Clinical trial NCT01636024: To Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of Inhaled AZD7594
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Safety
Pharmacokinetics
Pharmacodynamics of AZD7594
Keywords: Phase 1,
healthy volunteers,
safety,
tolerability,
pharmacokinetics,
pharmacodynamics,
single ascending dose study,
multiple
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-07-10
Enrollment: 73
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

Eligibility criteria: 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

Primary outcomes:
measure: Safety profile in terms of adverse events, ECG, blood pressure, pulse, physical examination, body temperature, haematology, clinical chemistry, urinalysis and spirometry.
timeFrame: Screening to 13 days post last dose.
Secondary outcomes:
measure: 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.
timeFrame: 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.
measure: 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)
timeFrame: 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.
measure: Pharmacodynamics of AZD7594 following a single dose in terms of: 24-hour plasma cortisol
timeFrame: 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.
measure: Pharmacodynamics of AZD7594 following a multiple doses in terms of: 24-hour plasma cortisol
timeFrame: 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.
measure: Pharmacodynamics of AZD7594 following multiple doses in terms of: Plasma cortisol after adrenocorticotropic hormone stimulation
timeFrame: screening and day 17 at 30 minutes and 1 hour post tetracosactide injection
measure: Pharmacodynamics of AZD7594 following multiple doses in terms of: Plasma dehydroepiandrosterone sulphate, plasma 4β-OH-cholesterol, and plasma osteocalcin
timeFrame: screening and day 17
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
state: UK
Study officials:
affiliation: AstraZeneca R&D, Molndal Sweden
name: Carin Jorup, MD
role: STUDY_DIRECTOR
References: