Study of Inhaled Glucocorticosteroids/Long-Acting Bronchodilator Drugs in Subjects With Asthma That Have Been Taking Inhaled Glucocorticosteroids (Study P04705AM1)

NCT00424008 | Completed Phase 3 Results

• 2 other identifiers: P04705SCH 418131
• Study Type: interventional
• Target: 722
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is being conducted to demonstrate the non-inferiority between two inhaled glucocorticosteroids and long-acting bronchodilator combination drugs called mometasone furoate/formoterol fumarate in a metered-dose inhaler (MDI) and fluticasone propionate/salmeterol in a dry powder inhaler (DPI) on lung function. Information on the onset of action, the overall safety, and how the drugs control asthma will also be assessed. The study is approximately 1 year in duration.

Conditions

Asthma

Keywords

Glucocorticosteroids; Dry Powder Inhaler; Bronchodilator; Metered-Dose Inhaler

Outcome Measures

Primary Outcomes (1)

• The Area Under the Curve From 0 to 12 Hours [AUC](0-12 hr) of the Change From Baseline to the Week 12 Endpoint in Forced Expiratory Volume in One Second (FEV1)

  Baseline to Week 12

Secondary Outcomes (3)

• Onset-of-action Based on Change From Baseline FEV1 at the 5 Min Pulmonary Function Test (PFT) Assessment on Day 1

  Baseline to 5 minutes post-dose on Day 1

• Change From Baseline in Asthma Control Questionnaire (ACQ) Total Score at Week 12 Endpoint

  Baseline to Week 12

• The Proportion of Symptom-free Days and Nights (Combined) Over the 12-week Treatment Period.

  Baseline to Week 12

Study Arms (2)

MF/F MDI 200/10 mcg BID

EXPERIMENTAL

Mometasone furoate 200 mcg and formoterol 10 mcg fixed dose combination taken twice daily.

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

F/SC DPI 250/50 mcg BID

ACTIVE COMPARATOR

Fluticasone propionate/salmeterol (F/SC) 250/50 mcg BID

Drug: Fluticasone propionate/salmeterol (F/SC) DPI

Interventions

Mometasone furoate/formoterol (MF/F) MDI DRUG

MF/F 200/10 mcg via a metered dose inhaler (MDI) twice daily for 52 weeks.

Also known as: SCH 418131

MF/F MDI 200/10 mcg BID

Fluticasone propionate/salmeterol (F/SC) DPI DRUG

Fluticasone propionate 250 mcg and salmeterol 50 mcg fixed dose combination dry powder inhaler taken twice daily for 52 weeks.

Also known as: Advair Diskus in the US/Seretide Diskus outside the US

F/SC DPI 250/50 mcg BID

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a diagnosis of asthma for at least 12 months' duration.
• A participant must have been using a medium daily dose of inhaled glucocorticosteroids (alone or in combination with long-acting beta 2-agonist \[LABA\]) for at least 12 weeks and must have been on a stable regimen for at least 2 weeks prior to Screening.
• If there is no inherent harm in changing the participant's current asthma therapy, the participant must be willing to discontinue his/her prescribed inhaled glucocorticosteroid (ICS) or ICS/LABA prior to initiating MF MDI run-in medication.
• The diagnosis of asthma must be documented by either demonstrating an increase in absolute forced expiratory volume in 1 second (FEV1) of at least 12% and a volume increase of at least 200 mL within approximately 15 to 20 minutes after administration of 4 inhalations of albuterol/salbutamol or of nebulized short-acting beta 2-agonist (SABA) OR peak expiratory flow (PEF) variability of more than 20% OR a diurnal variation PEF of more than 20% based on the difference between pre-bronchodilator (before taking albuterol/salbutamol) morning value and the post-bronchodilator value (after taking albuterol/salbutamol) from the evening before, expressed as a percentage of the mean daily PEF value on any day during the open-label Run-in Period.
• A participant must have a history of \>= 2 asthma-related unscheduled visits to a physician or to an emergency room within the past year AND \>= 3 asthma-related unscheduled visits within the past 2 years.
• Prior to randomization participants must have used a total of 12 or more inhalations of SABA rescue medication during the last 10 days of run-in.
• Clinical laboratory tests (complete blood counts \[CBC\], blood chemistries, including serum pregnancy for females of child-bearing potential, and urinalysis) conducted at the Screening Visit must be within normal limits or clinically acceptable to the investigator/sponsor before the participant is instructed to start using open-label MF MDI run-in medication.
• An electrocardiogram (ECG) performed at the Screening Visit, using a centralized trans-telephonic technology, must be clinically acceptable to the investigator.
• A chest x-ray performed at the Screening Visit, or within 12 months prior to the Screening Visit, must be clinically acceptable to the investigator.
• A non-pregnant female participant of childbearing potential must be using a medically acceptable, adequate form of birth control. A female participant of childbearing potential must have a negative serum pregnancy test at Screening in order to be considered eligible for enrollment.

You may not qualify if:

• A participant who demonstrates a change in absolute FEV1 of \> 20% at any time between the Screening and Baseline Visits on any 2 consecutive days between the Screening and Baseline visits.
• A participant who requires the use of greater than 8 inhalations per day of SABA MDI or 2 or more nebulized treatments per day of 2.5 mg SABA on any 2 consecutive days between the Screening and Baseline Visits.
• A participant who experiences a decrease in AM or PM PEF below the Run-in Period stability limit on any 2 consecutive days prior to randomization. The average AM and average PM PEF respective values from the preceding 7 days are added, divided by the number of non-missing values, and multiplied by 0.70 to determine the stability limit.
• A participant who experiences a clinical asthma exacerbation: defined as a clinical deterioration of asthma as judged by the clinical investigator between the Screening and Baseline Visits, that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication (including oral or other systemic corticosteroids, but allowing SABA).

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (2)

• Bernstein DI, Hebert J, Cheema A, Murphy KR, Cherrez-Ojeda I, Matiz-Bueno CE, Kuo WL, Nolte H. Efficacy and onset of action of mometasone furoate/formoterol and fluticasone propionate/salmeterol combination treatment in subjects with persistent asthma. Allergy Asthma Clin Immunol. 2011 Dec 7;7(1):21. doi: 10.1186/1710-1492-7-21.

  PMID: 22152089 RESULT

• Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.

  PMID: 36472162 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Mometasone Furoate; Formoterol Fumarate; Fluticasone; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Androstadienes; Androstenes; Androstanes; Albuterol; Phenethylamines; Ethylamines; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

The sponsor closed the study early, at 12 weeks treatment, for reasons that were not safety related. No efficacy analysis of data collected beyond 12 weeks of treatment was performed. All safety data were examined regardless of treatment duration.

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: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2007
• First Posted: January 18, 2007
• Study Start: April 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: May 20, 2024
• Results First Posted: November 1, 2010

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share