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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01636024
First received: July 5, 2012
Last updated: June 19, 2013
Last verified: June 2013
  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 ]

Enrollment: 73
Study Start Date: September 2012
Study Completion Date: June 2013
Primary Completion Date: June 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United Kingdom
Research Site
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: June 19, 2013
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 November 20, 2014