Asthma
Conditions
Keywords
Inhaled non-steroidal glucocorticoid receptor modulator, Asthma, Inhaled corticosteroids., Glucocorticoid receptor (GA) agonists., Chronic obstructive pulmonary disease., Short-acting B2 agonist., Fluticasone furoate.
Brief summary
This study will assess the efficacy and safety of multiple dose levels of AZD7594 administered once daily (QD) by inhalation in a 12-week treatment period on asthma subjects. The activity will be assessed by comparing AZD7594 to placebo. The comparison between active comparator (FF) and placebo will be used for bench marking. The efficacy is assessed by the evaluation of change in trough forced expiratory volume in 1 second (FEV1). The aim is to develop AZD7594 as a once daily inhaled non-steroidal selective GR modulator (SGRM), which may ultimately lead to better disease control of both chronic obstructive pulmonary disease (COPD) and asthma through improved efficacy and compliance. The overall rationale for developing a once daily AZD7594 in a dry powder inhaler (DPI) is to provide a safe and effective future treatment option for both asthma and COPD subjects.
Detailed description
This is a randomised, placebo-controlled, double-blind multi center (8 countries: Europe, United States \[US\], South Africa, and Japan) study conducted on 714 subjects (102 subject per arm) with asthma symptomatic on low dose inhaled corticosteroids (ICS). The study consists of 3 periods: * Run-in period (21-28 days; visits 1 to 3) * Treatment period (12-week; Visits 4 to 7) * Follow-up (1-week; visit 8). The Run-in period consist of 3 visits: Screening visit (1), reversibility visit (2) and randomization visit (3). All subjects will sign an informed consent form (ICF) prior to participating in any study-specific procedures. Subjects found to be eligible at Visit 1 (Screening Visit) will discontinue all asthma medications and switch to low dose budesonide (200 μg twice a day \[BID\] in Europe and 180 μg BID in US) and rescue medication will be taken as needed. Subjects on long-acting beta agonist (LABA), fixed dose combination ICS/LABA treatment or a long-acting muscarinic antagonist (LAMA) will return for Visit 2 between 2 to 7 days after Visit 1 to have a sufficient wash-out time of their asthma medications. If reversibility criteria are met at Visit 2, subjects will proceed to Visit 3 (Randomization will occur within 21 to 28 days of Visit 1). At Visit 3, subjects who remain symptomatic while on low dose budesonide will be randomized in an overall ratio of 1:1:1:1:1:1:1 to one of 7 possible treatments and will receive inhalation powder via oral route: * AZD7594 DPI 55μg \[nominal strength\]/50 μg \[delivered dose\] (QD) * AZD7594 DPI 99 μg/90 μg QD * AZD7594 DPI 198 μg/180 μg QD * AZD7594 DPI 396 μg/360 μg QD * AZD7594 DPI 792 μg/720 μg QD * Placebo for AZD7594 QD * FF 100 μg QD (open-label) The follow-up will be done by telephone contact within 7 to 10 days after Visit 7 or last investigational product (IP) intake. The total duration of the study will be between 113 to 135 days for each individual subject and is planned to run approximately 12 months (it should not exceed 18 months).
Interventions
DRUGAZD7594 DPI 55μg/50μg.
A non-steroidal and selective modulator of the GR.
DRUGAZD7594 DPI 99 µg/90 µg
A non-steroidal and selective modulator of the GR.
DRUGAZD7594 DPI 198 µg/180 µg
A non-steroidal and selective modulator of the GR.
DRUGAZD7594 DPI 396 µg/360 µg once daily.
A non-steroidal and selective modulator of the GR.
DRUGAZD7594 DPI 792 µg/720 µg
A non-steroidal and selective modulator of the GR.
DRUGPlacebo for AZD7594 once daily.
Placebo for AZD7594
DRUGFF 100 µg once daily (open-label)
Fluticasone furoate
Sponsors
Parexel
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
All double-blind medication kits will have similar appearance regardless of the IP (AZD7594 or placebo) contained in a DPI device and will be labelled using a unique medication identification number (Kit ID) that is linked to a treatment arm. IVRS/IWRS will assign the study medication to be dispensed to each subjects at Visit 3. Supplies of budesonide, FF and SABA (salbutamol/albuterol) will be open-label.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1\. Provision of informed consent prior to any study-specific procedures 2. Men and women 18 to 85 years of age, inclusive, with body mass index (BMI)≤35 3. Subjects need to be non-smokers or ex-smokers (have quit e cigarettes or other inhaled tobacco products ≥6 months before Visit 1) with a total smoking history of less than 10 pack-years (not applicable for e cigarettes) 4. Documented clinical diagnosis of asthma for ≥6 months before Visit 1 5. Subjects on stable medium to high dose ICS (equivalent of budesonide \>400 μg/day) or low to medium dose ICS/LABA for at least 4 weeks prior to screening (Visit 1) (Appendix A, GINA, 2018) 6. Subjects must demonstrate reversibility to inhaled bronchodilators at Visit 2 (a ≥12% and ≥200 mL improvement in FEV1 after administration of a 4 puffs of salbutamol/albuterol) 7. Pre-bronchodilator FEV1 at Visit 3 between 40% and 90% predicted at either -45 or -15 minutes pre-dose 8. At Visit 3, subjects need to be symptomatic on low dose ICS as evidenced by combined daily asthma mean symptom score of \>1 over the previous 7 days or SABA use on ≥3 of the last 7 days during the Run-in Period 9. Demonstrate the ability to use the study inhalation device properly 10. Subject able to perform acceptable pulmonary function testing for FEV1 according to American Thoracic Society/European Respiratory Society (ATS/ERS) acceptability criteria 11. Subject is willing and able to follow study procedures and restrictions. Women of child bearing potential (WOCBP) should be stable on their chosen method of highly effective birth control for a minimum of 3 months prior to Visit 1, and willing to use that for the entire duration of the study (from the time they sign the informed consent), and for 1 month after the last dose of IP 12. For optional inclusion in the Gx component of the study, subjects must provide separate informed consent for the genomic sampling and analysis
Exclusion criteria
1. Known or suspected hypersensitivity to any of the IPs, including budesonide, or excipients, including lactose 2. Systemic steroid use within the 6 weeks before Visit 1 3. Concomitant chronic respiratory disease (including current sleep apnea) 4. History or clinical suspicion of any clinically relevant or active disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study, or any other safety concerns in the opinion of the Investigator 5. Use of prohibited medications that cannot be stopped during the entire period of the study (starting Visit 1). 6. Subjects with \<80% eDiary compliance during Run in Period at Visit 3 7. ACQ-5 of ≥3 at Visit 1, Visit 2, or Visit 3 8. Daily rescue use of SABA ≥12 puffs for ≥3 consecutive days at any time during Run-in Period, before randomisation 9. Any clinically important abnormalities in rhythm, conduction or morphology of the digital ECG at rest and any abnormalities in the digital ECG (at Visit 1 or Visit 3) that, as considered by the Investigator, may interfere with the interpretation of QT interval corrected (QTc) interval changes 10. Prolonged QT interval corrected using Fridericia's formula (QTcF) ≥450 msec based on ECG at Visit 1 or Visit 3; or family history of long QT syndrome 11. PR (PQ) interval prolongation (\>240 msec), intermittent second or third degree atrial-ventricular (AV) block or AV dissociation at Visit 1 or Visit 3 12. Subjects with implantable cardiac defibrillator and subjects with sustained symptomatic ventricular and/or atrial tachyarrhythmia 13. Subjects with unstable angina pectoris or stable angina pectoris classified higher than Canadian Cardiovascular Society Class II, or a myocardial infarction or stroke within 6 months before Visit 1 14. History of hospitalisation within 12 months before Visit 1 caused by heart failure or a diagnosis of heart failure higher than New York Heart Association Class II 15. Subjects who are positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) at Visit 1 16. Donation of blood (≥ 450 mL) within 3 months or donation of plasma within 14 days before Visit 1 17. Suspected poor capability to follow instructions of the study, as judged by the Investigator 18. Previous participation or prior screen failure in the current study, or participation in any other research study within 1 month prior to Visit 1 19. Subject under treatment with biologicals such as monoclonal antibodies or chimeric biomolecules including omalizumab, mepolizumab, and reslizumab within 6 months or 5 half-lives before Visit 1, whichever is longer 20. Subject treated with any investigational drug within 30 days (or 5 half-lives, whichever is longer) prior to Visit 1 21. Positive drug screening result that cannot be justified by subject's medical history and its relevant treatment (over-the-counter product or a valid prescription), or history of or current alcohol or drug abuse (including marijuana and marijuana-containing valid prescriptions), as judged by the Investigator 22. Planned in-patient surgery, major dental procedure or hospitalisation during the study 23. Pregnant woman or lactating woman 24. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff, contract research organisation staff and/or staff at the study centre) 25. Suspicion of Gilbert's syndrome 26. Vulnerable persons (eg, persons kept in detention)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough FEV1 at Week 12 | At week 12 | Trough value was defined as the mean of the 2 measurements 30 minutes apart (23 hours after last dose) pre-dose for every visit throughout the Treatment Period (Visit 4/Week 2 to Visit 7/Week 12). Baseline was defined as the mean of the 2 measured values before first IP administration (30 minutes apart, at -45 minutes and -15 minutes, before IP administration) on Day 1 (Visit 3). Analyses were based on a Mixed-effects model for repeated measures (MMRM) with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates. To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose Inhaled corticosteroid (ICS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | At week 2, 4, 8, and 12 | Baseline was defined as the last value obtained prior to the first dose of investigational product. Analyses were based on a MMRM with change from baseline on the log-scale as the response, treatment, visit, treatment by visit interaction and region as fixed effects, and log-transformed baseline value and baseline by visit interaction as covariates. |
| Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | At week 12 | Trough value was defined as the mean of the 2 measurements 30 minutes apart (23 hours after last dose) pre-dose for every visit throughout the Treatment Period (Visit 4/Week 2 to Visit 7/Week 12). Baseline was defined as the mean of the 2 measured values before first IP administration (30 minutes apart, at -45 minutes and -15 minutes, before IP administration) on Day 1 (Visit 3). Analyses were based on a MMRM with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates. |
| Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | At week 12 | Baseline was defined as the ACQ-5 score at Visit 3. Analyses were based on a MMRM with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates. To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. Patients are asked to recall how their asthma was during the previous week and to evaluate their symptoms. The questionnaire has 5 items each item is scored on a scale of 0 to 6, where higher scores represent more severe impairment/symptoms. ACQ is the sum of the scores from all 5 items. |
| Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | Week 0 (7 days prior to randomisation) to Week 12 | Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate. To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. |
| Change From Baseline in Average Evening PEF Over the Treatment Period | Week 0 (7 days prior to randomisation) to Week 12 | Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate. To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. |
| Change From Baseline in Average Daily Use of Rescue Medication Over the Treatment Period | Week 0 (7 days prior to randomisation) to Week 12 | To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate. |
| Change From Baseline in Percent Night-time Awakening Days Over the Treatment Period | Week 0 (7 days prior to randomisation) to Week 12 | To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate. |
| Change From Baseline in Average Daily Asthma Symptom Score Over the Treatment Period | Week 0 (7 days prior to randomisation) to Week 12 | To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate. During the Run-in and Treatment Periods, subjects recorded the severity of their asthma symptoms during night-time and day-time each morning and evening, using the eDiary. Asthma symptom scores during night-time/day-time were assessed by the subject each morning/evening according to the following scoring system and recorded on the eDiary: 0: No asthma symptoms, 1: The subjects were aware of their asthma symptoms but they can easily tolerate the symptoms, 2: asthma was causing enough discomfort to cause problems with sleep, 3: Subjects were unable to sleep/do normal activities because of their asthma. |
| Change From Baseline in Percent Asthma Control Days Over the Treatment Period | Week 0 (7 days prior to randomisation) to Week 12 | To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. Asthma-control days is defined as days with no symptoms, nonight-waking, no reliever use, and no exacerbation. Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate. |
| Change From Baseline in Percent Rescue-free Days Over the Treatment Period | Week 0 (7 days prior to randomisation) to Week 12 | To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. A rescue-free day (RFD) was defined as a day where the number of puffs of medication for the relief of asthma symptoms was reported as zero. Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate. |
| Change From Baseline in Percent Symptom-free Days Over the Treatment Period | Week 0 (7 days prior to randomisation) to Week 12 | To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. Days without asthma symptoms, or symptom-free days, are defined as a day without asthma symptoms, short-acting β-agonist (SABA) use, systemic corticosteroid use, or need for urgent asthma care. |
| Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | At week 2, 4 and 8 | Trough value was defined as the mean of the 2 measurements 30 minutes apart (23 hours after last dose) pre-dose for every visit throughout the Treatment Period (Visit 4/Week 2 to Visit 7/Week 12). Baseline was defined as the mean of the 2 measured values before first IP administration (30 minutes apart, at -45 minutes and -15 minutes, before IP administration) on Day 1 (Visit 3). Analysis of covariance (ANCOVA) with treatment and region (ie, US, Japan, and RoW) as fixed effects, and baseline as covariate was used for the analysis of average over the Treatment Period. To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. |
| Observed Minimum Concentration at the End of the Dosing Interval (Css,Min) of AZD7594 at Day 84 | Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose) | Summary of PK parameter Css,min, observed minimum concentration, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter. |
| Time to Maximum Concentration at Steady State, Taken Directly From the Individual Concentration-time Curve (Tss, Max) of AZD7594 at Day 84 | Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose) | Summary of PK parameter tss, max, Time to maximum concentration at steady state, taken directly from the individual concentration-time curve, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter. |
| Time of Last Quantifiable Analyte Concentration (Tlast) of AZD7594 at Day 84 | Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose) | Summary of PK parameter Tlast, Time of last quantifiable analyte concentration, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter. |
| Area Under the Plasma Concentration-curve From Time Zero to the Time of Last Quantifiable Analyte Concentration (AUClast) of AZD7594 at Day 84 | Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose) | Summary of PK parameter AUClast, Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter. |
| Area Under the Plasma Concentration-curve Within a Dosing Interval (AUCτ) of AZD7594 at Day 84 | Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose) | Summary of PK parameter AUCτ, Area under the plasma concentration-curve within a dosing interval, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter. |
| Average Plasma Concentration During a Dosing Interval at Steady State (Css,Avg) of AZD7594 at Day 84 | Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose) | Summary of PK parameter Css,avg, Average plasma concentration during a dosing interval at steady state, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter. |
| Dose Normalised Css,Max (Css,Max/D) of AZD7594 at Day 84 | Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose) | Summary of PK parameter Css,max/D Dose normalised Css,max, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter. |
| Dose Normalised AUCτ (AUCτ/D) of AZD7594 at Day 84 | Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose) | Summary of PK parameter AUCτ/D, Dose normalised AUCτ, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter. |
| Percentage Fluctuation of AZD7594 at Day 84 | Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose) | To describe the (steady state) PK of AZD7594 in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (PK Analysis Set). The presented results are summary statistics of the PK parameter. No statistical analysis is done for this endpoint. Fluctuation index during a dosing interval estimated as 100\*(Css,max - Css,min)/Css,avg (%), where Css,min is the minimum concentration at the end of the dosing interval. |
| Change From Baseline in Area Under Plasma Cortisol Concentration-time Curve (AUEC0-24hrs Post Dose), of AZD7594 vs Placebo at Day 84 | At Day -1 (-24 to -12 h prior to the dose on Day 0) and at Day 84 (0 to 12 hours post dose) | Area under the plasma cortisol concentration-time curve from zero to 24 hours after dosing compared to Placebo, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter. |
| Number of Participants With Adverse Events | From screening to follow-up period (7 to 10 days after visit 7) | To evaluate the safety and tolerability of AZD7594 in relation to Placebo in asthmatics symptomatic on low dose ICS |
| Observed Maximum Concentration at Steady State (Css,Max) of AZD7594 at Day 84 | Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose) | Summary of PK parameter Css,mx, observed maximum concentration, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter. |
Countries
Bulgaria, Germany, Hungary, Japan, Poland, South Africa, Ukraine, United States
Participant flow
Recruitment details
The study was conducted in 92 sites in 8 countries; Bulgaria, Germany, Hungary, Poland, and Ukraine, United States (US), South Africa, and Japan. In this study, 806 patients (including 82 Japanese patients) were randomised. For sites in the US, no patients were randomised to the AZD7594 792 μg/720 μg once daily (QD) treatment arm.
Pre-assignment details
Subjects attended a Screening Visit within 28 days before receiving their first dose. All subjects underwent inclusion exclusion criteria assessment and all eligible subjects signed the informed consent before undergoing any study related procedures. One patient in the AZD7594 50 μg treatment arm did not receive any treatment and was randomised in error (protocol deviation).
Participants by arm
| Arm | Count |
|---|---|
| AZD7594 50 μg Oral inhalation of AZD5794 55 microgram/ 50 microgram (nominal dose/delivered dose) once daily. | 110 |
| AZD7594 90 μg Oral inhalation of AZD5794 99 microgram/ 90 microgram (nominal dose/delivered dose) once daily. | 112 |
| AZD7594 180 μg Oral inhalation of AZD5794 198 microgram/ 180 microgram (nominal dose/delivered dose) once daily. | 111 |
| AZD7594 360 μg Oral inhalation of AZD5794 396 microgram/ 360 microgram (nominal dose/delivered dose) once daily. | 113 |
| AZD7594 720 μg Oral inhalation of AZD5794 792 microgram/ 720 microgram (nominal dose/delivered dose) once daily. | 134 |
| Placebo to AZD7594 Oral inhalation of placebo to AZD7594 once daily. | 113 |
| Fluticasone Furoate Oral inhalation of fluticasone furoate 100 microgram once daily. | 112 |
| Total | 805 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 8 | 4 | 11 | 4 | 20 | 2 |
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 0 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Reason not specified | 0 | 1 | 0 | 1 | 1 | 2 | 1 |
| Overall Study | Study-specific withdrawal criteria | 10 | 8 | 7 | 6 | 4 | 18 | 4 |
| Overall Study | Withdrawal by Subject | 6 | 2 | 4 | 2 | 1 | 2 | 2 |
Baseline characteristics
| Characteristic | AZD7594 50 μg | AZD7594 180 μg | AZD7594 360 μg | AZD7594 720 μg | AZD7594 90 μg | Placebo to AZD7594 | Fluticasone Furoate | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 32 Participants | 21 Participants | 27 Participants | 20 Participants | 26 Participants | 30 Participants | 176 Participants |
| Age, Categorical Between 18 and 65 years | 90 Participants | 79 Participants | 92 Participants | 107 Participants | 92 Participants | 87 Participants | 82 Participants | 629 Participants |
| Age, Continuous | 52.2 Years STANDARD_DEVIATION 12.8 | 54.6 Years STANDARD_DEVIATION 14.5 | 52.8 Years STANDARD_DEVIATION 13.2 | 52.2 Years STANDARD_DEVIATION 13 | 53.2 Years STANDARD_DEVIATION 13.3 | 53.4 Years STANDARD_DEVIATION 13.7 | 53.7 Years STANDARD_DEVIATION 13.4 | 53.1 Years STANDARD_DEVIATION 13.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 10 Participants | 13 Participants | 16 Participants | 11 Participants | 13 Participants | 12 Participants | 84 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 2 Participants | 1 Participants | 5 Participants | 5 Participants | 7 Participants | 30 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 0 Participants | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 95 Participants | 94 Participants | 97 Participants | 115 Participants | 93 Participants | 92 Participants | 93 Participants | 679 Participants |
| Sex: Female, Male Female | 59 Participants | 72 Participants | 64 Participants | 79 Participants | 66 Participants | 68 Participants | 59 Participants | 467 Participants |
| Sex: Female, Male Male | 51 Participants | 39 Participants | 49 Participants | 55 Participants | 46 Participants | 45 Participants | 53 Participants | 338 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 110 | 0 / 112 | 0 / 111 | 1 / 113 | 0 / 134 | 0 / 113 | 0 / 112 |
| other Total, other adverse events | 14 / 110 | 15 / 112 | 8 / 111 | 14 / 113 | 8 / 134 | 24 / 113 | 11 / 112 |
| serious Total, serious adverse events | 0 / 110 | 3 / 112 | 1 / 111 | 3 / 113 | 3 / 134 | 0 / 113 | 1 / 112 |
Outcome results
Primary
Change From Baseline in Trough FEV1 at Week 12
Trough value was defined as the mean of the 2 measurements 30 minutes apart (23 hours after last dose) pre-dose for every visit throughout the Treatment Period (Visit 4/Week 2 to Visit 7/Week 12). Baseline was defined as the mean of the 2 measured values before first IP administration (30 minutes apart, at -45 minutes and -15 minutes, before IP administration) on Day 1 (Visit 3). Analyses were based on a Mixed-effects model for repeated measures (MMRM) with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates. To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose Inhaled corticosteroid (ICS).
Time frame: At week 12
Population: Full Analysis Set: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD7594 50 μg | Change From Baseline in Trough FEV1 at Week 12 | -0.013 Liters |
| AZD7594 90 μg | Change From Baseline in Trough FEV1 at Week 12 | -0.031 Liters |
| AZD7594 180 μg | Change From Baseline in Trough FEV1 at Week 12 | 0.062 Liters |
| AZD7594 360 μg | Change From Baseline in Trough FEV1 at Week 12 | 0.099 Liters |
| AZD7594 720 μg | Change From Baseline in Trough FEV1 at Week 12 | 0.104 Liters |
| Placebo to AZD7594 | Change From Baseline in Trough FEV1 at Week 12 | 0.022 Liters |
| Fluticasone Furoate | Change From Baseline in Trough FEV1 at Week 12 | 0.133 Liters |
p-value: 0.43795% CI: [-0.126, 0.054]Mixed Models Analysis
p-value: 0.23695% CI: [-0.143, 0.035]Mixed Models Analysis
p-value: 0.38995% CI: [-0.05, 0.128]Mixed Models Analysis
p-value: 0.09495% CI: [-0.013, 0.165]Mixed Models Analysis
p-value: 0.0695% CI: [-0.003, 0.167]Mixed Models Analysis
p-value: 0.01495% CI: [0.023, 0.199]Mixed Models Analysis
Secondary
Area Under the Plasma Concentration-curve From Time Zero to the Time of Last Quantifiable Analyte Concentration (AUClast) of AZD7594 at Day 84
Summary of PK parameter AUClast, Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter.
Time frame: Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
Population: All randomized patients participating in the PK subset, who took at least one dose of IP and for whom at least one of the primary PK parameters could be calculated, and who had no major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD7594 50 μg | Area Under the Plasma Concentration-curve From Time Zero to the Time of Last Quantifiable Analyte Concentration (AUClast) of AZD7594 at Day 84 | 167.50 h*pmol/L | Geometric Coefficient of Variation 123.5 |
| AZD7594 90 μg | Area Under the Plasma Concentration-curve From Time Zero to the Time of Last Quantifiable Analyte Concentration (AUClast) of AZD7594 at Day 84 | 573.00 h*pmol/L | Geometric Coefficient of Variation 116 |
| AZD7594 180 μg | Area Under the Plasma Concentration-curve From Time Zero to the Time of Last Quantifiable Analyte Concentration (AUClast) of AZD7594 at Day 84 | 719.10 h*pmol/L | Geometric Coefficient of Variation 134.58 |
| AZD7594 360 μg | Area Under the Plasma Concentration-curve From Time Zero to the Time of Last Quantifiable Analyte Concentration (AUClast) of AZD7594 at Day 84 | 1435.00 h*pmol/L | Geometric Coefficient of Variation 140.28 |
| AZD7594 720 μg | Area Under the Plasma Concentration-curve From Time Zero to the Time of Last Quantifiable Analyte Concentration (AUClast) of AZD7594 at Day 84 | 2622.00 h*pmol/L | Geometric Coefficient of Variation 98.88 |
Secondary
Area Under the Plasma Concentration-curve Within a Dosing Interval (AUCτ) of AZD7594 at Day 84
Summary of PK parameter AUCτ, Area under the plasma concentration-curve within a dosing interval, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter.
Time frame: Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
Population: All randomised patients participating in the PK subset, who took at least one dose of IP and for whom at least one of the primary PK parameters could be calculated, and who had no major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD7594 50 μg | Area Under the Plasma Concentration-curve Within a Dosing Interval (AUCτ) of AZD7594 at Day 84 | 530.50 h*pmol/L | Geometric Coefficient of Variation 32.57 |
| AZD7594 90 μg | Area Under the Plasma Concentration-curve Within a Dosing Interval (AUCτ) of AZD7594 at Day 84 | 928.60 h*pmol/L | Geometric Coefficient of Variation 37.52 |
| AZD7594 180 μg | Area Under the Plasma Concentration-curve Within a Dosing Interval (AUCτ) of AZD7594 at Day 84 | 1137.00 h*pmol/L | Geometric Coefficient of Variation 52.06 |
| AZD7594 360 μg | Area Under the Plasma Concentration-curve Within a Dosing Interval (AUCτ) of AZD7594 at Day 84 | 2205.00 h*pmol/L | Geometric Coefficient of Variation 52.32 |
| AZD7594 720 μg | Area Under the Plasma Concentration-curve Within a Dosing Interval (AUCτ) of AZD7594 at Day 84 | 2622.00 h*pmol/L | Geometric Coefficient of Variation 98.88 |
Secondary
Average Plasma Concentration During a Dosing Interval at Steady State (Css,Avg) of AZD7594 at Day 84
Summary of PK parameter Css,avg, Average plasma concentration during a dosing interval at steady state, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter.
Time frame: Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
Population: All randomised patients participating in the PK subset, who took at least one dose of IP and for whom at least one of the primary PK parameters could be calculated, and who had no major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD7594 50 μg | Average Plasma Concentration During a Dosing Interval at Steady State (Css,Avg) of AZD7594 at Day 84 | 22.10 pmol/L | Geometric Coefficient of Variation 32.57 |
| AZD7594 90 μg | Average Plasma Concentration During a Dosing Interval at Steady State (Css,Avg) of AZD7594 at Day 84 | 38.69 pmol/L | Geometric Coefficient of Variation 37.52 |
| AZD7594 180 μg | Average Plasma Concentration During a Dosing Interval at Steady State (Css,Avg) of AZD7594 at Day 84 | 47.37 pmol/L | Geometric Coefficient of Variation 52.06 |
| AZD7594 360 μg | Average Plasma Concentration During a Dosing Interval at Steady State (Css,Avg) of AZD7594 at Day 84 | 91.86 pmol/L | Geometric Coefficient of Variation 52.32 |
| AZD7594 720 μg | Average Plasma Concentration During a Dosing Interval at Steady State (Css,Avg) of AZD7594 at Day 84 | 109.30 pmol/L | Geometric Coefficient of Variation 98.88 |
Secondary
Change From Baseline in Area Under Plasma Cortisol Concentration-time Curve (AUEC0-24hrs Post Dose), of AZD7594 vs Placebo at Day 84
Area under the plasma cortisol concentration-time curve from zero to 24 hours after dosing compared to Placebo, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter.
Time frame: At Day -1 (-24 to -12 h prior to the dose on Day 0) and at Day 84 (0 to 12 hours post dose)
Population: All randomised patients who took at least one dose of IP and for whom 24-hour cortisol sampling was performed and baseline and post baseline AUEC0-24 could be calculated.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD7594 50 μg | Change From Baseline in Area Under Plasma Cortisol Concentration-time Curve (AUEC0-24hrs Post Dose), of AZD7594 vs Placebo at Day 84 | 1.029 ng*hr/mL |
| AZD7594 90 μg | Change From Baseline in Area Under Plasma Cortisol Concentration-time Curve (AUEC0-24hrs Post Dose), of AZD7594 vs Placebo at Day 84 | 1.140 ng*hr/mL |
| AZD7594 180 μg | Change From Baseline in Area Under Plasma Cortisol Concentration-time Curve (AUEC0-24hrs Post Dose), of AZD7594 vs Placebo at Day 84 | 1.151 ng*hr/mL |
| AZD7594 360 μg | Change From Baseline in Area Under Plasma Cortisol Concentration-time Curve (AUEC0-24hrs Post Dose), of AZD7594 vs Placebo at Day 84 | 1.003 ng*hr/mL |
| AZD7594 720 μg | Change From Baseline in Area Under Plasma Cortisol Concentration-time Curve (AUEC0-24hrs Post Dose), of AZD7594 vs Placebo at Day 84 | 0.934 ng*hr/mL |
| Placebo to AZD7594 | Change From Baseline in Area Under Plasma Cortisol Concentration-time Curve (AUEC0-24hrs Post Dose), of AZD7594 vs Placebo at Day 84 | 1.019 ng*hr/mL |
| Fluticasone Furoate | Change From Baseline in Area Under Plasma Cortisol Concentration-time Curve (AUEC0-24hrs Post Dose), of AZD7594 vs Placebo at Day 84 | 1.011 ng*hr/mL |
p-value: 0.90995% CI: [0.851, 1.199]Mixed Models Analysis
p-value: 0.21895% CI: [0.935, 1.336]Mixed Models Analysis
p-value: 0.18195% CI: [0.944, 1.349]Mixed Models Analysis
p-value: 0.85995% CI: [0.825, 1.174]Mixed Models Analysis
p-value: 0.28595% CI: [0.78, 1.077]Mixed Models Analysis
p-value: 0.92395% CI: [0.831, 1.182]Mixed Models Analysis
Secondary
Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period
Baseline was defined as the ACQ-5 score at Visit 3. Analyses were based on a MMRM with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates. To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. Patients are asked to recall how their asthma was during the previous week and to evaluate their symptoms. The questionnaire has 5 items each item is scored on a scale of 0 to 6, where higher scores represent more severe impairment/symptoms. ACQ is the sum of the scores from all 5 items.
Time frame: At week 12
Population: Full Analysis Set: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| AZD7594 50 μg | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Week 12 | -0.289 units on a scale |
| AZD7594 50 μg | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | -0.215 units on a scale |
| AZD7594 90 μg | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Week 12 | -0.394 units on a scale |
| AZD7594 90 μg | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | -0.230 units on a scale |
| AZD7594 180 μg | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Week 12 | -0.357 units on a scale |
| AZD7594 180 μg | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | -0.220 units on a scale |
| AZD7594 360 μg | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Week 12 | -0.330 units on a scale |
| AZD7594 360 μg | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | -0.291 units on a scale |
| AZD7594 720 μg | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Week 12 | -0.406 units on a scale |
| AZD7594 720 μg | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | -0.306 units on a scale |
| Placebo to AZD7594 | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Week 12 | -0.137 units on a scale |
| Placebo to AZD7594 | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | -0.090 units on a scale |
| Fluticasone Furoate | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Week 12 | -0.360 units on a scale |
| Fluticasone Furoate | Change From Baseline in Asthma Control Questionnaire -5 (ACQ-5) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | -0.269 units on a scale |
Comparison: Week 12p-value: 0.08895% CI: [-0.328, 0.023]Mixed Models Analysis
Comparison: Week 12p-value: 0.00495% CI: [-0.43, -0.084]Mixed Models Analysis
Comparison: Week 12p-value: 0.01295% CI: [-0.393, -0.049]Mixed Models Analysis
Comparison: Week 12p-value: 0.02995% CI: [-0.366, -0.02]Mixed Models Analysis
Comparison: Week 12p-value: 0.00195% CI: [-0.434, -0.104]Mixed Models Analysis
Comparison: Week 12p-value: 0.0195% CI: [-0.393, -0.054]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.05595% CI: [-0.253, 0.003]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.02995% CI: [-0.268, -0.014]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.04495% CI: [-0.257, -0.003]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.00295% CI: [-0.328, -0.074]Mixed Models Analysis
Comparison: Treatment period averagep-value: <0.00195% CI: [-0.339, -0.094]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.00595% CI: [-0.305, -0.053]Mixed Models Analysis
Secondary
Change From Baseline in Average Daily Asthma Symptom Score Over the Treatment Period
To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS (Full Analysis Set). Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate. During the Run-in and Treatment Periods, subjects recorded the severity of their asthma symptoms during night-time and day-time each morning and evening, using the eDiary. Asthma symptom scores during night-time/day-time were assessed by the subject each morning/evening according to the following scoring system and recorded on the eDiary: 0: No asthma symptoms, 1: The subjects were aware of their asthma symptoms but they can easily tolerate the symptoms, 2: asthma was causing enough discomfort to cause problems with sleep, 3: Subjects were unable to sleep/do normal activities because of their asthma.
Time frame: Week 0 (7 days prior to randomisation) to Week 12
Population: Full Analysis Set: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD7594 50 μg | Change From Baseline in Average Daily Asthma Symptom Score Over the Treatment Period | -0.303 units on a scale |
| AZD7594 90 μg | Change From Baseline in Average Daily Asthma Symptom Score Over the Treatment Period | -0.201 units on a scale |
| AZD7594 180 μg | Change From Baseline in Average Daily Asthma Symptom Score Over the Treatment Period | -0.229 units on a scale |
| AZD7594 360 μg | Change From Baseline in Average Daily Asthma Symptom Score Over the Treatment Period | -0.321 units on a scale |
| AZD7594 720 μg | Change From Baseline in Average Daily Asthma Symptom Score Over the Treatment Period | -0.275 units on a scale |
| Placebo to AZD7594 | Change From Baseline in Average Daily Asthma Symptom Score Over the Treatment Period | -0.091 units on a scale |
| Fluticasone Furoate | Change From Baseline in Average Daily Asthma Symptom Score Over the Treatment Period | -0.296 units on a scale |
Comparison: Treatment period averagep-value: <0.00195% CI: [-0.329, -0.094]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.06695% CI: [-0.228, 0.007]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.0295% CI: [-0.255, -0.022]Mixed Models Analysis
Comparison: Treatment period averagep-value: <0.00195% CI: [-0.35, -0.11]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.00195% CI: [-0.298, -0.071]Mixed Models Analysis
Comparison: Treatment period averagep-value: <0.00195% CI: [-0.321, -0.09]Mixed Models Analysis
Secondary
Change From Baseline in Average Daily Use of Rescue Medication Over the Treatment Period
To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate.
