Effects of Mometasone Furoate/Formoterol Combination Versus Mometasone Furoate Alone in Persistent Asthmatics (Study P04334AM1)(COMPLETED)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00383240
• Collaborator: Novartis (Industry)
• Enrollment: 781
• Arms: 4
• Duration (Months): 24

Study Details

Study Description

Brief Summary

This is a randomized, multi-center, double-blind, double-dummy, placebo-controlled, parallel-group study, evaluating the efficacy of mometasone furoate (MF) /formoterol fumarate (F)[MF/F] metered dose inhaler (MDI) versus MF for 26 weeks. Prior to the 26-week double-blind Treatment Period, subjects will receive open-label MF MDI 200 mcg twice daily (BID) for 2 to 3 weeks during the Run-in Period. Efficacy will be measured by The Area Under the Curve From 0 to 12 Hours [AUC](0-12 hours) of the Change From Baseline to the Week 12 Endpoint

in Forced Expiratory Volume in One Second (FEV1) [Time Frame: Baseline to Week 12] and Time-to-First Severe Asthma Exacerbation across the 26-week treatment period.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: mometasone furoate/formoterol fumarate combination MDI 200/10 mcg BID; Drug: Mometasone furoate MDI (MF MDI) 200 mcg; Drug: formoterol fumarate 10 mcg; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 781 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 26-Week Placebo-Controlled Efficacy and Safety Study of Mometasone Furoate/Formoterol Fumarate Combination Formulation Compared With Mometasone Furoate and Formoterol Monotherapy in Subjects With Persistent Asthma Previously Treated With Medium-Dose Inhaled Glucocorticosteroids
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MF/F MDI 200/10 mcg BID	Drug: mometasone furoate/formoterol fumarate combination MDI 200/10 mcg BID; MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 26 weeks; Other Names: SCH 418131
Experimental: MF MDI 200 mcg BID	Drug: Mometasone furoate MDI (MF MDI) 200 mcg; MF 200 mcg via metered dose inhaler twice daily for 26 weeks; Other Names: SCH 32088
Experimental: F MDI 10 mcg BID	Drug: formoterol fumarate 10 mcg; F via metered dose inhaler 10 mcg twice a day for 26 weeks; Other Names: Foradil
Placebo Comparator: Placebo BID	Drug: Placebo; Placebo metered dose inhaler twice a day for 26 weeks

Outcome Measures

Primary Outcome Measures

1. Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) for MF/F Versus MF [Baseline to Endpoint (12 weeks)]

2. Time-to-first Asthma Exacerbation Over the 26-week Treatment Period for the Comparison of MF/F Versus F [26-week Treatment Period]

   This endpoint was to measure the time it took for 50% of subjects in a treatment arm to experience a severe asthma exacerbation (also see the posted Other Pre-specified Outcome: Number of Participants With at Least One Severe Asthma Exacerbation)

Secondary Outcome Measures

1. Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S]) Total Score [Baseline to Week 26]

   AQLQ(S) consists of 32 questions each scaled from 1 (worst case) to 7 (best case). Standard deviations are pooled.

2. Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Score [Baseline to week 26]

   ACQ consists of seven questions each scaled from 0 (best case) to 6 (worst case).

3. Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta 2-agonist (SABA) [Baseline to Endpoint]

   Baseline is the proportion of nights of last week (Days -7 to 1) prior to first dose with nocturnal awakenings. Scale is measured as 0 to 1 with 0=no awakenings to 1=awakenings every night. Standard deviation is pooled.

Other Outcome Measures

1. Number of Participants With at Least One Severe Asthma Exacerbation [Baseline to Week 26]

   A severe asthma exacerbation was defined as a clinically judged deterioration of asthma or a meaningful reduction in lung function based on any of the following criteria during the Treatment Period: A decrease in FEV1 below the Treatment Period stability limit at any visit, A decrease in AM or PM peak flow below the Treatment Period stability limits on any 2 consecutive days, An occurrence of any clinical deterioration of asthma (ie, asthma attack) that resulted in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Adult and adolescent subjects of either sex and any race, at least 12 years of age or older, with a diagnosis of asthma of at least 12 months' duration, will be eligible for enrollment. Subjects must meet all of the inclusion criteria and none of the exclusion criteria to receive treatment assignment.

