A Study to Evaluate the Effect of Fluticasone/Formoterol Breath Actuated Inhaler (BAI) or Relvar® Ellipta® DPI on Ventilation Heterogeneity in Asthma

A Two-arm, Randomised, Assessor-blind, Parallel Group Study to Evaluate the Effect of Fluticasone/Formoterol Breath Actuated Inhaler (BAI) and Relvar® Ellipta® DPI on Ventilation Heterogeneity in Subjects With Partially Controlled or Uncontrolled Asthma

The purpose of this study is to demonstrate improvement of peripheral airway resistance (R5-R20) from baseline with fluticasone/formoterol breath actuated inhaler (BAI).

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Fluticasone/Vilanterol DPI (Relvar Ellipta DPI); Drug: Fluticasone/Formoterol BAI

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Glebe, New South Wales, Australia, NSW 2037
      • The Woolcock Institute Of Medical Research
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Epworth Eastern Medical Centre
    • Melbourne, Victoria, Australia, 3004
      • Allergy immunology and Respiratory medicine, The Alfred Hospital
• New Zealand
  • Dunedin, New Zealand, 9016
    • Otago Respiratory Research Unit
  • Auckland
    • Greenlane, Auckland, New Zealand, 1051
      • The New Zealand Respiratory and Sleep Institute
• Slovakia
  • Humenné, Slovakia, 066 01
    • INSPIRO, s.r.o. Ambulancia pneumológie a ftizeológie
  • Námestovo, Slovakia, 029 01
    • DAMIZA, s.r.o. Ambulancia pneumológie a ftizeológie
  • Poprad, Slovakia, 05801
    • Poliklinika ADUS, Pľúcna ambulancia
  • Prešov, Slovakia, 080 01
    • PULMO, s.r.o
  • Spišská Nová Ves, Slovakia, 052 01
    • Plucna ambulancia Hrebenar, s.r.o.
  • Topoľčany, Slovakia, 955 01
    • ANA JJ, s.r.o, Ambulancia klinickej imunológie a alergológie
• Sweden
  • Lund, Sweden, 221 85
    • Skane University Hospital
• United Kingdom
  • Bradford, United Kingdom, BD9 6RJ
    • Bradford Teaching Hospital
  • London, United Kingdom, SW3 6HP
    • Royal Brompton and Harefield Foundation Trust
  • Manchester, United Kingdom, M23 9QZ
    • University Hospital of South Manchester
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE3 9QP
      • Respiratory Biomedical Research Unit, Glenfield Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria for subjects on Seretide Accuhaler 250/50 µg at screening:

1. Male and female subjects ≥18 years old.
2. Adequate contraception
3. Documented clinical history of asthma for ≥6 months prior to screening visit
4. Using Seretide Accuhaler at a stable dose of 250/50 μg BID at screening for ≥ 8 weeks.
5. uncontrolled asthma as defined by Asthma Control Questionnaire (ACQ-6) score ≥ 1.0
6. R5-R20 ≥ 0.10 kPa/L/s as measured on impulse oscillometry during the screening visit.
7. Historical evidence (within 24 months) of eosinophilic airways disease evidenced by sputum eosinophil count ≥ 3% and/or FeNO 35 ppb.

Inclusion criteria for subjects on equivalent /higher dose or other ICS-LABAs or higher dose of Seretide at screening:

1. Male and female subjects ≥18 years old.
2. Adequate contraception
3. Documented clinical history of asthma for ≥6 months prior to screening visit

4. R5-R20 ≥0.07 kPa/L/s as measured on impulse oscillometry during the screening visit.

   • 5. Historical evidence (within past 24 months) of eosinophilic airways disease, evidenced by sputum eosinophil count ≥3% and/or FeNo ≥35 ppb.

