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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-005306-37 | EudraCT Number |
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This study will be a randomised, double-blind, multiple dose (14 days), placebo-controlled, multi-center study to assess efficacy and safety of three dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma.
This is a randomized, double-blind, multiple dosing (14 ± 1 days), placebo-controlled, incomplete block crossover, multi-center study to assess efficacy and safety of 3 dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma.
This multi-center study will be conducted at multiple sites in Europe. It is planned that approximately 48 patients with mild to moderate asthma will be randomized into the study
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1 | Experimental | Placebo once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3 |
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| Sequence 2 | Experimental | Placebo once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3 |
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| Sequence 3 | Experimental | Placebo once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3 |
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| Sequence 4 | Experimental | 58 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 800 μg AZD7594 once daily | Drug | Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 15 | Comparison of the efficacy of AZD7594 in terms of change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 15 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 14) with placebo | On Day 1 (pre-dose) and on Day 15 in each period |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 8 | The efficacy of AZD7594 was assessed in terms of change from baseline in fractional exhaled nitric oxide (FeNO) on Day 8 | On Day 1 (pre-dose) and on Day 8 in each period |
| Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 15 |
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Inclusion Criteria:
Body mass index of 18 to 35 kg/m2
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-5 of ≤ 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).
All patients need to have FeNO concentrations of ≥ 25 parts per billion at Visit 3
Demonstrate the ability to use the study inhalation device properly
Women must be of nonchildbearing potential defined as meeting 1 of the following criteria:
Male patients should be willing to use a condom to prevent pregnancy and exposure of a female partner to AZD7594 and should refrain from donating sperm or fathering a child from the first day of dosing until 3 months after the last dose of IMP.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rainard Fuhr, Dr. med. | PAREXEL International GmbH, Berlin, Germany | Principal Investigator |
| Ulrike Westerhausen, Dr. | Pneumologisches Studienzentrum, Berlin, Germany | Principal Investigator |
| Oliver Kornmann, Dr. | IKF Pneumologie GmbH, Frankfurt, Germany | Principal Investigator |
| Jutta Beier, Dr. med. | Insaf GmbH, Wiesbaden, Germany | Principal Investigator |
| Christine Grigat, Dr. | Clinical Research Hamburg GmbH, Hamburg, Germany | Principal Investigator |
| Andrea Ludwig-Sengpiel, Dr. | KLB Gesundheitsforschung Lübeck GmbH, Lübeck, Germany | Principal Investigator |
| Dirk Skowasch, Prof. | University hospital of Bonn, Department of Internal Medicine II, Bonn, Germany | Principal Investigator |
| Anne-Marie Kirsten, Dr. | Pneumologisches Forschungsinstitut an der LungenClinic Großhansdorf, Großhansdorf, Germany | Principal Investigator |
| Tanya Kralimarkova, Dr. |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Sofia | 1612 | Bulgaria | |||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30777086 | Derived | Brown MN, Fuhr R, Beier J, Su HL, Chen Y, Forsman H, Hamren UW, Jackson H, Aggarwal A. Efficacy and safety of AZD7594, an inhaled non-steroidal selective glucocorticoid receptor modulator, in patients with asthma: a phase 2a randomized, double blind, placebo-controlled crossover trial. Respir Res. 2019 Feb 18;20(1):37. doi: 10.1186/s12931-019-1000-7. |
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The study consisted of a 2-part run-in period, 3 treatment periods separated by intervening wash-out periods, and a final period of safety follow-up .
The study was conducted in Germany (9 centers) and Bulgaria (1 center). A total of 54 participants with mild to moderate asthma were randomized after screening, and received study treatment (AZD7594 or placebo) given over 3 Treatment Periods in an incomplete block crossover design.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1 (Placebo + AZD7594 58 μg + AZD7594 250 μg) | Participants received Placebo in Treatment Period 1 (1st intervention - 14 days), AZD7594 58 μg in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 250 μg treatment in Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Sequence 6 |
| Experimental |
250 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3 |
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| Sequence 8 | Experimental | 800 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3 |
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| Sequence 5 | Experimental | 58 µg AZD7594 once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3 |
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| Sequence 7 | Experimental | 250 µg AZD7594 once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3 |
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| Sequence 9 | Experimental | 800 µg AZD7594 once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3 |
|
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| 250 µg AZD7594 once daily | Drug | Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule |
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| 58 µg AZD7594 once daily | Drug | Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule |
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| Placebo once daily | Drug | Once daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule |
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| Salbutamol | Drug | Inhalation as needed |
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The efficacy of AZD7594 was assessed in terms of change from baseline in fractional exhaled nitric oxide (FeNO) on Day 15 |
| On Day 1 (pre-dose) and on Day 15 in each period |
| Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 8 | The efficacy of AZD7594 was assessed in terms of change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 8 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 7) | On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period |
| Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 15 | The efficacy of AZD7594 was assessed in terms of 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 last dose of investigational medicinal product [IMP] on Day 14) | On Day 1 (pre-dose) and on Day 15 (pre-dose) in each period |
| Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 8 | The efficacy of AZD7594 was assessed in terms of change from baseline in morning trough forced vital capacity (FVC) on Day 8 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 7) | On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period |
| Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Peak Expiratory Flow (mPEF) Before Administration Over the Treatment Period | The efficacy of AZD7594 was assessed in terms of change from baseline in morning peak expiratory flow (mPEF) before administration of the investigational medicinal product (IMP) in each treatment period. The first PEF measurement was on the evening of Visit 1. Every morning and every evening after Visit 1, patients were required to perform 3 maneuvers for PEF assessment. The highest value from among the 3 assessments was marked as mPEF with the date and time of the measurement. The final PEF assessment was done on the morning of Visit 11 (Day 15 of Treatment Period 3). | Every morning at pre-dose from Day 1 to Day 15 |
| Efficacy of AZD7594 by Assessment of the Change From Baseline in Evening Peak Expiratory Flow (ePEF) Before Administration Over the Treatment Period | The efficacy of AZD7594 was assessed in terms of change from baseline in evening peak expiratory flow (ePEF) in each treatment period. The first PEF measurement was on the evening of Visit 1. Every morning and every evening after Visit 1, patients were required to perform 3 maneuvers for PEF assessment. The highest value from among the 3 assessments was marked as ePEF together with the date and time of the measurement. The final PEF assessment was done on the morning of Visit 11 (Day 15 of Treatment Period 3). | Every evening from Day 1 to Day 14 in each period |
| Efficacy of AZD7594 by Assessment of the Change From Baseline in Average Daily Use of Rescue Salbutamol Over the Treatment Period | The efficacy of AZD7594 was assessed in terms of change from baseline in average daily use of salbutamol (each morning and evening) in each treatment period. | Every day from Day 1 to Day 15 (from evening of Day 1 to morning of Day 15) |
| Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 15 in Asthma Control Questionnaire-5 | The efficacy of AZD7594 was assessed in terms of change from baseline to Day 15 in Asthma Control Questionnaire-5 in each treatment period. Five questions were asked and each question was scored on a scale of 0 to 6, where a higher score represents a more severe impairment/symptom. The ACQ-5 score at a given visit was defined as the average of the scores given for each of the questions, calculated as ACQ-5 score = Sum of 5 scores/5. | At baseline and on Day 15 in each period |
| Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 8 in Asthma Control Questionnaire-5 | The efficacy of AZD7594 was assessed in terms of change from baseline to Day 15 in Asthma Control Questionnaire-5 in each treatment period. Five questions were asked and each question was scored on a scale of 0 to 6, where a lower score represents a more severe impairment/symptom. The ACQ-5 score at a given visit was defined as the average of the scores given for each of the questions, calculated as ACQ-5 score = Sum of 5 scores/5. | At baseline and on Day 8 in each period |
| Efficacy of AZD7594 by Assessment of Night-time Awakenings | The efficacy of AZD7594 was assessed in terms of change in nighttime awakenings in each treatment period. The patients were asked to answer 'Yes' or 'No' to the question of "Did your asthma cause you to wake up last night?". If yes, the number and percentage of days that had a night-time awakening were determined for each of the study periods. | At baseline and from Day 2 to Day 15 in each period |
| Efficacy of AZD7594 by Assessment of Daily Symptom Score | The efficacy of AZD7594 was assessed in terms of change in daily symptom score from baseline to average of treatment period post dose (Day 1-14) in each treatment period. Severity scores for asthma symptoms were recorded twice daily, once in the morning and once in the evening with the scoring system of 0-no asthma symptoms, 1-toleratable asthma symptoms, 2-discomfort asthma symptoms with normal activities (or with sleep) and 3-asthma symptoms with impaired normal activities (or to sleep). | At baseline and from Day 1 to Day 14 in each period |
| Efficacy of AZD7594 by Assessment of Asthma Control Days | The efficacy of AZD7594 was assessed in terms of amount of asthma control days in each treatment period. An asthma control day was defined as a day with asthma symptom score = 0, a night with no awakenings due to asthma symptoms and a day with no use of rescue medication. A given calendar day was defined as an asthma control day if it fulfills the criteria for a symptom-free day and for a rescue medication-free day | At baseline and from Day 1 to Day 14 post-dose in each period |
| Number of Participants With Adverse Events | Assessment of safety and tolerability of three dose levels of AZD7594 in participants with mild to moderate asthma. IP referred to investigational product. | From Screening to Follow-up (these two examinations are up to 165 days apart) |
| Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of Cmax of AZD7594 | Comparison of Cmax (maximum observed plasma concentration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose) | On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose) |
| Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of AUC(0-4) of AZD7594 | Comparison of AUC(0-4) (Area under the plasma concentration-time curve from time zero to 4 hours after administration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose). | On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose) |
| Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmax,ss of AZD7594 | Comparison of Cmax,ss (observed maximum plasma concentration at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) | On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) |
| Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-24) of AZD7594 | Comparison of AUC(0-24) (Area under the plasma concentration-time curve from time zero to 24 hours after administration) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) | On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) |
| Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-last) of AZD7594 | Comparison of AUC(0-last) (Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (Day 1 and Day 14)) of AZD7594 (i.e. in participants with intensive pharmacokinetic assessments) | On Day 1 and Day 14 in each period (in participants with intensive pharmacokinetic assessments, on Day 1 at pre-dose and 15 and 30 minutes, and 1, 2 and 4 h post-dose, on Day 14 at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) |
| Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of Tmax of AZD7594 | Comparison of tmax (time to reach maximum plasma concentration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose) | On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose) |
| Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Tmax,ss of AZD7594 | Comparison of tmax,ss (time to reach maximum plasma concentration at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) | On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) |
| Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cavg,ss of AZD7594 | Comparison of Cavg,ss (average plasma concentration during a dosing interval at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) | On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) |
| Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmax/D of AZD7594 | Comparison of Cmax/D (dose-normalized Cmax) of AZD7594 | On Day 1 in each period |
| Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-24)/D of AZD7594 | Comparison of AUC(0-24)/D (dose-normalized AUC(0-24)) of AZD7594 | On Day 14 in each period |
| Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmin of AZD7594 | Comparison of steady-state minimum (pre-dose) concentration (Cmin) of AZD7594 in each treatment period | On Day 14 at pre-dose in each period |
| COMAC Medical Ltd., Sofia, Bulgaria |
| Principal Investigator |
| Anneliese Linnhoff, Dr. med. | Praxis für Lungen- und Bronchialheilkunde, Allergologie und Umweltmedizin | Principal Investigator |
| Margret Jandl, Dr. | Hamburger Institut für Therapie Forschung GmbH | Principal Investigator |
| Berlin |
| 10717 |
| Germany |
| Research Site | Berlin | 10969 | Germany |
| Research Site | Berlin | 14050 | Germany |
| Research Site | Frankfurt | 60596 | Germany |
| Research Site | Großhansdorf | 22927 | Germany |
| Research Site | Hamburg | 20354 | Germany |
| Research Site | Hamburg | 22143 | Germany |
| Research Site | Lübeck | 23552 | Germany |
| Research Site | Wiesbaden | 65187 | Germany |
| FG001 |
| Sequence 2 (Placebo + AZD7594 250 μg + AZD7594 800 μg) |
Participants received Placebo in Treatment Period 1 (1st intervention - 14 days), AZD7594 250 μg in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 800 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| FG002 | Sequence 3 (Placebo + AZD7594 800 µg + AZD7594 58 µg) | Participants received Placebo in Treatment Period 1 (1st intervention - 14 days), AZD7594 800 μg in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 58 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| FG003 | Sequence 4 (AZD7594 58 μg + Placebo + AZD7594 800 μg) | Participants received AZD7594 58 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 800 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| FG004 | Sequence 5 (AZD7594 58 µg + AZD7594 800 µg + Placebo) | Participants received AZD7594 58 μg in Treatment Period 1 (1st intervention - 14 days), AZD7594 800 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| FG005 | Sequence 6 (AZD7594 250 μg + Placebo + AZD7594 58 μg) | Participants received AZD7594 250 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 58 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| FG006 | Sequence 7 (AZD7594 250 μg + AZD7594 58 μg + Placebo) | Participants received AZD7594 250 μg in Treatment Period 1 (1st intervention - 14 days), AZD7594 58 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention- 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| FG007 | Sequence 8 (AZD7594 800 μg + Placebo + AZD7594 250 μg) | Participants received AZD7594 800 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 250 μg Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| FG008 | Sequence 9 (AZD7594 800 μg + AZD7594 250 μg + Placebo) | Participant received AZD7594 800 μg in Treatment Period 1 (1st intervention 14 days), AZD7594 250 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Sequence 1 (Placebo + AZD7594 58 μg + AZD7594 250 μg) | Participants received Placebo in Treatment Period 1 (1st intervention - 14 days), AZD7594 58 μg in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 250 μg treatment in Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| BG001 | Sequence 2 (Placebo + AZD7594 250 μg + AZD7594 800 μg) | Participants received Placebo in Treatment Period 1 (1st intervention - 14 days), AZD7594 250 μg in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 800 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| BG002 | Sequence 3 (Placebo + AZD7594 800 µg + AZD7594 58 µg) | Participants received Placebo in Treatment Period 1 (1st intervention - 14 days), AZD7594 800 μg in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 58 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| BG003 | Sequence 4 (AZD7594 58 μg + Placebo + AZD7594 800 μg) | Participants received AZD7594 58 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 800 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| BG004 | Sequence 5 (AZD7594 58 µg + AZD7594 800 µg + Placebo) | Participants received AZD7594 58 μg in Treatment Period 1 (1st intervention - 14 days), AZD7594 800 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| BG005 | Sequence 6 (AZD7594 250 μg + Placebo + AZD7594 58 μg) | Participants received AZD7594 250 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 58 μg in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| BG006 | Sequence 7 (AZD7594 250 μg + AZD7594 58 μg + Placebo) | Participants received AZD7594 250 μg in Treatment Period 1 (1st intervention - 14 days), AZD7594 58 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention- 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| BG007 | Sequence 8 (AZD7594 800 μg + Placebo + AZD7594 250 μg) | Participants received AZD7594 800 μg in Treatment Period 1 (1st intervention - 14 days), Placebo in Treatment Period 2 (2nd intervention - 14 days) and AZD7594 250 μg Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| BG008 | Sequence 9 (AZD7594 800 μg + AZD7594 250 μg + Placebo) | Participant received AZD7594 800 μg in Treatment Period 1 (1st intervention 14 days), AZD7594 250 μg in Treatment Period 2 (2nd intervention - 14 days) and Placebo in Treatment Period 3 (3rd intervention - 14 days). After treatment periods 1 and 2, participants had an intervening wash-out period of 21 days. |
| BG009 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 15 | Comparison of the efficacy of AZD7594 in terms of change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 15 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 14) with placebo | All randomized participants who received at least one dose of randomized study drug, were included in the full analysis set (FAS), following the principle of intent to treat (ITT). Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | On Day 1 (pre-dose) and on Day 15 in each period |
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| Secondary | Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 8 | The efficacy of AZD7594 was assessed in terms of change from baseline in fractional exhaled nitric oxide (FeNO) on Day 8 | All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | Parts per billion (ppb) | On Day 1 (pre-dose) and on Day 8 in each period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 15 | The efficacy of AZD7594 was assessed in terms of change from baseline in fractional exhaled nitric oxide (FeNO) on Day 15 | All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | Parts per billion (ppb) | On Day 1 (pre-dose) and on Day 15 in each period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 8 | The efficacy of AZD7594 was assessed in terms of change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 8 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 7) | All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 15 | The efficacy of AZD7594 was assessed in terms of 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 last dose of investigational medicinal product [IMP] on Day 14) | All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | On Day 1 (pre-dose) and on Day 15 (pre-dose) in each period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 8 | The efficacy of AZD7594 was assessed in terms of change from baseline in morning trough forced vital capacity (FVC) on Day 8 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 7) | All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Peak Expiratory Flow (mPEF) Before Administration Over the Treatment Period | The efficacy of AZD7594 was assessed in terms of change from baseline in morning peak expiratory flow (mPEF) before administration of the investigational medicinal product (IMP) in each treatment period. The first PEF measurement was on the evening of Visit 1. Every morning and every evening after Visit 1, patients were required to perform 3 maneuvers for PEF assessment. The highest value from among the 3 assessments was marked as mPEF with the date and time of the measurement. The final PEF assessment was done on the morning of Visit 11 (Day 15 of Treatment Period 3). | All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | L/min | Every morning at pre-dose from Day 1 to Day 15 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of AZD7594 by Assessment of the Change From Baseline in Evening Peak Expiratory Flow (ePEF) Before Administration Over the Treatment Period | The efficacy of AZD7594 was assessed in terms of change from baseline in evening peak expiratory flow (ePEF) in each treatment period. The first PEF measurement was on the evening of Visit 1. Every morning and every evening after Visit 1, patients were required to perform 3 maneuvers for PEF assessment. The highest value from among the 3 assessments was marked as ePEF together with the date and time of the measurement. The final PEF assessment was done on the morning of Visit 11 (Day 15 of Treatment Period 3). | All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | L/min | Every evening from Day 1 to Day 14 in each period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of AZD7594 by Assessment of the Change From Baseline in Average Daily Use of Rescue Salbutamol Over the Treatment Period | The efficacy of AZD7594 was assessed in terms of change from baseline in average daily use of salbutamol (each morning and evening) in each treatment period. | All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | Number of inhalations per day | Every day from Day 1 to Day 15 (from evening of Day 1 to morning of Day 15) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 15 in Asthma Control Questionnaire-5 | The efficacy of AZD7594 was assessed in terms of change from baseline to Day 15 in Asthma Control Questionnaire-5 in each treatment period. Five questions were asked and each question was scored on a scale of 0 to 6, where a higher score represents a more severe impairment/symptom. The ACQ-5 score at a given visit was defined as the average of the scores given for each of the questions, calculated as ACQ-5 score = Sum of 5 scores/5. | All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | Unit on a scale | At baseline and on Day 15 in each period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 8 in Asthma Control Questionnaire-5 | The efficacy of AZD7594 was assessed in terms of change from baseline to Day 15 in Asthma Control Questionnaire-5 in each treatment period. Five questions were asked and each question was scored on a scale of 0 to 6, where a lower score represents a more severe impairment/symptom. The ACQ-5 score at a given visit was defined as the average of the scores given for each of the questions, calculated as ACQ-5 score = Sum of 5 scores/5. | All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | Unit on a scale | At baseline and on Day 8 in each period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of AZD7594 by Assessment of Night-time Awakenings | The efficacy of AZD7594 was assessed in terms of change in nighttime awakenings in each treatment period. The patients were asked to answer 'Yes' or 'No' to the question of "Did your asthma cause you to wake up last night?". If yes, the number and percentage of days that had a night-time awakening were determined for each of the study periods. | All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | Number of nighttime awakenings | At baseline and from Day 2 to Day 15 in each period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of AZD7594 by Assessment of Daily Symptom Score | The efficacy of AZD7594 was assessed in terms of change in daily symptom score from baseline to average of treatment period post dose (Day 1-14) in each treatment period. Severity scores for asthma symptoms were recorded twice daily, once in the morning and once in the evening with the scoring system of 0-no asthma symptoms, 1-toleratable asthma symptoms, 2-discomfort asthma symptoms with normal activities (or with sleep) and 3-asthma symptoms with impaired normal activities (or to sleep). | All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | Unit on a scale | At baseline and from Day 1 to Day 14 in each period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of AZD7594 by Assessment of Asthma Control Days | The efficacy of AZD7594 was assessed in terms of amount of asthma control days in each treatment period. An asthma control day was defined as a day with asthma symptom score = 0, a night with no awakenings due to asthma symptoms and a day with no use of rescue medication. A given calendar day was defined as an asthma control day if it fulfills the criteria for a symptom-free day and for a rescue medication-free day | All randomized participants who received at least one dose of randomized study drug, were included in the FAS, following the principle of ITT. Participants were included in the analysis according to the treatment to which they were randomized. | Posted | Least Squares Mean | 95% Confidence Interval | Asthma control days | At baseline and from Day 1 to Day 14 post-dose in each period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Adverse Events | Assessment of safety and tolerability of three dose levels of AZD7594 in participants with mild to moderate asthma. IP referred to investigational product. | The safety analysis set (SAF) included all randomized participants who received at least one dose of randomized study drug during the treatment periods of the study. This analysis set was classified by actual treatment received. If no participants received incorrect treatment then the SAF was identical to the FAS. | Posted | Number | Number of participants | From Screening to Follow-up (these two examinations are up to 165 days apart) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of Cmax of AZD7594 | Comparison of Cmax (maximum observed plasma concentration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose) | The PK analysis set (PKS) included the subset of all randomized participants for whom 24-hour PK sampling was performed on Day 14, for whom the primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | pmol/L | On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of AUC(0-4) of AZD7594 | Comparison of AUC(0-4) (Area under the plasma concentration-time curve from time zero to 4 hours after administration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose). | The subset of all randomized participants; 24-hour PK sampling was performed on Day 14, the primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*pmol/L | On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmax,ss of AZD7594 | Comparison of Cmax,ss (observed maximum plasma concentration at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) | PKS included the subset of all randomized participants for whom 24-hour PK sampling was performed on Day 14, for whom the primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | pmol/L | On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-24) of AZD7594 | Comparison of AUC(0-24) (Area under the plasma concentration-time curve from time zero to 24 hours after administration) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) | PKS included the subset of all randomized participants for whom 24-hour PK sampling was performed on Day 14, for whom the primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*pmol/L | On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-last) of AZD7594 | Comparison of AUC(0-last) (Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (Day 1 and Day 14)) of AZD7594 (i.e. in participants with intensive pharmacokinetic assessments) | PKS included the subset of all randomized participants for whom 24-hour PK sampling was performed on Day 14, for whom the primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*pmol/L | On Day 1 and Day 14 in each period (in participants with intensive pharmacokinetic assessments, on Day 1 at pre-dose and 15 and 30 minutes, and 1, 2 and 4 h post-dose, on Day 14 at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of Tmax of AZD7594 | Comparison of tmax (time to reach maximum plasma concentration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose) | PKS