Trial Outcomes & Findings for Effects of Mometasone Furoate/Formoterol Combination Versus Mometasone Furoate Alone in Persistent Asthmatics (Study P04334AM1)(COMPLETED) (NCT NCT00383240)

NCT ID: NCT00383240

Last Updated: 2024-05-20

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

781 participants

Primary outcome timeframe

Baseline to Endpoint (12 weeks)

Results posted on

2024-05-20

Participant Flow

Participant milestones

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

Reasons for withdrawal

Reasons for withdrawal
Measure	MF/F MDI 200/10 mcg BID mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	MF MDI 200 mcg BID Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	F MDI 10 mcg BID Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo BID Placebo MDI BID for 26 weeks
Overall Study Adverse Event	4	6	9	7
Overall Study Treatment Failure	8	13	47	46
Overall Study Lost to Follow-up	3	0	0	2
Overall Study Withdrawal by subject, reasons unrelated	6	3	8	8
Overall Study Withdrawal by subjects, reasons related	0	1	3	5
Overall Study Protocol Violation	4	5	9	6
Overall Study Did not meet protocol eligibility	9	4	9	3
Overall Study Administrative	1	1	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MF/F MDI 200/10 mcg BID n=191 Participants mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	MF MDI 200 mcg BID n=192 Participants Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	F MDI 10 mcg BID n=202 Participants Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo BID n=196 Participants Placebo MDI BID for 26 weeks	Total n=781 Participants Total of all reporting groups
Age, Categorical <=18 years	19 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants	16 Participants n=4 Participants	63 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	161 Participants n=5 Participants	173 Participants n=7 Participants	174 Participants n=5 Participants	169 Participants n=4 Participants	677 Participants n=21 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	11 Participants n=4 Participants	41 Participants n=21 Participants
Age, Continuous	42.9 years STANDARD_DEVIATION 16.3 • n=5 Participants	42.8 years STANDARD_DEVIATION 14.9 • n=7 Participants	41.9 years STANDARD_DEVIATION 15.3 • n=5 Participants	41.9 years STANDARD_DEVIATION 15.3 • n=4 Participants	42.4 years STANDARD_DEVIATION 15.4 • n=21 Participants
Sex: Female, Male Female	97 Participants n=5 Participants	112 Participants n=7 Participants	129 Participants n=5 Participants	122 Participants n=4 Participants	460 Participants n=21 Participants
Sex: Female, Male Male	94 Participants n=5 Participants	80 Participants n=7 Participants	73 Participants n=5 Participants	74 Participants n=4 Participants	321 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline to Endpoint (12 weeks)

Population: Intent to Treat (ITT) population

Outcome measures

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

PRIMARY outcome

Timeframe: 26-week Treatment Period

Population: All Randomized Subjects

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)

Outcome measures

Outcome measures
Measure	MF/F MDI 200/10 mcg BID n=191 Participants mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	MF MDI 200 mcg BID n=192 Participants Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	F MDI 10 mcg BID n=202 Participants Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo BID n=196 Participants Placebo MDI BID for 26 weeks
Time-to-first Asthma Exacerbation Over the 26-week Treatment Period for the Comparison of MF/F Versus F	NA days Inter-Quartile Range NA Since less than 50% of the subjects in the MF/F and MF treatment groups experienced an asthma exacerbation by the end of the 26 week treatment period, median time-to-first asthma exacerbation can not be determined but is at least 26 weeks.	NA days Inter-Quartile Range NA Since less than 50% of the subjects in the MF/F and MF treatment groups experienced an asthma exacerbation by the end of the 26 week treatment period, median time-to-first asthma exacerbation can not be determined but is at least 26 weeks.	92 days Inter-Quartile Range NA • Interval 24.0 to In the F treatment group a subject experienced an asthma exacerbation on day 193 since the event was observed on the final visit performed 10 days beyond the scheduled 26-week treatment period schedule. Therefore the InterQuartile Range is 24 to 193.	131 days Inter-Quartile Range NA • Interval 25.0 to Since less than 75% of the subjects in the placebo group experienced an asthma exacerbation by the end of the 26 week treatment period, 3rd quartile time-to-first asthma exacerbation can not be determined but is at least 26 weeks.

SECONDARY outcome

Timeframe: Baseline to Week 26

Population: ITT population with non-missing post-baseline AQLQ result

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

Outcome measures

Outcome measures
Measure	MF/F MDI 200/10 mcg BID n=183 Participants mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	MF MDI 200 mcg BID n=189 Participants Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	F MDI 10 mcg BID n=187 Participants Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo BID n=189 Participants Placebo MDI BID for 26 weeks
Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S]) Total Score Baseline (n=183/189/187/189, respectively)	5.38 units on a scale Standard Deviation 1.10	5.40 units on a scale Standard Deviation 1.13	5.51 units on a scale Standard Deviation 1.11	5.56 units on a scale Standard Deviation 1.06
Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S]) Total Score Change from Baseline to Endpoint (26 weeks)	0.49 units on a scale Standard Deviation 0.85	0.37 units on a scale Standard Deviation 0.85	0.05 units on a scale Standard Deviation 0.85	-0.01 units on a scale Standard Deviation 0.85

SECONDARY outcome

Timeframe: Baseline to week 26

Population: ITT population with non-missing post-baseline ACQ result

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

Outcome measures

Outcome measures
Measure	MF/F MDI 200/10 mcg BID n=179 Participants mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	MF MDI 200 mcg BID n=186 Participants Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	F MDI 10 mcg BID n=184 Participants Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo BID n=187 Participants Placebo MDI BID for 26 weeks
Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Score Change from Baseline to Endpoint (week 26)	-0.40 units on a scale Standard Deviation 0.74	-0.23 units on a scale Standard Deviation 0.74	0.11 units on a scale Standard Deviation 0.74	0.14 units on a scale Standard Deviation 0.74
Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Score Baseline (n=179/186/184/187, respectively)	1.47 units on a scale Standard Deviation 0.75	1.46 units on a scale Standard Deviation 0.77	1.43 units on a scale Standard Deviation 0.79	1.41 units on a scale Standard Deviation 0.75

SECONDARY outcome

Timeframe: Baseline to Endpoint

Population: ITT population from the entire 26-week treatment period

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.

Outcome measures

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

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 26

Population: All Randomized Subjects

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.

Outcome measures

Outcome measures
Measure	MF/F MDI 200/10 mcg BID n=191 Participants mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 200/10 mcg twice daily (BID) for 26 weeks	MF MDI 200 mcg BID n=192 Participants Mometasone furoate (MF) MDI 200 mcg BID for 26 weeks	F MDI 10 mcg BID n=202 Participants Formoterol fumarate (F) MDI 10 mcg BID for 26 weeks	Placebo BID n=196 Participants Placebo MDI BID for 26 weeks
Number of Participants With at Least One Severe Asthma Exacerbation	58 participants	65 participants	109 participants	109 participants

Adverse Events

OL MF MDI 200 MCG BID

Serious events: 4 serious events

Other events: 25 other events

Deaths: 0 deaths

MF/F MDI 200/10 MCG BID

Serious events: 5 serious events

Other events: 31 other events

Deaths: 0 deaths

MF MDI 200 MCG BID

Serious events: 3 serious events

Other events: 35 other events

Deaths: 0 deaths

F MDI 10 MCG BID

Serious events: 3 serious events

Other events: 29 other events

Deaths: 0 deaths

PLACEBO

Serious events: 3 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OL MF MDI 200 MCG BID n=984 participants at risk 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.	MF/F MDI 200/10 MCG BID n=191 participants at risk	MF MDI 200 MCG BID n=192 participants at risk	F MDI 10 MCG BID n=202 participants at risk	PLACEBO n=196 participants at risk
Infections and infestations DENGUE FEVER	0.10% 1/984 • Number of events 1	0.00% 0/191	0.00% 0/192	0.00% 0/202	0.00% 0/196
Infections and infestations GASTROENTERITIS	0.00% 0/984	0.00% 0/191	0.52% 1/192 • Number of events 1	0.00% 0/202	0.00% 0/196
Infections and infestations VIRAL INFECTION	0.00% 0/984	0.52% 1/191 • Number of events 1	0.00% 0/192	0.00% 0/202	0.00% 0/196
Injury, poisoning and procedural complications HUMERUS FRACTURE	0.00% 0/984	0.00% 0/191	0.00% 0/192	0.00% 0/202	0.51% 1/196 • Number of events 1
Injury, poisoning and procedural complications JOINT INJURY	0.10% 1/984 • Number of events 1	0.00% 0/191	0.00% 0/192	0.00% 0/202	0.00% 0/196
Metabolism and nutrition disorders HYPERGLYCAEMIA	0.00% 0/984	0.00% 0/191	0.00% 0/192	0.50% 1/202 • Number of events 1	0.00% 0/196
Musculoskeletal and connective tissue disorders BACK PAIN	0.10% 1/984 • Number of events 1	0.00% 0/191	0.00% 0/192	0.00% 0/202	0.00% 0/196
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MALIGNANT MELANOMA	0.00% 0/984	0.00% 0/191	0.00% 0/192	0.50% 1/202 • Number of events 1	0.00% 0/196
Neoplasms benign, malignant and unspecified (incl cysts and polyps) UTERINE LEIOMYOSARCOMA	0.00% 0/984	0.52% 1/191 • Number of events 1	0.00% 0/192	0.00% 0/202	0.00% 0/196
Nervous system disorders CONVULSION	0.00% 0/984	0.52% 1/191 • Number of events 1	0.00% 0/192	0.00% 0/202	0.00% 0/196
Nervous system disorders HYPOAESTHESIA	0.00% 0/984	0.52% 1/191 • Number of events 1	0.00% 0/192	0.00% 0/202	0.00% 0/196
Renal and urinary disorders NEPHROLITHIASIS	0.10% 1/984 • Number of events 1	0.00% 0/191	0.00% 0/192	0.00% 0/202	0.00% 0/196
Reproductive system and breast disorders ENDOMETRIOSIS	0.00% 0/984	0.00% 0/191	0.52% 1/192 • Number of events 1	0.00% 0/202	0.00% 0/196
Reproductive system and breast disorders UTERINE HAEMORRHAGE	0.10% 1/984 • Number of events 1	0.00% 0/191	0.00% 0/192	0.00% 0/202	0.00% 0/196
Reproductive system and breast disorders VAGINAL HAEMORRHAGE	0.00% 0/984	0.52% 1/191 • Number of events 1	0.00% 0/192	0.00% 0/202	0.00% 0/196
Respiratory, thoracic and mediastinal disorders ASTHMA	0.00% 0/984	0.00% 0/191	0.52% 1/192 • Number of events 1	0.50% 1/202 • Number of events 1	0.00% 0/196
Skin and subcutaneous tissue disorders DERMATITIS ATOPIC	0.00% 0/984	0.00% 0/191	0.00% 0/192	0.00% 0/202	0.51% 1/196 • Number of events 1
Skin and subcutaneous tissue disorders ECZEMA	0.00% 0/984	0.52% 1/191 • Number of events 1	0.00% 0/192	0.00% 0/202	0.00% 0/196
Surgical and medical procedures SPINAL DECOMPRESSION	0.00% 0/984	0.00% 0/191	0.00% 0/192	0.00% 0/202	0.51% 1/196 • Number of events 1

Other adverse events

Other adverse events
Measure	OL MF MDI 200 MCG BID n=984 participants at risk 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.	MF/F MDI 200/10 MCG BID n=191 participants at risk	MF MDI 200 MCG BID n=192 participants at risk	F MDI 10 MCG BID n=202 participants at risk	PLACEBO n=196 participants at risk
Infections and infestations NASOPHARYNGITIS	0.81% 8/984 • Number of events 8	6.3% 12/191 • Number of events 13	7.8% 15/192 • Number of events 22	6.4% 13/202 • Number of events 14	3.6% 7/196 • Number of events 8
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	0.71% 7/984 • Number of events 7	5.8% 11/191 • Number of events 13	8.3% 16/192 • Number of events 16	5.9% 12/202 • Number of events 16	8.7% 17/196 • Number of events 17
Nervous system disorders HEADACHE	1.1% 11/984 • Number of events 13	4.7% 9/191 • Number of events 10	5.2% 10/192 • Number of events 17	3.0% 6/202 • Number of events 8	3.6% 7/196 • Number of events 10

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60