Trial Outcomes & Findings for Study of Safety of Foradil in Patients With Persistent Asthma (NCT NCT01845025)

NCT ID: NCT01845025

Last Updated: 2017-03-21

Results Overview

The primary safety endpoint was the number of first occurrence(s) of any composite endpoint. The composite events include asthma-related deaths, asthma-related intubations and asthma-related hospitalizations. The number of events includes all adjudication confirmed events, one patient could experience multiple events during the course of study; Event rate = 100 \* n patients with any events / total N patients in treatment group.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 827 participants
• Primary outcome timeframe: 26 weeks
• Results posted on: 2017-03-21

Participant Flow

Following the decision to stop further enrollment into the study, 1121 patients had been screened, of whom 825 were randomized. Of the 820 patients randomized and treated and part of Intent To Treat (ITT analysis) 5 patients were randomized but were excluded from the ITT analyses as they did not take study medication.

827 actual in the protocol section came from the IRT because 2 patients were randomized twice but only counted once.

Participant milestones

Measure	FOM 12 mcg + FP Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation
Overall Study STARTED	411	409
Overall Study COMPLETED	326	332
Overall Study NOT COMPLETED	85	77

Reasons for withdrawal

Measure	FOM 12 mcg + FP Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation
Overall Study Adverse Event	6	3
Overall Study Unsatisfactory therapeutic effect	4	2
Overall Study Withdrawal by Subject	48	44
Overall Study Lost to Follow-up	13	13
Overall Study Administrative problems	8	8
Overall Study Death	2	0
Overall Study Protocol deviation	3	6
Overall Study Missing	1	1

Baseline Characteristics

Study of Safety of Foradil in Patients With Persistent Asthma

Baseline characteristics by cohort

Measure	FOM 12 mcg + FP n=411 Participants Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) n=409 Participants fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation	Total n=820 Participants Total of all reporting groups
Age, Continuous	44.7 years STANDARD_DEVIATION 16.67 • n=93 Participants	45.6 years STANDARD_DEVIATION 17.02 • n=4 Participants	45.2 years STANDARD_DEVIATION 16.84 • n=27 Participants
Sex: Female, Male Female	284 Participants n=93 Participants	272 Participants n=4 Participants	556 Participants n=27 Participants
Sex: Female, Male Male	127 Participants n=93 Participants	137 Participants n=4 Participants	264 Participants n=27 Participants

PRIMARY outcome

Timeframe: 26 weeks

Population: Intent to treat (ITT) population included all randomized patients who took at least one dose (one inhalation) of study medication

The primary safety endpoint was the number of first occurrence(s) of any composite endpoint. The composite events include asthma-related deaths, asthma-related intubations and asthma-related hospitalizations. The number of events includes all adjudication confirmed events, one patient could experience multiple events during the course of study; Event rate = 100 * n patients with any events / total N patients in treatment group.

Outcome measures

Measure	FOM 12 mcg + FP n=411 Participants Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) n=409 Participants fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation
Number of First Occurrence(s) of Any Composite Endpoint Including Asthma-related Hospitalizations, Intubations and Deaths During the Study at 26 Weeks Asthma-related death	0 number of occurences	0 number of occurences
Number of First Occurrence(s) of Any Composite Endpoint Including Asthma-related Hospitalizations, Intubations and Deaths During the Study at 26 Weeks Composite event	3 number of occurences	3 number of occurences
Number of First Occurrence(s) of Any Composite Endpoint Including Asthma-related Hospitalizations, Intubations and Deaths During the Study at 26 Weeks Asthma-related intubation	0 number of occurences	0 number of occurences
Number of First Occurrence(s) of Any Composite Endpoint Including Asthma-related Hospitalizations, Intubations and Deaths During the Study at 26 Weeks Asthma-related hospitalization	3 number of occurences	3 number of occurences

SECONDARY outcome

Timeframe: 26 weeks

Population: Intent to treat (ITT) population included all randomized patients who took at least one dose (one inhalation) of study medication

Number of asthma exacerbations events

Outcome measures

Measure	FOM 12 mcg + FP n=411 Participants Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) n=409 Participants fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation
Number of Asthma Exacerbations at 26 Weeks	1.3 events Standard Deviation 0.62	1.2 events Standard Deviation 0.51

SECONDARY outcome

Timeframe: 26 weeks

Population: Intent to treat (ITT) population included all randomized patients who took at least one dose (one inhalation) of study medication

The percentage of days of school/work missed during the treatment period (26 weeks). Overall percentage of school days missed for each student patient or of work days missed is calculated by total number of days missed divided by total days of treatment.

