100/10 mcg BID v MF MDI 100 mcg BID
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
181
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||
Method |
cLDA with multiple imputation | |||||||||||||||||||||||||||||||||
Parameter type |
LSM Difference | |||||||||||||||||||||||||||||||||
Point estimate |
4.2
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
2.5 | |||||||||||||||||||||||||||||||||
upper limit |
5.91 | |||||||||||||||||||||||||||||||||
Statistical analysis title |
MF/F 100/10 mcg MDI BID vs MF 100 mcg MDI BID | |||||||||||||||||||||||||||||||||
Statistical analysis description |
Comparative analysis of MF/F vs MF for the change from baseline in % predicted FEV1 at 15 minutes post-dose on Day 1. This endpoint was multiplicity controlled.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
MF/F MDI 100/10 mcg BID v MF MDI 100 mcg BID
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
181
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||
Method |
cLDA with multiple imputation | |||||||||||||||||||||||||||||||||
Parameter type |
LSM Difference | |||||||||||||||||||||||||||||||||
Point estimate |
6.64
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
4.89 | |||||||||||||||||||||||||||||||||
upper limit |
8.39 | |||||||||||||||||||||||||||||||||
Statistical analysis title |
MF/F 100/10 mcg MDI BID vs MF 100 mcg MDI BID | |||||||||||||||||||||||||||||||||
Statistical analysis description |
Comparative analysis of MF/F vs MF for the change from baseline in % predicted FEV1 at 30 minutes post-dose on Day 1. This endpoint was multiplicity controlled.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
MF/F MDI 100/10 mcg BID v MF MDI 100 mcg BID
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
181
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||
Method |
cLDA with multiple imputation | |||||||||||||||||||||||||||||||||
Parameter type |
LSM Difference | |||||||||||||||||||||||||||||||||
Point estimate |
6.89
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
5.1 | |||||||||||||||||||||||||||||||||
upper limit |
8.67 | |||||||||||||||||||||||||||||||||
Statistical analysis title |
MF/F 100/10 mcg MDI BID vs MF 100 mcg MDI BID | |||||||||||||||||||||||||||||||||
Statistical analysis description |
Comparative analysis of MF/F vs MF for the change from baseline in % predicted FEV1 at 60 minutes post-dose on Day 1. This endpoint was multiplicity controlled.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
MF/F MDI 100/10 mcg BID v MF MDI 100 mcg BID
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
181
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||
Method |
cLDA with multiple imputation | |||||||||||||||||||||||||||||||||
Parameter type |
LSM Difference | |||||||||||||||||||||||||||||||||
Point estimate |
6.19
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
4.09 | |||||||||||||||||||||||||||||||||
upper limit |
8.28 | |||||||||||||||||||||||||||||||||
Statistical analysis title |
MF/F 100/10 mcg MDI BID vs MF 100 mcg MDI BID | |||||||||||||||||||||||||||||||||
Statistical analysis description |
Comparative analysis of MF/F vs MF for the change from baseline in % predicted FEV1 at 2 hours post-dose on Day 1. This endpoint was multiplicity controlled.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
MF/F MDI 100/10 mcg BID v MF MDI 100 mcg BID
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
181
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||
Method |
cLDA with multiple imputation | |||||||||||||||||||||||||||||||||
Parameter type |
LSM Difference | |||||||||||||||||||||||||||||||||
Point estimate |
7.04
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
4.74 | |||||||||||||||||||||||||||||||||
upper limit |
9.35 | |||||||||||||||||||||||||||||||||
Statistical analysis title |
MF/F 100/10 mcg MDI BID vs MF 100 mch MDI BID | |||||||||||||||||||||||||||||||||
Statistical analysis description |
Comparative analysis of MF/F vs MF for the change from baseline in % predicted FEV1 at 4 hours post-dose on Day 1. This endpoint was multiplicity controlled.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
MF/F MDI 100/10 mcg BID v MF MDI 100 mcg BID
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
181
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||
Method |
cLDA with multiple imputation | |||||||||||||||||||||||||||||||||
Parameter type |
LSM Difference | |||||||||||||||||||||||||||||||||
Point estimate |
6.05
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
3.53 | |||||||||||||||||||||||||||||||||
upper limit |
8.56 | |||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||
End point title |
Change from Baseline AM Post-Dose % Predicted FEV1 AUC 0-4 Hours on Day 1 and Week 12 of Treatment | |||||||||||||||||||||
End point 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 postdose. Units are standardized to percent predicted FEV1 by dividing the AUC calculation by the duration of the observed AUC. The analysed population was all participants who received at least one dose of randomised trial medication with at least one efficacy evaluation.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Day 1 and Week 12
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Statistical analysis title |
MF/F 100/10 mcg BID vs. MF 100 mcg BID | |||||||||||||||||||||
Statistical analysis description |
Comparative analysis of MF/F vs MF for the change from baseline in % predicted FEV1 on Day 1
|
|||||||||||||||||||||
Comparison groups |
MF/F MDI 100/10 mcg BID v MF MDI 100 mcg BID
|
|||||||||||||||||||||
Number of subjects included in analysis |
180
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||
Method |
cLDA without multiple imputation | |||||||||||||||||||||
Parameter type |
LSM Difference (4 hr post-dose) | |||||||||||||||||||||
Point estimate |
6.32
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
4.36 | |||||||||||||||||||||
upper limit |
8.27 | |||||||||||||||||||||
Statistical analysis title |
MF/F 100/10 mcg BID vs. MF 100 mcg BID | |||||||||||||||||||||
Statistical analysis description |
