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

Phase 3

Completed

Conditions: Chronic Obstructive Pulmonary Disease (COPD)

Interventions: Drug: Mometasone furoate/formoterol (MF/F) combination
Drug: Mometasone furoate MDI (MF MDI)
Drug: Formoterol MDI
Drug: Placebo

Registration Number: NCT00383435

Lead Sponsor: Organon and Co

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1055

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MF/F MDI 200/10 mcg BID	Mometasone furoate/formoterol (MF/F) combination	-
MF MDI 400 mcg BID	Mometasone furoate MDI (MF MDI)	-
Formoterol MDI 10 mcg BID	Formoterol MDI	-
Placebo MDI BID	Placebo	-
MF/F MDI 400/10 mcg BID	Mometasone furoate/formoterol (MF/F) combination	-

Primary Outcome Measures

Name	Time	Method
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)	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.
Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1	Baseline to Endpoint (13 weeks)	Endpoint was the last post-baseline non-missing result through Week 13 carried forward.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms)	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.
Number of Participants With Partly Stable COPD	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.
Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score	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 range 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 is the last post-baseline non-missing result through the 26 week evaluation carried forward.
Number of Participants With Mild, Moderate, or Severe COPD Exacerbations	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.