Key Inclusion Criteria Include

• A subject must have been using a medium daily dose of inhaled glucocorticosteroid (ICS) (either alone or in combination with a long-acting beta agonist (LABA)) for at least 12 weeks and must have been on a stable regimen (daily dose unchanged) for at least 2 weeks prior to Screening. Medium daily doses of ICS are defined as follows:

• 500 to 1000 mcg beclomethasone chlorofluorocarbon (CFC)

• 250 to 500 mcg beclomethasone hydrofluoroalkane (HFA)

• 600 to 1000 mcg budesonide dry powder inhaler (DPI)

• 1000 to 2000 mcg flunisolide

• 250 to 500 mcg fluticasone

• 400 mcg MF

• 1000 to 2000 mcg triamcinolone acetonide

Note: Dose delivery by method or modality other than those noted above must be equivalent.

• If, based upon the medical judgment of the investigator, there is no inherent harm in changing the subject's current asthma therapy, then the subject (and parent/guardian, if applicable) must be willing to discontinue his/her prescribed ICS or ICS/LABA combination at the Screening Visit, and be transferred to open-label treatment with MF MDI 200 mcg BID for 2 to 3 weeks prior to the Baseline/Randomization Visit.

• To document the diagnosis of asthma and assure the subject's responsiveness to bronchodilators before randomization one of the following methods can be used at the

Screening Visit, Day -14, or thereafter, but prior to the Baseline Visit:

1. The subject must demonstrate an increase in absolute FEV1 of at least 12% and at least 200 mL within 15 minutes after administration of four inhalations of albuterol/salbutamol (total dose of 360 to 400 mcg) or of nebulized SABA (2.5 mg) if confirmed as standard office practice, OR

2. The subject must demonstrate a peak expiratory flow (PEF) variability of more than 20% expressed as a percentage of the highest and lowest morning prebronchodilator PEF over at least 1 week, OR

3. The subject must demonstrate a diurnal variation in PEF of more than 20% based on the difference between the prebronchodilator morning value and the postbronchodilator value from the evening before, expressed as a percentage of the mean daily PEF value.

• At the Screening Visit, the subject's FEV1 must be ≥60% and ≤90% predicted.

• At the Baseline Visit, the subject's FEV1 must be ≥60% and ≤85% predicted when all restricted medications have been withheld for the appropriate intervals.

• Clinical laboratory tests (complete blood counts [CBC], blood chemistries, and urinalysis) conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor. An electrocardiogram (ECG) using a centralized trans-telephonic technology at the Screening Visit must be clinically acceptable to the investigator. A chest x-ray performed at the Screening Visit, or within 12 months prior to the Screening Visit, must be clinically acceptable to the investigator.

• A female subject of childbearing potential must have been using a medically acceptable, adequate form of birth control. This includes: 1) hormonal contraceptives as prescribed by a physician (oral combined, hormonal implant); 2) medically prescribed intra-uterine device (IUD); 3) condom in combination with a spermicide (double barrier method); 4) monogamous relationship with a male partner who has had a vasectomy. The subject must have started this birth control method at least 3 months prior to Screening (with the exception of condom in combination with spermicide), and must agree to continue its use for the duration of the study. A female subject of childbearing potential who is not currently sexually active must agree and consent to using a medically acceptable birth control method should she become sexually active during the course of this study. Women who have been surgically sterilized or are at least 1 year postmenopausal are not considered to be of childbearing potential. A female subject of childbearing potential must have a negative serum pregnancy test at Screening in order to be considered eligible for enrollment.

Key Exclusion Criteria Include

• A subject who demonstrates a change (increase or decrease) in absolute FEV1 of >20% at any time from the Screening Visit up to and including the Baseline Visit.

• A subject who requires the use of greater than eight inhalations per day of SABA MDI, or two or more nebulized treatments per day of 2.5 mg SABA, on any 2 consecutive days from the Screening Visit up to and including the Baseline Visit.

• A subject who experiences a decrease in AM or PM PEF below the Screening Period stability limit on any 2 consecutive days prior to Randomization.

• A subject who experiences an occurrence of any clinical deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication (other than SABA) as judged by the clinical investigator at any time from the Screening Visit up to and including the Baseline Visit.

• A subject who is a smoker or ex-smoker and has smoked within the previous year or has had a cumulative smoking history >10 pack-years

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co
• Novartis

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00383240
• Other Study ID Numbers: P04334; EUDRACT No.: 2006-001578-25
• First Posted: Oct 3, 2006
• Last Update Posted: Feb 16, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Asthma; Mometasone Furoate; Formoterol Fumarate

Study Results

Participant Flow

Arm/Group Title	MF/F MDI 200/10 mcg BID	MF MDI 200 mcg BID	F MDI 10 mcg BID	Placebo BID
Arm/Group Description	mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo MDI BID for 26 weeks
Period Title: Overall Study
STARTED	191	192	202	196
COMPLETED	156	159	117	119
NOT COMPLETED	35	33	85	77

Baseline Characteristics

Arm/Group Title	MF/F MDI 200/10 mcg BID	MF MDI 200 mcg BID	F MDI 10 mcg BID	Placebo BID	Total
Arm/Group Description	mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo MDI BID for 26 weeks	Total of all reporting groups
Overall Participants	191	192	202	196	781
Age (Count of Participants)
<=18 years	19 9.9%	10 5.2%	18 8.9%	16 8.2%	63 8.1%
Between 18 and 65 years	161 84.3%	173 90.1%	174 86.1%	169 86.2%	677 86.7%
>=65 years	11 5.8%	9 4.7%	10 5%	11 5.6%	41 5.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.9 (16.3)	42.8 (14.9)	41.9 (15.3)	41.9 (15.3)	42.4 (15.4)
Sex: Female, Male (Count of Participants)
Female	97 50.8%	112 58.3%	129 63.9%	122 62.2%	460 58.9%
Male	94 49.2%	80 41.7%	73 36.1%	74 37.8%	321 41.1%

Outcome Measures

1. Primary Outcome

Title	Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) for MF/F Versus MF
Time Frame	Baseline to Endpoint (12 weeks)

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) population

Arm/Group Title	MF/F MDI 200/10 mcg BID	MF MDI 200 mcg BID	F MDI 10 mcg BID	Placebo BID
Arm/Group Description	mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo MDI BID for 26 weeks
Measure Participants	190	190	202	193
Baseline (n=188/189/198/192, respectively)	3.20 (2.96)	1.29 (2.96)	2.73 (2.96)	1.42 (2.96)
Endpoint (Change from Baseline)	3.19 (3.98)	1.31 (3.98)	1.60 (3.98)	0.51 (3.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MF/F MDI 200/10 mcg BID, MF MDI 200 mcg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MF/F MDI 200/10 mcg BID, F MDI 10 mcg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MF/F MDI 200/10 mcg BID, Placebo BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MF MDI 200 mcg BID, F MDI 10 mcg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.491
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	MF MDI 200 mcg BID, Placebo BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.055
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	F MDI 10 mcg BID, Placebo BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S]) Total Score
Description	AQLQ(S) consists of 32 questions each scaled from 1 (worst case) to 7 (best case). Standard deviations are pooled.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

ITT population with non-missing post-baseline AQLQ result

Arm/Group Title	MF/F MDI 200/10 mcg BID	MF MDI 200 mcg BID	F MDI 10 mcg BID	Placebo BID
Arm/Group Description	mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo MDI BID for 26 weeks
Measure Participants	183	189	187	189
Baseline (n=183/189/187/189, respectively)	5.38 (1.10)	5.40 (1.13)	5.51 (1.11)	5.56 (1.06)
Change from Baseline to Endpoint (26 weeks)	0.49 (0.85)	0.37 (0.85)	0.05 (0.85)	-0.01 (0.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MF/F MDI 200/10 mcg BID, MF MDI 200 mcg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.174
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MF/F MDI 200/10 mcg BID, F MDI 10 mcg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MF/F MDI 200/10 mcg BID, Placebo BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MF MDI 200 mcg BID, F MDI 10 mcg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	MF MDI 200 mcg BID, Placebo BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	F MDI 10 mcg BID, Placebo BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.521
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

3. Primary Outcome

Title	Time-to-first Asthma Exacerbation Over the 26-week Treatment Period for the Comparison of MF/F Versus F
Description	This endpoint was to measure the time it took for 50% of subjects in a treatment arm to experience a severe asthma exacerbation (also see the posted Other Pre-specified Outcome: Number of Participants With at Least One Severe Asthma Exacerbation)
Time Frame	26-week Treatment Period

Outcome Measure Data

Analysis Population Description

All Randomized Subjects

Arm/Group Title	MF/F MDI 200/10 mcg BID	MF MDI 200 mcg BID	F MDI 10 mcg BID	Placebo BID
Arm/Group Description	mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo MDI BID for 26 weeks
Measure Participants	191	192	202	196
Median (Inter-Quartile Range) [days]	NA (NA)	NA (NA)	92 (NA)	131 (NA)

4. Secondary Outcome

Title	Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Score
Description	ACQ consists of seven questions each scaled from 0 (best case) to 6 (worst case).
Time Frame	Baseline to week 26

Outcome Measure Data

Analysis Population Description

ITT population with non-missing post-baseline ACQ result

Arm/Group Title	MF/F MDI 200/10 mcg BID	MF MDI 200 mcg BID	F MDI 10 mcg BID	Placebo BID
Arm/Group Description	mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo MDI BID for 26 weeks
Measure Participants	179	186	184	187
Baseline (n=179/186/184/187, respectively)	1.47 (0.75)	1.46 (0.77)	1.43 (0.79)	1.41 (0.75)
Change from Baseline to Endpoint (week 26)	-0.40 (0.74)	-0.23 (0.74)	0.11 (0.74)	0.14 (0.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MF/F MDI 200/10 mcg BID, MF MDI 200 mcg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.026
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MF/F MDI 200/10 mcg BID, F MDI 10 mcg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MF/F MDI 200/10 mcg BID, Placebo BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MF MDI 200 mcg BID, F MDI 10 mcg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	MF MDI 200 mcg BID, Placebo BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	F MDI 10 mcg BID, Placebo BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.738
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta 2-agonist (SABA)
Description	Baseline is the proportion of nights of last week (Days -7 to 1) prior to first dose with nocturnal awakenings. Scale is measured as 0 to 1 with 0=no awakenings to 1=awakenings every night. Standard deviation is pooled.
Time Frame	Baseline to Endpoint

Outcome Measure Data

Analysis Population Description

ITT population from the entire 26-week treatment period

Arm/Group Title	MF/F MDI 200/10 mcg BID	MF MDI 200 mcg BID	F MDI 10 mcg BID	Placebo BID
Arm/Group Description	mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo MDI BID for 26 weeks
Measure Participants	186	191	199	194
Baseline (n=186/191/199/194, respectively)	0.18 (0.31)	0.16 (0.27)	0.16 (0.27)	0.15 (0.27)
Change from Baseline to Endpoint	-0.08 (0.17)	-0.05 (0.17)	0.01 (0.17)	0.00 (0.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MF/F MDI 200/10 mcg BID, MF MDI 200 mcg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.063
	Comments	P-Value for endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	MF/F MDI 200/10 mcg BID, F MDI 10 mcg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	MF/F MDI 200/10 mcg BID, Placebo BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	MF MDI 200 mcg BID, F MDI 10 mcg BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	MF MDI 200 mcg BID, Placebo BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	F MDI 10 mcg BID, Placebo BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.601
	Comments	P-Value for Endpoint
	Method	ANCOVA
	Comments

6. Other Pre-specified Outcome

Title	Number of Participants With at Least One Severe Asthma Exacerbation
Description	A severe asthma exacerbation was defined as a clinically judged deterioration of asthma or a meaningful reduction in lung function based on any of the following criteria during the Treatment Period: A decrease in FEV1 below the Treatment Period stability limit at any visit, A decrease in AM or PM peak flow below the Treatment Period stability limits on any 2 consecutive days, An occurrence of any clinical deterioration of asthma (ie, asthma attack) that resulted in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

All Randomized Subjects

Arm/Group Title	MF/F MDI 200/10 mcg BID	MF MDI 200 mcg BID	F MDI 10 mcg BID	Placebo BID
Arm/Group Description	mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo MDI BID for 26 weeks
Measure Participants	191	192	202	196
Number [participants]	58 30.4%	65 33.9%	109 54%	109 55.6%

