- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00383721
Effects of Mometasone Furoate/Formoterol Combination Versus Formoterol and Mometasone Furoate Alone in Chronic Obstructive Pulmonary Disease (COPD) (Study P04230AM4)(COMPLETED)
A Randomized, 26-Week, Placebo-Controlled Efficacy and Safety Study With a 26-Week Long-Term Safety Extension, of High- and Medium-Dose Inhaled Mometasone Furoate/Formoterol Fixed-Dose Combination Formulation Compared With Formoterol and High-Dose Inhaled Mometasone Furoate Monotherapy in Subjects With Moderate to Severe COPD
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Moderate to severe COPD based on prebronchodilator FEV1/forced vital capacity (FVC) ratio of <=70%.
- At Screening & Baseline, postbronchodilator FEV1 must be >= 60% predicted normal & >=25% predicted normal.
- COPD symptoms for >=24 months.
- >=2 COPD exacerbations requiring course of oral corticosteroid &/or antibiotics within 2-12 months before screening.
- Ex- or current smoker with smoking history >=10 pack years.
- Only albuterol/salbutamol for relief for at least 2 weeks prior to randomization.
- Withdraw from parenteral & oral steroids, anticholinergics, & antibiotics 4 weeks prior to Screening.
- No harm in changing current COPD therapy, willing to discontinue his/her anticholinergics, inhaled corticosteroids (ICS) or ICS/long-acting beta agonists (LABA) at Screening, & transferred to albuterol/salbutamol for relief for 2 weeks prior to Randomization.
- Lab tests conducted at Screening must be acceptable to investigator. Electrocardiogram (ECG) performed at Screening or within 30 days prior to Screening must be acceptable to investigator. Chest X-ray or computerized tomography (CT) scan is acceptable within 12 months prior to Screening must be acceptable to investigator.
- Female of childbearing potential must use birth control. Includes: hormonal contraceptives, intra-uterine device (IUD), condom in combination with spermicide, monogamous relationship with male partner who had vasectomy. Started birth control at least 3 months prior to Screening (exception condom), & must agree to continue. Female who is not currently sexually active must agree/consent to using a method should she become sexually active. Women who have been surgically sterilized or are at least 1 year postmenopausal are not considered to be of childbearing potential. Female must have negative serum pregnancy test at Screening.
Exclusion Criteria:
- Evidence (upon visual inspection) of oropharyngeal candidiasis at Baseline with or without treatment. If there is evidence at Screening, may be treated as appropriate & visit can be scheduled upon resolution. If there is evidence at Baseline, may be treated as appropriate & visit can be rescheduled upon resolution.
- History of renal, hepatic, cardiovascular, metabolic, neurologic, hematologic, ophthalmological, respiratory, gastrointestinal, cerebrovascular, or other which could interfere with study or require treatment which might interfere with study. Examples include (but are not limited to) hypertension treated with beta-blockers), active hepatitis, coronary artery disease, arrhythmia, significant QTc prolongation (ie QTcF or QTcB [Fridericia or Bazett corrections, respectively >500 milliseconds (msecs)]) 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 asthma, bronchiectasis, cystic fibrosis. Others which are well-controlled & stable (eg hypertension not requiring beta-blockers) will not prohibit participation if appropriate to investigator.
- Allergy/sensitivity to glucocorticosteroids, beta-2 agonists, study drug/excipients.
- Female who is breast-feeding, pregnant, or intends to become pregnant.
- Illicit drug user.
- Human immunodeficiency virus (HIV) positive (testing not conducted).
- Unable to correctly use oral MDI.
- Taking any restricted medications prior to Screening without meeting washout.
- Cannot adhere to permitted concomitant & prohibited medications.
- May not participate in this same study at another investigational site. Cannot participate in different investigational study at any site, during same time.
- Not be randomized into study more than once.
- No person directly associated with administration of study may participate.
- Previously participated in MF/F trial.
- Increase in absolute volume of >=400 milliliters (mL) at Screening or prior to Baseline within 30 minutes after administration of 4 inhalations of albuterol/salbutamol (total dose of 360 to 400 mcg), or nebulized 2.5 mg albuterol/salbutamol.
- Asthma.
- Lobectomy, pneumonectomy or lung volume reduction surgery.
- Lung cancer.
- Requires long-term administration of oxygen (>15 hours/day).
- Alpha-1-antitrypsin deficiency.
A history and/or presence of intraocular pressure in either eye >=22 millimeters of mercury (mm Hg), glaucoma, and/or posterior subcapsular cataracts. A subject who has undergone incisional or intraocular surgery in which the natural lens is still present in the eye. A subject with a history of penetrating trauma to both eyes. A subject with one or more of the following Lens Opacities Classification System (LOCS) III grades at screening:
- nuclear opalescence (NO): >=3.0,
- nuclear color (NC): >=3.0,
- cortical cataract (C): >=2.0,
- posterior subcapsular (P): >=0.5.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: MF/F MDI 400/10 mcg BID
|
MF/F 400/10 mcg via a metered dose inhaler (MDI) twice daily for 52 weeks
Other Names:
MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 52 weeks
Other Names:
|
Experimental: MF/F MDI 200/10 mcg BID
|
MF/F 400/10 mcg via a metered dose inhaler (MDI) twice daily for 52 weeks
Other Names:
MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 52 weeks
Other Names:
|
Experimental: MF MDI 400 mcg BID
|
MF 400 mcg via metered dose inhaler twice daily for 52 weeks
Other Names:
|
Active Comparator: Formoterol MDI 10 mcg BID
|
Formoterol 10 mcg via metered dose inhaler twice a day for 52 weeks
Other Names:
|
Placebo Comparator: Placebo MDI BID
|
Placebo MDI twice a day for 26 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 13 in Forced Expiratory Volume (Liters) in 1 Second (FEV1)
Time Frame: Baseline to Endpoint (13 weeks)
|
FEV1 AUC was standardized to liters.
