Official Title: “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”

This is a randomized, placebo-controlled, parallel-group, multi-site, double-blind study evaluating the efficacy of mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 400/10 mcg twice daily (BID) and MF/F MDI 200/10 mcg BID compared with MF 400 mcg BID and F 10 mcg BID in adults at least 40 years of age, with moderate to severe chronic obstructive pulmonary disease (COPD). This is a 26 week Efficacy and Safety study with a 26 week safety extension. Efficacy is not measured for 52 weeks. Efficacy will be measured by the mean change from Baseline to Week 26 in area under the forced expiratory volume in one second concentration time curve from 0 to 12 hours (FEV1 AUC[0-12hr]). Efficacy will also be measured by time-to-first COPD exacerbation over the 52-week Treatment Period for the comparison of MF/F versus F. Secondary efficacy variable will be COPD control scores from diary.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2009

Intervention(s) in this Clinical Trial

• Drug: Mometasone furoate/formoterol (MF/F) combination
  • MF/F 400/10 mcg via a metered dose inhaler (MDI) twice daily for 52 weeks
• Drug: Mometasone furoate/formoterol (MF/F) combination
  • MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 52 weeks
• Drug: Mometasone furoate MDI (MF MDI)
  • MF 400 mcg via metered dose inhaler twice daily for 52 weeks
• Drug: Formoterol MDI
  • Formoterol 10 mcg via metered dose inhaler twice a day for 52 weeks
• Drug: Placebo
  • Placebo MDI twice a day for 26 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: MF/F MDI 400/10 mcg BID
• Experimental: MF/F MDI 200/10 mcg BID
• Experimental: MF MDI 400 mcg BID
• Active Comparator: Formoterol MDI 10 mcg BID
• Placebo Comparator: Placebo MDI BID

Primary Measures

• To assess the contribution of F 10 mcg BID to the combination: The mean AUC (0-12 hr) of the change from baseline to wk 13 Endpoint.
  • Time Frame: from Baseline to the Week 13 Endpoint
    Safety Issue?: No
• To assess the contribution of MF to the combination: Mean change from baseline to wk 13 endpoint in AM predose FEV1
  • Time Frame: from Baseline to the Week 13 Endpoint
    Safety Issue?: No

Secondary Measures

• Change from BL to endpoint in St George's Respiratory Questionaire total score.
  • Time Frame: Change from Baseline to the Week 26 Endpoint
    Safety Issue?: No
• Change from BL in proportion of COPD symptom-free nights over Tx Period.
  • Time Frame: Change from Baseline to the Week 26 Endpoint
    Safety Issue?: No
• Proportion of subjects with partly stable COPD at endpoint
  • Time Frame: Change from Baseline to the Week 26 Endpoint
    Safety Issue?: No
• Time-to-first COPD exacerbation over the Tx Period.
  • Time Frame: Change from Baseline to the Week 26 Endpoint
    Safety Issue?: No

Inclusion Criteria:

• Moderate to severe COPD based on prebronchodilator FEV1/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, ICS or ICS/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. ECG performed at
• Screening or within 30 days prior to Screening must be acceptable to investigator.
• Chest X-ray or 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, 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) insulin-dependent diabetes, hypertension 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, 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.
• 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 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).
• α-1-antitrypsin deficiency.
• A history and/or presence of intraocular pressure in either eye ≥22 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 LOCS III grades at screening:
• NO: ≥3.0
• NC: ≥3.0
• C: ≥2.0
• P: ≥0.5

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Schering-Plough

Overall Clinical Trial Officials and Contacts

Jonathan Sadeh, MD Study Director Schering-Plough  

Overall Contact: SP Clinical Trial Registry Call Center 1-888-772-8734 

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00383721

Study ID Number: P04230

ClinicalTrials.gov Identifier: NCT00383721

Health Authority: United States: Food and Drug Administration