AsthmaPhase 2NCT02479412
A Multiple Dosing (14 Days) Study to Assess Efficacy and Safety of Three Dose Levels of AZD7594, Given Once Daily by Inhalation, in Patients With Mild to Moderate Asthma
A Phase 2 study testing 800 μg AZD7594 once daily, 250 µg AZD7594 once daily and 58 µg AZD7594 once daily in people with Asthma and Efficacy, run by AstraZeneca at 10 sites in 2 countries.
Trial summary
This study will be a randomised, double-blind, multiple dose (14 days), placebo-controlled, multi-center study to assess efficacy and safety of three dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- What is being tested?
- 800 μg AZD7594 once daily, 250 µg AZD7594 once daily and 58 µg AZD7594 once daily
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 25 Jun 2015to 8 Feb 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Body mass index of 18 to 35 kg/m2
- Men and women 18 to 75 years of age, inclusive
- Patients need to be non-smokers or ex-smokers (quit ≥ 6 months before the Visit 1) with total smoking history of < 10 pack years
- Documented clinical diagnosis of asthma for ≥ 6 months before the Visit 1
- Patients on low-dose inhaled corticosteroids (ICS) (equivalent of budesonide ≤ 400 μg per day) or low-dose ICS/long-acting β-2 agonist (LABA), or not on any inhaled steroids, or patients on montelukast
- Patients should be controlled on low dose budesonide during the first 14 ±2 days of Run-in Part 1, i.e., they need to have ACQ-5 of ≤ 1.5 at Visit 2.
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- Prebronchodilator FEV1 at Visit 3 should be between 40% and 90% of predicted (mean of 2 predose measurements taken 30 minutes apart).
- All patients need to have FeNO concentrations of ≥ 25 parts per billion at Visit 3
- Demonstrate the ability to use the study inhalation device properly
- Women must be of nonchildbearing potential defined as meeting 1 of the following criteria:
- Permanently or surgically sterilized, including hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy
- Postmenopausal; aged ≤ 50 years and have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle stimulating hormone levels in the postmenopausal range
- Postmenopausal; aged > 50 years and have been amenorrheic for 12 months or more, following cessation of all exogenous hormonal treatments
- Male patients should be willing to use a condom to prevent pregnancy and exposure of a female partner to AZD7594 and should refrain from donating sperm or fathering a child from the first day of dosing until 3 months after the last dose of IMP.
Who cannot join
- Known or suspected hypersensitivity to the IMPs or excipients, including lactose
- Systemic steroid use in the 6 weeks before Visit 1
- Any active disease other than asthma
- Patients on medium to high-dose ICS (equivalent of budesonide > 400 μg per day) or on inhaled anticholinergic combination within the 6 weeks prior to Visit 1
- Compliance with the eDiary of at least 80% of the days is expected in both Run-in and Treatment Periods. Patients with < 80% eDiary compliance during Run-in Periods would not be randomized
- Treatment with biologicals such as monoclonal antibodies or chimeric biomolecules including omalizumab within 6 months or 5 half-lives before Visit 1, whichever is longer
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- History or clinical suspicion of any clinically relevant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study, or any other safety concerns in the opinion of the Investigator
- ACQ-5 ≥ 3 at any time between Visits 1 and 3
- Any contraindication against the use of vagolytic or sympathomimetic drugs as judged by the Investigator.
- Patients with hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus (HIV)
- Donation of blood (≥ 450 mL) within 3 months or donation of plasma within 14 days before Visit 1
- Pregnant woman or a nursing mother
- Suspicion of Gilbert's syndrome
- Vulnerable persons (e.g., persons kept in detention)
- ACQ-5 of ≥ 3 or daily rescue use of ≥ 12 puffs for ≥ 3 consecutive days during the enrollment period
- Hypersensitivity to the active substance or to any of the excipients of the Run-in medication (i.e., budesonide)
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
Germany9 sites
Research Site
Berlin, 10717
Research Site
Berlin, 10969
Research Site
Berlin, 14050
Research Site
Frankfurt, 60596
Research Site
Großhansdorf, 22927
Research Site
Hamburg, 20354
Research Site
Hamburg, 22143
Research Site
Lübeck, 23552
Research Site
Wiesbaden, 65187
About this study
Official title: A RANDOMIZED, DOUBLE BLIND, MULTIPLE DOSING (14 DAYS), PLACEBO-CONTROLLED, INCOMPLETE BLOCK CROSSOVER, MULTI CENTER STUDY TO ASSESS EFFICACY AND SAFETY OF THREE DOSE LEVELS OF AZD7594, GIVEN ONCE DAILY BY INHALATION, IN PATIENTS WITH MILD TO MODERATE ASTHMA
This study will be a randomised, double-blind, multiple dose (14 days), placebo-controlled, multi-center study to assess efficacy and safety of three dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma.
