AsthmaPhase 1NCT04072562
A Study to Evaluate the Amount of Drug That Becomes Available to the Blood Circulation When Inhaled by a Nebulizer and Dry Powder Inhaler in Healthy Subjects.
A Phase 1 study testing AZD7594 in people with Asthma, run by AstraZeneca at 1 site in Germany.
Trial summary
The purpose of this study is to assess the relative bioavailability of the AZD7594 nebulized formulations (test) and the dry powder formulation (reference). The study results will provide information on the pharmacokinetic (PK) profile following use of the 2 devices to be used in further clinical development. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- AZD7594
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteGermany
- Study dates
- 19 Sep 2019to 28 Nov 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and female subjects aged 18 - 55 years (inclusive) at Screening with suitable veins for cannulation or repeated venepuncture.
- Females must have a negative pregnancy test at screening and on admission to the unit for each treatment period, and must not be lactating. Women of child-bearing potential (WOCBP) must 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 14 days after the last dose of IMP. They must agree not to become pregnant or donate ova throughout the study and for 14 days after the last dose of IMP. Male subjects must be surgically sterile or be willing to use a condom during the study.
- Have a body mass index (BMI) between 18 and 29.9 kg/m2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive).
- Subject is able to understand and communicate in German.
Who cannot join
- History of any clinically significant disease or disorder which, in the opinion of the PI, 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.
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- History of Gilbert's syndrome, history of cholecystectomy or gall stone.
- History of tuberculosis, any other significant lung diseases like surgeries, asthma, chronic obstructive pulmonary disease.
- Upper respiratory tract infections (excluding otitis media) within 14 days of the first study day, or lower respiratory tract infection within 3 months prior to Screening.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
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- Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, at screening and first admission to the study unit (first treatment period) as judged by the PI.
- Any clinically significant abnormal findings in vital signs at screening and first admission to the study unit (first treatment period), as judged by the PI, and defined as:
- Systolic BP <90 mmHg or ≥140 mmHg and diastolic BP <50 mmHg or ≥90 mmHg
- Heart rate <50 bpm or >90 bpm
- Any clinically significant abnormalities on 12-lead ECG at screening and first admission to the study unit (first treatment period), as judged by the PI, and defined as:
- Sick sinus syndrome
- Arrhythmia
- Prolonged QT interval corrected using Fridericia's formula > 450 ms
- Any positive result at screening for serum hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) results.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit whichever is the longest. Note: subjects consented and screened, but not randomised in this study or other clinical studies, are not excluded.
- Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity to AZD7594 or formulation excipients, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to AZD7594.
- Note: subjects with hay fever are allowed to participate, unless hay fever is active
- Current smokers or those who have smoked or used nicotine products (including e-cigarettes; >10 pack-year) within the 6 months prior to screening.
- Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the PI or positive screen for drugs of abuse, cotinine, and/or alcohol at screening or on each admission to the clinical unit.
- Use of drugs with enzyme-inducing properties within 3 weeks prior to the first administration of IMP or herbal preparations/medications including, but not limited to, St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng. Subjects should stop using these herbal medications 14 days prior to the first administration of IMP.
- Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life.
- Note: Hormonal replacement therapy (HRT) and systemic contraceptives are allowed for females.
- Subjects not able to perform a technically acceptable spirometry and/or not able to use the DPI correctly or not able to tolerate the pre-defined inhalation/nebulization.
- Subjects with a pregnant partner.
- Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.
- Subjects who have previously received AZD7594.
- Vulnerable subjects, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Single-centre, Randomised, 3-period, 3-treatment, Single-dose, Crossover Study to Assess the Relative Bioavailability of AZD7594 Inhaled Via a Nebulizer and Via a Dry Powder Inhaler in Healthy Subjects
The purpose of this study is to assess the relative bioavailability of the AZD7594 nebulized formulations (test) and the dry powder formulation (reference).
The study results will provide information on the pharmacokinetic (PK) profile following use of the 2 devices to be used in further clinical development.
