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

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00383552
First received: September 29, 2006
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Mometasone Furoate/Formoterol Fumarate Combination MDI 100/10 mcg BID
Drug: Mometasone Furoate MDI (MF MDI)
Drug: Formoterol Fumarate 10 mcg
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A 26-Week Placebo-Controlled Efficacy and Safety Study of Mometasone Furoate/Formoterol Fumarate Combination Formulation Compared With Mometasone Furoate and Formoterol Monotherapy in Subjects With Persistent Asthma Previously Treated With Low-Dose Inhaled Glucocorticosteroids

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • Median Time-to-first Severe Asthma Exacerbation Over the 26-week Treatment Period [ Time Frame: Across the 26 week treatment period ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With at Least One Severe Asthma Exacerbation at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline to Week 26 in the Asthma Control Questionnaire (ACQ) Total Score [ Time Frame: Baseline to Week 26 ] [ Designated as safety issue: No ]
    ACQ consists of seven questions each scaled from 0 (best case) to 6 (worst case). The comparison was for MF/F vs placebo. Standard deviation was pooled.

  • Change From Baseline to Week 26 in Asthma Quality of Life Questionnaire With Standarized Activities (AQLQ[S]) Total Score [ Time Frame: Baseline to Week 26 ] [ Designated as safety issue: No ]
    AQLQ(S) consists of 32 questions each scaled from 1 (worst case) to 7 (best case). The comparison was for MF/F vs placebo. Standard deviation was pooled.

  • 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) [ Time Frame: Baseline to Endpoint ] [ Designated as safety issue: No ]
    Baseline is 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 vs placebo. Standard deviation was pooled.

  • Change From Baseline in AM FEV1 Pre-dose Assessment, or Trough FEV1, at Week 12 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    Trough FEV1 is a measure of the end-of-dosing interval. The comparison was for MF/F vs F. Standard deviation was pooled.

  • AUC(0-12 Hour) of the Change From Baseline to Week 12 in FEV1 for Each Body Mass Index (BMI) Subgroup [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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. BMI is a number calculated from a person's weight and height. The higher the number, the higher the amount of fat. The comparison was for MF/F vs placebo. Standard deviation was pooled.


Enrollment: 746
Study Start Date: September 2006
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MF/F MDI 100/10 mcg BID Drug: Mometasone Furoate/Formoterol Fumarate Combination MDI 100/10 mcg BID
MF/F 100/10 mcg via a metered dose inhaler (MDI) twice daily for 26 weeks
Other Name: SCH 418131
Experimental: MF MDI 100 mcg BID Drug: Mometasone Furoate MDI (MF MDI)
MF 100 mcg via metered dose inhaler twice daily for 26 weeks
Other Name: SCH 32088
Experimental: F MDI 10 mcg BID Drug: Formoterol Fumarate 10 mcg
F via metered dose inhaler 10 mcg twice a day for 26 weeks
Other Name: Foradil
Placebo Comparator: Placebo BID Drug: Placebo
Placebo metered dose inhaler twice a day for 26 weeks

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • >=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:

200-500 mcg beclomethasone chlorofluorocarbon (CFC),

100-250 mcg beclomethasone hydrofluoroalkane (HFA),

200-600 mcg budesonide dry powder inhaler (DPI),

500-1000 mcg flunisolide,

100-250 mcg fluticasone,

200 mcg MF,

400-1000 mcg triamcinolone acetonide,

80 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

Demonstrate diurnal variation in PEF of >20% based on difference between prebronchodilator (before taking albuterol/salbutamol) morning value & postbronchodilator value (after taking albuterol/salbutamol) from evening before, expressed as percentage of mean daily PEF value.

  • At Screening Visit, FEV1 must be >=60% & <=90% predicted.
  • At Baseline Visit, FEV1 must be >=60% & <=85% predicted when all restricted drugs have been withheld for appropriate intervals.
  • Lab tests at Screening Visit must be normal or acceptable to investigator/sponsor and include serum pregnancy for females of child-bearing potential). Electrocardiogram (ECG) at Screening Visit, using centralized trans-telephonic technology must be acceptable to investigator. Chest x-ray performed at Screening Visit or within 12 months prior to Screening Visit must be acceptable to investigator.
  • Subject (legal representation, if applicable) must be willing to give written informed consent & able to adhere to schedules.
  • A non-pregnant woman of childbearing potential must use birth control. Includes: hormonal contraceptives including hormonal vaginal ring, hormonal implant or depot-injectable; Intrauterine device (IUD); medically prescribed topically-applied transdermal contraceptive patch; condom in combination with spermicide; monogamous relationship with male who had vasectomy. Started birth control method >=3 months prior to Screening (exception condom), & must agree to continue its use. Female of childbearing potential who is not currently sexually active must agree & consent to using birth control, should she become active. Women who have been surgically sterilized or are >=1 year postmenopausal are not considered to be of childbearing potential. Female must have negative serum pregnancy test at Screening.

Exclusion Criteria:

  • 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).
  • Unable to use oral MDI inhaler.
  • Has been taking any restricted medications prior to Screening without meeting required washout.
  • Cannot adhere to prohibited & permitted concomitant medications.
  • May not participate in same study at another site. Cannot participate in different study at any site, during same time.
  • Must not be randomized into study more than once.
  • No person directly associated with administration of study may participate.
  • Previously participated in trial with MF/F.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00383552     History of Changes
Other Study ID Numbers: P04073, Doc ID: 3100873;, EUDRACT No: 2006-001577-13;
Study First Received: September 29, 2006
Results First Received: July 15, 2010
Last Updated: April 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Formoterol
Mometasone furoate
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Anti-Allergic Agents

ClinicalTrials.gov processed this record on September 18, 2014