Safety, Pharmacokinetics, Pharmacodynamics of AZD7594
Conditions
Keywords
Phase 1,, healthy volunteers,, safety,, tolerability,, pharmacokinetics,, pharmacodynamics,, single ascending dose study,, multiple
Brief summary
The purpose of this study is to evaluate the safety profile and look at levels of AZD7594 and biomarkers in blood when the drug is administered inhaled to healthy subjects
Detailed description
A Phase I, Single Centre, Double-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Ascending Inhaled Doses of AZD7594 in Healthy Male Volunteers
Interventions
DRUGAZD7594
Suspension inhaled via Spira nebuliser
DRUGPlacebo to match
Matching placebo inhaled via Spira nebuliser
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male volunteers aged 18-45 years inclusive with suitable veins for cannulation or repeated vein puncture * Have a body mass index (BMI) between 18 and 30 kg/m2 and weight between 50 and 100 kg (inclusive) * Be able to inhale from the Spira nebuliser used in the study * Be willing to use a condom with spermicide to prevent pregnancy and drug exposure of a female partner
Exclusion criteria
* History of any clinically significant disease or disorder * Current smokers * Any clinically relevant abnormal findings
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety profile in terms of adverse events, ECG, blood pressure, pulse, physical examination, body temperature, haematology, clinical chemistry, urinalysis and spirometry. | Screening to 13 days post last dose. | No statistical tests will be performed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Multiple dose PK of AZD7594 in terms of: Cmax, tmax, λz, t1λz, AUC(0-last), AUC(0-24), AUC, CL/F, Vz/F, MRT, Cmax/D, AUC/D,AUC(0-24)/D, Cavg, %Fluctuation, Rac(Cmax) and Rac(AUC(0-24) and time-dependency (AUC(0-24) and AUC) | pre-dose and at 5, 15 and 30 min and 1, 2, 4, 6, 9, 12, 18, 24, 48, 72 hours and 96 h post-dose. Days 6-15: Pre-dose samples only.From day 16: pre-dose and 5, 15 and 30 min and 1, 2, 4, 6, 9, 12, 18, 24, 36 and 48 h post-dose. | CL/F- Apparent plasma clearance;Vz/F- Apparent volume of distribution during terminal phase; MRT- Mean residence time; Rac Cmax-Accumulation ratio of Cmax |
| Pharmacodynamics of AZD7594 following a single dose in terms of: 24-hour plasma cortisol | screening and on the dosing day at the following time points 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24. On the dosing day also at 36 and 48 hours post dose. | — |
| Single dose pharmacokinetics (PK) of AZD7594 in terms of : Cmax, tmax, λz, t1/2λz, AUC(0-last), AUC(0-24), AUC, CL/F, Vz/F, MRT, Cmax/D, AUC/D, AUC(0-24)/D. | pre-dose and at 5, 15 and 30 minutes and 1, 2, 4, 6, 9, 12, 18, 24, 36 and 48 hours post-dose. From cohort four 72 and 96 hours post-dose samples will also be taken. | Cmax- max plasma concentration;tmax-Time to max plasma concentration,λz- terminal rate constant;t1/2λz - Terminal half-life;AUC(0-24) - Area under the plasma concentration time curve from zero to 24 hours;AUC- Area under the plasma concentration |
| Pharmacodynamics of AZD7594 following multiple doses in terms of: Plasma cortisol after adrenocorticotropic hormone stimulation | screening and day 17 at 30 minutes and 1 hour post tetracosactide injection | — |
| Pharmacodynamics of AZD7594 following multiple doses in terms of: Plasma dehydroepiandrosterone sulphate, plasma 4β-OH-cholesterol, and plasma osteocalcin | screening and day 17 | — |
| Pharmacodynamics of AZD7594 following a multiple doses in terms of: 24-hour plasma cortisol | screening and days 1 and 16 at the following time points 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 hours. On day 1 also at 36 and 48 hours. | — |
Countries
United Kingdom
Outcome results
None listed