Time-to-First Serious Asthma Outcomes (SAO): Number of First SAO in the MF/F vs MF Arms
The primary safety outcome was the time-to-first SAO (a composite endpoint of adjudicated asthma-related hospitalizations, adjudicated asthma-related intubations, and adjudicated asthma-related deaths). To accomplish this, the number of participants experiencing a first SAO was collected for 26 weeks following initiation of study treatment (or 7 days after the last treatment dose, whichever occurred later). Data generated by this methodology were used to compute a hazard ratio (HR) and 95% confidence interval (CI), modeling the likelihood of a first SAO occurring at any given time in the MF/F arm relative to the MF arm. Although data were sufficient to generate a HR and 95% CI, time-to-first SAO in the overall population could not be accurately reported due to insufficient SAO occurrence. Therefore, the number of first SAO in either arm is reported as a descriptive measure. For each participant, first SAO denotes first event per participant. (NCT01471340)
Timeframe: 26 weeks, or 7 days after the last treatment dose, whichever occurred later
| Intervention | Serious asthma outcomes (Number) |
|---|
| MF/F MDI BID | 39 |
| MF MDI BID | 32 |
Time-to-First Severe Asthma Exacerbation (SAEX): Number of First SAEX in the MF/F vs MF Arms
The key secondary efficacy outcome was time-to-first protocol-defined asthma exacerbation (SAEX). The SAEX were deteriorations of asthma requiring: use of systemic corticosteroids (tablets, suspension, or injection) for >= 3 consecutive days, in-patient hospitalization >= 24 hours, or an emergency department (ED) visit < 24 hours that required systemic corticosteroids in the MF/F MDI BID arm versus the MF MDI BID arm. The number of first SAEX occurred from initiation of study treatment to 7 days after the last treatment (modified intention-to-treat). This outcome was measured as the HR and 95% CI for the number of first SAEX in the MF/F MDI BID arm versus the number of first SAEX in the MF MDI BID arm. Given insufficient data for SAEX events, it was not informative to report the time-to-first SAEX in the overall population. Therefore, the number of first SAEXs in either arm is reported as a descriptive measure. For each participant, first SAEX denotes first event per participant. (NCT01471340)
Timeframe: 26 weeks, plus 7 days after the last treatment
| Intervention | Asthma exacerbations (Number) |
|---|
| MF/F MDI BID | 708 |
| MF MDI BID | 779 |
Number of SAO Components in MF/F Participants vs MF Participants
To further examine the primary safety outcome, each adjudicated component of the SAO composite endpoint (asthma-related hospitalization, asthma-related intubation and asthma-related death), was tabulated for descriptive purposes only to show the relative contribution of each component to the SAO composite. Hospitalizations were defined as an in-patient stay of >= 24 hour in a hospital, emergency department or equivalent healthcare facility. Intubation was defined as endotracheal intubation only. (NCT01471340)
Timeframe: 26 weeks, or 7 days after the last treatment dose, whichever occurred later
| Intervention | SAO components (Number) |
|---|
| First SAO | Asthma-related hospitalizations | Asthma-related intubations | Asthma-related deaths |
|---|
| MF MDI BID | 32 | 32 | 0 | 0 |
,| MF/F MDI BID | 39 | 39 | 0 | 0 |
Number of Participants Who Discontinued From the Study Due to an AE
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. (NCT01566149)
Timeframe: Up to Week 12
| Intervention | participants (Number) |
|---|
| MF/F 200/10 mcg MDI BID | 0 |
| MF/F 400/10 mcg MDI BID | 1 |
Number of Participants With At Least One Adverse Event (AE)
An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. (NCT01566149)
Timeframe: Up to Week 14
| Intervention | participants (Number) |
|---|
| MF/F 200/10 mcg MDI BID | 5 |
| MF/F 400/10 mcg MDI BID | 8 |
Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12
Baseline was defined as the highest FEV1 value of three assessments prior to first dose of study drug. If two (or all three) spirometry efforts had identical FEV1, the FEV1 from the effort with the highest Forced Vital Capacity (FVC) was to be recorded. Week 12 FEV1 was assessed as the morning FEV1 at the end of the dosing interval (trough FEV1). For participants who discontinued prior to Week 12, the FEV1 measurement from the discontinuation visit was to be be carried forward to Week 12 if (and only if) the participant's study medication compliance rate prior to discontinuation was at least 85%. (NCT01566149)
Timeframe: Baseline and Week 12
| Intervention | liters (Mean) |
|---|
| Baseline FEV1 | Week 12 FEV1 | Change from Baseline in FEV1 at Week 12 |
|---|
| MF/F 200/10 mcg MDI BID | 2.397 | 2.503 | 0.106 |
,| MF/F 400/10 mcg MDI BID | 2.215 | 2.270 | 0.054 |