Read the detailed description
This study will be an open-label, randomised, 3 period, 3-treatment, crossover study in healthy subjects (males and females), performed at a single clinical unit.
The study will comprise:
- A screening period of maximum 28 days;
- Three treatment periods during which subjects will be resident from the morning (fasting conditions) of the day before dosing with AZD7594 (Day -1) until at least 48 hours after dosing; discharged on the morning of Day 3;
- Two ambulatory visits (Day 4 and Day 5) within each treatment period; and
- A final visit 10 to 14 days after the last administration of AZD7594.
- There will be a minimum washout period of 10 days between each dose administration.
A total of 24 subjects will be randomised to receive single doses of AZD7594 on 3 occasions, under fasted conditions (overnight fast of at least 10 hours):
- Treatment A: 0.7 mg (delivered dose) AZD7594 via nebulizer, test
- Treatment B: 1.6 mg (delivered dose) AZD7594 via nebulizer, test
- Treatment C: 720 μg (delivered dose) AZD7594 via dry powder inhaler (DPI), reference
Each subject will be involved in the study for approximately 10 to 12 weeks.
- Conditions
- Asthma
- Being tested
- AZD7594
- Keywords
- Bioavailability, Pharmacokinetics, Safety, Selective glucocorticoid receptor modulator
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD7594Drug
Treatment A: The study drug is a nebulizer suspension with strength 2.8 mg/mL using 2 mL in the device. The study drug is administered via oral inhalation.
Treatment B: The study drug is a nebulizer suspension with strength 6.3 mg/mL using 2 mL in the device. The study drug was administered via oral inhalation.
Treatment C: The study drug is an inhalation powder. The study drug was administered via oral inhalation.
| Study group | Role | What they receive |
|---|---|---|
| AZD7594 0.7 mg | Experimental | The study subjects will receive AZD7594 via nebulizer, during 8 minutes: 0.7 mg, delivered dose 1 inhalation Receives: Drug: AZD7594 |
| AZD7594 1.6 mg | Experimental | The study subjects will receive AZD7594 via nebulizer, during 8 minutes: 1.6 mg, delivered dose 1 inhalation Receives: Drug: AZD7594 |
| AZD7594 720 μg | Active comparator | The study subjects will receive AZD7594 via DPI: 0.72 mg, delivered dose (792 µg nominal dose) 1 inhalation Receives: Drug: AZD7594 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed plasma concentration (Cmax)
To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL
Measured: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Area under plasma concentration-time curve from zero to infinity (AUC)
To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL
Measured: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t)
To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL
Measured: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Individual ratios of test versus reference for AUC
To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL
Measured: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Individual ratios of test versus reference for AUC0-t
To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL
Measured: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Individual ratios of test versus reference for Cmax
To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL
Measured: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Secondary outcomes (46)
Time to reach maximum observed plasma concentration (tmax)
To evaluate the PK profiles of AZD7594 when administered as the two formulations
Measured: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Terminal elimination rate constant (λz)
To evaluate the PK profiles of AZD7594 when administered as the two formulations
Measured: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Half-life associated with terminal slope (λz) of a semilogarithmic concentration-time curve (t1/2λz)
To evaluate the PK profiles of AZD7594 when administered as the two formulations
Measured: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT)
To evaluate the PK profiles of AZD7594 when administered as the two formulations
Measured: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
To evaluate the PK profiles of AZD7594 when administered as the two formulations
Measured: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
To evaluate the PK profiles of AZD7594 when administered as the two formulations
Measured: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Number of participants with adverse events
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in systolic BP
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in diastolic BP
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in pulse rate
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in body temperature
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in ECG
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in physical examination
To further assess the safety of single doses of AZD7594 in healthy volunteers. The complete physical examinations will include an assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in spirometry
