Trial Outcomes & Findings for Study of Inhaled Glucocorticosteroids/Long-Acting Bronchodilator Drugs in Subjects With Asthma That Have Been Taking Inhaled Glucocorticosteroids (Study P04705AM1) (NCT NCT00424008)

NCT ID: NCT00424008

Last Updated: 2024-05-20

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

722 participants

Primary outcome timeframe

Baseline to Week 12

Results posted on

2024-05-20

Participant Flow

In order to standardize treatment prior to randomization, participants entered a 2- to 4-week open-label Run-in period where they received MF MDI 200 mcg BID. Participants who continued to meet eligibility criteria at the completion of the Run-in Period were randomized into the study.

Participant milestones

Participant milestones
Measure	MF/F MDI 200/10 mcg BID Mometasone furoate 200 mcg and formoterol 10 mcg (MF/F) fixed dose combination taken twice daily (BID) via a metered-dose inhaler (MDI).	F/SC DPI 250/50 mcg BID Fluticasone propionate/salmeterol (F/SC) 250/50 mcg Dry Powder Inhaler (DPI) BID
Overall Study STARTED	371	351
Overall Study COMPLETED	22	16
Overall Study NOT COMPLETED	349	335

Reasons for withdrawal

Reasons for withdrawal
Measure	MF/F MDI 200/10 mcg BID Mometasone furoate 200 mcg and formoterol 10 mcg (MF/F) fixed dose combination taken twice daily (BID) via a metered-dose inhaler (MDI).	F/SC DPI 250/50 mcg BID Fluticasone propionate/salmeterol (F/SC) 250/50 mcg Dry Powder Inhaler (DPI) BID
Overall Study Adverse Event	8	6
Overall Study Lack of Efficacy	40	34
Overall Study Lost to Follow-up	1	2
Overall Study Withdrawal by Subject	5	8
Overall Study Noncompliance with protocol	13	7
Overall Study Did not meet protocol eligibility	16	21
Overall Study Administrative	266	257

Baseline Characteristics

Study of Inhaled Glucocorticosteroids/Long-Acting Bronchodilator Drugs in Subjects With Asthma That Have Been Taking Inhaled Glucocorticosteroids (Study P04705AM1)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MF/F MDI 200/10 mcg BID n=371 Participants Mometasone furoate 200 mcg and formoterol 10 mcg (MF/F) fixed dose combination taken twice daily (BID) via a metered-dose inhaler (MDI).	F/SC DPI 250/50 mcg BID n=351 Participants Fluticasone propionate/salmeterol (F/SC) 250/50 mcg Dry Powder Inhaler (DPI) BID	Total n=722 Participants Total of all reporting groups
Age, Customized 12 to <18 years	22 participants n=5 Participants	18 participants n=7 Participants	40 participants n=5 Participants
Age, Customized 18 to <65 years	321 participants n=5 Participants	308 participants n=7 Participants	629 participants n=5 Participants
Age, Customized >=65 years	28 participants n=5 Participants	25 participants n=7 Participants	53 participants n=5 Participants
Sex: Female, Male Female	239 Participants n=5 Participants	220 Participants n=7 Participants	459 Participants n=5 Participants
Sex: Female, Male Male	132 Participants n=5 Participants	131 Participants n=7 Participants	263 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 12

Population: Efficacy analyses were based on randomized subjects with Baseline and any post-baseline data (intent-to-treat principle). The standard deviation is pooled. Least Squares Mean scores are obtained from an analysis of covariance model correcting for treatment, site effects, and the Baseline FEV1 (liters) as a covariate.

Outcome measures

Outcome measures
Measure	MF/F MDI 200/10 mcg BID n=366 Participants Mometasone furoate 200 mcg and formoterol 10 mcg (MF/F) fixed dose combination taken twice daily (BID) via a metered-dose inhaler (MDI).	F/SC DPI 250/50 mcg BID n=346 Participants Fluticasone propionate/salmeterol (F/SC) 250/50 mcg Dry Powder Inhaler (DPI) BID
The Area Under the Curve From 0 to 12 Hours [AUC](0-12 hr) of the Change From Baseline to the Week 12 Endpoint in Forced Expiratory Volume in One Second (FEV1)	3.43 Liter x hour Standard Deviation 3.83 • Interval -0.56 to 0.79	3.24 Liter x hour Standard Deviation 3.83 • Interval -0.56 to 0.79

SECONDARY outcome

Timeframe: Baseline to 5 minutes post-dose on Day 1

Population: Participants with data at Day One 5 minutes post-dose. The standard deviation is pooled. Least Squares Mean scores are obtained from an analysis of covariance model correcting for treatment, site effects, and the Baseline FEV1 (liters) as a covariate.

PFTs, including FEV1, were done on Day 1. Evaluations included 30 min before and immediately before the first dose, the mean of which was Baseline, and at intervals from 5 min to 12 hrs postdose. Onset of action was defined as statistically significant improvement of MF/F over F/SC in Change from Baseline FEV1 at the 5-min postdose evaluation on Day 1. The same series of PFTs were done at Week 12. Change from Baseline to Week 12 evaluations were calculated using the same Day 1 predose scores for Baseline. The Week-12 evaluation consisted of AUC FEV1 scores across the 12-hour postdose interval.

Outcome measures

Outcome measures
Measure	MF/F MDI 200/10 mcg BID n=365 Participants Mometasone furoate 200 mcg and formoterol 10 mcg (MF/F) fixed dose combination taken twice daily (BID) via a metered-dose inhaler (MDI).	F/SC DPI 250/50 mcg BID n=348 Participants Fluticasone propionate/salmeterol (F/SC) 250/50 mcg Dry Powder Inhaler (DPI) BID
Onset-of-action Based on Change From Baseline FEV1 at the 5 Min Pulmonary Function Test (PFT) Assessment on Day 1	0.20 Liters Standard Deviation 0.20	0.09 Liters Standard Deviation 0.20

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Efficacy analyses were based on randomized subjects with Baseline and any postbaseline data (intent-to-treat principle). The standard deviation is pooled. Least Squares Mean scores are obtained from an analysis of covariance model correcting for treatment, site effects, and the Baseline ACQ score as a covariate.

The Asthma Control Questionnaire (ACQ) by Juniper et al. is a mean of 7 equally weighted composite scores; each scaled from 0=best case scenario to 6=worst case scenario on an integer scale. Composites include the following: How Often Woken by Asthma, How Bad Were Asthma Symptoms When You Woke, Activity Limitations, Shortness of Breath, Wheezing, Average Daily Short-Acting Beta 2-Agonist (SABA) Puffs, and physician-evaluated lung function. With the exception of physician-evaluated lung function collected at the visit, evaluations were over the last week recall period.

Outcome measures

Outcome measures
Measure	MF/F MDI 200/10 mcg BID n=350 Participants Mometasone furoate 200 mcg and formoterol 10 mcg (MF/F) fixed dose combination taken twice daily (BID) via a metered-dose inhaler (MDI).	F/SC DPI 250/50 mcg BID n=331 Participants Fluticasone propionate/salmeterol (F/SC) 250/50 mcg Dry Powder Inhaler (DPI) BID
Change From Baseline in Asthma Control Questionnaire (ACQ) Total Score at Week 12 Endpoint	-0.65 Scores on a scale Standard Deviation 0.61	-0.65 Scores on a scale Standard Deviation 0.61

SECONDARY outcome

Timeframe: Baseline to Week 12

For each day of the evaluation period, symptoms were collected in the morning for the night's evaluation, and in the evening for the day's evaluation. Symptoms included coughing, wheezing, and difficulty breathing, each integer-scaled from 0=none to 3=severe. A symptom-free Day/Night is defined as a combined score of 0 across the morning and evening evaluations. The proportion of 0 scores across the Baseline period, and across the 12-week treatment period, is calculated to determine the overall proportion of symptom-free Days/Nights for each of these periods.

Outcome measures

Outcome measures
Measure	MF/F MDI 200/10 mcg BID n=364 Participants Mometasone furoate 200 mcg and formoterol 10 mcg (MF/F) fixed dose combination taken twice daily (BID) via a metered-dose inhaler (MDI).	F/SC DPI 250/50 mcg BID n=349 Participants Fluticasone propionate/salmeterol (F/SC) 250/50 mcg Dry Powder Inhaler (DPI) BID
The Proportion of Symptom-free Days and Nights (Combined) Over the 12-week Treatment Period. Baseline (over the last week prior to first dose)	0.19 Proportion of symptom-free days/nights Standard Deviation 0.28	0.18 Proportion of symptom-free days/nights Standard Deviation 0.28
The Proportion of Symptom-free Days and Nights (Combined) Over the 12-week Treatment Period. Actual proportion over the 12-wk treatment period	0.42 Proportion of symptom-free days/nights Standard Deviation 0.32	0.43 Proportion of symptom-free days/nights Standard Deviation 0.32
The Proportion of Symptom-free Days and Nights (Combined) Over the 12-week Treatment Period. Change from Baseline to over the 12-wk tx period	0.24 Proportion of symptom-free days/nights Standard Deviation 0.32	0.25 Proportion of symptom-free days/nights Standard Deviation 0.32

