To Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of Inhaled AZD7594 - Full Text View

Purpose

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

Condition	Intervention	Phase
Safety Pharmacokinetics Pharmacodynamics of AZD7594	Drug: AZD7594 Drug: Placebo to match	Phase 1

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

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Safety profile in terms of adverse events, ECG, blood pressure, pulse, physical examination, body temperature, haematology, clinical chemistry, urinalysis and spirometry. [ Time Frame: Screening to 13 days post last dose. ] [ Designated as safety issue: Yes ]
No statistical tests will be performed

Secondary Outcome Measures:

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. [ Time Frame: 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. ] [ Designated as safety issue: No ]
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
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) [ Time Frame: 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. ] [ Designated as safety issue: No ]
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 [ Time Frame: 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. ] [ Designated as safety issue: No ]
Pharmacodynamics of AZD7594 following a multiple doses in terms of: 24-hour plasma cortisol [ Time Frame: 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. ] [ Designated as safety issue: No ]
Pharmacodynamics of AZD7594 following multiple doses in terms of: Plasma cortisol after adrenocorticotropic hormone stimulation [ Time Frame: screening and day 17 at 30 minutes and 1 hour post tetracosactide injection ] [ Designated as safety issue: No ]
Pharmacodynamics of AZD7594 following multiple doses in terms of: Plasma dehydroepiandrosterone sulphate, plasma 4β-OH-cholesterol, and plasma osteocalcin [ Time Frame: screening and day 17 ] [ Designated as safety issue: No ]

Estimated Enrollment:	108
Study Start Date:	September 2012
Estimated Study Completion Date:	May 2013
Estimated Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Subjects will participate in 1 of up to 9 groups in Part A (single ascending dose part) or 1 of 4 groups in Part B (multiple ascending dose part). Ratio of subjects receiving AZD7594 versus placebo is 6:2 in part A and 6:3 in Part B.	Drug: AZD7594 Suspension inhaled via Spira nebuliser
Placebo Comparator: 2 Subjects will participate in 1 of up to 9 groups in Part A or 1 of 4 groups in Part B. Ratio of subjects receiving AZD7594 versus placebo is 6:2 in part A and 6:3 in Part B.	Drug: Placebo to match Matching placebo inhaled via Spira nebuliser

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

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01636024

Contacts

Contact: AstraZeneca Clinical Study Information	800-236-9933	information.center@astrazeneca.com
Contact: Quintiles Drug Research Unit Call Centr	0800 634 1132

Locations

United Kingdom
Research Site	Recruiting
London, UK, United Kingdom

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:

Carin Jorup, MD

AstraZeneca R&D, Molndal Sweden

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01636024 History of Changes
Other Study ID Numbers:	D3740C00001
Study First Received:	July 5, 2012
Last Updated:	October 8, 2012
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:

Phase 1,
healthy volunteers,
safety,
tolerability,

pharmacokinetics,
pharmacodynamics,
single ascending dose study,
multiple

ClinicalTrials.gov processed this record on May 16, 2013