Asthma
Conditions
Keywords
Budesonide/Formoterol SPIROMAX®, SYMBICORT® TURBOHALER®, Asthma
Brief summary
The primary objective of the study is to establish whether budesonide/formoterol fumarate dihydrate (BF) Spiromax 160/4.5 micrograms (mcg) is as effective as Symbicort Turbohaler 200/6 mcg administered twice daily in participants with persistent asthma.
Interventions
DRUGBudesonide/Formoterol SPIROMAX®
BF Spiromax will be administered per dose and schedule specified in the arm.
Symbicort Turbohaler will be administered per dose and schedule specified in the arm.
DRUGSYMBICORT placebo
SYMBICORT placebo multi-dose dry powder inhaler (DPI) identical in appearance to SYMBICORT TURBOHALER will be administered per dose and schedule specified in the arm.
DRUGSPIROMAX Placebo
SPIROMAX Placebo multi-dose dry powder inhaler (DPI) identical in appearance to BF SPIROMAX will be administered per dose and schedule specified in the arm.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participants 12 years and older as of the screening visit. Male or female participants 18 years and older, as of the screening visit, in countries where local regulations or the regulatory status of study medication permit enrollment of adult participants only. * General good health, and free of any concomitant conditions or treatment that could interfere with study conduct, influence the interpretation of study observations/results, or put the participant at increased risk during the study. * Asthma Diagnosis: The asthma diagnosis must be in accordance with the Global Initiative for Asthma (GINA)
Exclusion criteria
* History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures. * Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that is not resolved within 2 weeks before the screening visit. In addition, the participant must be excluded if such infection occurs between the screening visit and the baseline visit. * Any asthma exacerbation requiring oral corticosteroids within 1 month of the screening visit. A participant must not have been hospitalized for asthma within 6 months before the screening visit. * Presence of glaucoma, cataracts, ocular herpes simplex, or malignancy other than basal cell carcinoma. * Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular conditions (for example, congestive heart failure, known aortic aneurysm, clinically significant cardiac arrhythmia or coronary heart disease), hepatic, renal, hematological, neuropsychological, endocrine conditions (for example, uncontrolled diabetes mellitus, uncontrolled thyroid disorder, Addison's disease, Cushing's syndrome), gastrointestinal conditions (for example, poorly-controlled peptic ulcer, gastroesophageal reflux disease \[GERD\]), or pulmonary conditions (for example, chronic bronchitis, emphysema, bronchiectasis with the need for treatment, cystic fibrosis, bronchopulmonary dysplasia, chronic obstructive pulmonary disease). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the participant at risk through participation, or which could affect the efficacy or safety analysis if the disease/condition became exacerbated during the study. NOTE: Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline, Weeks 1 to 12 (averaged over 12 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Average of Daily Evening (PM) PEF Over the 12-Week Treatment Period | Baseline, Weeks 1 to 12 (averaged over 12 weeks) | 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. |
| Number of Participants With Adverse Events (AEs) | Baseline up to Week 12 | 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'. |
| Number of Participants With Signs of Oral Candidiasis (Thrush) | Baseline, Week 4, Week 8, Week 12 | Examinations were performed by a qualified professional. |
| Number of Participants With Positive Swab of Oral Candidiasis (Thrush) | Baseline, Week 4, Week 8, Week 12 | Swab samples were collected by a qualified professional. |
Countries
Austria, Belgium, Czechia, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Russia, Spain, Sweden, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 303 |
| 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. | 302 |
| Total | 605 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Non-compliance | 1 | 1 |
| Overall Study | Other than specified | 3 | 5 |
| Overall Study | Protocol Violation | 3 | 5 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Total | BF Spiromax | Symbicort Turbohaler |
|---|---|---|---|
| Age, Continuous | 47.5 years STANDARD_DEVIATION 16.56 | 48.1 years STANDARD_DEVIATION 16.24 | 46.9 years STANDARD_DEVIATION 16.89 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 596 Participants | 297 Participants | 299 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 3 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 597 Participants | 297 Participants | 300 Participants |
| Sex: Female, Male Female | 333 Participants | 172 Participants | 161 Participants |
| Sex: Female, Male Male | 272 Participants | 131 Participants | 141 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 303 | 0 / 299 |
| other Total, other adverse events | 47 / 303 | 44 / 299 |
| serious Total, serious adverse events | 1 / 303 | 3 / 299 |
Outcome results
Primary
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
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BF Spiromax | 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 |
| Symbicort Turbohaler | 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 | 21.796 liters (L)/minute (min) | Standard Error 2.745 |
p-value: 0.338795% CI: [-9.02, 3.11]Mixed Models Analysis
Secondary
Change From Baseline in Weekly Average of Daily Evening (PM) PEF Over the 12-Week Treatment Period
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BF Spiromax | 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 |
| Symbicort Turbohaler | Change From Baseline in Weekly Average of Daily Evening (PM) PEF Over the 12-Week Treatment Period | 21.740 L/min | Standard Error 2.622 |
Secondary
Number of Participants With Adverse Events (AEs)
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'.