Adverse Events

Arm/Group Title	OL MF MDI 200 MCG BID		MF/F MDI 200/10 MCG BID		MF MDI 200 MCG BID		F MDI 10 MCG BID		PLACEBO
Arm/Group Description	Participants received 2 to 3 weeks (approximately) of open-label (OL), run-in medication with MF MDI 200 mcg BID prior to the 26-week double-blind treatment period.
All Cause Mortality
	OL MF MDI 200 MCG BID		MF/F MDI 200/10 MCG BID		MF MDI 200 MCG BID		F MDI 10 MCG BID		PLACEBO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	OL MF MDI 200 MCG BID		MF/F MDI 200/10 MCG BID		MF MDI 200 MCG BID		F MDI 10 MCG BID		PLACEBO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/984 (0.4%)		5/191 (2.6%)		3/192 (1.6%)		3/202 (1.5%)		3/196 (1.5%)
Infections and infestations
DENGUE FEVER	1/984 (0.1%)	1	0/191 (0%)	0	0/192 (0%)	0	0/202 (0%)	0	0/196 (0%)	0
GASTROENTERITIS	0/984 (0%)	0	0/191 (0%)	0	1/192 (0.5%)	1	0/202 (0%)	0	0/196 (0%)	0
VIRAL INFECTION	0/984 (0%)	0	1/191 (0.5%)	1	0/192 (0%)	0	0/202 (0%)	0	0/196 (0%)	0
Injury, poisoning and procedural complications
HUMERUS FRACTURE	0/984 (0%)	0	0/191 (0%)	0	0/192 (0%)	0	0/202 (0%)	0	1/196 (0.5%)	1
JOINT INJURY	1/984 (0.1%)	1	0/191 (0%)	0	0/192 (0%)	0	0/202 (0%)	0	0/196 (0%)	0
Metabolism and nutrition disorders
HYPERGLYCAEMIA	0/984 (0%)	0	0/191 (0%)	0	0/192 (0%)	0	1/202 (0.5%)	1	0/196 (0%)	0
Musculoskeletal and connective tissue disorders
BACK PAIN	1/984 (0.1%)	1	0/191 (0%)	0	0/192 (0%)	0	0/202 (0%)	0	0/196 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT MELANOMA	0/984 (0%)	0	0/191 (0%)	0	0/192 (0%)	0	1/202 (0.5%)	1	0/196 (0%)	0
UTERINE LEIOMYOSARCOMA	0/984 (0%)	0	1/191 (0.5%)	1	0/192 (0%)	0	0/202 (0%)	0	0/196 (0%)	0
Nervous system disorders
CONVULSION	0/984 (0%)	0	1/191 (0.5%)	1	0/192 (0%)	0	0/202 (0%)	0	0/196 (0%)	0
HYPOAESTHESIA	0/984 (0%)	0	1/191 (0.5%)	1	0/192 (0%)	0	0/202 (0%)	0	0/196 (0%)	0
Renal and urinary disorders
NEPHROLITHIASIS	1/984 (0.1%)	1	0/191 (0%)	0	0/192 (0%)	0	0/202 (0%)	0	0/196 (0%)	0
Reproductive system and breast disorders
ENDOMETRIOSIS	0/984 (0%)	0	0/191 (0%)	0	1/192 (0.5%)	1	0/202 (0%)	0	0/196 (0%)	0
UTERINE HAEMORRHAGE	1/984 (0.1%)	1	0/191 (0%)	0	0/192 (0%)	0	0/202 (0%)	0	0/196 (0%)	0
VAGINAL HAEMORRHAGE	0/984 (0%)	0	1/191 (0.5%)	1	0/192 (0%)	0	0/202 (0%)	0	0/196 (0%)	0
Respiratory, thoracic and mediastinal disorders
ASTHMA	0/984 (0%)	0	0/191 (0%)	0	1/192 (0.5%)	1	1/202 (0.5%)	1	0/196 (0%)	0
Skin and subcutaneous tissue disorders
DERMATITIS ATOPIC	0/984 (0%)	0	0/191 (0%)	0	0/192 (0%)	0	0/202 (0%)	0	1/196 (0.5%)	1
ECZEMA	0/984 (0%)	0	1/191 (0.5%)	1	0/192 (0%)	0	0/202 (0%)	0	0/196 (0%)	0
Surgical and medical procedures
SPINAL DECOMPRESSION	0/984 (0%)	0	0/191 (0%)	0	0/192 (0%)	0	0/202 (0%)	0	1/196 (0.5%)	1
Other (Not Including Serious) Adverse Events
	OL MF MDI 200 MCG BID		MF/F MDI 200/10 MCG BID		MF MDI 200 MCG BID		F MDI 10 MCG BID		PLACEBO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/984 (2.5%)		31/191 (16.2%)		35/192 (18.2%)		29/202 (14.4%)		30/196 (15.3%)
Infections and infestations
NASOPHARYNGITIS	8/984 (0.8%)	8	12/191 (6.3%)	13	15/192 (7.8%)	22	13/202 (6.4%)	14	7/196 (3.6%)	8
UPPER RESPIRATORY TRACT INFECTION	7/984 (0.7%)	7	11/191 (5.8%)	13	16/192 (8.3%)	16	12/202 (5.9%)	16	17/196 (8.7%)	17
Nervous system disorders
HEADACHE	11/984 (1.1%)	13	9/191 (4.7%)	10	10/192 (5.2%)	17	6/202 (3%)	8	7/196 (3.6%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.