Read the detailed description
This is a randomized, double-blind, multiple dosing (14 ± 1 days), placebo-controlled, incomplete block crossover, multi-center study to assess efficacy and safety of 3 dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma.
This multi-center study will be conducted at multiple sites in Europe. It is planned that approximately 48 patients with mild to moderate asthma will be randomized into the study
- Being tested
- 800 μg AZD7594 once daily, 250 µg AZD7594 once daily, 58 µg AZD7594 once daily, Placebo once daily, Salbutamol
- Keywords
- Mild to moderate asthma, FEV1, efficacy, safety
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
800 μg AZD7594 once dailyDrug
Also called High dose of AZD7594
Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule
250 µg AZD7594 once dailyDrug
Also called Medium dose of AZD7594
Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule
58 µg AZD7594 once dailyDrug
Also called Low dose of AZD7594
Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule
Placebo once dailyDrug
Also called Placebo
Once daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule
SalbutamolDrug
Also called Rescue medication
Inhalation as needed
| Study group | Role | What they receive |
|---|---|---|
| Sequence 1 | Experimental | Placebo once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3 Receives: Drug: 250 µg AZD7594 once daily; Drug: 58 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol |
| Sequence 2 | Experimental | Placebo once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3 Receives: Drug: 800 μg AZD7594 once daily; Drug: 250 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol |
| Sequence 3 | Experimental | Placebo once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3 Receives: Drug: 800 μg AZD7594 once daily; Drug: 58 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol |
| Sequence 4 | Experimental | 58 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3 Receives: Drug: 800 μg AZD7594 once daily; Drug: 58 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol |
| Sequence 6 | Experimental | 250 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3 Receives: Drug: 250 µg AZD7594 once daily; Drug: 58 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol |
| Sequence 8 | Experimental | 800 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3 Receives: Drug: 800 μg AZD7594 once daily; Drug: 250 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol |
| Sequence 5 | Experimental | 58 µg AZD7594 once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3 Receives: Drug: 800 μg AZD7594 once daily; Drug: 58 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol |
| Sequence 7 | Experimental | 250 µg AZD7594 once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3 Receives: Drug: 250 µg AZD7594 once daily; Drug: 58 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol |
| Sequence 9 | Experimental | 800 µg AZD7594 once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3 Receives: Drug: 800 μg AZD7594 once daily; Drug: 250 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 15
Comparison of the efficacy of AZD7594 in terms of change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 15 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 14) with placebo
Measured: On Day 1 (pre-dose) and on Day 15 in each period
Secondary outcomes (25)
Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 8
The efficacy of AZD7594 was assessed in terms of change from baseline in fractional exhaled nitric oxide (FeNO) on Day 8
Measured: On Day 1 (pre-dose) and on Day 8 in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 15
The efficacy of AZD7594 was assessed in terms of change from baseline in fractional exhaled nitric oxide (FeNO) on Day 15
Measured: On Day 1 (pre-dose) and on Day 15 in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 8
The efficacy of AZD7594 was assessed in terms of change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 8 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 7)
Measured: On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 15
The efficacy of AZD7594 was assessed in terms of change from baseline in morning trough forced vital capacity (FVC) on Day 15 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 14)
Measured: On Day 1 (pre-dose) and on Day 15 (pre-dose) in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 8
The efficacy of AZD7594 was assessed in terms of change from baseline in morning trough forced vital capacity (FVC) on Day 8 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 7)
Measured: On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Peak Expiratory Flow (mPEF) Before Administration Over the Treatment Period
The efficacy of AZD7594 was assessed in terms of change from baseline in morning peak expiratory flow (mPEF) before administration of the investigational medicinal product (IMP) in each treatment period. The first PEF measurement was on the evening of Visit 1. Every morning and every evening after Visit 1, patients were required to perform 3 maneuvers for PEF assessment. The highest value from among the 3 assessments was marked as mPEF with the date and time of the measurement. The final PEF assessment was done on the morning of Visit 11 (Day 15 of Treatment Period 3).