Adverse Events

Open-label (OL) MF MDI * 200 MCG BID

Serious events: 0 serious events

Other events: 43 other events

Deaths: 0 deaths

MF/F MDI * 200/10 MCG * BID

Serious events: 6 serious events

Other events: 85 other events

Deaths: 0 deaths

F/SC DPI * 250/50 MCG BID

Serious events: 8 serious events

Other events: 77 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Open-label (OL) MF MDI * 200 MCG BID n=983 participants at risk Mometasone furoate 200 mcg taken twice daily (BID) via a metered-dose inhaler (MDI).	MF/F MDI * 200/10 MCG * BID n=371 participants at risk Mometasone furoate 200 mcg and formoterol 10 mcg (MF/F) fixed dose combination taken twice daily (BID) via a metered-dose inhaler (MDI).	F/SC DPI * 250/50 MCG BID n=351 participants at risk Fluticasone propionate/salmeterol (F/SC) 250/50 mcg Dry Powder Inhaler (DPI) BID
Infections and infestations Nasopharyngitis	0.51% 5/983 • Number of events 5 This study included a 2 to 4-week open-label (OL) run-in period prior to randomization. The OL MF MDI 200 mcg BID group includes all screened participants who were administered at least one dose. Participants who continued to meet eligibility criteria at the completion of the OL run-in period were subsequently randomized to either MF/F or F/SC.	8.9% 33/371 • Number of events 38 This study included a 2 to 4-week open-label (OL) run-in period prior to randomization. The OL MF MDI 200 mcg BID group includes all screened participants who were administered at least one dose. Participants who continued to meet eligibility criteria at the completion of the OL run-in period were subsequently randomized to either MF/F or F/SC.	6.8% 24/351 • Number of events 27 This study included a 2 to 4-week open-label (OL) run-in period prior to randomization. The OL MF MDI 200 mcg BID group includes all screened participants who were administered at least one dose. Participants who continued to meet eligibility criteria at the completion of the OL run-in period were subsequently randomized to either MF/F or F/SC.
Infections and infestations Upper Respiratory Tract Infection	0.20% 2/983 • Number of events 2 This study included a 2 to 4-week open-label (OL) run-in period prior to randomization. The OL MF MDI 200 mcg BID group includes all screened participants who were administered at least one dose. Participants who continued to meet eligibility criteria at the completion of the OL run-in period were subsequently randomized to either MF/F or F/SC.	6.7% 25/371 • Number of events 31 This study included a 2 to 4-week open-label (OL) run-in period prior to randomization. The OL MF MDI 200 mcg BID group includes all screened participants who were administered at least one dose. Participants who continued to meet eligibility criteria at the completion of the OL run-in period were subsequently randomized to either MF/F or F/SC.	4.6% 16/351 • Number of events 20 This study included a 2 to 4-week open-label (OL) run-in period prior to randomization. The OL MF MDI 200 mcg BID group includes all screened participants who were administered at least one dose. Participants who continued to meet eligibility criteria at the completion of the OL run-in period were subsequently randomized to either MF/F or F/SC.
Nervous system disorders Headache	3.8% 37/983 • Number of events 50 This study included a 2 to 4-week open-label (OL) run-in period prior to randomization. The OL MF MDI 200 mcg BID group includes all screened participants who were administered at least one dose. Participants who continued to meet eligibility criteria at the completion of the OL run-in period were subsequently randomized to either MF/F or F/SC.	11.3% 42/371 • Number of events 109 This study included a 2 to 4-week open-label (OL) run-in period prior to randomization. The OL MF MDI 200 mcg BID group includes all screened participants who were administered at least one dose. Participants who continued to meet eligibility criteria at the completion of the OL run-in period were subsequently randomized to either MF/F or F/SC.	12.8% 45/351 • Number of events 88 This study included a 2 to 4-week open-label (OL) run-in period prior to randomization. The OL MF MDI 200 mcg BID group includes all screened participants who were administered at least one dose. Participants who continued to meet eligibility criteria at the completion of the OL run-in period were subsequently randomized to either MF/F or F/SC.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator agrees not to publish/present any interim results without prior sponsor written consent. The investigator agrees to provide to the sponsor, 45 days prior to submission, review copies for publication that report any study results. The sponsor has the right to review and comment. If the parties disagree, investigator agrees to meet with the sponsor, prior to submission for publication, to discuss and resolve any such issues/disagreement.
Publication restrictions are in place

Restriction type: OTHER