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This study is an open label, randomized, three-way crossover study to assess the effect of particle size on the PK and safety of single inhaled doses of AZD7594 in healthy subjects (males aged 18 to 55 years [inclusive]). The study will be performed at a single study center.
The study will comprise:
There will be a minimum wash-out period of 21 and maximum of 28 days between each dose administration.
Subjects will attend a Screening Visit within 28 days before receiving their first dose of AZD7594, if they are found to be eligible, they return for Treatment Period 1, when they will have baseline assessments, and then will be randomized into one of the 6 treatments sequences. For each Treatment Period, the subjects will receive their investigational medicinal product (IMP) dose in the morning of Day 1, will have further assessments for 48 hours after dosing (residential period) and will return to the study center for ambulatory visits 72, 96, 144 and 240 hours after dosing, (Day 4, Day 5, Day 7 and Day 11 respectively).
Each subject will receive AZD7594 as a single inhaled dose of 440 µg (nominal dose) of each of the following treatments, administered via Dry powder inhaler (DPI):
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A - AZD7594 | Experimental | Treatment A - AZD7594 inhalation powder Particle size Large |
|
| Treatment B - AZD7594 | Experimental | Treatment B - AZD7594 inhalation powder Particle size Medium |
|
| Treatment C - AZD7594 | Experimental | Treatment C - AZD7594 inhalation powder Particle size Small |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Treatment A - AZD7594 | Drug | Particle size Large as a single inhaled dose of 440 µg (nominal dose), administered via DPI |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area under plasma concentration-time curve from time zero to infinity (AUC) | Assessment of AUC in healthy male volunteers after the administration of single inhaled dose of AZD7594. | Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose |
| Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC last) | Assessment of AUC last in healthy male volunteers after the administration of single inhaled dose of AZD7594. | Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose |
| Maximum observed plasma concentration (Cmax) | Assessment of Cmax in healthy male volunteers after the administration of single inhaled dose of AZD7594. | Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose |
| Measure | Description | Time Frame |
|---|---|---|
| Time to reach maximum observed plasma concentration (tmax) | Assessment of tmax in healthy male volunteers after the administration of single inhaled dose of AZD7594. | Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose |
| Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t ½,λz) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dr. Thomas Körnicke | PAREXEL Early Phase Clinical Unit Berlin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Berlin | 14050 | Germany |
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| Treatment B - AZD7594 | Drug | Particle size Medium as a single inhaled dose of 440 µg (nominal dose), administered via DPI |
|
| Treatment C - AZD7594 | Drug | Particle size Small as a single inhaled dose of 440 µg (nominal dose), administered via DPI |
|
Assessment of t ½,λz in healthy male volunteers after the administration of single inhaled dose of AZD7594. |
| Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose |
| Mean residence time from zero to infinity (MRT) | Assessment of MRT in healthy male volunteers after the administration of single inhaled dose of AZD7594. | pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose |
| Terminal elimination rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (λz) | Assessment of λz in healthy male volunteers after the administration of single inhaled dose of AZD7594. | Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose |
| Apparent total body clearance of drug from plasma after extravascular administration, estimated as dose divided by AUC (CL/F) | Assessment of CL/F in healthy male volunteers after the administration of single inhaled dose of AZD7594. | pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose |
| Apparent volume of distribution during the terminal phase after extravascular administration estimated by dividing CL/F by λz (Vz/F) | Assessment of (Vz/F) in healthy male volunteers after the administration of single inhaled dose of AZD7594. | pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose |
| Adverse events (AEs) | Assessment of the safety in terms of the incidences of the AEs after the administration of single inhaled dose of AZD7594. | Throughout the study ie. from screening (Day -28) upto follow up visit i.e.. 10 days after last IMP administration |
| Physical examination | Assessment of the safety in terms of the physical examination after the administration of single inhaled dose of AZD7594. | On screening (Day -28), Day 1 to 3 and follow up visit i.e., 10 days after last IMP administration |
| Electrocardiogram (ECG) | Assessment of the safety in terms of the ECG after the administration of single inhaled dose of AZD7594. | Safety ECG will be performed prior to IMP administration and 1, 4 and 24 hours post-IMP administration on Day 1 of each Treatment Period |
| Vital signs (systolic and diastolic blood pressure [BP], pulse rate) | Assessment of the safety in terms of the Vital signs (systolic and diastolic blood pressure, pulse rate) after the administration of single inhaled dose of AZD7594. | Vital signs: pulse, blood pressure and oral body temperature will be measured, pre-dose and 1, 4, 24 hours post dose of each Treatment Period |
| Spirometry | Assessment of the safety in terms of the spirometry after the administration of single inhaled dose of AZD7594. | On Day 1 of each Treatment Period spirometry will be performed pre-dose and at 0.5 and 1 hours post dose |
| Clinical laboratory assessments (hematology, clinical chemistry (including serum potassium and glucose) | Assessment of the safety in terms of the Clinical laboratory assessments (hematology, clinical chemistry (including serum potassium and glucose) after the administration of single inhaled dose of AZD7594. | Safety laboratory tests will be performed at screening, Day 1, Day 11, 240 h post dose and follow up visit |
| ID | Term |
|---|---|
| D001249 | Asthma |
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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