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AsthmaPhase 3NCT00381485

Effects of Mometasone Furoate/Formoterol Combination Versus Mometasone Furoate Alone in Persistent Asthmatics (Study P04431AM2)(COMPLETED)

A Phase 3 study testing Mometasone furoate/formoterol (MF/F) combination and Mometasone furoate MDI (MF MDI) in people with Asthma, run by Organon and Co.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a randomized, multicenter, double blind, parallel-group study evaluating the efficacy of mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 400/10 mcg twice daily (BID) compared with MF MDI 400 mcg BID for 12 weeks. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Asthma
What is being tested?
Mometasone furoate/formoterol (MF/F) combination and Mometasone furoate MDI (MF MDI)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
834 participants
Where
No sites listed yet
Study dates
1 Jul 2006to 1 Jan 2008
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • A subject must be at least 12 years of age, of either sex, and of any race, with a diagnosis of asthma of at least 12 months duration that is consistent with the following definition:
  • The diagnosis of asthma is based upon clinical history and examination, pulmonary function parameters, and response to beta2-agonists, according to international guidelines.
  • A subject must have been using a high dose of inhaled glucocorticosteroid (ICS) either alone or in combination with a long-acting beta2 agonist (LABA) for at least 12 weeks prior to Screening, with no use of oral glucocorticosteroids within 30 days prior to Screening. A subject must have been on a stable asthma regimen (daily dose unchanged) for at least 2 weeks prior to Screening. High daily doses of ICS are defined as follows:
  • >1000 mcg beclomethasone chlorofluorocarbon (CFC)
  • >500 mcg beclomethasone hydrofluoroalkane (HFA)
  • >1000 mcg budesonide dry powder inhaler (DPI)
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  • >2000 mcg flunisolide
  • >500 mcg fluticasone
  • >400 mcg MF
  • >2000 mcg triamcinolone acetonide
  • >320 mcg ciclesonide
  • Note: Dose delivery by method or modality other than those noted above must be equivalent.
  • A subject must have experienced at least one severe exacerbation requiring a course of oral glucocorticosteroid 2 to 12 months prior to Screening.
  • If, based upon the medical judgment of the investigator, there is no inherent harm in changing the subject's current asthma therapy, then the subject (and parent/guardian, if applicable) must be willing to discontinue his/her prescribed ICS or ICS/LABA prior to initiating MF MDI run-in medication.
  • To document the diagnosis of asthma and assure the subject's responsiveness to bronchodilators before randomization, one of the following methods can be used at the Screening Visit, Day-14, or thereafter, but prior to the Baseline Visit:
  • The subject must demonstrate an increase in absolute FEV1 of at least 12% and at least 200 mL within approximately 15 to 20 minutes after administration of four inhalations of albuterol/salbutamol (total dose of 360 to 400 mcg).
  • The subject must demonstrate a peak expiratory flow (PEF) variability of more than 20% expressed as a percent of the best and lowest morning pre-bronchodilator PEF over at least 1 week.
  • The subject must demonstrate a diurnal variation in PEF of more than 20% based on the difference between the prebronchodilator (before taking albuterol/salbutamol) morning value and the postbronchodilator value (after taking albuterol/salbutamol) from the evening before, expressed as a percentage of the mean daily PEF value. Note: If a subject is to qualify using diurnal variation, the subject should be instructed to perform his/her PEF evaluation after using his/her bronchodilator in the evening.
  • At the Screening Visit, the subject's FEV1 must be >=50% predicted when all restricted medications have been withheld for the appropriate intervals.
  • At the Baseline Visit, the subject's FEV1 must be >=50% and <=85% predicted when all restricted medications have been withheld for the appropriate intervals.
  • The subject (and parent/guardian for a subject under the age of legal consent) must be willing to give written informed consent and be able to adhere to dose and visit schedules.
  • A female subject of childbearing potential must be using a medically acceptable, adequate form of birth control. This includes:
  • hormonal contraceptive as prescribed by a physician (oral combined, hormonal vaginal ring, hormonal implant or depot-injectable);
  • medically prescribed intra-uterine device (IUD);
  • medically prescribed topically-applied transdermal contraceptive patch;
  • condom in combination with a spermicide (double-barrier method);
  • 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 female 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 female subject of childbearing potential must have a negative serum pregnancy test at Screening in order to be considered eligible for the open-label MF MDI Run-in Period.

Who cannot join

  • A subject who demonstrates a change (increase or decrease) in absolute FEV1 of >20% at any time from the Screening Visit up to and including the Baseline Visit. Pulmonary function tests (PFTs) will be performed in the morning.
  • A subject who requires the use of >8 inhalations per day of short-acting beta agonists (SABA) MDI or >=2 nebulized treatments per day of 2.5 mg SABA, on any 2 consecutive days from the Screening Visit up to and including the Baseline Visit.
  • A subject who experiences a decrease in AM or PM peak expiratory flow (PEF) below the Run-in Period stability limit on any 2 consecutive days prior to randomization.
  • 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 [including oral or other systemic corticosteroids, but allowing SABAs]), at any time from the Screening Visit up to and including the Baseline Visit.
  • A subject who has been treated in the emergency room (for a severe asthma exacerbation), or admitted to the hospital for management of airway obstruction, within the last 3 months.
  • A subject who has ever required ventilator support for respiratory failure secondary to asthma.
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  • A subject who has experienced an upper or lower respiratory tract infection (viral or bacterial) within the previous 2 weeks prior to Screening and Baseline Visits. Visits can be rescheduled 2 weeks after complete resolution of the event to re-assess eligibility.
  • 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.
  • A subject with a clinically significant abnormal vital sign.
  • A subject with evidence (upon visual inspection, laboratory culture is not required) of clinically significant oropharyngeal candidiasis at Baseline (Visit 3) with or without treatment. If there is evidence of oropharyngeal candidiasis at Screening or Pre-Baseline Visit, 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 subject with a history of clinically significant renal, hepatic, cardiovascular, metabolic, neurologic, hematologic, ophthalmologic, respiratory, gastrointestinal, cerebrovascular, or other significant medical illness or disorder which, in the judgment of the investigator, could interfere with the study, or require treatment that might interfere with the study. Specific examples include (but are not limited to) insulin-dependent diabetes, hypertension being treated with beta blockers, active hepatitis, coronary artery disease, arrhythmia, stroke, severe rheumatoid arthritis, chronic open-angle glaucoma or posterior subcapsular cataracts, acquired immune deficiency syndrome (AIDS), or conditions that may interfere with respiratory function such as clinically diagnosed chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, bronchiectasis, cystic fibrosis, etc. Other conditions that are well-controlled and stable (eg, hypertension not requiring beta blockers) will not prohibit participation if deemed appropriate per the investigator's judgment.
  • A subject who is known to be allergic to or intolerant of ICS, beta2 agonists, or any of the excipients present in the medications used in this study.
  • A female subject who is breast-feeding, pregnant, or intends to become pregnant while participating in this study.
  • A subject who is a known illicit drug user.
  • A subject who is known to be human immunodeficiency virus (HIV) positive (HIV testing will not be conducted in this study).
  • A subject who is unable to correctly use an oral MDI inhaler.
  • A subject who has been taking any of the restricted medications prior to Screening without meeting the required washout timeframes.
  • A subject who cannot adhere to the permitted concomitant medications and prohibited medications.
  • A subject participating in this study may not participate in this same study at another investigational site. In addition, a subject cannot participate in a different investigational study at any site, during the same timeframe of this study.
  • A subject must not be randomized into this study more than once.
  • No person directly associated with the administration of the study may participate as a study subject. No family member of the investigational study staff may participate in this study.
  • A subject who previously participated in a trial with MF/F.
  • Subjects with a history of significant QTC prolongation (ie, QTc>500 msec) are excluded from participation in the study.

About this study

Official title: A 12-Week Efficacy and Safety Study of Two Doses of Mometasone Furoate/Formoterol Combination Formulation Compared With Mometasone Furoate Monotherapy, in Persistent Asthmatics Previously Treated With High-Dose Inhaled Glucocorticosteroids

This is a randomized, multicenter, double blind, parallel-group study evaluating the efficacy of mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 400/10 mcg twice daily (BID) compared with MF MDI 400 mcg BID for 12 weeks. Prior to the 12-week double-blind treatment period, subjects will receive open-label MF MDI 400 mcg BID for 2 to 3 weeks during the run-in period. Efficacy will be measured by the area under the curve from 0 to 12 hours [AUC](0-12 hr) of the change from Baseline to the Week 12 Endpoint in forced expiratory volume in one second (FEV1).

