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

NCT00381485 | Completed Phase 3 Results

• 3 other identifiers: P04431Doc ID: 3166301EUDRACT No.: 2005-005910-20
• Study Type: interventional
• Target: 834
• Locations: 0 countries
• Sites: N/A

Brief 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. 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

Outcome Measures

Primary Outcomes (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.

  Baseline to Week 12

Secondary Outcomes (3)

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

  Baseline to Week 12

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

  Baseline to Week 12

• 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)

  12-week Treatment Period

Study Arms (3)

MF/F MDI 400/10 mcg BID

EXPERIMENTAL

Mometasone 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

Drug: Mometasone furoate/formoterol (MF/F) combination

MF/F MDI 200/10 mcg BID

EXPERIMENTAL

Mometasone 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

Drug: Mometasone furoate/formoterol (MF/F) combination

MF MDI 400 mcg BID

ACTIVE COMPARATOR

Mometasone 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

Drug: Mometasone furoate MDI (MF MDI)

Interventions

Mometasone furoate/formoterol (MF/F) combination DRUG

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

Also known as: SCH 418131

MF/F MDI 400/10 mcg BID

Mometasone furoate MDI (MF MDI) DRUG

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

Also known as: SCH 32088

MF MDI 400 mcg BID

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• \>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:

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Organon and Co: lead
• Novartis: collaborator

Related Publications (2)

• 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.

  PMID: 36472162 DERIVED

• 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.

  PMID: 20687982 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Mometasone Furoate; Formoterol Fumarate

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Vice President, Late Stage Development Group Leader
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@spcorp.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2006
• First Posted: September 27, 2006
• Study Start: July 1, 2006
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: May 20, 2024
• Results First Posted: March 7, 2011

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share