Time frame: Baseline up to Week 12
Population: The safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BF Spiromax | Number of Participants With Adverse Events (AEs) | 117 Participants |
| Symbicort Turbohaler | Number of Participants With Adverse Events (AEs) | 106 Participants |
Secondary
Number of Participants With Positive Swab of Oral Candidiasis (Thrush)
Swab samples were collected by a qualified professional.
Time frame: Baseline, Week 4, Week 8, Week 12
Population: The safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BF Spiromax | Number of Participants With Positive Swab of Oral Candidiasis (Thrush) | Week 8 | 0 Participants |
| BF Spiromax | Number of Participants With Positive Swab of Oral Candidiasis (Thrush) | Baseline | 1 Participants |
| BF Spiromax | Number of Participants With Positive Swab of Oral Candidiasis (Thrush) | Week 12 | 1 Participants |
| BF Spiromax | Number of Participants With Positive Swab of Oral Candidiasis (Thrush) | Week 4 | 0 Participants |
| Symbicort Turbohaler | Number of Participants With Positive Swab of Oral Candidiasis (Thrush) | Week 12 | 1 Participants |
| Symbicort Turbohaler | Number of Participants With Positive Swab of Oral Candidiasis (Thrush) | Week 4 | 0 Participants |
| Symbicort Turbohaler | Number of Participants With Positive Swab of Oral Candidiasis (Thrush) | Week 8 | 0 Participants |
| Symbicort Turbohaler | Number of Participants With Positive Swab of Oral Candidiasis (Thrush) | Baseline | 0 Participants |
Secondary
Number of Participants With Signs of Oral Candidiasis (Thrush)
Examinations were performed by a qualified professional.
Time frame: Baseline, Week 4, Week 8, Week 12
Population: The safety population included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BF Spiromax | Number of Participants With Signs of Oral Candidiasis (Thrush) | Baseline | 0 Participants |
| BF Spiromax | Number of Participants With Signs of Oral Candidiasis (Thrush) | Week 4 | 1 Participants |
| BF Spiromax | Number of Participants With Signs of Oral Candidiasis (Thrush) | Week 8 | 1 Participants |
| BF Spiromax | Number of Participants With Signs of Oral Candidiasis (Thrush) | Week 12 | 2 Participants |
| Symbicort Turbohaler | Number of Participants With Signs of Oral Candidiasis (Thrush) | Week 12 | 3 Participants |
| Symbicort Turbohaler | Number of Participants With Signs of Oral Candidiasis (Thrush) | Baseline | 0 Participants |
| Symbicort Turbohaler | Number of Participants With Signs of Oral Candidiasis (Thrush) | Week 8 | 2 Participants |
| Symbicort Turbohaler | Number of Participants With Signs of Oral Candidiasis (Thrush) | Week 4 | 0 Participants |