Effects of Mometasone Furoate/Formoterol Combination Versus Mometasone Furoate Alone in Persistent Asthmatics (Study P04073AM1)(COMPLETED)

NCT00383552 | Completed Phase 3 Results

• 3 other identifiers: P04073Doc ID: 3100873;EUDRACT No: 2006-001577-13;
• Study Type: interventional
• Target: 746
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, multi-center, double-blind, double-dummy, placebo-controlled, parallel-group study, evaluating the efficacy of mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) versus MF for 26 weeks. Prior to the 26-week double-blind Treatment Period, participants will receive open-label (OL) MF MDI 100 mcg twice daily (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 hours) of the change from Baseline to the Week 12 Endpoint in Forced Expiratory Volume in One Second (FEV1) and by the time-to-first severe asthma exacerbation across the 26-week treatment period.

Conditions

Asthma

Outcome Measures

Primary Outcomes (3)

• 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 vs MF. Standard deviation was pooled.

  Baseline to Week 12

• Median Time-to-first Severe Asthma Exacerbation Over the 26-week Treatment Period

  Severe asthma exacerbation refers to an occurrence of a decrease below 80% of Baseline in FEV1, a decrease below 70% of Baseline in PEF on 2 consecutive days or a clinical deterioration of asthma resulting in emergency treatment, hospitalization or treatment with asthma medication.

  Across the 26 week treatment period

• Number of Participants With at Least One Severe Asthma Exacerbation at Week 26

  Severe asthma exacerbation refers to an occurrence of a decrease below 80% of Baseline in FEV1, a decrease below 70% of Baseline in PEF on 2 consecutive days and or a clinical deterioration of asthma resulting in emergency treatment, hospitalization or treatment with asthma medication.

  Week 26

Secondary Outcomes (5)

• Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Total Score

  Baseline to Week 26

• Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standarized Activities (AQLQ[S]) Total Score

  Baseline to Week 26

• Change From Baseline in Proportion of Nights Across the Treatment Period With Nocturnal Awakenings Due to Asthma Which Require Use of Short-acting Beta Agonists (SABA)

  Baseline to Endpoint

• Change From Baseline in AM FEV1 Pre-dose Assessment, or Trough FEV1, at Week 12

  Baseline to Week 12

• AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup

  Baseline to Week 12

Study Arms (4)

MF/F MDI 100/10 mcg BID

EXPERIMENTAL

Drug: Mometasone Furoate/Formoterol Fumarate Combination MDI 100/10 mcg BID

MF MDI 100 mcg BID

EXPERIMENTAL

Drug: Mometasone Furoate MDI (MF MDI)

F MDI 10 mcg BID

EXPERIMENTAL

Drug: Formoterol Fumarate 10 mcg

Placebo BID

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Mometasone Furoate/Formoterol Fumarate Combination MDI 100/10 mcg BID DRUG

MF/F 100/10 mcg via a metered dose inhaler (MDI) twice daily for 26 weeks

Also known as: SCH 418131

MF/F MDI 100/10 mcg BID

Mometasone Furoate MDI (MF MDI) DRUG

MF 100 mcg via metered dose inhaler twice daily for 26 weeks

Also known as: SCH 32088

MF MDI 100 mcg BID

Formoterol Fumarate 10 mcg DRUG

F via metered dose inhaler 10 mcg twice a day for 26 weeks

Also known as: Foradil

F MDI 10 mcg BID

Placebo DRUG

Placebo metered dose inhaler twice a day for 26 weeks

Placebo 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:

• \>=12 years, either sex, any race, asthma diagnosis \>=12 months that is consistent with the following: Diagnosis based on clinical history \& examination, pulmonary function parameters \& response to beta-2-agonists, according to international guidelines.
• Been using low daily dose of inhaled corticosteroid (ICS) (either alone or in combination with long-acting beta agonist \[LABA\]) \>=12 weeks \& been on stable asthma regimen for \>=2 weeks prior to Screening. Low daily doses of ICS are:
• mcg beclomethasone chlorofluorocarbon (CFC),
• mcg beclomethasone hydrofluoroalkane (HFA),
• mcg budesonide dry powder inhaler (DPI),
• mcg flunisolide,
• mcg fluticasone,
• mcg MF,
• mcg triamcinolone acetonide,
• to 160 mcg ciclesonide.
• Note: Dose delivery by method/modality other than these must be equivalent.
• No harm in changing current asthma therapy to investigator, subject (legal representation, if applicable) must be willing to discontinue his/her ICS or ICS/LABA combination prior to initiating MF MDI run-in medication at Screening Visit, \& transferred to open-label treatment with MF MDI 100 mcg BID for 2-3 weeks prior to Baseline Visit.
• To document diagnosis of asthma \& assure responsiveness to bronchodilators before randomization 1 of these can be used at Screening Visit or thereafter, but prior to Baseline Visit:
• Demonstrate increase in absolute FEV1 \>=12% \& \>=200 mL within approximately 15 to 20 minutes after administration of 4 inhalations of albuterol/salbutamol (total dose 360-400 mcg) or nebulized short-acting beta agonist (SABA) (2.5 mg) if confirmed as standard office practice, OR
• Demonstrate peak expiratory flow (PEF) variability \>20% expressed as percentage of the mean highest \& lowest morning prebronchodilator (before taking albuterol/salbutamol) PEF over \>=1 week, OR

You may not qualify if:

• Increase/decrease in absolute FEV1 of \>20% at any time from Screening Visit up to \& including Baseline Visit. Pulmonary function tests (PFTs) will be performed in the morning.
• \>8 inhalations/day of SABA MDI or \>=2 nebulized treatments/day of 2.5 mg SABA on 2 consecutive days from Screening Visit up to \& including Baseline Visit.
• Decrease in AM/PM PEF below Screening Period stability limit on 2 consecutive days prior to randomization.
• Asthma deterioration results in emergency treatment, hospitalization, or treatment with additional, excluded asthma medication (including oral or other systemic corticosteroids, but allowing SABA) as judged by investigator at any time from Screening Visit up to \& including Baseline Visit.
• Treated in emergency room (ER) (for severe asthma exacerbation requiring systemic glucocorticosteroid treatment) or admitted to hospital for management of airway obstruction within last 3 months.
• Ever required ventilator support for respiratory failure secondary to asthma.
• Upper/lower respiratory tract infection within previous 2 weeks prior to Screening \& Baseline Visits. Visits can be rescheduled 2 weeks after complete resolution.
• Smoker or ex-smoker \& has smoked within previous year or has cumulative smoking history \>10 pack-years.
• Significant abnormal vital sign.
• Evidence upon visual inspection of significant oropharyngeal candidiasis at Baseline or earlier with or without treatment. If there is evidence at Screening or Pre-Baseline Visit, may be treated as appropriate \& Baseline Visit can be scheduled upon resolution.
• History of significant renal, hepatic, cardiovascular, metabolic, neurologic, hematologic, ophthalmologic, respiratory, gastrointestinal, cerebrovascular, or other which, in judgment of investigator, could interfere with study or require treatment which might interfere with study. Examples include (but are not limited to) insulin-dependent diabetes, hypertension being treated with beta-blockers, active hepatitis, coronary artery disease, arrhythmia, significant QTc prolongation (ie QTcF or QTcB \[Fridericia or Bazett corrections, respectively \>500 msecs), stroke, severe rheumatoid arthritis, chronic open-angle glaucoma or posterior subcapsular cataracts (including prior cataract surgery), acquired immune deficiency syndrome (AIDS), or conditions that may interfere with respiratory function such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, bronchiectasis, cystic fibrosis. Others which are well-controlled \& stable (eg hypertension not requiring beta-blockers) will not prohibit participation if deemed appropriate by investigator.
• Allergic/intolerant of glucocorticoids, beta-2-agonists, or any inactive excipients in study drugs.
• Female who is breast-feeding, pregnant, or intends to become pregnant while in study.
• Illicit drug user.
• Human immunodeficiency virus (HIV) positive (testing not done).

Sponsors & Collaborators

• Organon and Co: lead
• Novartis: collaborator

Related Publications (1)

• Meltzer EO, Kuna P, Nolte H, Nayak AS, Laforce C; P04073 Study Investigators. Mometasone furoate/formoterol reduces asthma deteriorations and improves lung function. Eur Respir J. 2012 Feb;39(2):279-89. doi: 10.1183/09031936.00020310. Epub 2011 Aug 4.

  PMID: 21828036 RESULT

MeSH Terms

Conditions

Asthma

Interventions

Mometasone Furoate; BID protein, human; 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: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• 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 29, 2006
• First Posted: October 3, 2006
• Study Start: September 1, 2006
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: May 17, 2024
• Results First Posted: October 25, 2011

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share