Time frame: Week 0 (7 days prior to randomisation) to Week 12
Population: Full Analysis Set: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD7594 50 μg | Change From Baseline in Average Daily Use of Rescue Medication Over the Treatment Period | -0.370 number of puffs |
| AZD7594 90 μg | Change From Baseline in Average Daily Use of Rescue Medication Over the Treatment Period | -0.282 number of puffs |
| AZD7594 180 μg | Change From Baseline in Average Daily Use of Rescue Medication Over the Treatment Period | -0.226 number of puffs |
| AZD7594 360 μg | Change From Baseline in Average Daily Use of Rescue Medication Over the Treatment Period | -0.435 number of puffs |
| AZD7594 720 μg | Change From Baseline in Average Daily Use of Rescue Medication Over the Treatment Period | -0.435 number of puffs |
| Placebo to AZD7594 | Change From Baseline in Average Daily Use of Rescue Medication Over the Treatment Period | -0.127 number of puffs |
| Fluticasone Furoate | Change From Baseline in Average Daily Use of Rescue Medication Over the Treatment Period | -0.304 number of puffs |
Comparison: Treatment period averagep-value: 0.01295% CI: [-0.431, -0.054]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.10895% CI: [-0.344, 0.034]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.29595% CI: [-0.286, 0.087]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.00295% CI: [-0.5, -0.116]Mixed Models Analysis
Comparison: Treatment period averagep-value: <0.00195% CI: [-0.489, -0.126]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.06295% CI: [-0.362, 0.009]Mixed Models Analysis
Secondary
Change From Baseline in Average Evening PEF Over the Treatment Period
Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate. To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS.
Time frame: Week 0 (7 days prior to randomisation) to Week 12
Population: Full Analysis set: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD7594 50 μg | Change From Baseline in Average Evening PEF Over the Treatment Period | -5.418 L/min |
| AZD7594 90 μg | Change From Baseline in Average Evening PEF Over the Treatment Period | -5.654 L/min |
| AZD7594 180 μg | Change From Baseline in Average Evening PEF Over the Treatment Period | -3.983 L/min |
| AZD7594 360 μg | Change From Baseline in Average Evening PEF Over the Treatment Period | 2.441 L/min |
| AZD7594 720 μg | Change From Baseline in Average Evening PEF Over the Treatment Period | 4.178 L/min |
| Placebo to AZD7594 | Change From Baseline in Average Evening PEF Over the Treatment Period | -7.816 L/min |
| Fluticasone Furoate | Change From Baseline in Average Evening PEF Over the Treatment Period | -1.687 L/min |
Comparison: Treatment period averagep-value: 0.59795% CI: [-6.494, 11.29]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.62995% CI: [-6.623, 10.948]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.38995% CI: [-4.907, 12.573]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.02295% CI: [1.456, 19.059]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.00595% CI: [3.571, 20.417]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.16395% CI: [-2.479, 14.737]Mixed Models Analysis
Secondary
Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period
Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate. To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS.
Time frame: Week 0 (7 days prior to randomisation) to Week 12
Population: Full Analysis Set: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD7594 50 μg | Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | -4.036 L/min |
| AZD7594 90 μg | Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | -5.718 L/min |
| AZD7594 180 μg | Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | -2.576 L/min |
| AZD7594 360 μg | Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | 3.745 L/min |
| AZD7594 720 μg | Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | 4.900 L/min |
| Placebo to AZD7594 | Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | -11.699 L/min |
| Fluticasone Furoate | Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | -1.208 L/min |
Comparison: Treatment period averagep-value: 0.09795% CI: [-1.403, 16.73]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.1995% CI: [-2.98, 14.941]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.04595% CI: [0.195, 18.052]Mixed Models Analysis
Comparison: Treatment period averagep-value: <0.00195% CI: [6.443, 24.445]Mixed Models Analysis
Comparison: Treatment period averagep-value: <0.00195% CI: [8.031, 25.167]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.01995% CI: [1.726, 19.256]Mixed Models Analysis
Secondary
Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period
Baseline was defined as the last value obtained prior to the first dose of investigational product. Analyses were based on a MMRM with change from baseline on the log-scale as the response, treatment, visit, treatment by visit interaction and region as fixed effects, and log-transformed baseline value and baseline by visit interaction as covariates.
Time frame: At week 2, 4, 8, and 12
Population: Full Analysis Set: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|---|
| AZD7594 50 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 8 | 1.294 ppb |
| AZD7594 50 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 2 | 1.307 ppb |
| AZD7594 50 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Treatment Period Avg | 1.298 ppb |
| AZD7594 50 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 4 | 1.229 ppb |
| AZD7594 50 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 12 | 1.367 ppb |
| AZD7594 90 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 8 | 1.316 ppb |
| AZD7594 90 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 4 | 1.203 ppb |
| AZD7594 90 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 12 | 1.405 ppb |
| AZD7594 90 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 2 | 1.223 ppb |
| AZD7594 90 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Treatment Period Avg | 1.284 ppb |
| AZD7594 180 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Treatment Period Avg | 1.231 ppb |
| AZD7594 180 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 4 | 1.220 ppb |
| AZD7594 180 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 2 | 1.175 ppb |
| AZD7594 180 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 8 | 1.250 ppb |
| AZD7594 180 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 12 | 1.281 ppb |
| AZD7594 360 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 8 | 1.206 ppb |
| AZD7594 360 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 2 | 1.152 ppb |
| AZD7594 360 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 4 | 1.118 ppb |
| AZD7594 360 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 12 | 1.198 ppb |
| AZD7594 360 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Treatment Period Avg | 1.168 ppb |
| AZD7594 720 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 2 | 0.959 ppb |
| AZD7594 720 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Treatment Period Avg | 0.979 ppb |
| AZD7594 720 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 8 | 1.021 ppb |
| AZD7594 720 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 12 | 0.958 ppb |
| AZD7594 720 μg | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 4 | 0.980 ppb |
| Placebo to AZD7594 | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 2 | 1.396 ppb |
| Placebo to AZD7594 | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Treatment Period Avg | 1.399 ppb |
| Placebo to AZD7594 | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 12 | 1.474 ppb |
| Placebo to AZD7594 | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 4 | 1.321 ppb |
| Placebo to AZD7594 | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 8 | 1.411 ppb |
| Fluticasone Furoate | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 12 | 0.918 ppb |
| Fluticasone Furoate | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 4 | 0.928 ppb |
| Fluticasone Furoate | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 8 | 0.906 ppb |
| Fluticasone Furoate | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Week 2 | 0.880 ppb |
| Fluticasone Furoate | Change From Baseline in Fractional Exhaled Nitic Oxide (FENO) at Weeks 2, 4, 8, 12 and Average Over the Treatment Period | Treatment Period Avg | 0.908 ppb |
Comparison: Week 2p-value: 0.32295% CI: [0.822, 1.067]Mixed Models Analysis
Comparison: Week 2p-value: 0.04795% CI: [0.768, 0.999]Mixed Models Analysis
Comparison: Week 2p-value: 0.0195% CI: [0.739, 0.959]Mixed Models Analysis
Comparison: Week 2p-value: 0.00495% CI: [0.724, 0.941]Mixed Models Analysis
Comparison: Week 2p-value: <0.00195% CI: [0.606, 0.779]Mixed Models Analysis
Comparison: Week 2p-value: <0.00195% CI: [0.553, 0.719]Mixed Models Analysis
Comparison: Week 4p-value: 0.32995% CI: [0.805, 1.076]Mixed Models Analysis
Comparison: Week 4p-value: 0.20395% CI: [0.789, 1.052]Mixed Models Analysis
Comparison: Week 4p-value: 0.27395% CI: [0.8, 1.065]Mixed Models Analysis
Comparison: Week 4p-value: 0.02395% CI: [0.734, 0.977]Mixed Models Analysis
Comparison: Week 4p-value: <0.00195% CI: [0.646, 0.852]Mixed Models Analysis
Comparison: Week 4p-value: <0.00195% CI: [0.609, 0.81]Mixed Models Analysis
Comparison: Week 8p-value: 0.28395% CI: [0.783, 1.074]Mixed Models Analysis
Comparison: Week 8p-value: 0.38695% CI: [0.797, 1.092]Mixed Models Analysis
Comparison: Week 8p-value: 0.12695% CI: [0.758, 1.035]Mixed Models Analysis
Comparison: Week 8p-value: 0.0595% CI: [0.731, 1]Mixed Models Analysis
Comparison: Week 8p-value: <0.00195% CI: [0.623, 0.84]Mixed Models Analysis
Comparison: Week 8p-value: <0.00195% CI: [0.55, 0.749]Mixed Models Analysis
Comparison: Week 12p-value: 0.35995% CI: [0.789, 1.09]Mixed Models Analysis
Comparison: Week 12p-value: 0.55695% CI: [0.813, 1.118]Mixed Models Analysis
Comparison: Week 12p-value: 0.08495% CI: [0.742, 1.019]Mixed Models Analysis
Comparison: Week 12p-value: 0.01195% CI: [0.693, 0.953]Mixed Models Analysis
Comparison: Week 12p-value: <0.00195% CI: [0.559, 0.757]Mixed Models Analysis
Comparison: Week 12p-value: <0.00195% CI: [0.533, 0.729]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.23195% CI: [0.821, 1.049]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.1795% CI: [0.812, 1.037]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.03995% CI: [0.778, 0.994]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.00495% CI: [0.739, 0.943]Mixed Models Analysis
Comparison: Treatment period averagep-value: <0.00195% CI: [0.622, 0.787]Mixed Models Analysis
Comparison: Treatment period averagep-value: <0.00195% CI: [0.575, 0.732]Mixed Models Analysis
Secondary
Change From Baseline in Percent Asthma Control Days Over the Treatment Period
To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. Asthma-control days is defined as days with no symptoms, nonight-waking, no reliever use, and no exacerbation. Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate.
Time frame: Week 0 (7 days prior to randomisation) to Week 12
Population: Full Analysis Set: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD7594 50 μg | Change From Baseline in Percent Asthma Control Days Over the Treatment Period | 15.470 percent |
| AZD7594 90 μg | Change From Baseline in Percent Asthma Control Days Over the Treatment Period | 11.362 percent |
| AZD7594 180 μg | Change From Baseline in Percent Asthma Control Days Over the Treatment Period | 12.646 percent |
| AZD7594 360 μg | Change From Baseline in Percent Asthma Control Days Over the Treatment Period | 15.925 percent |
| AZD7594 720 μg | Change From Baseline in Percent Asthma Control Days Over the Treatment Period | 14.479 percent |
| Placebo to AZD7594 | Change From Baseline in Percent Asthma Control Days Over the Treatment Period | 5.859 percent |
| Fluticasone Furoate | Change From Baseline in Percent Asthma Control Days Over the Treatment Period | 13.037 percent |
Comparison: Treatment period averagep-value: 0.02695% CI: [1.18, 18.042]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.295% CI: [-2.927, 13.933]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.1195% CI: [-1.546, 15.119]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.02295% CI: [1.461, 18.672]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.03895% CI: [0.489, 16.75]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.0995% CI: [-1.112, 15.467]Mixed Models Analysis
Secondary
Change From Baseline in Percent Night-time Awakening Days Over the Treatment Period
To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate.
Time frame: Week 0 (7 days prior to randomisation) to Week 12
Population: Full Analysis Set: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD7594 50 μg | Change From Baseline in Percent Night-time Awakening Days Over the Treatment Period | -14.281 percentage |
| AZD7594 90 μg | Change From Baseline in Percent Night-time Awakening Days Over the Treatment Period | -12.260 percentage |
| AZD7594 180 μg | Change From Baseline in Percent Night-time Awakening Days Over the Treatment Period | -8.649 percentage |
| AZD7594 360 μg | Change From Baseline in Percent Night-time Awakening Days Over the Treatment Period | -12.085 percentage |
| AZD7594 720 μg | Change From Baseline in Percent Night-time Awakening Days Over the Treatment Period | -13.017 percentage |
| Placebo to AZD7594 | Change From Baseline in Percent Night-time Awakening Days Over the Treatment Period | -4.288 percentage |
| Fluticasone Furoate | Change From Baseline in Percent Night-time Awakening Days Over the Treatment Period | -15.910 percentage |
Comparison: Treatment period averagep-value: <0.00195% CI: [-15.795, -4.191]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.00695% CI: [-13.694, -2.251]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.13395% CI: [-10.051, 1.329]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.00895% CI: [-13.555, -2.04]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.00295% CI: [-14.195, -3.264]Mixed Models Analysis
Comparison: Treatment period averagep-value: <0.00195% CI: [-17.211, -6.034]Mixed Models Analysis
Secondary
Change From Baseline in Percent Rescue-free Days Over the Treatment Period
To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. A rescue-free day (RFD) was defined as a day where the number of puffs of medication for the relief of asthma symptoms was reported as zero. Baseline was defined as the average over the 7 days prior to randomisation. Analyses were based on an ANCOVA model with treatment and region as fixed effects, and baseline value as a covariate.
Time frame: Week 0 (7 days prior to randomisation) to Week 12
Population: Full Analysis Set: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD7594 50 μg | Change From Baseline in Percent Rescue-free Days Over the Treatment Period | 31.138 percent |
| AZD7594 90 μg | Change From Baseline in Percent Rescue-free Days Over the Treatment Period | 24.178 percent |
| AZD7594 180 μg | Change From Baseline in Percent Rescue-free Days Over the Treatment Period | 21.960 percent |
| AZD7594 360 μg | Change From Baseline in Percent Rescue-free Days Over the Treatment Period | 34.991 percent |
| AZD7594 720 μg | Change From Baseline in Percent Rescue-free Days Over the Treatment Period | 30.775 percent |
| Placebo to AZD7594 | Change From Baseline in Percent Rescue-free Days Over the Treatment Period | 23.202 percent |
| Fluticasone Furoate | Change From Baseline in Percent Rescue-free Days Over the Treatment Period | 28.260 percent |
Comparison: Treatment period averagep-value: 0.12395% CI: [-2.16, 18.031]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.84995% CI: [-9.112, 11.065]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.80795% CI: [-11.233, 8.748]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.02595% CI: [1.488, 22.09]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.12795% CI: [-2.16, 17.307]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.31895% CI: [-4.874, 14.99]Mixed Models Analysis
Secondary
Change From Baseline in Percent Symptom-free Days Over the Treatment Period
To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS. Days without asthma symptoms, or symptom-free days, are defined as a day without asthma symptoms, short-acting β-agonist (SABA) use, systemic corticosteroid use, or need for urgent asthma care.
Time frame: Week 0 (7 days prior to randomisation) to Week 12
Population: Full Analysis Set: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD7594 50 μg | Change From Baseline in Percent Symptom-free Days Over the Treatment Period | 13.780 percent |
| AZD7594 90 μg | Change From Baseline in Percent Symptom-free Days Over the Treatment Period | 10.521 percent |
| AZD7594 180 μg | Change From Baseline in Percent Symptom-free Days Over the Treatment Period | 11.935 percent |
| AZD7594 360 μg | Change From Baseline in Percent Symptom-free Days Over the Treatment Period | 14.673 percent |
| AZD7594 720 μg | Change From Baseline in Percent Symptom-free Days Over the Treatment Period | 13.451 percent |
| Placebo to AZD7594 | Change From Baseline in Percent Symptom-free Days Over the Treatment Period | 3.329 percent |
| Fluticasone Furoate | Change From Baseline in Percent Symptom-free Days Over the Treatment Period | 14.018 percent |
Comparison: Treatment period averagep-value: 0.01595% CI: [2.046, 18.855]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.09395% CI: [-1.208, 15.592]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.04295% CI: [0.298, 16.913]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.0195% CI: [2.773, 19.914]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.01495% CI: [2.021, 18.222]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.01195% CI: [2.424, 18.953]Mixed Models Analysis
Secondary
Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period
Trough value was defined as the mean of the 2 measurements 30 minutes apart (23 hours after last dose) pre-dose for every visit throughout the Treatment Period (Visit 4/Week 2 to Visit 7/Week 12). Baseline was defined as the mean of the 2 measured values before first IP administration (30 minutes apart, at -45 minutes and -15 minutes, before IP administration) on Day 1 (Visit 3). Analysis of covariance (ANCOVA) with treatment and region (ie, US, Japan, and RoW) as fixed effects, and baseline as covariate was used for the analysis of average over the Treatment Period. To investigate the clinical efficacy of AZD7594 at different dose levels in asthmatics symptomatic on low dose ICS.