Exclusion Criteria for all subjects:

1. Any severe chronic respiratory disease other than asthma.
2. Subject has a smoking history ≥10 "pack years" (i.e., at least 1 pack of 20 cigarettes/day for 10 years or 10 packs/day for 1 year, etc.)
3. Current smoking history within 12 months prior to the screening visit
4. Near fatal or life-threatening (including intubation) asthma within the past year.
5. Known history of systemic (injectable or oral) corticosteroid medication within 1 month of visit 1.
6. Evidence of a clinically unstable disease as determined by medical history or physical examination that, in the investigator's opinion, precludes entry into the study. 'Clinically unstable' is defined as any disease that, in the opinion of the Investigator, would put the subject at risk through study participation, or which would affect the outcome of the study.
7. In the investigator's opinion a clinically significant upper or lower respiratory infection within 4 weeks prior to visit 1.
8. Current evidence or known history of alcohol and/or substance abuse within 12 months prior to the screening visit.
9. Subject has taken β-blocking agents, tricyclic antidepressants, monoamine oxidase inhibitors, astemizole, quinidine type antiarrhythmics, or potent CYP 3A4 inhibitors such as ketoconazole within 1 week prior to screening visit.
10. Current use of bronchodilators / anti-inflammatory agents other than those specified in the protocol.
11. Known or suspected sensitivity to study drug or excipients.
12. Participation in a clinical drug study within 30 days of the screening visit.
13. Current participation in a clinical study.

Exclusion Criteria for subset of subjects undergoing OR-MRI and HD-CT

1. Contraindication for MRI scanning (as assessed by local MRI safety questionnaire), which includes, but is not limited to: presence of non-MRI compatible artificial heart valves, hydrocephalus shunts, intracranial aneurysm clips, joint replacements or metal implants, pacemakers or other cardiac rhythm management devices, claustrophobia, history of metal in the eye, presence of shrapnel from a war injury, callipers or braces, dentures, dental plates or hearing aids that include metal and cannot be removed, history of epilepsy or black-outs, ear implants, piercings cannot be removed, intrauterine contraceptive device or coil.
2. Inability to stay in the supine position for the duration of the scanning procedure
3. Obesity (body weight >140kg).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: fluticasone/vilanterol DPI (Relvar Ellipta DPI); Inhalation powder. 92/22µg, I inhalation od	Drug: Fluticasone/Vilanterol DPI (Relvar Ellipta DPI)
Experimental: Fluticasone/formoterol BAI; Pressurised suspension for inhalation 125/5µg, 2 inhalations bid	Drug: Fluticasone/Formoterol BAI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measuring peripheral airway resistance (R5-R20)	Measuring peripheral airway resistance (R5-R20)	From baseline to week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
measure ventilation heterogeneity (using Functional Respiratory Imaging)	measures of ventilation heterogeneity	From baseline to week 9
Measuring distal airway volume and resistance (using impulse oscillometry)	Measuring distal airway volume and resistance (using Functional Respiratory Imaging (FRI)	From baseline to week 8 and 9
Evaluate asthma control (using ACQ-6) )	Evaluate asthma control (using ACQ-6) )	From baseline to week 4 and 8
Evaluate health status (using AQLQ)	Evaluate health status (using AQLQ)	From baseline to week 4 and 8

Collaborators and Investigators

• Sponsor: Mundipharma Research Limited

Publications and helpful links

Helpful Links

• Link to Eu CT Register

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2016
• Primary Completion (Actual): August 14, 2017
• Study Completion (Actual): August 14, 2017

Study Registration Dates

• First Submitted: April 11, 2016
• First Submitted That Met QC Criteria: April 27, 2016
• First Posted (Estimate): April 28, 2016

Study Record Updates

• Last Update Posted (Actual): October 23, 2018
• Last Update Submitted That Met QC Criteria: October 22, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: asthma; Small airway disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Fluticasone; Xhance; Formoterol Fumarate
• Other Study ID Numbers: KFL3502; 2015-000801-38 (EudraCT Number)