E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Inhaled Fluticasone/Formoterol improves both large and small airway function in moderate to severe persistent asthma.
The primary objective of this study is to demonstrate a statistically significant change in both OE-MRI imaging biomarkers [oxygen exponential washout time (ôdown) and major airway ventilation (Tvent) time] using dynamic OE-MRI in moderate-to-severe asthmatics, within 30 minutes of administration of two observed inhalations via spacer of Fluticasone/Formoterol [250/10].
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E.2.2 | Secondary objectives of the trial |
• To demonstrate significant improvement of conventional lung physiological measurements (LCI, Scond and Sacin) within 60 minutes of administration of Fluticasone/Formoterol. • To investigate alterations in other OE-MRI imaging markers including ventilated fraction, exponential wash-in time (ôup), maximum ÄPO2, V/Q. • To investigate degree of regional lung variation in response to Fluticasone/Formoterol on OE-MRI.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria for Asthma Patients
• Asthma • Aged 18-70 years • GINA treatment steps 3/4 • Physician diagnosis and one or more of the following (i) PC20 ≤ 8 mg/ml, (ii) bronchodilator reversibility FEV1 > 12%/200mls, (iii) Peak flow variability of ≥ 20% over 2 weeks • Post-bronchodilator FEV1% predicted of ≥ 60% and an FEV1/FVC ratio of < 70% • Willing and able to give informed consent
Inclusion Criteria for Healthy Volunteers
• No prior history of respiratory disease or symptoms • Aged 18-70 years • Normal spirometry and methacholine PC20 ≥ 16 mg/ml • Willing and able to give informed consent
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E.4 | Principal exclusion criteria |
Exclusion Criteria for Asthma Patients
* Exacerbation within the previous 6 weeks requiring oral steroids * Concurrent leukotriene receptor antagonist or theophylline * Non reversible active lung disease e.g. bronchiectasis * Current smoker/ ≥ 10 pack year smoking history * Use of beta blocker, tricyclic antidepressant, mono amine oxidase inhibitor, quinidine type anti arrhythmic, or potent CYP3A4 inhibitors within the past week * Unable to provide informed consent * Pregnancy or lactating at the time of consent (or) if identified as pregnant by a pregnancy test during the first study visit. * History of poor treatment adherence * Claustrophobia * Metallic implants/screen failure on MRI safety questionnaire * <18 years or >70 years
Exclusion Criteria for Healthy Volunteers
Non reversible active lung disease e.g. bronchiectasis Current smoker/ ≥ 10 pack year smoking history Use of beta blocker, tricyclic antidepressant, mono amine oxidase inhibitor, quinidine type anti arrhythmic, or potent CYP3A4 inhibitors within the past week Unable to provide informed consent Pregnancy or lactating at the time of consent (or) if identified as pregnant by a pregnancy test during the first study visit. Claustrophobia Metallic implants/screen failure on MRI safety questionnaire <18 years or >70 years
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to demonstrate a statistically significant change in both oxygen exponential washout time (ôdown) and major airway ventilation (Tvent) time using dynamic OE-MRI in moderate-to-severe asthmatics (GINA 3-4), within 30 minutes of administration of two observed inhalations via spacer of Fluticasone/Formoterol [250/10]. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
30 minutes post inhlation of Flutiform. |
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E.5.2 | Secondary end point(s) |
• To demonstrate significant improvement of conventional SF6 multiple breath washout physiological measurements (LCI, Scond and Sacin) within 30 minutes of administration of Fluticasone/Formoterol. • To investigate alterations in other OE-MRI parameters including ventilated fraction, exponential wash-in time (τup), maximum ΔPO2, V/Q (see section 7.9). • To investigate degree of spatial heterogeneity in response to Fluticasone/Formoterol on OE-MRI |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
30 minutes post inhlation of Flutiform. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Imaging biomarker assessment |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 1 |