Conditions
Asthma
Being tested
Mometasone furoate/formoterol (MF/F) combination, Mometasone furoate MDI (MF MDI)
Medical subject headings
Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mometasone furoate/formoterol (MF/F) combinationDrug

    Also called SCH 418131

    MF/F 400/10 mcg via a metered dose inhaler (MDI) twice daily for 12 weeks

  • Mometasone furoate/formoterol (MF/F) combinationDrug

    Also called SCH 418131

    MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 12 weeks

  • Mometasone furoate MDI (MF MDI)Drug

    Also called SCH 32088

    MF 400 mcg via metered dose inhaler twice daily for 12 weeks

Study groups in NCT00381485
Study groupRoleWhat they receive
MF/F MDI 400/10 mcg BIDExperimentalMometasone Furoate 400 mcg and formoterol 10 mcg fixed dose combination taken twice daily Participants received 2 to 3 weeks (approximately) of open-label, run-in medication with MF MDI 400 mcg BID prior to the 12-week double-blind treatment period
Receives: Drug: Mometasone furoate/formoterol (MF/F) combination
MF/F MDI 200/10 mcg BIDExperimentalMometasone Furoate 200 mcg and formoterol 10 mcg fixed dose combination taken twice daily Participants received 2 to 3 weeks (approximately) of open-label, run-in medication with MF MDI 400 mcg BID prior to the 12-week double-blind treatment period
Receives: Drug: Mometasone furoate/formoterol (MF/F) combination
MF MDI 400 mcg BIDActive comparatorMometasone Furoate 400 mcg taken twice daily Participants received 2 to 3 weeks (approximately) of open-label, run-in medication with MF MDI 400 mcg BID prior to the 12-week double-blind treatment period
Receives: Drug: Mometasone furoate MDI (MF MDI)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1)

    The average of the two predose FEV1 measurements (30 minutes prior to dosing and 0 hour, immediately prior to dosing) at the Baseline Visit were subtracted from each of the serial measurements over the 12-hour period. The AUC was calculated based on these changes from Baseline evaluations. The comparison was for MF/F versus MF. Standard deviation was pooled.

    Measured: Baseline to Week 12

Secondary outcomes (3)

  1. Change From Baseline to Week 12 in Asthma Control Questionnaire (ACQ) Total Score

    ACQ consists of seven questions each scaled from 0 (best case) to 6 (worst case). The ACQ Total score was the mean of the individual seven questions. The comparison was for MF/F versus placebo. Standard deviation was pooled.

    Measured: Baseline to Week 12

  2. Change From Baseline to Week 12 in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ[S]) Total Score

    AQLQ(S) consists of 32 questions each scaled from 1 (worst case) to 7 (best case). The AQLQ(S) Total score was the mean of the individual 32 questions. The comparison was for MF/F versus placebo. Standard deviation was pooled.

    Measured: Baseline to Week 12

  3. Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma That Require Use of Short-Acting Beta Agonists (SABA)

    Baseline was the proportion of nights of the last week (Days -7 to 1) prior to first dose with nocturnal awakenings. Scale is measured as 0 to 1 with 0 = no awakenings to 1 = awakenings every night. The comparison was for MF/F versus placebo. Standard deviation was pooled.

    Measured: 12-week Treatment Period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2006 (estimated)
  2. Study start1 Jul 2006
  3. Primary completion1 Jan 2008
  4. Study completion1 Jan 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
834 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00381485
Sponsor's protocol ID
P04431
Other IDs
Doc ID: 3166301, EUDRACT No.: 2005-005910-20
Status last verified
Feb 2022
First submitted
26 Sep 2006
Last updated
20 May 2024
Data monitoring committee
No
Individual data sharing
No

Publications

  • Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.

    PubMed 36472162

  • Weinstein SF, Corren J, Murphy K, Nolte H, White M; Study Investigators of P04431. Twelve-week efficacy and safety study of mometasone furoate/formoterol 200/10 microg and 400/10 microg combination treatments in patients with persistent asthma previously receiving high-dose inhaled corticosteroids. Allergy Asthma Proc. 2010 Jul-Aug;31(4):280-9. doi: 10.2500/aap.2010.31.3381. Epub 2010 Aug 3.

    PubMed 20687982

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Mometasone furoate/formoterol (MF/F) combination and Mometasone furoate MDI (MF MDI) in people with Asthma, run by Organon and Co.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 May 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Mar 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 12 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) (time frame: Baseline to Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00381485, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2024.

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