Outcome measures

Measure	FOM 12 mcg + FP n=411 Participants Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) n=409 Participants fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation
Percentage of Days of School/Work Missed at 26 Weeks	0.97 percentage of days Standard Deviation 4.558	0.56 percentage of days Standard Deviation 1.641

SECONDARY outcome

Timeframe: 26 weeks

Population: Intent to treat (ITT) population included all randomized patients who took at least one dose (one inhalation) of study medication

The percentage of days with limited ability to perform normal daily activities during the treatment period (26 weeks). Percentage is calculated as total number of days when the patient had limited ability to perform normal daily activities divided by total days of treatment.

Outcome measures

Measure	FOM 12 mcg + FP n=411 Participants Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) n=409 Participants fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation
Percentage of Days With Limited Ability to Perform Normal Daily Activities at 26 Weeks	4.73 percentage of days Standard Deviation 12.774	4.75 percentage of days Standard Deviation 12.705

SECONDARY outcome

Timeframe: 26 weeks

Population: Intent to treat (ITT) population included all randomized patients who took at least one dose (one inhalation) of study medication

Percentage of days with nighttime awakenings during the treatment period (26 weeks)

Outcome measures

Measure	FOM 12 mcg + FP n=411 Participants Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) n=409 Participants fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation
Percentage of Days With Nighttime Awakenings at 26 Weeks	4.55 percentage of days Standard Deviation 9.577	4.20 percentage of days Standard Deviation 8.956

SECONDARY outcome

Timeframe: 26 weeks

Population: Intent to treat (ITT) population included all randomized patients who took at least one dose (one inhalation) of study medication

Percentage of rescue free days is calculated as total number of days with no rescue medication was taken divided by total days of treatment.

Outcome measures

Measure	FOM 12 mcg + FP n=411 Participants Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) n=409 Participants fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation
Percentage of Days With no Rescue Medication Use at 26 Weeks	76.97 percentage of days Standard Deviation 27.255	73.29 percentage of days Standard Deviation 30.640

SECONDARY outcome

Timeframe: 26 weeks

Population: Intent to treat (ITT) population included all randomized patients who took at least one dose (one inhalation) of study medication

Percentage of days with no symptoms during the treatment period (26 weeks). Percentage is calculated as total number of days with no symptoms divided by total days of treatment.

Outcome measures

Measure	FOM 12 mcg + FP n=411 Participants Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) n=409 Participants fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation
Percentage of Days With no Symptoms at 26 Weeks	79.47 percentage of days Standard Deviation 25.501	77.64 percentage of days Standard Deviation 28.394

SECONDARY outcome

Timeframe: baseline and 26 weeks

Population: Intent to treat (ITT) population included all randomized patients who took at least one dose (one inhalation) of study medication

Change from baseline in Asthma control Questionnaire (ACQ - 6) total score at week 26. Results of the Asthma control questionnaire (ACQ-6); The average score of the six questions is calculated as the sum of scores divided by the number of questions that were answered at the time point, as long as there were at least 4 questions answered. The ACQ6 score is calculated as the mean of the responses to the first 6 questions of the ACQ. The ACQ is a scale containing 7 questions, each question has a 7-point scale which ranges from 0 to 6; a total score of 0 corresponds to no impairment and a total score of 6 corresponds to maximum impairment.

Outcome measures

Measure	FOM 12 mcg + FP n=411 Participants Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) n=409 Participants fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation
Change From Baseline in Asthma Control Questionnaire (ACQ - 6) Total Score at Week 26	-0.65 total score on a scale Standard Deviation 1.224	-0.59 total score on a scale Standard Deviation 1.094

SECONDARY outcome

Timeframe: Week 4, Week 12, and Week 26

Population: Intent to treat (ITT) population included all randomized patients who took at least one dose (one inhalation) of study medication

Unplanned healthcare utilization by visit (Telephone contact with study doctor (MD); Telephone contact with other physician (MD) or healthcare provider (HCP); Unscheduled or unplanned visit to study doctor (including home visits); Unscheduled or unplanned visit to other physician or healthcare provider (including home visits); Emergency department or hospital visit (< 24 hours); Hospital admission or Emergency department visit (> 24 hours).