Measured: Every morning at pre-dose from Day 1 to Day 15
Efficacy of AZD7594 by Assessment of the Change From Baseline in Evening Peak Expiratory Flow (ePEF) Before Administration Over the Treatment Period
The efficacy of AZD7594 was assessed in terms of change from baseline in evening peak expiratory flow (ePEF) in each treatment period. The first PEF measurement was on the evening of Visit 1. Every morning and every evening after Visit 1, patients were required to perform 3 maneuvers for PEF assessment. The highest value from among the 3 assessments was marked as ePEF together with the date and time of the measurement. The final PEF assessment was done on the morning of Visit 11 (Day 15 of Treatment Period 3).
Measured: Every evening from Day 1 to Day 14 in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline in Average Daily Use of Rescue Salbutamol Over the Treatment Period
The efficacy of AZD7594 was assessed in terms of change from baseline in average daily use of salbutamol (each morning and evening) in each treatment period.
Measured: Every day from Day 1 to Day 15 (from evening of Day 1 to morning of Day 15)
Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 15 in Asthma Control Questionnaire-5
The efficacy of AZD7594 was assessed in terms of change from baseline to Day 15 in Asthma Control Questionnaire-5 in each treatment period. Five questions were asked and each question was scored on a scale of 0 to 6, where a higher score represents a more severe impairment/symptom. The ACQ-5 score at a given visit was defined as the average of the scores given for each of the questions, calculated as ACQ-5 score = Sum of 5 scores/5.
Measured: At baseline and on Day 15 in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 8 in Asthma Control Questionnaire-5
The efficacy of AZD7594 was assessed in terms of change from baseline to Day 15 in Asthma Control Questionnaire-5 in each treatment period. Five questions were asked and each question was scored on a scale of 0 to 6, where a lower score represents a more severe impairment/symptom. The ACQ-5 score at a given visit was defined as the average of the scores given for each of the questions, calculated as ACQ-5 score = Sum of 5 scores/5.
Measured: At baseline and on Day 8 in each period
Efficacy of AZD7594 by Assessment of Night-time Awakenings
The efficacy of AZD7594 was assessed in terms of change in nighttime awakenings in each treatment period. The patients were asked to answer 'Yes' or 'No' to the question of "Did your asthma cause you to wake up last night?". If yes, the number and percentage of days that had a night-time awakening were determined for each of the study periods.
Measured: At baseline and from Day 2 to Day 15 in each period
Efficacy of AZD7594 by Assessment of Daily Symptom Score
The efficacy of AZD7594 was assessed in terms of change in daily symptom score from baseline to average of treatment period post dose (Day 1-14) in each treatment period. Severity scores for asthma symptoms were recorded twice daily, once in the morning and once in the evening with the scoring system of 0-no asthma symptoms, 1-toleratable asthma symptoms, 2-discomfort asthma symptoms with normal activities (or with sleep) and 3-asthma symptoms with impaired normal activities (or to sleep).
Measured: At baseline and from Day 1 to Day 14 in each period
Efficacy of AZD7594 by Assessment of Asthma Control Days
The efficacy of AZD7594 was assessed in terms of amount of asthma control days in each treatment period. An asthma control day was defined as a day with asthma symptom score = 0, a night with no awakenings due to asthma symptoms and a day with no use of rescue medication. A given calendar day was defined as an asthma control day if it fulfills the criteria for a symptom-free day and for a rescue medication-free day
Measured: At baseline and from Day 1 to Day 14 post-dose in each period
Number of Participants With Adverse Events
Assessment of safety and tolerability of three dose levels of AZD7594 in participants with mild to moderate asthma. IP referred to investigational product.
Measured: From Screening to Follow-up (these two examinations are up to 165 days apart)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of Cmax of AZD7594
Comparison of Cmax (maximum observed plasma concentration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Measured: On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of AUC(0-4) of AZD7594
Comparison of AUC(0-4) (Area under the plasma concentration-time curve from time zero to 4 hours after administration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose).
