Asthma
Conditions
Brief summary
This study is a placebo-controlled study with 8-weeks of double-blind treatment of mometasone furoate dry powder inhaler (MF DPI) 200 mcg twice daily (BID) using two different inhalers, preceded by the Screening Period and by 2 weeks of open-label treatment with one inhalation of MF DPI 200 mcg twice daily in corticosteroid-dependent asthmatic subjects. The objective of this study is to evaluate the therapeutic equivalency of the 100 mcg and 200 mcg MF DPIs when providing the same total daily dose (400 mcg/day).
Interventions
DRUGPlacebo
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
18 years of age, either sex, any race, with a diagnosis of asthma of at least 12 months' duration. * Must be on a stable regimen of a medium daily dose of ICS for at least 4 weeks immediately prior to Screening. Medium daily doses of ICS are: * \>500 to 1000 mcg beclomethasone CFC * \>250 to 500 mcg beclomethasone HFA * \>600 to 1000 mcg budesonide DPI * \>1000 to 2000 mcg flunisolide * \>250 to 500 mcg fluticasone * 400 mcg MF * \>1000 to 2000 mcg triamcinolone acetonide. * Must have a documented reversibility test obtained within 12 months prior to signing the informed consent form. Otherwise, to document a diagnosis of asthma and ensure the subject's responsiveness to bronchodilators, one of the following methods can be used at the Screening Visit, or thereafter, but prior to the Baseline Visit: * An increase in absolute FEV1 of \>=12% and \>=200 mL within 30 minutes of administration of 4 puffs of albuterol. * A PEF variability of \>20%, expressed as a percent of the best and lowest morning pre-bronchodilator PEF over at least 1 week. * A diurnal variation in PEF of \>20% based on the difference between the pre-bronchodilator AM value and the post-bronchodilator value from the evening before, expressed as a percentage of the mean daily PEF value any day during the Run-in Period. * At Screening and Baseline, the subject's FEV1 must be \>=60% predicted, when all restricted medications have been withheld for the appropriate intervals. If, based on the clinical judgment of the investigator, there is no harm in changing the subject's asthma therapy, subjects on LABAs must be willing to discontinue the LABA and be transferred to open-label treatment with MF MDI 200 mcg BID for 2 weeks prior to randomization. * Clinical laboratory tests conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor before the subject is instructed to start using open-label MF DPI run-in medication. A chest x-ray performed at the Screening Visit or any type of chest imaging within 12 months prior to the Screening Visit must be clinically acceptable to the investigator. * A female of childbearing potential must be using a medically acceptable, adequate form of birth control. This includes: 1) hormonal contraceptives as prescribed by a physician (oral combined, hormonal implant); 2) medically prescribed IUD; 3) condom in combination with a spermicide (double-barrier method); 4) monogamous relationship with a male partner who has had a vasectomy. The subject must have started this birth control method at least 3 months prior to Screening (with the exception of condom in combination with spermicide), and must agree to continue its use for the duration of the study. A subject of childbearing potential who is not currently sexually active must agree and consent to using a medically acceptable method should she become sexually active during the course of this study. Women who have been surgically sterilized or are at least 1 year postmenopausal are not considered to be of childbearing potential. A subject of childbearing potential must have a negative serum pregnancy test at Screening.
