Clinical trial NCT02753712: A Study to Evaluate the Effect of Fluticasone/Formoterol Breath Actuated Inhaler (BAI) or Relvar® Ellipta® DPI on Ventilation Heterogeneity in Asthma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Small airway disease
asthma
Lead sponsor: Mundipharma Research Limited
Sponsor class: INDUSTRY
First posted: 2016-04-28
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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).

Primary outcomes:
measure: Measuring peripheral airway resistance (R5-R20)
timeFrame: From baseline to week 8
Secondary outcomes:
measure: measure ventilation heterogeneity (using Functional Respiratory Imaging)
timeFrame: From baseline to week 9
measure: Measuring distal airway volume and resistance (using impulse oscillometry)
timeFrame: From baseline to week 8 and 9
measure: Evaluate asthma control (using ACQ-6) )
timeFrame: From baseline to week 4 and 8
measure: Evaluate health status (using AQLQ)
timeFrame: From baseline to week 4 and 8
Other outcomes:
Locations:
city: Glebe
country: Australia
facility: The Woolcock Institute of Medical Research
state: New South Wales
city: Box Hill
country: Australia
facility: Epworth Eastern Medical Centre
state: Victoria
city: Melbourne
country: Australia
facility: Allergy immunology and Respiratory medicine, The Alfred Hospital
state: Victoria
city: Greenlane
country: New Zealand
facility: The New Zealand Respiratory and Sleep Institute
state: Auckland
city: Dunedin
country: New Zealand
facility: Otago Respiratory Research Unit
city: Humenné
country: Slovakia
facility: INSPIRO, s.r.o. Ambulancia pneumológie a ftizeológie
city: Námestovo
country: Slovakia
facility: DAMIZA, s.r.o. Ambulancia pneumológie a ftizeológie
city: Poprad
country: Slovakia
facility: Poliklinika ADUS, Pľúcna ambulancia
city: Prešov
country: Slovakia
facility: PULMO, s.r.o
city: Spišská Nová Ves
country: Slovakia
facility: Pľúcna ambulancia Hrebenár, s.r.o.
city: Topoľčany
country: Slovakia
facility: ANA JJ, s.r.o, Ambulancia klinickej imunológie a alergológie
city: Lund
country: Sweden
facility: Skane University Hospital
city: Leicester
country: United Kingdom
facility: Respiratory Biomedical Research Unit, Glenfield Hospital
state: Leicestershire
city: Bradford
country: United Kingdom
facility: Bradford Teaching Hospital
city: London
country: United Kingdom
facility: Royal Brompton and Harefield Foundation Trust
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester
Study officials:
References: