Trial Outcomes & Findings for Efficacy and Safety Evaluation of Budesonide/Formoterol SPIROMAX® Inhalation Powder Versus SYMBICORT® TURBOHALER® (NCT NCT01803555)
NCT ID: NCT01803555
Last Updated: 2023-12-08
Results Overview
PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Baseline trough morning PEF was defined as the average value of recorded (nonmissing) morning assessments 5 out of the last 7 days prior to randomization. The first day before randomization consisted of the electronic patient diary entry at home on the morning of the randomization visit (Baseline \[Day 1\]) and the first day postrandomization consisted of the electronic patient diary entry at home on the morning of the day after the randomization visit (Baseline \[Day 1\]). For postdose weekly average of trough morning PEF measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of morning PEF values divided by the number of nonmissing assessments. The final value for change from baseline was calculated as the average of the weekly change from baseline averaged over 12 weeks.
COMPLETED
PHASE3
605 participants
Baseline, Weeks 1 to 12 (averaged over 12 weeks)
2023-12-08
Participant Flow
Participant milestones
| Measure |
BF Spiromax
Participants received budesonide/formoterol Spiromax (BF)(budesonide/formoterol fumarate dihydrate 160/4.5 micrograms \[mcg\]) 2 inhalations twice daily and Symbicort placebo 2 inhalations twice daily for 12 weeks.
|
Symbicort Turbohaler
Participants received Symbicort Turbohaler (budesonide/formoterol fumarate dihydrate 200/6 mcg) 2 inhalations twice daily and placebo Spiromax 2 inhalations twice daily for 12 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
303
|
302
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
303
|
299
|
|
Overall Study
COMPLETED
|
290
|
284
|
|
Overall Study
NOT COMPLETED
|
13
|
18
|
Reasons for withdrawal
| Measure |
BF Spiromax
Participants received budesonide/formoterol Spiromax (BF)(budesonide/formoterol fumarate dihydrate 160/4.5 micrograms \[mcg\]) 2 inhalations twice daily and Symbicort placebo 2 inhalations twice daily for 12 weeks.
|
Symbicort Turbohaler
Participants received Symbicort Turbohaler (budesonide/formoterol fumarate dihydrate 200/6 mcg) 2 inhalations twice daily and placebo Spiromax 2 inhalations twice daily for 12 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
3
|
3
|
|
Overall Study
Non-compliance
|
1
|
1
|
|
Overall Study
Protocol Violation
|
3
|
5
|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
|
Overall Study
Other than specified
|
3
|
5
|
Baseline Characteristics
Efficacy and Safety Evaluation of Budesonide/Formoterol SPIROMAX® Inhalation Powder Versus SYMBICORT® TURBOHALER®
Baseline characteristics by cohort
| Measure |
BF Spiromax
n=303 Participants
Participants received budesonide/formoterol Spiromax (BF)(budesonide/formoterol fumarate dihydrate 160/4.5 micrograms \[mcg\]) 2 inhalations twice daily and Symbicort placebo 2 inhalations twice daily for 12 weeks.
|
Symbicort Turbohaler
n=302 Participants
Participants received Symbicort Turbohaler (budesonide/formoterol fumarate dihydrate 200/6 mcg) 2 inhalations twice daily and placebo Spiromax 2 inhalations twice daily for 12 weeks.
|
Total
n=605 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
48.1 years
STANDARD_DEVIATION 16.24 • n=5 Participants
|
46.9 years
STANDARD_DEVIATION 16.89 • n=7 Participants
|
47.5 years
STANDARD_DEVIATION 16.56 • n=5 Participants
|
|
Sex: Female, Male
Female
|
172 Participants
n=5 Participants
|
161 Participants
n=7 Participants
|
333 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
131 Participants
n=5 Participants
|
141 Participants
n=7 Participants
|
272 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
297 Participants
n=5 Participants
|
299 Participants
n=7 Participants
|
596 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
297 Participants
n=5 Participants
|
300 Participants
n=7 Participants
|
597 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaskan Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Weeks 1 to 12 (averaged over 12 weeks)Population: The per-protocol (PP) population included all data from randomized participants obtained before experiencing major protocol deviations (that is, protocol violations). Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Baseline trough morning PEF was defined as the average value of recorded (nonmissing) morning assessments 5 out of the last 7 days prior to randomization. The first day before randomization consisted of the electronic patient diary entry at home on the morning of the randomization visit (Baseline \[Day 1\]) and the first day postrandomization consisted of the electronic patient diary entry at home on the morning of the day after the randomization visit (Baseline \[Day 1\]). For postdose weekly average of trough morning PEF measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of morning PEF values divided by the number of nonmissing assessments. The final value for change from baseline was calculated as the average of the weekly change from baseline averaged over 12 weeks.
Outcome measures
| Measure |
BF Spiromax
n=289 Participants
Participants received budesonide/formoterol Spiromax (BF)(budesonide/formoterol fumarate dihydrate 160/4.5 micrograms \[mcg\]) 2 inhalations twice daily and Symbicort placebo 2 inhalations twice daily for 12 weeks.
|
Symbicort Turbohaler
n=284 Participants
Participants received Symbicort Turbohaler (budesonide/formoterol fumarate dihydrate 200/6 mcg) 2 inhalations twice daily and placebo Spiromax 2 inhalations twice daily for 12 weeks.
|
|---|---|---|
|
Change From Baseline in Weekly Average of Daily Trough (Predose and Pre-rescue Bronchodilator) Morning (AM) Peak Expiratory Flow (PEF) Over the 12-Week Treatment Period
|
18.839 liters (L)/minute (min)
Standard Error 2.754
|
21.796 liters (L)/minute (min)
Standard Error 2.745
|
SECONDARY outcome
Timeframe: Baseline, Weeks 1 to 12 (averaged over 12 weeks)Population: The PP population included all data from randomized participants obtained before experiencing major protocol deviations (that is, protocol violations). Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Baseline was defined as the average value of the recorded (nonmissing) assessments over the 7 days prior to randomization. For postdose weekly average of evening PEF measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of evening PEF values divided by the number of nonmissing assessments. The final value for change from baseline was calculated as the average of the weekly change from baseline averaged over 12 weeks.
Outcome measures
| Measure |
BF Spiromax
n=289 Participants
Participants received budesonide/formoterol Spiromax (BF)(budesonide/formoterol fumarate dihydrate 160/4.5 micrograms \[mcg\]) 2 inhalations twice daily and Symbicort placebo 2 inhalations twice daily for 12 weeks.
|
Symbicort Turbohaler
n=284 Participants
Participants received Symbicort Turbohaler (budesonide/formoterol fumarate dihydrate 200/6 mcg) 2 inhalations twice daily and placebo Spiromax 2 inhalations twice daily for 12 weeks.
|
|---|---|---|
|
Change From Baseline in Weekly Average of Daily Evening (PM) PEF Over the 12-Week Treatment Period
|
18.661 L/min
Standard Error 2.631
|
21.740 L/min
Standard Error 2.622
|
SECONDARY outcome
Timeframe: Baseline up to Week 12Population: The safety population included all randomized participants who received at least 1 dose of study medication.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
Outcome measures
| Measure |
BF Spiromax
n=303 Participants
Participants received budesonide/formoterol Spiromax (BF)(budesonide/formoterol fumarate dihydrate 160/4.5 micrograms \[mcg\]) 2 inhalations twice daily and Symbicort placebo 2 inhalations twice daily for 12 weeks.
|
Symbicort Turbohaler
n=299 Participants
Participants received Symbicort Turbohaler (budesonide/formoterol fumarate dihydrate 200/6 mcg) 2 inhalations twice daily and placebo Spiromax 2 inhalations twice daily for 12 weeks.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
|
117 Participants
|
106 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12Population: The safety population included all randomized participants who received at least 1 dose of study medication.
Examinations were performed by a qualified professional.
Outcome measures
| Measure |
BF Spiromax
n=303 Participants
Participants received budesonide/formoterol Spiromax (BF)(budesonide/formoterol fumarate dihydrate 160/4.5 micrograms \[mcg\]) 2 inhalations twice daily and Symbicort placebo 2 inhalations twice daily for 12 weeks.
|
Symbicort Turbohaler
n=299 Participants
Participants received Symbicort Turbohaler (budesonide/formoterol fumarate dihydrate 200/6 mcg) 2 inhalations twice daily and placebo Spiromax 2 inhalations twice daily for 12 weeks.
|
|---|---|---|
|
Number of Participants With Signs of Oral Candidiasis (Thrush)
Baseline
|
0 Participants
|
0 Participants
|
|
Number of Participants With Signs of Oral Candidiasis (Thrush)
Week 4
|
1 Participants
|
0 Participants
|
|
Number of Participants With Signs of Oral Candidiasis (Thrush)
Week 8
|
1 Participants
|
2 Participants
|
|
Number of Participants With Signs of Oral Candidiasis (Thrush)
Week 12
|
2 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8, Week 12Population: The safety population included all randomized participants who received at least 1 dose of study medication.
Swab samples were collected by a qualified professional.
Outcome measures
| Measure |
BF Spiromax
n=303 Participants
Participants received budesonide/formoterol Spiromax (BF)(budesonide/formoterol fumarate dihydrate 160/4.5 micrograms \[mcg\]) 2 inhalations twice daily and Symbicort placebo 2 inhalations twice daily for 12 weeks.
|
Symbicort Turbohaler
n=299 Participants
Participants received Symbicort Turbohaler (budesonide/formoterol fumarate dihydrate 200/6 mcg) 2 inhalations twice daily and placebo Spiromax 2 inhalations twice daily for 12 weeks.
|
|---|---|---|
|
Number of Participants With Positive Swab of Oral Candidiasis (Thrush)
Week 12
|
1 Participants
|
1 Participants
|
|
Number of Participants With Positive Swab of Oral Candidiasis (Thrush)
Baseline
|
1 Participants
|
0 Participants
|
|
Number of Participants With Positive Swab of Oral Candidiasis (Thrush)
Week 4
|
0 Participants
|
0 Participants
|
|
Number of Participants With Positive Swab of Oral Candidiasis (Thrush)
Week 8
|
0 Participants
|
0 Participants
|
Adverse Events
BF Spiromax
Symbicort Turbohaler
Serious adverse events
| Measure |
BF Spiromax
n=303 participants at risk
Participants received budesonide/formoterol Spiromax (BF)(budesonide/formoterol fumarate dihydrate 160/4.5 micrograms \[mcg\]) 2 inhalations twice daily and Symbicort placebo 2 inhalations twice daily for 12 weeks.
|
Symbicort Turbohaler
n=299 participants at risk
Participants received Symbicort Turbohaler (budesonide/formoterol fumarate dihydrate 200/6 mcg) 2 inhalations twice daily and placebo Spiromax 2 inhalations twice daily for 12 weeks.
|
|---|---|---|
|
Cardiac disorders
Bradycardia
|
0.00%
0/303 • Baseline up to Week 12
The safety population included all randomized participants who received at least 1 dose of study medication.
|
0.33%
1/299 • Number of events 1 • Baseline up to Week 12
The safety population included all randomized participants who received at least 1 dose of study medication.
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/303 • Baseline up to Week 12
The safety population included all randomized participants who received at least 1 dose of study medication.
|
0.33%
1/299 • Number of events 1 • Baseline up to Week 12
The safety population included all randomized participants who received at least 1 dose of study medication.
|
|
Infections and infestations
Pneumonia
|
0.33%
1/303 • Number of events 1 • Baseline up to Week 12
The safety population included all randomized participants who received at least 1 dose of study medication.
|
0.00%
0/299 • Baseline up to Week 12
The safety population included all randomized participants who received at least 1 dose of study medication.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/303 • Baseline up to Week 12
The safety population included all randomized participants who received at least 1 dose of study medication.
|
0.33%
1/299 • Number of events 1 • Baseline up to Week 12
The safety population included all randomized participants who received at least 1 dose of study medication.
|
Other adverse events
| Measure |
BF Spiromax
n=303 participants at risk
Participants received budesonide/formoterol Spiromax (BF)(budesonide/formoterol fumarate dihydrate 160/4.5 micrograms \[mcg\]) 2 inhalations twice daily and Symbicort placebo 2 inhalations twice daily for 12 weeks.
|
Symbicort Turbohaler
n=299 participants at risk
Participants received Symbicort Turbohaler (budesonide/formoterol fumarate dihydrate 200/6 mcg) 2 inhalations twice daily and placebo Spiromax 2 inhalations twice daily for 12 weeks.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
10.2%
31/303 • Number of events 36 • Baseline up to Week 12
The safety population included all randomized participants who received at least 1 dose of study medication.
|
8.4%
25/299 • Number of events 27 • Baseline up to Week 12
The safety population included all randomized participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Headache
|
5.9%
18/303 • Number of events 31 • Baseline up to Week 12
The safety population included all randomized participants who received at least 1 dose of study medication.
|
8.0%
24/299 • Number of events 57 • Baseline up to Week 12
The safety population included all randomized participants who received at least 1 dose of study medication.
|
Additional Information
Director, Clinical Research
Teva Branded Pharmaceutical Products R&D, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
- Publication restrictions are in place
Restriction type: OTHER