Exclusion criteria
* A change in absolute FEV1 of \>20% at any time from the Screening Visit up to and including the Baseline Visit. * A clinical asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization, or treatment with additional, excluded asthma medication at any time from the Screening Visit up to and including the Baseline Visit). * Treatment in the emergency department or admission to the hospital for an asthma exacerbation 12 months prior to Screening. * An upper or lower respiratory tract infection within the 4 weeks of to Screening. Visits can be rescheduled to meet this requirement. * Evidence of clinically significant oropharyngeal candidiasis at Baseline with or without treatment. If there is evidence of oropharyngeal candidiasis at Screening and/or during the MF DPI Run-in Period, the subject may be treated as appropriate and the Baseline Visit can be scheduled upon resolution. If there is evidence of oropharyngeal candidiasis at the Baseline Visit, the subject may be treated as appropriate and the visit can be rescheduled upon resolution. * A smoker or ex-smoker and has smoked within the previous year or has had a cumulative smoking history \>10 pack-years. * Requires more than twelve inhalations of albuterol or more than 2 treatments with nebulized beta-agonists on any 2 consecutive days during the Run-in Period. * Ever required mechanical ventilation secondary to an asthma exacerbation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Average AM Peak Expiratory Flow (PEF) Over the 7 Days of Week 8. | Baseline and Week 8 End | Week 8 End = The last 7 days of data with the last day within the range of Days 51 to 64. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MF DPI 2 x 100 mcg BID 2 inhalations of mometasone furoate dry powder inhaler (MF DPI) 100 mcg plus 1 inhalation of placebo matching MF DPI 200 mcg twice daily (BID) for 8 weeks | 268 |
| MF DPI 1 x 200 mcg BID 1 inhalation of MF DPI 200 mcg plus 2 inhalations of placebo matching MF DPI 100 mcg twice daily for 8 weeks | 268 |
| Placebo BID 2 inhalations of placebo matching MF DPI 100 mcg plus 1 inhalation of placebo matching MF DPI 200 mcg twice daily for 8 weeks | 136 |
| Total | 672 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 7 | 6 |
| Overall Study | Did not meet protocol eligibility | 2 | 2 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 | 2 |
| Overall Study | Protocol Violation | 2 | 4 | 2 |
| Overall Study | Treatment Failure | 8 | 9 | 22 |
| Overall Study | Withdrawal by Subject | 3 | 5 | 1 |
| Overall Study | Withdrawal by subject treatment related | 3 | 1 | 2 |
Baseline characteristics
| Characteristic | MF DPI 2 x 100 mcg BID | MF DPI 1 x 200 mcg BID | Placebo BID | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 13 Participants | 5 Participants | 27 Participants |
| Age, Categorical Between 18 and 65 years | 259 Participants | 255 Participants | 131 Participants | 645 Participants |
| Sex: Female, Male Female | 182 Participants | 178 Participants | 104 Participants | 464 Participants |
| Sex: Female, Male Male | 86 Participants | 90 Participants | 32 Participants | 208 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 950 | 19 / 268 | 30 / 268 | 16 / 135 |
| serious Total, serious adverse events | 1 / 950 | 3 / 268 | 2 / 268 | 2 / 135 |
Outcome results
Primary
Change From Baseline in the Average AM Peak Expiratory Flow (PEF) Over the 7 Days of Week 8.
Week 8 End = The last 7 days of data with the last day within the range of Days 51 to 64.
Time frame: Baseline and Week 8 End
Population: All treated subjects included all but one placebo-treated subject from the All Randomized Subjects data set, who was randomized, but never treated in either the open-label or double-blind Treatment Periods due to non-compliance with the protocol
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MF DPI 2 x 100 mcg BID | Change From Baseline in the Average AM Peak Expiratory Flow (PEF) Over the 7 Days of Week 8. | Baseline | 361.8 liters/minute | Standard Deviation 96.7 |
| MF DPI 2 x 100 mcg BID | Change From Baseline in the Average AM Peak Expiratory Flow (PEF) Over the 7 Days of Week 8. | Week 8 End | 6.03 liters/minute | Standard Deviation 37 |
| MF DPI 1 x 200 mcg BID | Change From Baseline in the Average AM Peak Expiratory Flow (PEF) Over the 7 Days of Week 8. | Baseline | 374.3 liters/minute | Standard Deviation 96.7 |
| MF DPI 1 x 200 mcg BID | Change From Baseline in the Average AM Peak Expiratory Flow (PEF) Over the 7 Days of Week 8. | Week 8 End | 7.65 liters/minute | Standard Deviation 37 |
| Placebo BID | Change From Baseline in the Average AM Peak Expiratory Flow (PEF) Over the 7 Days of Week 8. | Baseline | 348.4 liters/minute | Standard Deviation 96.7 |
| Placebo BID | Change From Baseline in the Average AM Peak Expiratory Flow (PEF) Over the 7 Days of Week 8. | Week 8 End | -7.93 liters/minute | Standard Deviation 37 |
Comparison: Week 8 End scoresp-value: 0.65495% CI: [-8.74, 5.49]ANOVA
Comparison: Week 8 End scoresp-value: 0.003ANOVA
Comparison: Week 8 End scoresp-value: 0.001ANOVA