Endpoint was the last post-baseline non-missing result through Week 13 carried forward.
|
Baseline to Endpoint (13 weeks)
|
Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1
Time Frame: Baseline to Endpoint (13 weeks)
|
Endpoint was the last post-baseline non-missing result through Week 13 carried forward.
|
Baseline to Endpoint (13 weeks)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score
Time Frame: Baseline to Endpoint (26 weeks)
|
SGRQ consisted of 76 items aggregated into 3 component scores: symptoms (frequency/severity), activity (cause or limited by breathlessness), impact (social functioning, psychological disturbances from airway disease), & total score. Best health scores have a low numeric value. All component scores & total score ranged from 0-100, with a higher score indicating greater disease burden. A 4-point increase over placebo (and Baseline) was considered the minimum clinically important difference. Endpoint was the last post-baseline non-missing result through the 26 week evaluation carried forward. |
Baseline to Endpoint (26 weeks)
|
Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms)
Time Frame: Baseline to Endpoint (26 weeks)
|
Prior to the use of study drug rescue medication (in the morning upon awakening) the participant evaluated the COPD symptoms of wheezing, cough, and difficulty breathing.
A symptom-free night was defined as a combined score of 0 (no symptoms) across all three COPD symptoms evaluated the following morning.
Proportion for Baseline included data from the last week before the first dose.
Proportion for Endpoint included data across the entire 26-week treatment period.
|
Baseline to Endpoint (26 weeks)
|
Number of Participants With Partly Stable COPD
Time Frame: Endpoint (26 weeks)
|
Partly stable COPD was a composite measure that included the following COPD outcomes: (1) No oral steroid rescue medication; (2) No AM or PM COPD weekly average symptom score greater than 2 during at least 7 of 8 weeks; (3) No moderate or severe exacerbations; (4) No unscheduled visits due to COPD worsenings; (5) No study discontinuation due to treatment failure or treatment-related adverse event as determined by the investigator. |
Endpoint (26 weeks)
|
Number of Participants With Mild, Moderate, or Severe COPD Exacerbations
Time Frame: Endpoint (26 weeks)
|
Mild = 12 or more inhalations/day of inhaled rescue medication or 2 or more nebulized treatments/day of inhaled rescue medication. Moderate = treatment with antibiotics or oral steroids. Severe = emergency room treatment or hospitalizations of survival curves. If an event was composed of multiple criteria, the most severe criteria was assigned to the event. |
Endpoint (26 weeks)
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- Maspero J, Cherrez I, Doherty DE, Tashkin DP, Kuna P, Kuo WL, Gates D, Nolte H, Chylack LT Jr. Appraisal of lens opacity with mometasone furoate/formoterol fumarate combination in patients with COPD or asthma. Respir Med. 2014 Sep;108(9):1355-62. doi: 10.1016/j.rmed.2014.04.015. Epub 2014 May 2.
- Tashkin DP, Doherty DE, Kerwin E, Matiz-Bueno CE, Knorr B, Shekar T, Gates D, Staudinger H. Efficacy and safety characteristics of mometasone furoate/formoterol fumarate fixed-dose combination in subjects with moderate to very severe COPD: findings from pooled analysis of two randomized, 52-week placebo-controlled trials. Int J Chron Obstruct Pulmon Dis. 2012;7:73-86. doi: 10.2147/COPD.S29444. Epub 2012 Feb 3.
- Doherty DE, Tashkin DP, Kerwin E, Knorr BA, Shekar T, Banerjee S, Staudinger H. Effects of mometasone furoate/formoterol fumarate fixed-dose combination formulation on chronic obstructive pulmonary disease (COPD): results from a 52-week Phase III trial in subjects with moderate-to-very severe COPD. Int J Chron Obstruct Pulmon Dis. 2012;7:57-71. doi: 10.2147/COPD.S27320. Epub 2012 Feb 3.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Lung Diseases
- Lung Diseases, Obstructive
- Pulmonary Disease, Chronic Obstructive
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Adrenergic Agonists
- Dermatologic Agents
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Anti-Allergic Agents
- Adrenergic beta-2 Receptor Agonists
- Adrenergic beta-Agonists
- Mometasone Furoate
- Formoterol Fumarate
Other Study ID Numbers
- P04230
- Doc ID: 3227335,
- Eudract No: 2006-002309-30,
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf
http://engagezone.msd.com/ds_documentation.php
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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