Asthma Clinical Trial
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
Verified date | December 2019 |
Source | AstraZeneca |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 24 |
Est. completion date | November 28, 2019 |
Est. primary completion date | November 28, 2019 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 55 Years |
Eligibility |
Inclusion Criteria: 1. Provision of signed and dated, written informed consent prior to any study specific procedures. 2. Healthy male and female subjects aged 18 - 55 years (inclusive) at Screening with suitable veins for cannulation or repeated venepuncture. 3. 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. 4. 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). 5. Subject is able to understand and communicate in German. Exclusion Criteria: 1. 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. 2. History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. 3. History of Gilbert's syndrome, history of cholecystectomy or gall stone. 4. History of tuberculosis, any other significant lung diseases like surgeries, asthma, chronic obstructive pulmonary disease. 5. 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. 6. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP. 7. 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. 8. 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 9. 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 10. Any positive result at screening for serum hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) results. 11. 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. 12. Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening. 13. 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 14. Current smokers or those who have smoked or used nicotine products (including e-cigarettes; >10 pack-year) within the 6 months prior to screening. 15. 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. 16. 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. 17. 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. 18. 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. 19. Subjects with a pregnant partner. 20. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives. 21. Subjects who have previously received AZD7594. 22. Vulnerable subjects, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order. |
Country | Name | City | State |
---|---|---|---|
Germany | Research Site | Berlin |
Lead Sponsor | Collaborator |
---|---|
AstraZeneca | Parexel |
Germany,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | AZD7594 concentrations in dried blood PK sample | To assess AZD7594 concentrations in dried blood PK samples (collected via both venepuncture and finger prick) and compare with wet blood and plasma PK samples. | Days 1, 2 and 3 (2, 6, 12, 24 and 48 h post dose) | |
Primary | 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 | 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) | |
Primary | 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 | 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) | |
Primary | 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 | 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) | |
Primary | 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 | 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) | |
Primary | 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 | 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) | |
Primary | 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 | 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 | Time to reach maximum observed plasma concentration (tmax) | To evaluate the PK profiles of AZD7594 when administered as the two formulations | 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 | Terminal elimination rate constant (?z) | To evaluate the PK profiles of AZD7594 when administered as the two formulations | 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 | Half-life associated with terminal slope (?z) of a semilogarithmic concentration-time curve (t1/2?z) | To evaluate the PK profiles of AZD7594 when administered as the two formulations | 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 | 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 | 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 | 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 | 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 | 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 | 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 | Number of participants with adverse events | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in systolic BP | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in diastolic BP | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in pulse rate | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in body temperature | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in ECG | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | 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. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | 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. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in haemoglobin | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in haematocrit | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in white blood cell count | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in red blood cell count | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in mean corpuscular volume (MCV) | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in mean corpuscular haemoglobin (MCH) | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | 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 | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in neutrophils absolute count | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in lymphocytes absolute count | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in monocytes absolute count | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in eosinophils absolute count | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in basophils absolute count | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in platelets | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in reticulocytes absolute count | To further assess the safety of single doses of AZD7594 in healthy volunteers | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in sodium | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in potassium | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in urea | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in creatinine | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in albumin | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in calcium | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in phosphate | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in glucose (fasting) | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in C-reactive protein | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in T4 hormone | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in thyroid-stimulating hormone | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | 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) | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in total bilirubin (TBL) | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in unconjugated bilirubin | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in follicle stimulating hormone (FSH) | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | Number of participants with abnormal findings in lutenizing hormone (LH) | To further assess the safety of single doses of AZD7594 in healthy volunteers. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | 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 | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) | |
Secondary | 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. | From Screening (Day -28) up to the Follow-up visit (10 to 14 days after last dose) |
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