Efficacy and Safety of Two Dry Power Inhalers (DPIs) Used for the Application of Mometasone in the Treatment of Asthma

An Open-label, Comparative, Randomized, Parallel, Multicenter Study to Determine the Efficacy and Safety of Two Dry Powder Inhalers (DPIs) Used for the Application of Mometasone in the Treatment of Asthma

Mometasone furoate (MF) is a new potent synthetic corticosteroid. Internationally, MF is administered by a breath-actuated DPI and supplied in multidose devices. Capsules to be administered through a monodose device that would offer an alternative to MF DPI multidose treatment in terms of cost-effectiveness were developed in Brazil. The aim of the present non-inferiority clinical study was to evaluate both devices in terms of efficacy and safety.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Device: OXIMAX; Device: ASMANEX TWISTHALER

Detailed Description

Background: Internationally, MF is administered by a breath-actuated DPI and supplied in multidose devices. Capsules to be administered through a monodose device that would offer an alternative to MF DPI multidose treatment in terms of cost-effectiveness were developed in Brazil. Results of laboratory analysis for respirable fraction, content uniformity of emitted dose and of the bulk powder and for percentage of particles < 1 micra of both MF 200 µg and MF 400 µg capsules have indicated their equivalent performance in comparison to MF DPI multidose.

Aim: The aim of the present non-inferiority clinical study was to evaluate both devices in terms of efficacy and safety.

Methods: Ninety-seven adult patients with moderate persistent asthma were randomized in two groups to receive for 60 days a dose of 400 µg of DPI MF once daily (at evening) using multidose or monodose device. Follow-up visits were scheduled at Days 7, 14, 28, 42 and 56. Efficacy was assessed by means of pulmonary function tests (spirometry - FEV1 and PEFR) at each visit. In addition, subjects have recorded twice daily PEFR, symptom scores and use of rescue medication throughout the study. Response to therapy was also assessed. Safety evaluations included monitoring of adverse events, vital signs, clinical laboratory tests (plasma cortisol concentrations were assessed at enrollment and repeated after 60 days of MF treatment; cortrosyn test was performed at the enrollment and after 60 days of MF treatment), and physical examination.

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil
    • UNIRIO
  • São Paulo, Brazil
    • Hospital do Servidor Publico Estadual
  • São Paulo, Brazil
    • Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo
  • São Paulo, Brazil
    • Hospital Heliópolis
  • Minas Gerais
    • Juíz de Fora, Minas Gerais, Brazil
      • Hospital Universitário da Universidade Federal de Juíz de Fora

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A diagnosis of asthma for at least 6 months
• Baseline FEV1 must be > = 55% and < = 85% of predicted
• Increase in absolute FEV1 of >12%, with an absolute volume increase of at least 200 mL after reversibility testing
• Use of an adequate form of birth control by non-pregnant women of childbearing potential

• Absence of use of the following medication prior to the inclusion:

  • Beta 2 agonist short-acting (inhaled, oral)-12 Hours
  • Beta 2 agonist long-acting (inhaled)-48 Hours
  • Ipratropium bromide-12 hours
  • Cromolyn sodium, nedocromil-07 days
  • Astemizole-03 months
  • Cetotifeno-03 months
  • Another investigational drug-01 month
  • Theophyline-2 weeks
  • Antihistamines-07 days
  • Anticholinergics-07 days
  • Leukotriene modifiers-2 weeks
  • Oral decongestant long-acting-72 hours
  • Oral decongestant short-acting-24 hours

Exclusion Criteria:

• Women who were pregnant, breast-feeding, or are pre-menarcheal.
• Subjects who have used any investigational drug within the last 30 days
• Subjects who were receiving immunotherapy
• Subjects requiring the use of >12 puffs per day of Salbutamol on any 2 consecutive days
• Smokers or ex-smokers
• Subjects who are allergic to corticosteroids or beta-agonists
• Subjects who have required inpatient hospitalization for asthma control within the previous 3 months
• Subjects who have required ventilator support for respiratory failure secondary to their asthma within the last 5 years
• Subjects who have been treated in the emergency room (for a severe asthma exacerbation), or admitted to the hospital for management of airway obstruction, on two or more occasions within the last six months
• Subjects with clinical evidence of emphysema, chronic bronchitis, bronchiectasis, or cystic fibrosis
• Subjects with a significant history of renal, hepatic, cardiovascular, metabolic, neurologic, hematological, respiratory, gastrointestinal, cerebrovascular, or other significant medical illness or disorder which, in the judgment of the investigator, could have interfered with the study, or required treatment which might have interfered with the study
• Subjects who have experienced an upper or lower respiratory tract infection (viral or bacterial) within the previous 2 weeks prior to enrollment
• Subjects who have clinically significant abnormalities on chest x-ray at the Screening Visit or within the previous year
• Subjects who are known to be HIV positive
• Subjects who are known to be illicit drug abusers
• Subjects with hypothalamic-pituitary-adrenal (HPA) axis disturbances
• Subjects with severe pulmonary airflow obstruction showing to be life-threatening characterized by cyanosis, confusion, somnolence, coma or tiredness, thorax silent to hearing or showing weak respiration,PEFR <25% of the predicted normal, bradycardia (heartbeats bellow 60 beats per minute)
• Subjects with baseline FEV1 < 55% of the predicted normal
• Subjects with uncontrolled hypertension
• Subjects with suspected pneumonia, pneumothorax, pneumomediastinum, pulmonary tuberculosis, alpha-1 anti-trypsin deficiency, lung mycosis (blastomycosis, histoplasmic) or pulmonary cystic fibrosis
• Subjects with history of thoracic surgery or any previous malignancy of the lung
• Subjects with significant heart disease (e.g., previous acute myocardial infarction, angina pectoris, pulmonary edema or other cardiovascular disease which is characterized as life-threatening
• Subjects receiving beta-adrenergic blocking agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monodose device; Mometasone furoate 400 µg DPI capsules administered through a monodose device.	Device: OXIMAX
Active Comparator: Multidose device; Mometasone furoate 400 µg DPI capsules administered through a multidose device	Device: ASMANEX TWISTHALER

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in Forced Expired Volume in one second (FEV1) and Peak Expiratory Flow Rate (PEFR) measured by spirometry; number of puffs/day of rescue medication (Salbutamol) used by the subjects.	56 days after initiation of therapy

Secondary Outcome Measures

Outcome Measure	Time Frame
PEFR daily measurements, daily scores for asthma symptoms, response to therapy made by the Investigator, safety (hypothalamic-pituitary-adrenal axis evaluation and clinical laboratory measurements) and tolerability (adverse events).	56 days after initiation of therapy

Collaborators and Investigators

• Sponsor: Mantecorp Industria Quimica e Farmaceutica Ltd.
• Investigators: Principal Investigator: Carlos Alberto C Pereira, MD, PhD, Hospital do Servidor Público Estadual, São Paulo

Publications and helpful links

General Publications

• Pereira CA, Vianna FF, Cukier A, Stelmach R, Oliveira JC, Carvalho EV, Gomes EP, Mayo SV, Chibante AM, Domingues CP. Efficacy and safety of two dry-powder inhalers for the administration of mometasone furoate in asthma patients. J Bras Pneumol. 2010 Jul-Aug;36(4):410-6. doi: 10.1590/s1806-37132010000400004. English, Portuguese.

Study record dates

Study Major Dates

• Study Start: October 1, 2002
• Study Completion (Actual): August 1, 2003

Study Registration Dates

• First Submitted: August 12, 2009
• First Submitted That Met QC Criteria: September 9, 2009
• First Posted (Estimate): September 11, 2009

Study Record Updates

• Last Update Posted (Estimate): September 11, 2009
• Last Update Submitted That Met QC Criteria: September 9, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: Asthma; Mometasone furoate; Inhalation devices; Forced expiratory volume
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Inflammatory Agents; Dermatologic Agents; Anti-Allergic Agents; Mometasone Furoate
• Other Study ID Numbers: ASM/P/01/1