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

NCT01636024 | Completed Phase 1

• 1 other identifier: D3740C00001
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

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

Conditions

Safety; Pharmacokinetics; Pharmacodynamics of AZD7594

Keywords

Phase 1,; healthy volunteers,; safety,; tolerability,; pharmacokinetics,; pharmacodynamics,; single ascending dose study,; multiple

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (6)

• 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.

• 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.

• 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.

• 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.

• 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

Study Arms (2)

1

EXPERIMENTAL

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

2

PLACEBO COMPARATOR

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

Interventions

AZD7594 DRUG

Suspension inhaled via Spira nebuliser

1

Placebo to match DRUG

Matching placebo inhaled via Spira nebuliser

2

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• History of any clinically significant disease or disorder
• Current smokers
• Any clinically relevant abnormal findings

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

London, UK, United Kingdom

Location

MeSH Terms

Interventions

velsecorat

Study Officials

• Carin Jorup, MD

  AstraZeneca R&D, Molndal Sweden

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2012
• First Posted: July 10, 2012
• Study Start: September 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: June 20, 2013

Record last verified: 2013-06

Locations

GB (1)