Effects of Mometasone Furoate/Formoterol Combination Versus Formoterol and Mometasone Furoate Alone in Chronic Obstructive Pulmonary Disease (COPD) (Study P04230AM4)(COMPLETED)

NCT00383721 | Completed Phase 3 Results DMC

• 3 other identifiers: P04230Doc ID: 3227335,Eudract No: 2006-002309-30,
• Study Type: interventional
• Target: 1,196
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Outcome Measures

Primary Outcomes (2)

• 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)

  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

  Endpoint was the last post-baseline non-missing result through Week 13 carried forward.

  Baseline to Endpoint (13 weeks)

Secondary Outcomes (4)

• Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score

  Baseline to Endpoint (26 weeks)

• Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms)

  Baseline to Endpoint (26 weeks)

• Number of Participants With Partly Stable COPD

  Endpoint (26 weeks)

• Number of Participants With Mild, Moderate, or Severe COPD Exacerbations

  Endpoint (26 weeks)

Study Arms (5)

MF/F MDI 400/10 mcg BID

EXPERIMENTAL

Drug: Mometasone furoate/formoterol (MF/F) combination

MF/F MDI 200/10 mcg BID

EXPERIMENTAL

Drug: Mometasone furoate/formoterol (MF/F) combination

MF MDI 400 mcg BID

EXPERIMENTAL

Drug: Mometasone furoate MDI (MF MDI)

Formoterol MDI 10 mcg BID

ACTIVE COMPARATOR

Drug: Formoterol MDI

Placebo MDI BID

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Mometasone furoate/formoterol (MF/F) combination DRUG

MF/F 400/10 mcg via a metered dose inhaler (MDI) twice daily for 52 weeks

Also known as: SCH 418131

MF/F MDI 400/10 mcg BID

Mometasone furoate MDI (MF MDI) DRUG

MF 400 mcg via metered dose inhaler twice daily for 52 weeks

Also known as: SCH 32088

MF MDI 400 mcg BID

Formoterol MDI DRUG

Formoterol 10 mcg via metered dose inhaler twice a day for 52 weeks

Also known as: Foradil

Formoterol MDI 10 mcg BID

Placebo DRUG

Placebo MDI twice a day for 26 weeks

Placebo MDI BID

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Organon and Co: lead
• Novartis: collaborator

Related Publications (3)

• 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.

  PMID: 25044280 DERIVED

• 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.

  PMID: 22334770 DERIVED

• 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.

  PMID: 22334769 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Mometasone Furoate; Formoterol Fumarate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2006
• First Posted: October 3, 2006
• Study Start: September 1, 2006
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: May 23, 2024
• Results First Posted: October 26, 2011

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share