Comparative analysis of MF/F vs MF for the change from baseline in % predicted FEV1 at Week 12
|
|||||||||||||||||||||
Comparison groups |
MF/F MDI 100/10 mcg BID v MF MDI 100 mcg BID
|
|||||||||||||||||||||
Number of subjects included in analysis |
180
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.026 | |||||||||||||||||||||
Method |
cLDA without multiple imputation | |||||||||||||||||||||
Parameter type |
LSM Difference (4 hr post-dose) | |||||||||||||||||||||
Point estimate |
3.33
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
0.41 | |||||||||||||||||||||
upper limit |
6.26 | |||||||||||||||||||||
|
|||||||||||||||||||
End point 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 | ||||||||||||||||||
End point 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. The analysed population was all participants who received at least one dose of randomised trial medication with at least one efficacy evaluation across the treatment period.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline and Weeks 4, 8, and 12 (Averaged)
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
MF/F 100/10 MDI BID vs MF 100 mcg MDI BID | ||||||||||||||||||
Statistical analysis description |
Comparative analysis of MF/F vs MF for the change from baseline in AM pre-dose % predicted FEV1 averaged across Weeks 4, 8, and 12
|
||||||||||||||||||
Comparison groups |
MF/F MDI 100/10 mcg BID v MF MDI 100 mcg BID
|
||||||||||||||||||
Number of subjects included in analysis |
181
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.197 | ||||||||||||||||||
Method |
cLDA without multiple imputation | ||||||||||||||||||
Parameter type |
LSM Difference | ||||||||||||||||||
Point estimate |
1.63
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-0.85 | ||||||||||||||||||
upper limit |
4.11 | ||||||||||||||||||
|
|||||||||||||||||||
End point 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 | ||||||||||||||||||
End point 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. The analysed population included all participants who received at least one dose of randomised trial medication with at least one efficacy evaluation.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline and Weeks 1-12 (Averaged)
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
MF/F 100/10 MDI BID vs MF 100 mcg MDI BID | ||||||||||||||||||
Statistical analysis description |
Comparative analysis of MF/F vs MF for the change from baseline in SABA use over 12 weeks
|
||||||||||||||||||
Comparison groups |
MF/F MDI 100/10 mcg BID v MF MDI 100 mcg BID
|
||||||||||||||||||
Number of subjects included in analysis |
181
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.968 | ||||||||||||||||||
Method |
cLDA without multiple imputation | ||||||||||||||||||
Parameter type |
LSM Difference | ||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-0.07 | ||||||||||||||||||
upper limit |
0.07 | ||||||||||||||||||
|
||||||||||||||||
End point title |
Participants Using SABA Rescue Medication Across Weeks 1-12 of the Treatment Period | |||||||||||||||
End point 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. Data were provided for all participants who received at least one dose of randomized trial medication and had at least one efficacy evaluation.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Baseline and Weeks 1-12 (Averaged)
|
|||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
||||||||||
End point title |
Participants Whose SABA Rescue Medication Use Increased Across Weeks 1-12 of the Treatment Period | |||||||||
End point 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. The analysed population included all participants who received at least one dose of randomised trial medication with at least one efficacy evaluation.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Weeks 1-12 (Averaged)
|
|||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
|||||||||
End point title |
Area Under the Plasma Concentration-Time Curve of Mometasone Furoate from Time 0 to 12 hours (AUC0-12) | ||||||||
End point 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. The analysis population was participants who consented to take part in the PK sub-trial and had evaluable data for AUC(0-12).
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Area Under the Plasma Concentration-Time Curve of Mometasone Furoate From Time 0 to Time of Last Measurable Concentration (AUC0-last) | ||||||||
End point 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. The analysis population was participants who consented to take part in the PK sub-trial and had evaluable data for AUC(0-last).
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Maximum Plasma Concentration (Cmax) of Mometsone Furoate | ||||||||
End point 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. The analysis population was participants who consented to take part in the PK sub-trial and had evaluable data for Cmax.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Time to Maximum Plasma Concentration (Tmax) of Mometsone Furoate | ||||||||
End point 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. The analysis population was participants who consented to take part in the PK sub-trial and had evaluable data for Tmax.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Predose, 0.75, 1.5, 3, 8, and 12 hours postdose at Week 12
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 26 weeks
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
All participants who received double-blind treatment
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MF MDI 100 mcg
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MF/F MDI 100/10 mcg
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
04 Oct 2016 |
The control-based imputation of missing %-predicted FEV1 data was amended to become part of the primary analysis (it was originally proposed as a sensitivity analysis). The original, primary method of imputation based on the Missing-At-Random assumption, was moved to one of the supportive analyses. Note that the primary endpoint, %-predicted FEV1, remains the same. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