Measured: On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmax,ss of AZD7594
Comparison of Cmax,ss (observed maximum plasma concentration at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Measured: On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-24) of AZD7594
Comparison of AUC(0-24) (Area under the plasma concentration-time curve from time zero to 24 hours after administration) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Measured: On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-last) of AZD7594
Comparison of AUC(0-last) (Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (Day 1 and Day 14)) of AZD7594 (i.e. in participants with intensive pharmacokinetic assessments)
Measured: On Day 1 and Day 14 in each period (in participants with intensive pharmacokinetic assessments, on Day 1 at pre-dose and 15 and 30 minutes, and 1, 2 and 4 h post-dose, on Day 14 at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of Tmax of AZD7594
Comparison of tmax (time to reach maximum plasma concentration) of AZD7594 on Day 1 of each treatment period; up to 6 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Measured: On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Tmax,ss of AZD7594
Comparison of tmax,ss (time to reach maximum plasma concentration at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Measured: On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cavg,ss of AZD7594
Comparison of Cavg,ss (average plasma concentration during a dosing interval at steady state) of AZD7594 on Day 14 of each treatment period; up to 10 samples were collected in each period (i.e. in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Measured: On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmax/D of AZD7594
Comparison of Cmax/D (dose-normalized Cmax) of AZD7594
Measured: On Day 1 in each period
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-24)/D of AZD7594
Comparison of AUC(0-24)/D (dose-normalized AUC(0-24)) of AZD7594
Measured: On Day 14 in each period
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmin of AZD7594
Comparison of steady-state minimum (pre-dose) concentration (Cmin) of AZD7594 in each treatment period
Measured: On Day 14 at pre-dose in each period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2015 (estimated)
- Study start25 Jun 2015
- Primary completion8 Feb 2016
- Study completion8 Feb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rainard Fuhr, Dr. med., Principal investigator, PAREXEL International GmbH, Berlin, GermanyUlrike Westerhausen, Dr., Principal investigator, Pneumologisches Studienzentrum, Berlin, GermanyOliver Kornmann, Dr., Principal investigator, IKF Pneumologie GmbH, Frankfurt, GermanyJutta Beier, Dr. med., Principal investigator, Insaf GmbH, Wiesbaden, GermanyChristine Grigat, Dr., Principal investigator, Clinical Research Hamburg GmbH, Hamburg, GermanyAndrea Ludwig-Sengpiel, Dr., Principal investigator, KLB Gesundheitsforschung Lübeck GmbH, Lübeck, GermanyDirk Skowasch, Prof., Principal investigator, University hospital of Bonn, Department of Internal Medicine II, Bonn, GermanyAnne-Marie Kirsten, Dr., Principal investigator, Pneumologisches Forschungsinstitut an der LungenClinic Großhansdorf, Großhansdorf, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02479412
- Sponsor's protocol ID
- D3741C00003
- Other IDs
- 2014-005306-37, 2014
- Status last verified
- Aug 2017
- First submitted
- 17 Jun 2015
- Last updated
- 15 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Brown MN, Fuhr R, Beier J, Su HL, Chen Y, Forsman H, Hamren UW, Jackson H, Aggarwal A. Efficacy and safety of AZD7594, an inhaled non-steroidal selective glucocorticoid receptor modulator, in patients with asthma: a phase 2a randomized, double blind, placebo-controlled crossover trial. Respir Res. 2019 Feb 18;20(1):37. doi: 10.1186/s12931-019-1000-7.
PubMed 30777086
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A RANDOMIZED, DOUBLE BLIND, MULTIPLE DOSING (14 DAYS), PLACEBO-CONTROLLED, INCOMPLETE BLOCK CROSSOVER, MULTI CENTER STUDY TO ASSESS EFFICACY AND SAFETY OF THREE DOSE LEVELS OF AZD7594, GIVEN ONCE DAILY BY INHALATION, IN PATIENTS WITH MILD TO MODERATE ASTHMA
- ClinicalTrials.gov ID
- NCT02479412
- Acronym / sponsor ID
- D3741C00003
- Keywords
- Mild to moderate asthma, FEV1, efficacy, safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 25 Jun 2015 (actual)
- Primary completion
- 8 Feb 2016 (actual)
- Study completion
- 8 Feb 2016 (actual)
- First posted
- 24 Jun 2015 (estimated)
- Results
- Posted 23 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will be a randomised, double-blind, multiple dose (14 days), placebo-controlled, multi-center study to assess efficacy and safety of three dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma.
Detailed description
This is a randomized, double-blind, multiple dosing (14 ± 1 days), placebo-controlled, incomplete block crossover, multi-center study to assess efficacy and safety of 3 dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma.
This multi-center study will be conducted at multiple sites in Europe. It is planned that approximately 48 patients with mild to moderate asthma will be randomized into the study
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Sequence 1 | Experimental | Drug: 250 µg AZD7594 once daily, Drug: 58 µg AZD7594 once daily, Drug: Placebo once daily, Drug: SalbutamolPlacebo once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3 |
| Sequence 2 | Experimental | Drug: 800 μg AZD7594 once daily, Drug: 250 µg AZD7594 once daily, Drug: Placebo once daily, Drug: SalbutamolPlacebo once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3 |
| Sequence 3 | Experimental | Drug: 800 μg AZD7594 once daily, Drug: 58 µg AZD7594 once daily, Drug: Placebo once daily, Drug: SalbutamolPlacebo once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3 |
| Sequence 4 | Experimental | Drug: 800 μg AZD7594 once daily, Drug: 58 µg AZD7594 once daily, Drug: Placebo once daily, Drug: Salbutamol58 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3 |
| Sequence 6 | Experimental | Drug: 250 µg AZD7594 once daily, Drug: 58 µg AZD7594 once daily, Drug: Placebo once daily, Drug: Salbutamol250 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3 |
| Sequence 8 | Experimental | Drug: 800 μg AZD7594 once daily, Drug: 250 µg AZD7594 once daily, Drug: Placebo once daily, Drug: Salbutamol800 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3 |
| Sequence 5 | Experimental | Drug: 800 μg AZD7594 once daily, Drug: 58 µg AZD7594 once daily, Drug: Placebo once daily, Drug: Salbutamol58 µg AZD7594 once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3 |
| Sequence 7 | Experimental | Drug: 250 µg AZD7594 once daily, Drug: 58 µg AZD7594 once daily, Drug: Placebo once daily, Drug: Salbutamol250 µg AZD7594 once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3 |
| Sequence 9 | Experimental | Drug: 800 μg AZD7594 once daily, Drug: 250 µg AZD7594 once daily, Drug: Placebo once daily, Drug: Salbutamol800 µg AZD7594 once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Body mass index of 18 to 35 kg/m2
- Men and women 18 to 75 years of age, inclusive
- Patients need to be non-smokers or ex-smokers (quit ≥ 6 months before the Visit 1) with total smoking history of < 10 pack years
- Documented clinical diagnosis of asthma for ≥ 6 months before the Visit 1
- Patients on low-dose inhaled corticosteroids (ICS) (equivalent of budesonide ≤ 400 μg per day) or low-dose ICS/long-acting β-2 agonist (LABA), or not on any inhaled steroids, or patients on montelukast
Key exclusion criteria (16 listed)
- Known or suspected hypersensitivity to the IMPs or excipients, including lactose
- Systemic steroid use in the 6 weeks before Visit 1
- Any active disease other than asthma
- Patients on medium to high-dose ICS (equivalent of budesonide > 400 μg per day) or on inhaled anticholinergic combination within the 6 weeks prior to Visit 1
- Compliance with the eDiary of at least 80% of the days is expected in both Run-in and Treatment Periods. Patients with < 80% eDiary compliance during Run-in Periods would not be randomized
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 800 μg AZD7594 once dailyAlso: High dose of AZD7594Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule | Drug | Sequence 2, Sequence 3, Sequence 4, Sequence 5, Sequence 8, Sequence 9 |
| 250 µg AZD7594 once dailyAlso: Medium dose of AZD7594Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule | Drug | Sequence 1, Sequence 2, Sequence 6, Sequence 7, Sequence 8, Sequence 9 |
| 58 µg AZD7594 once dailyAlso: Low dose of AZD7594Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule | Drug | Sequence 1, Sequence 3, Sequence 4, Sequence 5, Sequence 6, Sequence 7 |
| Placebo once dailyAlso: PlaceboOnce daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule | Drug | Sequence 1, Sequence 2, Sequence 3, Sequence 4, Sequence 5, Sequence 6, Sequence 7, Sequence 8, Sequence 9 |
| SalbutamolAlso: Rescue medicationInhalation as needed | Drug | Sequence 1, Sequence 2, Sequence 3, Sequence 4, Sequence 5, Sequence 6, Sequence 7, Sequence 8, Sequence 9 |
Primary outcome
Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 15
Time frame: On Day 1 (pre-dose) and on Day 15 in each period
