Effects of Mometasone Furoate/Formoterol Combination Versus Formoterol and Mometasone Furoate Alone in COPD (Study P04229AM4)(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

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). All placebo-treated subjects and active-treated

subjects who will not participate in the safety extension will be discontinued

and will have their Final Visit at Week 26. Subjects who continue into the

26-week safety extension will have their Final Visit at Week 52. Efficacy will be measured by the mean change from Baseline to Week 13 in area under the forced expiratory volume in one second concentration time curve from 0 to 12 hours (FEV1 AUC[0-12hr]) and change from Baseline to Week 13 in AM predose FEV1.

Inclusion Criteria:

• Moderate to severe COPD based on prebronchodilator FEV1/forced vital capacity (FVC) ratio of <=70%.
• At Screening, postbronchodilator FEV1 must be <=60% predicted normal & >=25% predicted normal.
• COPD symptoms for >=24 months.
• 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 at least 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 Visit or within 30 days prior to Screening must be acceptable to investigator. Chest x-ray performed at Screening or within 12 months prior to Screening must be acceptable to investigator.
• Women who have

been surgically sterilized or are at least 1 year postmenopausal are not

considered to be of childbearing potential. A female subject of childbearing

potential must have a negative serum pregnancy test at Screening in order to

be considered eligible for enrollment. 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), & agree to continue. Female who is not currently sexually active must agree/consent to use a method should she become sexually active. Women 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 Visit, 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 being 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 deemed appropriate per 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 of study.
• 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.
• Blood eosinophil count greater than 0.57 x 10^3/microliter (uL).
• Lobectomy, pneumonectomy or lung volume reduction surgery.
• Lung cancer.
• Requires long-term administration of oxygen (>15 hours per day).
• A subject who experiences an exacerbation of COPD requiring medical

intervention within 4 weeks prior to randomization, beta-blocking agents, or

treatment with additional excluded medication (other than short-acting beta agonists (SABA)/short-acting

anticholinergic to be used as rescue medication).

• alpha-1-antitrypsin deficiency.
• Cataract extractions on both eyes.
• 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.