To further assess the safety of single doses of AZD7594 in healthy volunteers. All spirometry measurements will be performed using the Jaeger Masterscope for which calibration will be performed daily using a 3 L calibration syringe. Spirometry measurements with the Jaeger Masterscope will be performed according to European Respiratory Society/American Thoracic Society guidelines. Global Lung Function Initiative 2012 reference values will be used.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in haemoglobin
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in haematocrit
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in white blood cell count
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in red blood cell count
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in mean corpuscular volume (MCV)
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in mean corpuscular haemoglobin (MCH)
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in mean corpuscular hemoglobin concentration (MCHC)
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in neutrophils absolute count
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in lymphocytes absolute count
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in monocytes absolute count
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in eosinophils absolute count
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in basophils absolute count
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in platelets
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in reticulocytes absolute count
To further assess the safety of single doses of AZD7594 in healthy volunteers
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in sodium
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in potassium
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in urea
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in creatinine
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in albumin
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in calcium
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in phosphate
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in glucose (fasting)
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in C-reactive protein
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in T4 hormone
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in thyroid-stimulating hormone
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in liver enzymes
To further assess the safety of single doses of AZD7594 in healthy volunteers. The laboratory variables to be measured are: Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT)
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in total bilirubin (TBL)
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in unconjugated bilirubin
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in follicle stimulating hormone (FSH)
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in lutenizing hormone (LH)
To further assess the safety of single doses of AZD7594 in healthy volunteers.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in coagulation
To further assess the safety of single doses of AZD7594 in healthy volunteers. The laboratory variables to be measured are: international normalized ratio and activated partial thrombin time
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in urinalysis
To further assess the safety of single doses of AZD7594 in healthy volunteers. The laboratory variables to be measured are: protein, glucose, and blood.
Measured: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start19 Sep 2019
- Primary completion28 Nov 2019
- Study completion28 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Rainard Fuhr, Principal investigator, Parexel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04072562
- Sponsor's protocol ID
- D3742C00001
- Status last verified
- Dec 2019
- First submitted
- 19 Jul 2019
- Last updated
- 16 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-centre, Randomised, 3-period, 3-treatment, Single-dose, Crossover Study to Assess the Relative Bioavailability of AZD7594 Inhaled Via a Nebulizer and Via a Dry Powder Inhaler in Healthy Subjects
- ClinicalTrials.gov ID
- NCT04072562
- Acronym / sponsor ID
- D3742C00001
- Conditions
- Asthma
- Keywords
- Bioavailability, Pharmacokinetics, Safety, Selective glucocorticoid receptor modulator
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 19 Sep 2019 (actual)
- Primary completion
- 28 Nov 2019 (actual)
- Study completion
- 28 Nov 2019 (actual)
- First posted
- 28 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the relative bioavailability of the AZD7594 nebulized formulations (test) and the dry powder formulation (reference).
The study results will provide information on the pharmacokinetic (PK) profile following use of the 2 devices to be used in further clinical development.
Detailed description
This study will be an open-label, randomised, 3 period, 3-treatment, crossover study in healthy subjects (males and females), performed at a single clinical unit.
The study will comprise:
- A screening period of maximum 28 days;
- Three treatment periods during which subjects will be resident from the morning (fasting conditions) of the day before dosing with AZD7594 (Day -1) until at least 48 hours after dosing; discharged on the morning of Day 3;
- Two ambulatory visits (Day 4 and Day 5) within each treatment period; and
- A final visit 10 to 14 days after the last administration of AZD7594.
- There will be a minimum washout period of 10 days between each dose administration.
A total of 24 subjects will be randomised to receive single doses of AZD7594 on 3 occasions, under fasted conditions (overnight fast of at least 10 hours):
- Treatment A: 0.7 mg (delivered dose) AZD7594 via nebulizer, test
- Treatment B: 1.6 mg (delivered dose) AZD7594 via nebulizer, test
- Treatment C: 720 μg (delivered dose) AZD7594 via dry powder inhaler (DPI), reference
Each subject will be involved in the study for approximately 10 to 12 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| AZD7594 0.7 mg | Experimental | Drug: AZD7594The study subjects will receive AZD7594 via nebulizer, during 8 minutes: 0.7 mg, delivered dose 1 inhalation |
| AZD7594 1.6 mg | Experimental | Drug: AZD7594The study subjects will receive AZD7594 via nebulizer, during 8 minutes: 1.6 mg, delivered dose 1 inhalation |
| AZD7594 720 μg | Active comparator | Drug: AZD7594The study subjects will receive AZD7594 via DPI: 0.72 mg, delivered dose (792 µg nominal dose) 1 inhalation |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and female subjects aged 18 - 55 years (inclusive) at Screening with suitable veins for cannulation or repeated venepuncture.
- Females must have a negative pregnancy test at screening and on admission to the unit for each treatment period, and must not be lactating. Women of child-bearing potential (WOCBP) must 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 14 days after the last dose of IMP. They must agree not to become pregnant or donate ova throughout the study and for 14 days after the last dose of IMP. Male subjects must be surgically sterile or be willing to use a condom during the study.
- Have a body mass index (BMI) between 18 and 29.9 kg/m2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive).
- Subject is able to understand and communicate in German.
Key exclusion criteria (29 listed)
- History of any clinically significant disease or disorder which, in the opinion of the PI, 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.
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- History of Gilbert's syndrome, history of cholecystectomy or gall stone.
- History of tuberculosis, any other significant lung diseases like surgeries, asthma, chronic obstructive pulmonary disease.
- Upper respiratory tract infections (excluding otitis media) within 14 days of the first study day, or lower respiratory tract infection within 3 months prior to Screening.
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 |
|---|---|---|
| AZD7594Treatment A: The study drug is a nebulizer suspension with strength 2.8 mg/mL using 2 mL in the device. The study drug is administered via oral inhalation. Treatment B: The study drug is a nebulizer suspension with strength 6.3 mg/mL using 2 mL in the device. The study drug was administered via oral inhalation. Treatment C: The study drug is an inhalation powder. The study drug was administered via oral inhalation. | Drug | AZD7594 0.7 mg, AZD7594 1.6 mg, AZD7594 720 μg |
Primary outcome
Maximum observed plasma concentration (Cmax)
Time frame: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL
Area under plasma concentration-time curve from zero to infinity (AUC)
Time frame: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t)
Time frame: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL
Individual ratios of test versus reference for AUC
Time frame: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL
Individual ratios of test versus reference for AUC0-t
Time frame: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL
Individual ratios of test versus reference for Cmax
Time frame: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL
46 secondary outcomes
Time to reach maximum observed plasma concentration (tmax)
Time frame: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Terminal elimination rate constant (λz)
Time frame: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Half-life associated with terminal slope (λz) of a semilogarithmic concentration-time curve (t1/2λz)
Time frame: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT)
Time frame: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
Time frame: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
Time frame: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)
Number of participants with adverse events
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in systolic BP
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in diastolic BP
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in pulse rate
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in body temperature
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in ECG
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in physical examination
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in spirometry
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in haemoglobin
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in haematocrit
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in white blood cell count
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in red blood cell count
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in mean corpuscular volume (MCV)
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in mean corpuscular haemoglobin (MCH)
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in mean corpuscular hemoglobin concentration (MCHC)
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in neutrophils absolute count
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in lymphocytes absolute count
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in monocytes absolute count
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in eosinophils absolute count
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in basophils absolute count
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in platelets
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in reticulocytes absolute count
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in sodium
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in potassium
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in urea
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in creatinine
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in albumin
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in calcium
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in phosphate
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in glucose (fasting)
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in C-reactive protein
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in T4 hormone
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in thyroid-stimulating hormone
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Number of participants with abnormal findings in liver enzymes
Time frame: From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2019.
- Individual participant dataSharing planned: No
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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 principal investigator
Parexel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD7594 in people with Asthma, run by AstraZeneca at 1 site in Germany.
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 5 inclusion and 29 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 16 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum observed plasma concentration (Cmax) (time frame: At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Dec 2019.