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

Mundipharma

Status and phase: Completed; Phase 3

Conditions: Asthma

Treatments: Drug: Fluticasone/Vilanterol DPI (Relvar Ellipta DPI); Drug: Fluticasone/Formoterol BAI

Study type: Interventional

Funder types: Industry

Identifiers

NCT02753712

KFL3502

2015-000801-38 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 105 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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105 participants in 2 patient groups

fluticasone/vilanterol DPI (Relvar Ellipta DPI)

Active Comparator group

Description:

Inhalation powder. 92/22µg, I inhalation od

Treatment:

Drug: Fluticasone/Vilanterol DPI (Relvar Ellipta DPI)

Fluticasone/formoterol BAI

Experimental group

Description:

Pressurised suspension for inhalation 125/5µg, 2 inhalations bid

Treatment:

Drug: Fluticasone/Formoterol BAI