Comparison of the efficacy of AZD7594 in terms of change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 15 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product [IMP] on Day 14) with placebo
25 secondary outcomes
Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 8
Time frame: On Day 1 (pre-dose) and on Day 8 in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 15
Time frame: On Day 1 (pre-dose) and on Day 15 in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 8
Time frame: On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 15
Time frame: On Day 1 (pre-dose) and on Day 15 (pre-dose) in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 8
Time frame: On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Peak Expiratory Flow (mPEF) Before Administration Over the Treatment Period
Time frame: Every morning at pre-dose from Day 1 to Day 15
Efficacy of AZD7594 by Assessment of the Change From Baseline in Evening Peak Expiratory Flow (ePEF) Before Administration Over the Treatment Period
Time frame: Every evening from Day 1 to Day 14 in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline in Average Daily Use of Rescue Salbutamol Over the Treatment Period
Time frame: Every day from Day 1 to Day 15 (from evening of Day 1 to morning of Day 15)
Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 15 in Asthma Control Questionnaire-5
Time frame: At baseline and on Day 15 in each period
Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 8 in Asthma Control Questionnaire-5
Time frame: At baseline and on Day 8 in each period
Efficacy of AZD7594 by Assessment of Night-time Awakenings
Time frame: At baseline and from Day 2 to Day 15 in each period
Efficacy of AZD7594 by Assessment of Daily Symptom Score
Time frame: At baseline and from Day 1 to Day 14 in each period
Efficacy of AZD7594 by Assessment of Asthma Control Days
Time frame: At baseline and from Day 1 to Day 14 post-dose in each period
Number of Participants With Adverse Events
Time frame: From Screening to Follow-up (these two examinations are up to 165 days apart)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of Cmax of AZD7594
Time frame: On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of AUC(0-4) of AZD7594
Time frame: On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmax,ss of AZD7594
Time frame: On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-24) of AZD7594
Time frame: On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-last) of AZD7594
Time frame: On Day 1 and Day 14 in each period (in participants with intensive pharmacokinetic assessments, on Day 1 at pre-dose and 15 and 30 minutes, and 1, 2 and 4 h post-dose, on Day 14 at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of Tmax of AZD7594
Time frame: On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Tmax,ss of AZD7594
Time frame: On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cavg,ss of AZD7594
Time frame: On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose)
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmax/D of AZD7594
Time frame: On Day 1 in each period
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-24)/D of AZD7594
Time frame: On Day 14 in each period
Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmin of AZD7594
Time frame: On Day 14 at pre-dose in each period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30777086Brown MN, Fuhr R, Beier J, Su HL, Chen Y, Forsman H, Hamren UW, Jackson H, Aggarwal A. Efficacy and safety of AZD7594, an inhaled non-steroidal selective glucocorticoid receptor modulator, in patients with asthma: a phase 2a randomized, double blind, placebo-controlled crossover trial. Respir Res. 2019 Feb 18;20(1):37. doi: 10.1186/s12931-019-1000-7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rainard Fuhr, Dr. med. principal investigator
PAREXEL International GmbH, Berlin, Germany
Ulrike Westerhausen, Dr. principal investigator
Pneumologisches Studienzentrum, Berlin, Germany
Oliver Kornmann, Dr. principal investigator
IKF Pneumologie GmbH, Frankfurt, Germany
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 800 μg AZD7594 once daily, 250 µg AZD7594 once daily and 58 µg AZD7594 once daily in people with Asthma and Efficacy, run by AstraZeneca at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany, Bulgaria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 15 (time frame: On Day 1 (pre-dose) and on Day 15 in each period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02479412, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2018.