To Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of Inhaled AZD7594

Pharmacokinetics Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01636024
• Other study ID #: D3740C00001
• Status: Completed
• Phase: Phase 1
• First received: July 5, 2012
• Last updated: June 19, 2013
• Start date: September 2012
• Est. completion date: June 2013

Study information

• Verified date: June 2013
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Pharmacodynamics of AZD7594
• Pharmacokinetics
• Safety

Intervention

Drug:
• AZD7594
Suspension inhaled via Spira nebuliser
• Placebo to match
Matching placebo inhaled via Spira nebuliser

Locations

Country	Name	City	State
United Kingdom	Research Site	London	UK

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety profile in terms of adverse events, ECG, blood pressure, pulse, physical examination, body temperature, haematology, clinical chemistry, urinalysis and spirometry.	No statistical tests will be performed	Screening to 13 days post last dose.	Yes
Secondary	Single dose pharmacokinetics (PK) of AZD7594 in terms of : Cmax, tmax, ?z, t1/2?z, AUC(0-last), AUC(0-24), AUC, CL/F, Vz/F, MRT, Cmax/D, AUC/D, AUC(0-24)/D.	Cmax- max plasma concentration;tmax-Time to max plasma concentration,?z- terminal rate constant;t1/2?z - Terminal half-life;AUC(0-24) - Area under the plasma concentration time curve from zero to 24 hours;AUC- Area under the plasma concentration	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.	No
Secondary	Multiple dose PK of AZD7594 in terms of: Cmax, tmax, ?z, t1?z, 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)	CL/F- Apparent plasma clearance;Vz/F- Apparent volume of distribution during terminal phase; MRT- Mean residence time; Rac Cmax-Accumulation ratio of Cmax	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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	No
Secondary	Pharmacodynamics of AZD7594 following multiple doses in terms of: Plasma dehydroepiandrosterone sulphate, plasma 4ß-OH-cholesterol, and plasma osteocalcin		screening and day 17	No