Time frame: At week 2, 4 and 8
Population: Full analysis set: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| AZD7594 50 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 2 | 0.018 Liters |
| AZD7594 50 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 4 | -0.002 Liters |
| AZD7594 50 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 8 | 0.019 Liters |
| AZD7594 50 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Treatment Period Avg | 0.005 Liters |
| AZD7594 90 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Treatment Period Avg | 0.006 Liters |
| AZD7594 90 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 8 | 0.007 Liters |
| AZD7594 90 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 2 | 0.011 Liters |
| AZD7594 90 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 4 | 0.039 Liters |
| AZD7594 180 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 8 | 0.071 Liters |
| AZD7594 180 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 4 | 0.078 Liters |
| AZD7594 180 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 2 | 0.067 Liters |
| AZD7594 180 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Treatment Period Avg | 0.069 Liters |
| AZD7594 360 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 2 | 0.091 Liters |
| AZD7594 360 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 4 | 0.086 Liters |
| AZD7594 360 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 8 | 0.102 Liters |
| AZD7594 360 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Treatment Period Avg | 0.094 Liters |
| AZD7594 720 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 2 | 0.093 Liters |
| AZD7594 720 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Treatment Period Avg | 0.108 Liters |
| AZD7594 720 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 4 | 0.094 Liters |
| AZD7594 720 μg | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 8 | 0.141 Liters |
| Placebo to AZD7594 | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 4 | -0.020 Liters |
| Placebo to AZD7594 | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 2 | -0.011 Liters |
| Placebo to AZD7594 | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 8 | 0.002 Liters |
| Placebo to AZD7594 | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Treatment Period Avg | -0.002 Liters |
| Fluticasone Furoate | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 8 | 0.124 Liters |
| Fluticasone Furoate | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 2 | 0.107 Liters |
| Fluticasone Furoate | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Week 4 | 0.145 Liters |
| Fluticasone Furoate | Change From Baseline in Trough FEV1 at Weeks 2, 4, 8 and Average Over the Treatment Period | Treatment Period Avg | 0.127 Liters |
Comparison: Week 2p-value: 0.46395% CI: [-0.048, 0.105]Mixed Models Analysis
Comparison: Week 2p-value: 0.57695% CI: [-0.055, 0.098]Mixed Models Analysis
Comparison: Week 2p-value: 0.04795% CI: [0.001, 0.154]Mixed Models Analysis
Comparison: Week 2p-value: 0.00995% CI: [0.025, 0.179]Mixed Models Analysis
Comparison: Week 2p-value: 0.00695% CI: [0.031, 0.178]Mixed Models Analysis
Comparison: Week 2p-value: 0.00395% CI: [0.041, 0.194]Mixed Models Analysis
Comparison: Week 4p-value: 0.68595% CI: [-0.068, 0.103]Mixed Models Analysis
Comparison: Week 4p-value: 0.17695% CI: [-0.026, 0.144]Mixed Models Analysis
Comparison: Week 4p-value: 0.02495% CI: [0.013, 0.183]Mixed Models Analysis
Comparison: Week 4p-value: 0.01495% CI: [0.021, 0.191]Mixed Models Analysis
Comparison: Week 4p-value: 0.00695% CI: [0.032, 0.196]Mixed Models Analysis
Comparison: Week 4p-value: <0.00195% CI: [0.081, 0.249]Mixed Models Analysis
Comparison: Week 8p-value: 0.70795% CI: [-0.072, 0.106]Mixed Models Analysis
Comparison: Week 8p-value: 0.90495% CI: [-0.083, 0.094]Mixed Models Analysis
Comparison: Week 8p-value: 0.12195% CI: [-0.018, 0.157]Mixed Models Analysis
Comparison: Week 8p-value: 0.02695% CI: [0.012, 0.188]Mixed Models Analysis
Comparison: Week 8p-value: 0.00195% CI: [0.055, 0.224]Mixed Models Analysis
Comparison: Week 8p-value: 0.00695% CI: [0.035, 0.209]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.85695% CI: [-0.068, 0.081]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.83295% CI: [-0.066, 0.082]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.0695% CI: [-0.003, 0.145]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.01195% CI: [0.022, 0.17]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.00395% CI: [0.039, 0.181]Mixed Models Analysis
Comparison: Treatment period averagep-value: <0.00195% CI: [0.055, 0.202]Mixed Models Analysis
Secondary
Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period
Trough value was defined as the mean of the 2 measurements 30 minutes apart (23 hours after last dose) pre-dose for every visit throughout the Treatment Period (Visit 4/Week 2 to Visit 7/Week 12). Baseline was defined as the mean of the 2 measured values before first IP administration (30 minutes apart, at -45 minutes and -15 minutes, before IP administration) on Day 1 (Visit 3). Analyses were based on a MMRM with treatment, visit, treatment by visit interaction and region as fixed effects, and baseline value and baseline by visit interaction as covariates.
Time frame: At week 12
Population: Full Analysis Set: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| AZD7594 50 μg | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Week 12 | 0.027 Liters |
| AZD7594 50 μg | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | 0.044 Liters |
| AZD7594 90 μg | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Week 12 | -0.017 Liters |
| AZD7594 90 μg | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | 0.019 Liters |
| AZD7594 180 μg | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Week 12 | 0.076 Liters |
| AZD7594 180 μg | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | 0.087 Liters |
| AZD7594 360 μg | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Week 12 | 0.119 Liters |
| AZD7594 360 μg | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | 0.127 Liters |
| AZD7594 720 μg | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Week 12 | 0.088 Liters |
| AZD7594 720 μg | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | 0.091 Liters |
| Placebo to AZD7594 | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Week 12 | 0.061 Liters |
| Placebo to AZD7594 | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | 0.046 Liters |
| Fluticasone Furoate | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Week 12 | 0.118 Liters |
| Fluticasone Furoate | Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12 and Average Over the Treatment Period | Treatment Period Avg | 0.121 Liters |
Comparison: Week 12p-value: 0.51995% CI: [-0.139, 0.07]Mixed Models Analysis
Comparison: Week 12p-value: 0.14195% CI: [-0.181, 0.026]Mixed Models Analysis
Comparison: Week 12p-value: 0.77295% CI: [-0.088, 0.119]Mixed Models Analysis
Comparison: Week 12p-value: 0.2795% CI: [-0.045, 0.162]Mixed Models Analysis
Comparison: Week 12p-value: 0.59295% CI: [-0.072, 0.126]Mixed Models Analysis
Comparison: Week 12p-value: 0.27595% CI: [-0.045, 0.158]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.96395% CI: [-0.087, 0.083]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.53395% CI: [-0.112, 0.058]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.34295% CI: [-0.044, 0.126]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.06195% CI: [-0.004, 0.165]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.27895% CI: [-0.037, 0.127]Mixed Models Analysis
Comparison: Treatment period averagep-value: 0.07995% CI: [-0.009, 0.159]Mixed Models Analysis
Secondary
Dose Normalised AUCτ (AUCτ/D) of AZD7594 at Day 84
Summary of PK parameter AUCτ/D, Dose normalised AUCτ, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter.
Time frame: Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
Population: All randomised patients participating in the PK subset, who took at least one dose of IP and for whom at least one of the primary PK parameters could be calculated, and who had no major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD7594 50 μg | Dose Normalised AUCτ (AUCτ/D) of AZD7594 at Day 84 | 6436.00 h*pmol/μmol | Geometric Coefficient of Variation 32.57 |
| AZD7594 90 μg | Dose Normalised AUCτ (AUCτ/D) of AZD7594 at Day 84 | 6259.00 h*pmol/μmol | Geometric Coefficient of Variation 37.52 |
| AZD7594 180 μg | Dose Normalised AUCτ (AUCτ/D) of AZD7594 at Day 84 | 3831.00 h*pmol/μmol | Geometric Coefficient of Variation 52.06 |
| AZD7594 360 μg | Dose Normalised AUCτ (AUCτ/D) of AZD7594 at Day 84 | 3715.00 h*pmol/μmol | Geometric Coefficient of Variation 52.32 |
| AZD7594 720 μg | Dose Normalised AUCτ (AUCτ/D) of AZD7594 at Day 84 | 2209.00 h*pmol/μmol | Geometric Coefficient of Variation 98.88 |
Secondary
Dose Normalised Css,Max (Css,Max/D) of AZD7594 at Day 84
Summary of PK parameter Css,max/D Dose normalised Css,max, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter.
Time frame: Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
Population: All randomised patients participating in the PK subset, who took at least one dose of IP and for whom at least one of the primary PK parameters could be calculated, and who had no major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD7594 50 μg | Dose Normalised Css,Max (Css,Max/D) of AZD7594 at Day 84 | 587.80 pmol/L/umol | Geometric Coefficient of Variation 68.65 |
| AZD7594 90 μg | Dose Normalised Css,Max (Css,Max/D) of AZD7594 at Day 84 | 774.40 pmol/L/umol | Geometric Coefficient of Variation 99.12 |
| AZD7594 180 μg | Dose Normalised Css,Max (Css,Max/D) of AZD7594 at Day 84 | 234.90 pmol/L/umol | Geometric Coefficient of Variation 105.94 |
| AZD7594 360 μg | Dose Normalised Css,Max (Css,Max/D) of AZD7594 at Day 84 | 260.40 pmol/L/umol | Geometric Coefficient of Variation 144.67 |
| AZD7594 720 μg | Dose Normalised Css,Max (Css,Max/D) of AZD7594 at Day 84 | 168.50 pmol/L/umol | Geometric Coefficient of Variation 113.05 |
Secondary
Number of Participants With Adverse Events
To evaluate the safety and tolerability of AZD7594 in relation to Placebo in asthmatics symptomatic on low dose ICS
Time frame: From screening to follow-up period (7 to 10 days after visit 7)
Population: All participants randomised and receiving at least 1 dose of randomised study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD7594 50 μg | Number of Participants With Adverse Events | Any SAE | 0 Participants |
| AZD7594 50 μg | Number of Participants With Adverse Events | Any AE leading to discontinuation of IP | 6 Participants |
| AZD7594 50 μg | Number of Participants With Adverse Events | Any AE | 35 Participants |
| AZD7594 50 μg | Number of Participants With Adverse Events | death | 0 Participants |
| AZD7594 90 μg | Number of Participants With Adverse Events | Any AE | 45 Participants |
| AZD7594 90 μg | Number of Participants With Adverse Events | death | 0 Participants |
| AZD7594 90 μg | Number of Participants With Adverse Events | Any AE leading to discontinuation of IP | 8 Participants |
| AZD7594 90 μg | Number of Participants With Adverse Events | Any SAE | 3 Participants |
| AZD7594 180 μg | Number of Participants With Adverse Events | death | 0 Participants |
| AZD7594 180 μg | Number of Participants With Adverse Events | Any AE | 39 Participants |
| AZD7594 180 μg | Number of Participants With Adverse Events | Any AE leading to discontinuation of IP | 4 Participants |
| AZD7594 180 μg | Number of Participants With Adverse Events | Any SAE | 1 Participants |
| AZD7594 360 μg | Number of Participants With Adverse Events | death | 1 Participants |
| AZD7594 360 μg | Number of Participants With Adverse Events | Any SAE | 3 Participants |
| AZD7594 360 μg | Number of Participants With Adverse Events | Any AE | 54 Participants |
| AZD7594 360 μg | Number of Participants With Adverse Events | Any AE leading to discontinuation of IP | 11 Participants |
| AZD7594 720 μg | Number of Participants With Adverse Events | Any SAE | 3 Participants |
| AZD7594 720 μg | Number of Participants With Adverse Events | death | 0 Participants |
| AZD7594 720 μg | Number of Participants With Adverse Events | Any AE | 46 Participants |
| AZD7594 720 μg | Number of Participants With Adverse Events | Any AE leading to discontinuation of IP | 4 Participants |
| Placebo to AZD7594 | Number of Participants With Adverse Events | death | 0 Participants |
| Placebo to AZD7594 | Number of Participants With Adverse Events | Any AE | 47 Participants |
| Placebo to AZD7594 | Number of Participants With Adverse Events | Any SAE | 0 Participants |
| Placebo to AZD7594 | Number of Participants With Adverse Events | Any AE leading to discontinuation of IP | 20 Participants |
| Fluticasone Furoate | Number of Participants With Adverse Events | Any AE | 34 Participants |
| Fluticasone Furoate | Number of Participants With Adverse Events | death | 0 Participants |
| Fluticasone Furoate | Number of Participants With Adverse Events | Any AE leading to discontinuation of IP | 2 Participants |
| Fluticasone Furoate | Number of Participants With Adverse Events | Any SAE | 1 Participants |
Secondary
Observed Maximum Concentration at Steady State (Css,Max) of AZD7594 at Day 84
Summary of PK parameter Css,mx, observed maximum concentration, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter.
Time frame: Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
Population: All randomised patients participating in the PK subset, who took at least one dose of IP and for whom at least one of the primary PK parameters could be calculated, and who had no major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD7594 50 μg | Observed Maximum Concentration at Steady State (Css,Max) of AZD7594 at Day 84 | 48.45 pmol/L | Geometric Coefficient of Variation 68.65 |
| AZD7594 90 μg | Observed Maximum Concentration at Steady State (Css,Max) of AZD7594 at Day 84 | 114.90 pmol/L | Geometric Coefficient of Variation 99.12 |
| AZD7594 180 μg | Observed Maximum Concentration at Steady State (Css,Max) of AZD7594 at Day 84 | 69.71 pmol/L | Geometric Coefficient of Variation 105.94 |
| AZD7594 360 μg | Observed Maximum Concentration at Steady State (Css,Max) of AZD7594 at Day 84 | 154.50 pmol/L | Geometric Coefficient of Variation 144.67 |
| AZD7594 720 μg | Observed Maximum Concentration at Steady State (Css,Max) of AZD7594 at Day 84 | 200.00 pmol/L | Geometric Coefficient of Variation 113.05 |
Secondary
Observed Minimum Concentration at the End of the Dosing Interval (Css,Min) of AZD7594 at Day 84
Summary of PK parameter Css,min, observed minimum concentration, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter.
Time frame: Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
Population: All randomised patients participating in the PK subset, who took at least one dose of IP and for whom at least one of the primary PK parameters could be calculated, and who had no major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD7594 50 μg | Observed Minimum Concentration at the End of the Dosing Interval (Css,Min) of AZD7594 at Day 84 | 14.41 pmol/L | Geometric Coefficient of Variation 37.59 |
| AZD7594 90 μg | Observed Minimum Concentration at the End of the Dosing Interval (Css,Min) of AZD7594 at Day 84 | 21.45 pmol/L | Geometric Coefficient of Variation 43.12 |
| AZD7594 180 μg | Observed Minimum Concentration at the End of the Dosing Interval (Css,Min) of AZD7594 at Day 84 | 30.22 pmol/L | Geometric Coefficient of Variation 43.28 |
| AZD7594 360 μg | Observed Minimum Concentration at the End of the Dosing Interval (Css,Min) of AZD7594 at Day 84 | 70.58 pmol/L | Geometric Coefficient of Variation 46.22 |
| AZD7594 720 μg | Observed Minimum Concentration at the End of the Dosing Interval (Css,Min) of AZD7594 at Day 84 | 85.13 pmol/L | Geometric Coefficient of Variation 108.41 |
Secondary
Percentage Fluctuation of AZD7594 at Day 84
To describe the (steady state) PK of AZD7594 in a subset of asthmatics symptomatic on low dose ICS (subset of subjects at EU sites) (PK Analysis Set). The presented results are summary statistics of the PK parameter. No statistical analysis is done for this endpoint. Fluctuation index during a dosing interval estimated as 100\*(Css,max - Css,min)/Css,avg (%), where Css,min is the minimum concentration at the end of the dosing interval.
Time frame: Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
Population: All randomised patients participating in the PK subset, who took at least one dose of IP and for whom at least one of the primary PK parameters could be calculated, and who had no major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD7594 50 μg | Percentage Fluctuation of AZD7594 at Day 84 | 387.80 percentage | Geometric Coefficient of Variation 21.97 |
| AZD7594 90 μg | Percentage Fluctuation of AZD7594 at Day 84 | 326.60 percentage | Geometric Coefficient of Variation 37.4 |
| AZD7594 180 μg | Percentage Fluctuation of AZD7594 at Day 84 | 148.90 percentage | Geometric Coefficient of Variation 38.27 |
| AZD7594 360 μg | Percentage Fluctuation of AZD7594 at Day 84 | 172.10 percentage | Geometric Coefficient of Variation 44.32 |
| AZD7594 720 μg | Percentage Fluctuation of AZD7594 at Day 84 | 98.22 percentage | Geometric Coefficient of Variation 61.36 |
Secondary
Time of Last Quantifiable Analyte Concentration (Tlast) of AZD7594 at Day 84
Summary of PK parameter Tlast, Time of last quantifiable analyte concentration, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter.
Time frame: Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
Population: All randomised patients participating in the PK subset, who took at least one dose of IP and for whom at least one of the primary PK parameters could be calculated, and who had no major protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD7594 50 μg | Time of Last Quantifiable Analyte Concentration (Tlast) of AZD7594 at Day 84 | 8.01 hours |
| AZD7594 90 μg | Time of Last Quantifiable Analyte Concentration (Tlast) of AZD7594 at Day 84 | 24.00 hours |
| AZD7594 180 μg | Time of Last Quantifiable Analyte Concentration (Tlast) of AZD7594 at Day 84 | 24.00 hours |
| AZD7594 360 μg | Time of Last Quantifiable Analyte Concentration (Tlast) of AZD7594 at Day 84 | 24.00 hours |
| AZD7594 720 μg | Time of Last Quantifiable Analyte Concentration (Tlast) of AZD7594 at Day 84 | 24.00 hours |
Secondary
Time to Maximum Concentration at Steady State, Taken Directly From the Individual Concentration-time Curve (Tss, Max) of AZD7594 at Day 84
Summary of PK parameter tss, max, Time to maximum concentration at steady state, taken directly from the individual concentration-time curve, of AZD7594 at day 84 in PK analysis set. The presented results are summary statistics of the PK parameter.
Time frame: Day 84 (pre-dose and 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 16.0 and 24 h post-dose)
Population: All randomised patients participating in the PK subset, who took at least one dose of IP and for whom at least one of the primary PK parameters could be calculated, and who had no major protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD7594 50 μg | Time to Maximum Concentration at Steady State, Taken Directly From the Individual Concentration-time Curve (Tss, Max) of AZD7594 at Day 84 | 0.25 hours |
| AZD7594 90 μg | Time to Maximum Concentration at Steady State, Taken Directly From the Individual Concentration-time Curve (Tss, Max) of AZD7594 at Day 84 | 0.25 hours |
| AZD7594 180 μg | Time to Maximum Concentration at Steady State, Taken Directly From the Individual Concentration-time Curve (Tss, Max) of AZD7594 at Day 84 | 0.25 hours |
| AZD7594 360 μg | Time to Maximum Concentration at Steady State, Taken Directly From the Individual Concentration-time Curve (Tss, Max) of AZD7594 at Day 84 | 0.25 hours |
| AZD7594 720 μg | Time to Maximum Concentration at Steady State, Taken Directly From the Individual Concentration-time Curve (Tss, Max) of AZD7594 at Day 84 | 0.25 hours |