Outcome measures

Measure	FOM 12 mcg + FP n=411 Participants Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) n=409 Participants fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) Telephone contact with other MD or HCP: V3	5 unplanned visits	9 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) unplanned visit to study MD;include home:V3	7 unplanned visits	13 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) unplanned visit to other MD or HCP incl.home:V4	15 unplanned visits	16 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) Emergency or hospital visit (< 24 hours):V4	3 unplanned visits	4 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) Telephone contact with study MD: V3	19 unplanned visits	18 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) unplanned visit to other MD or HCP incl.home:V3	5 unplanned visits	9 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) Emergency or hospital visit (< 24 hours):V3	3 unplanned visits	4 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) Hospital admission or Emergency visit (>24hrs):V3	1 unplanned visits	1 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) Telephone contact with study MD: V4	25 unplanned visits	17 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) Telephone contact with other MD or HCP: V4	5 unplanned visits	7 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) unplanned visit to study MD;include home:V4	10 unplanned visits	15 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) Hospital admission or Emergency visit (>24hrs):V4	0 unplanned visits	2 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) Telephone contact with study MD: V5	14 unplanned visits	9 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) Telephone contact with other MD or HCP: V5	8 unplanned visits	2 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) unplanned visit to study MD;include home:V5	6 unplanned visits	9 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) unplanned visit to other MD or HCP incl.home:V5	10 unplanned visits	7 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) Emergency or hospital visit (< 24 hours):V5	4 unplanned visits	6 unplanned visits
Unplanned Healthcare Utilization at Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 26) Hospital admission or Emergency visit (>24hrs):V5	2 unplanned visits	0 unplanned visits

Adverse Events

FOM 12 mcg + FP

Serious events: 10 serious events

Other events: 5 other events

Deaths: 0 deaths

Fluticasone Propionate (FP)

Serious events: 9 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	FOM 12 mcg + FP n=411 participants at risk Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) n=409 participants at risk fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation
Cardiac disorders Atrial fibrillation	0.24% 1/411	0.00% 0/409
Cardiac disorders Cardiac failure congestive	0.24% 1/411	0.00% 0/409
Gastrointestinal disorders Abdominal pain	0.24% 1/411	0.00% 0/409
Gastrointestinal disorders Duodenal ulcer	0.24% 1/411	0.00% 0/409
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/411	0.24% 1/409
Infections and infestations Cellulitis	0.00% 0/411	0.24% 1/409
Infections and infestations Pneumonia	0.24% 1/411	0.24% 1/409
Infections and infestations Pneumonia bacterial	0.24% 1/411	0.00% 0/409
Infections and infestations Tracheobronchitis	0.00% 0/411	0.24% 1/409
Injury, poisoning and procedural complications Alcohol poisoning	0.00% 0/411	0.24% 1/409
Injury, poisoning and procedural complications Overdose	0.00% 0/411	0.24% 1/409
Injury, poisoning and procedural complications Road traffic accident	0.24% 1/411	0.00% 0/409
Musculoskeletal and connective tissue disorders Osteoarthritis	0.49% 2/411	0.00% 0/409
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.24% 1/411	0.00% 0/409
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/411	0.24% 1/409
Nervous system disorders Cerebrovascular accident	0.00% 0/411	0.24% 1/409
Nervous system disorders Dizziness	0.24% 1/411	0.00% 0/409
Nervous system disorders Dyskinesia	0.00% 0/411	0.24% 1/409
Nervous system disorders Presyncope	0.24% 1/411	0.00% 0/409
Psychiatric disorders Anxiety	0.00% 0/411	0.24% 1/409
Psychiatric disorders Suicide attempt	0.00% 0/411	0.24% 1/409
Renal and urinary disorders Nephrolithiasis	0.00% 0/411	0.24% 1/409
Respiratory, thoracic and mediastinal disorders Asthma	0.49% 2/411	0.49% 2/409
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/411	0.24% 1/409

Other adverse events

Measure	FOM 12 mcg + FP n=411 participants at risk Formoterol 12 mcg + fluticasone propionate 100 mcg, 250 mcg or 500 mcg for inhalation	Fluticasone Propionate (FP) n=409 participants at risk fluticasone propionate 100 mcg, 250 mcg or 500 mcg + Placebo to Match Formoterol 12 mcg for inhalation
Respiratory, thoracic and mediastinal disorders Asthma	1.2% 5/411	2.2% 9/409

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
• Publication restrictions are in place

Restriction type: OTHER