included the subset of all randomized participants for whom 24-hour PK sampling was performed on Day 14, for whom the primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data. | Posted | Median | Full Range | Hour | On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Tmax,ss of AZD7594 | Comparison of tmax,ss (time to reach maximum plasma concentration at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) | PKS included the subset of all randomized participants for whom 24-hour PK sampling was performed on Day 14, for whom the primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data. | Posted | Median | Full Range | Hour | On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cavg,ss of AZD7594 | Comparison of Cavg,ss (average plasma concentration during a dosing interval at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) | PKS included the subset of all randomized participants for whom 24-hour PK sampling was performed on Day 14, for whom the primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | pmol/L | On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmax/D of AZD7594 | Comparison of Cmax/D (dose-normalized Cmax) of AZD7594 | PKS included the subset of all randomized participants for whom 24-hour PK sampling was performed on Day 14, for whom the primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | pmol/L/μmol | On Day 1 in each period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-24)/D of AZD7594 | Comparison of AUC(0-24)/D (dose-normalized AUC(0-24)) of AZD7594 | PKS included the subset of all randomized participants for whom 24-hour PK sampling was performed on Day 14, for whom the primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*pmol/L/ μmol | On Day 14 in each period |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmin of AZD7594 | Comparison of steady-state minimum (pre-dose) concentration (Cmin) of AZD7594 in each treatment period | The subset of all randomized participants, 24-hour PK sampling was performed on Day 14, primary PK parameters (Cmax , AUC(0-4), Cmax,ss, AUC(0-24)) were calculated in at least one treatment period, and who had no major protocol deviations considered to impact the analysis of the PK data. Cmin was not determined for AZD7594 58 μg | Posted | Geometric Mean | Geometric Coefficient of Variation | pmol/L | On Day 14 at pre-dose in each period |
|
|
From Screening to Follow-up (these two examinations are up to 165 days apart)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo (PBO) | Placebo for AZD7594 DPI once daily | 0 | 52 | 17 | 52 | ||
| EG001 | AZD7594 58 μg | AZD7594 DPI once daily - 2 capsules of 29 μg | 0 | 34 | 13 | 34 | ||
| EG002 | AZD7594 250 μg | AZD7594 DPI once daily - 2 capsules of 125 μg | 0 | 34 | 9 | 34 | ||
| EG003 | AZD7594 800 μg | AZD7594 DPI once daily - 2 capsules of 400 μg | 0 | 34 | 12 | 34 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Gastrointestinal infection | Infections and infestations | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Nasal inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Hepatosplenomegaly | Hepatobiliary disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Anaemia vitamin B12 deficiency | Blood and lymphatic system disorders | MedDRA version 18.1. | Non-systematic Assessment |
| |
| Eye irritation | Eye disorders | MedDRA version 18.1. | Non-systematic Assessment |
|
If a publication (e.g., in a scientific journal) based on the results of this study is envisaged, approval from AstraZeneca will be obtained and a draft manuscript will be submitted to AstraZeneca for scrutiny and comment. The choice of conduit will be mutually agreed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Leader | AstraZeneca AB | +46 31 7761000 | ClinicalTrialTransparency@astrazeneca.com |
| ID | Term |
|---|---|
| D001249 | Asthma |
| 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 |
Not provided
Not provided
| ID | Term |
|---|---|
| C000708431 | velsecorat |
| D000420 | Albuterol |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
Not provided
Not provided
| Male |
|
| AZD7594 800 µg vs.PBO |
|
| Mixed Models Analysis |
| 0.1827 |
| Mean Difference (Final Values) |
| 0.07604 |
| Standard Error of the Mean |
| 0.05663 |
| 2-Sided |
| 95 |
| -0.03645 |
| 0.1885 |
| Superiority or Other |
| AZD7594 800 μg vs. PBO | Mixed Models Analysis | 0.0108 | Mean Difference (Final Values) | 0.1478 | Standard Error of the Mean | 0.05679 | 2-Sided | 95 | 0.03494 | 0.2606 | Superiority or Other |
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| Counts |
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| Participants |
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| Participants |
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AZD7594 DPI once daily - 2 capsules of 400 μg
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AZD7594 DPI once daily - 2 capsules of 400 μg
|
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| Units | Counts |
|---|---|
| Participants |
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AZD7594 DPI once daily - 2 capsules of 400 μg
|
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| Participants |
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| Participants |
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