Asthma
Conditions
Brief summary
The purpose of this study is to evaluate the long-term safety of mometasone furoate/formoterol (MF/F) metered dose inhaler (MDI) 200/10 mcg twice-a-day (BID) and MF/F MDI 400/10 mcg BID and two doses of fluticasone/salmeterol combination (F/SC) (250/50 mcg BID and 500/50 mcg BID) in subjects with persistent asthma who require maintenance treatment on inhaled glucocorticosteroids (ICS); evaluator-blind. In addition, the extrapulmonary effects on 24-hour plasma cortisol area under curve (AUC), of MF/F MDI 200/10 mcg BID, MF/F MDI 400/10 mcg BID, F/SC MDI 250/50 mcg BID, and F/SC MDI 500/50 mcg BID will be evaluated.
Interventions
DRUGmometasone furoate combination MDI 200/10 mcg BID
MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 1 year
DRUGmometasone furoate combination MDI 400/10 mcg BID
MF/F 400/10 mcg via a metered dose inhaler (MDI) twice daily for 1 year
DRUGFluticasone/Salmeterol 250/50 mcg BID
F/SC 250/50 twice daily for 1 year
DRUGFluticasone/Salmeterol 500/50 mcg BID
F/SC 500/50 twice daily for 1 year
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects of either sex and any race, at least 12 years of age, with a diagnosis of asthma of at least 12 months. * Use of medium or high daily dose of ICS (alone or in combination with long-acting beta-agonist \[LABA\]) for at least 12 weeks prior to Screening and have been on a stable regimen for at least 2 weeks prior to Screening. * Medium daily doses of ICS: * \> 500 to 1000 mcg beclomethasone chlorofluorocarbon (CFC) * \> 250 to 500 mcg beclomethasone hydrofluoroalkane (HFA) * \> 600 to 1000 mcg budesonide dry powder inhaler (DPI) * \> 1000 to 2000 mcg flunisolide * \> 250 to 500 mcg fluticasone * 400 mcg MF * \> 1000 to 2000 mcg triamcinolone acetonide * High daily doses of ICS: * \> 1000 mcg beclomethasone CFC * \> 500 mcg beclomethasone HFA * \> 1000 mcg budesonide DPI * \> 2000 mcg flunisolide * \> 500 mcg fluticasone * \> 400 mcg MF * \> 2000 mcg triamcinolone acetonide * If there is no inherent harm in changing the subject's current asthma therapy, the subject must discontinue prescribed ICS or ICS/LABA combination at Baseline. * Must show evidence of reversibility within the last 12 months or during the Screening Period. Historical reversibility defined as an increase in absolute forced expiratory volume in 1 second (FEV1) of \>= 12% and \>= 200 mL will qualify if performed within 12 months of Screening. If no historical reversibility, subject must demonstrate an absolute FEV1 of \>= 12% and \>= 200 mL within 10 to 15 minutes after four puffs of salbutamol at Visit 1 or anytime prior to Baseline. * At Screening and Baseline, FEV1 must be \>= 50% predicted, when restricted medications are withheld for the appropriate intervals. * Complete blood count, blood chemistries, urinalysis, and electrocardiogram (ECG) conducted at Screening must be within normal limits or clinically acceptable to the investigator/sponsor. A chest x-ray performed at Screening or within 12 months prior must be clinically acceptable. * A female of childbearing potential must be using a medically acceptable, adequate form of birth control: * prescribed hormonal contraceptives; * medically prescribed intrauterine device (IUD); * medically prescribed transdermal contraceptive; * condom in combination with spermicide; * monogamous relationship with a male partner who has had a vasectomy. Birth control must have started at least 3 months prior to Screening. Subject 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 to use a medically acceptable method should she become sexually active during the 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. Key
Exclusion criteria
* A change (increase or decrease) in absolute FEV1 of \> 20% at any time from the Screening Visit up to, and including, the Baseline Visit. * A subject who requires the use of \> 12 inhalations per day of short-acting beta-agonist (SABA) MDI or \> 2 nebulized treatments per day of 2.5 mg salbutamol, on any 2 consecutive days from the Screening Visit up to, and including, the Baseline Visit. * A subject who experiences a clinical asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication \[other than SABA\]) at any time from the Screening Visit up to, and including, the Baseline Visit. * A subject who has ever required ventilator support for respiratory failure secondary to asthma. * A subject who is a smoker or ex-smoker and has smoked within the previous year or has had a cumulative smoking history \> 10 pack-years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of All Randomized Subjects Reporting Adverse Events (AEs). | 1 year | AEs that are considered Related, Severe, and Serious, as determined by the investigator and using specific criteria defined in the protocol, are included in the primary results. |
Participant flow
Pre-assignment details
Subjects starting study are those subjects who completed screening procedures and randomized.
Participants by arm
| Arm | Count |
|---|---|
| MF/F 200/10 mcg BID MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 1 year | 141 |
| MF/F 400/10 mcg BID MF/F 400/10 mcg via a metered dose inhaler (MDI) twice daily for 1 year | 130 |
| F/SC 250/50 mcg BID F/SC 250/50 twice daily for 1 year | 68 |
| F/SC 500/50 mcg BID F/SC 500/50 twice daily for 1 year | 65 |
| Total | 404 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative | 2 | 2 | 0 | 1 |
| Overall Study | Adverse Event | 5 | 6 | 2 | 0 |
| Overall Study | Did not meet protocol eligibility | 0 | 1 | 0 | 2 |
| Overall Study | Lost to Follow-up | 3 | 3 | 2 | 0 |
| Overall Study | Noncompliance with protocol | 8 | 6 | 2 | 1 |
| Overall Study | Subject withdrew-related to study drug | 1 | 0 | 0 | 1 |
| Overall Study | Subject withdrew-unrelated to study drug | 0 | 3 | 4 | 2 |
| Overall Study | Treatment Failure | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | MF/F 200/10 mcg BID | MF/F 400/10 mcg BID | F/SC 250/50 mcg BID | F/SC 500/50 mcg BID | Total |
|---|---|---|---|---|---|
| Age, Continuous | 32.7 years STANDARD_DEVIATION 15.2 | 39.3 years STANDARD_DEVIATION 14.5 | 32.4 years STANDARD_DEVIATION 14.9 | 37.1 years STANDARD_DEVIATION 15 | 35.5 years STANDARD_DEVIATION 15.2 |
| Sex: Female, Male Female | 92 Participants | 86 Participants | 38 Participants | 40 Participants | 256 Participants |
| Sex: Female, Male Male | 49 Participants | 44 Participants | 30 Participants | 25 Participants | 148 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 | 93 / 141 | 82 / 130 | 51 / 68 | 41 / 65 |
| serious Total, serious adverse events | 7 / 141 | 8 / 130 | 4 / 68 | 2 / 65 |
Outcome results
Primary
The Number of All Randomized Subjects Reporting Adverse Events (AEs).
AEs that are considered Related, Severe, and Serious, as determined by the investigator and using specific criteria defined in the protocol, are included in the primary results.
Time frame: 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MF/F 200/10 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Treatment-Emergent Adverse Events (TEAE) | 109 participants |
| MF/F 200/10 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Related Adverse Events | 40 participants |
| MF/F 200/10 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Severe Adverse Events | 8 participants |
| MF/F 200/10 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Serious Adverse Events | 7 participants |
| MF/F 400/10 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Related Adverse Events | 30 participants |
| MF/F 400/10 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Severe Adverse Events | 5 participants |
| MF/F 400/10 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Serious Adverse Events | 8 participants |
| MF/F 400/10 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Treatment-Emergent Adverse Events (TEAE) | 103 participants |
| F/SC 250/50 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Severe Adverse Events | 4 participants |
| F/SC 250/50 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Related Adverse Events | 16 participants |
| F/SC 250/50 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Serious Adverse Events | 4 participants |
| F/SC 250/50 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Treatment-Emergent Adverse Events (TEAE) | 56 participants |
| F/SC 500/50 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Serious Adverse Events | 2 participants |
| F/SC 500/50 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Related Adverse Events | 13 participants |
| F/SC 500/50 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Treatment-Emergent Adverse Events (TEAE) | 50 participants |
| F/SC 500/50 mcg BID | The Number of All Randomized Subjects Reporting Adverse Events (AEs). | Severe Adverse Events | 4 participants |