E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with mild to moderate asthma |
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E.1.1.1 | Medical condition in easily understood language |
Patients with mild to moderate asthma |
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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 | 18.0 |
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 |
The primary objective is to investigate the efficacy of AZD7594 as measured by change in trough forced expiratory volume in 1 second (FEV1) from baseline, as compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
To investigate the effect of AZD7594 on patient-reported outcomes of Asthma Control Questionnaire (ACQ-5), daily symptoms, nighttime awakenings, use of daily rescue medication and morning peak expiratory flow (mPEF) and evening peak expiratory flow (ePEF)
• To investigate the effect of AZD7594 on airway inflammation and hyper-reactivity, as measured by fractional exhaled nitric oxide (FeNO)
• To investigate the pharmacokinetic (PK) profile of AZD7594 in patients with mild to moderate asthma
• To investigate cortisol suppression from AZD7594, as measured by 24-hour plasma cortisol level |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Men and women 18 to 75 years of age, inclusive
• Patients need to be non-smokers or ex-smokers (quit ≥ 6 months before the Visit 1) with total smoking history of <10 pack years.
• Documented clinical diagnosis of asthma for ≥ 6 months before the Visit 1
• Patients on low-dose inhaled corticosteroids (ICS) (equivalent of budesonide ≤ 400 μg per day) or low-dose ICS/long-acting β-2 agonist (LABA), or not on any inhaled steroids, or patients on montelukast
• Patients should be controlled on low dose budesonide during the first 14 ± 2 days of Run-in Part 1, i.e., they need to have ACQ-5of ≤ 1.5 at Visit 2.
• Prebronchodilator FEV1 at Visit 3 should be between 40% and 90% of predicted (mean of 2 predose measurements taken 30 minutes apart). |
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E.4 | Principal exclusion criteria |
• Known or suspected hypersensitivity to the IMPs or excipients, including lactose
• Systemic steroid use in the 6 weeks before Visit 1
• Any active disease other than asthma
• Patients on medium to high-dose ICS (equivalent of budesonide > 400 μg per day) or on inhaled anticholinergic combination within the 6 weeks prior to Visit 1
• Compliance with the eDiary of at least 80% of the days is expected in both Run-in and Treatment Periods. Patients with < 80% eDiary compliance during Run-in Periods would not be randomized |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy:
Change from baseline in morning trough FEV1 on Day 15 (defined as the average of the values at 23:00 and 23:30 hours after last dose of IMP on Day 14
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy:
In each period: before the first dose and in the morning of Day 15
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E.5.2 | Secondary end point(s) |
Efficacy:
• Change from baseline in FeNO on Day 8
• Change from baseline in FeNO on Day 15
• Change from baseline in morning trough FEV1 on Day 8 (defined as the average of the values at 23:00 and 23:30 hours after the dose of IMP on Day 7)
• Change from baseline in morning trough forced vital capacity (FVC) on Day 15 (defined as the average of the values at 23:00 and 23:30 hours after the dose of IMP on Day 14)
• Change from baseline in morning trough FVC on Day 8 (defined as the average of the values at 23:00 and 23:30 hours after the dose of IMP on Day 7)
• Change from baseline in mPEF before administration over the Treatment Period
• Change from baseline in ePEF over the Treatment Period
• Change from baseline in average daily use of rescue salbutamol over the Treatment Period
• Change from baseline in ACQ-5 on Day 15
• Change from baseline in ACQ-5 on Day 8
• Change from baseline in nighttime awakenings over the Treatment Period
• Change from baseline in daily symptom score over the Treatment Period
• Change from baseline in asthma control days over the Treatment Period
Pharmacokinetics (PK, intense PK subgroup):
• Observed maximum plasma concentration (Cmax, Day 1 only)
• Area under the plasma concentration-time curve from time zero to 4 hours after administration (AUC[0-4], Day 1 only)
• Observed maximum plasma concentration at steady state (Cmax,ss, Day 14 only)
• Area under the plasma concentration-time curve from time zero to 24 hours after administration (AUC[0-24], Day 14 only)
• Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC[0-last], Days 1 and 14)
• Time to reach maximum plasma concentration (tmax, Day 1 only)
• Time to reach maximum plasma concentration at steady state (tmax,ss, Day 14 only)
• Average plasma concentration during a dosing interval at steady state (Cavg,ss, Day 14 only)
• Dose-normalized Cmax (Cmax/D)
• Dose-normalized AUC(0-24) (AUC[0-24]/D)
• Predose concentration (Cmin)
Safety
adverse events (AEs), FEV1, physical examination findings, vital signs, digital electrcardiograms (dECGs) and laboratoryassessments.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy:
in each period: before first dosing, on Day 8, on Day 15, in the morning and evening from Day 1 to Day 14
Pharmacokinetics (PK, intense PK subgroup):
On Day 1 in each period, blood samples for PK measurements will be collected before administration and 15 and 30 minutes, and 1, 2 and 4 hours after administration.
On Day 14 in each period, blood samples for PK measurements will be collected before administration and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 hours after administration.
Safety:
Throughout the study |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |