Asthma Bronciale MedDRA version: 18.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 18.1 Level: LLT Classification code 10003555 Term: Asthma bronchial System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 18.1 Level: LLT Classification code 10068462 Term: Eosinophilic asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Flutiform 125micrograms / 5 micrograms per actuation pressurised inhalation, suspension
Product Name: Fluticasone/ formoterol BAI 125/5 µg
Product Code: K-haler
Pharmaceutical Form: Pressu
Sponsors
Mundipharma Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants to be included in the study are those who meet all of the following criteria: Inclusion criteria (for participants on Seretide Accuhaler 250/50 µg at screening): 1. Male and female participants =18 years old. 2. Female participants less than one year post-menopausal must have a negative urine pregnancy test recorded at the screening visit prior to the first dose of study medication, be non-lactating, and willing to use adequate and highly effective methods of contraception throughout the study. A highly effective method of birth control is defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs (Intrauterine Device, hormonal), true sexual abstinence, where this is in line with the preferred and usual lifestyle of the participant, or vasectomised partner. Note: Periodic abstinence (calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for duration of study, and withdrawal are not acceptable methods of 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 past 24 months) of eosinophilic airways disease, evidenced by sputum eosinophil count = 3% and/or FeNO = 35 ppb. 8. Good compliance with current asthma medication(s) in the Investigators opinion. 9. Willing and able to substitute pre-study prescribed inhaled asthma medication for the entire duration of the study. 10. Willing and able to attend all study visits. 11. Written informed consent obtained. Inclusion criteria (for participants on equivalent /higher dose or other ICS-LABAs or higher dose of Seretide at screening): 1. Male and females participants =18 years old. 2. Female participants less than one year post-menopausal must have a negative urine pregnancy test recorded at the screening visit prior to the first dose of study medication, be non-lactating, and willing to use adequate and highly effective methods of contraception throughout the study. A highly effective method of birth control is defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs (Intrauterine Device, hormonal), true sexual abstinence where this is in line with the preferred and usual lifestyle of the participant, or vasectomised partner. Note: Periodic abstinence (calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for duration of study, and withdrawal are not acceptable methods of 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. 6. Good compliance with current asthma me
Exclusion criteria
Exclusion criteria: Participants to be excluded from the study are those who meet any of the following criteria: 1. Any severe chronic respiratory disease other than asthma. 2. Participant 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 participant 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. Participant has taken ß-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 participants undergoing OE-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 that 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 >140 kg). Randomisation Criteria required following Run-in 1. R5-R20 = 0.10 kPa/L/s 2. ACQ-6 score =1.0
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To show the improvement of small airway (as measured by airway resistance) in patient's taking fluticasone/formoterol breath actuated inhaler (BAI). ;Secondary Objective: - To show that fluticasone/formoterol breath actuated inhaler (BAI) has a better effect on small airway (as measured by airway resistance) than Relvar Ellipta Dry Powder Inhaler (DPI.) - To compare the effect of fluticasone/formoterol BAI and Relvar Ellipta DPI on other measures of ventilation heterogeneity (the uneven distribution of breathed in air within the lung). - To compare the effect of fluticasone/formoterol BAI and Relvar Ellipta DPI on small airway function, volume and resistance using imaging techniques (CT&MRI scans) - To evaluate the control of a patient's asthma and their general health status after treatment with fluticasone/formoterol BAI and Relvar Ellipta DPI ;Primary end point(s): The primary objective of the study is to demonstrate improvement of peripheral airway resistance (R5-R20) from baseline with fluticasone/formoterol breath actuated inhaler (BAI) based on the mean change in R5-R20 from baseline to week 8.;Timepoint(s) of evaluation of this end point: Week 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints – Impulse oscillometry (IOS) • Change in R5-R20 from baseline to week 4 and 9 • Change in R5 (total airway resistance) from baseline to week 4, 8 and 9 • Change in AX (Area under reactance) from baseline to week 4, 8 and 9 • Change in Fres (resonant frequency) from baseline to week 4, 8 and 9 • Change in X5 (reactance at 5Hz) from baseline to week 4, 8 and 9 • Change in delta X5 (within breath reactance difference) from baseline to week 4, 8 and 9 Secondary endpoints – Body plethysmography • Change in sRaw from baseline to week 8 • Change in lung volumes (RV, TLC, FRC) from baseline to week 8 • Change in RV/TLC from baseline to week 8 Secondary endpoints – Multiple breath nitrogen washout (MBNWT) • Change in Scond (ventilation heterogeneity in convection dependent airways) from baseline to week 8 and 9 • Change in Sacin (ventilation heterogeneity in diffusion-dependent airways) from baseline to week 8 and 9 • Change in lung clearance index (LCI) from baseline to week 8 and 9 Secondary endpoints – Functional respiratory Imaging (FRI) • Change in FRI parameters from baseline to week 8 and 9 o Lung and Lobar Volumes at FRC and TLC o Airway Volumes at FRC and TLC (iVaw) o Air Trapping o Airway Resistance (iRaw) o Internal Lobar Airflow Distribution o Airway Wall Thickness (iVaww) o Aerosol deposition concentrations Secondary endpoints – Oxygen enhanced – Magnetic Resonance Imaging (OE-MRI) • Change in the below parameters from baseline to week 8 and 9; o Maximal change in the partial pressure of oxygen in lung tissue (? PO2max_l). PO2 is determined from the change in OE-MRI signal due to the inhalation of elevated levels of oxygen while being scanned. ? PO2max is the maximum observed ? PO2 during the dynamic OE-MRI scanning procedure. o Median wash-in time (t_up_l) and wash-out time (t_down_l). Wash-in and wash-out times are derived using an | — |
Countries
Australia, Slovakia, Sweden
Contacts
Public ContactClinical Research Organisation
Secret Files OY
Outcome results
None listed