NCT02645253

Completed

Phase 1

A Phase I, Randomized, Single-blind, Placebo-controlled, Sequential-group, Single-center Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of AZD7594 Given Once Daily as Inhaled Formulation in Healthy Japanese Men

AstraZeneca1 site in 1 country27 target enrollmentJanuary 12, 2016

ConditionsAsthma Chronic Obstructive Pulmonary Disease COPD

InterventionsAZD7594 inhalation powder (200 μg)AZD7594 placebo inhalation powder AZD7594 inhalation powder (400 μg)AZD7594 pressurized inhalation suspension (200 μg)AZD7594 placebo pressurized inhalation suspension

DrugsAZD7594 inhalation powder (200 μg)AZD7594 inhalation powder (400 μg)AZD7594 pressurized inhalation suspension (200 μg)AZD7594 placebo inhalation powder AZD7594 placebo pressurized inhalation suspension

Overview

Phase: Phase 1
Intervention: AZD7594 inhalation powder (200 μg)
Conditions: Asthma
Sponsor: AstraZeneca
Enrollment: 27
Locations: 1
Primary Endpoint: Safety and Tolerability of AZD7594 by Assessment of the Number of Participants With Adverse Events
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a randomized, single-blind, placebo-controlled, sequential-group study to assess the safety and tolerability as well as how the drug (AZD7594) affects the body (pharmacodynamics [PD]) and how the body affects the drug (pharmacokinetics [PK]) when AZD7594 is given as single and multiple ascending doses once daily by inhalation to healthy male Japanese subjects, compared with placebo (non-active drug)

Detailed Description

This is a phase I, randomized, single-blind, placebo controlled, sequential-group design study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD7594 after single and multiple ascending doses given once daily by inhalation in healthy male Japanese subjects, compared with placebo

Registry

clinicaltrials.gov

Start Date

January 12, 2016

End Date

April 17, 2016

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Male

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Provision of signed and dated, written informed consent prior to any study specific procedures.
•Healthy male Japanese subjects aged 20 to 45 years with suitable veins for cannulation or repeated venipuncture.
•A Japanese male subject is defined as being born in Japan, having both parents and four grandparents who are Japanese. The subject must not have lived outside of Japan for more than 5 years.
•Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 45 kg and no more than 100 kg inclusive.
•Provision of signed, written and dated informed consent for optional genetic research Note: If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.

Exclusion Criteria

•History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
•History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
•Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational drug administration.
•Any contraindication against the use of vagolytic or sympaticomimetic drugs, as judged by the investigator.
•Any clinically significant abnormalities in clinical chemistry, hematology, urinalysis, physical examination, vital signs, electrocardiogram (ECG) or lung function results at baseline, as judged by the investigator.
•Known Gilbert's syndrome, family history of Gilbert's syndrome or suspicion of Gilbert's syndrome based on liver function tests.
•Use of systemic glucocorticosteroids within 6 weeks of enrollment.
•Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV).
•Known or suspected hypersensitivity to investigational product or excipients.
•Plasma donation within one month of screening or any blood donation/blood loss \> 500 mL during the 3 months prior to screening.

Arms & Interventions

Cohort 1

AZD7594 inhalation powder (200 μg) or AZD7594 placebo inhalation powder via multi-dose dry powder inhaler (DPI)

Intervention: AZD7594 inhalation powder (200 μg)

Cohort 1

AZD7594 inhalation powder (200 μg) or AZD7594 placebo inhalation powder via multi-dose dry powder inhaler (DPI)

Intervention: AZD7594 placebo inhalation powder

Cohort 2

AZD7594 inhalation powder (400 μg) or AZD7594 placebo inhalation powder via multi-dose dry powder inhaler (DPI)

Intervention: AZD7594 inhalation powder (400 μg)

Cohort 2

AZD7594 inhalation powder (400 μg) or AZD7594 placebo inhalation powder via multi-dose dry powder inhaler (DPI)

Intervention: AZD7594 placebo inhalation powder

Cohort 3

1600 μg AZD7594 inhalation powder (4 x 400 μg) or AZD7594 placebo inhalation powder via multi-dose dry powder inhaler (DPI)

Intervention: AZD7594 inhalation powder (400 μg)

Cohort 3

1600 μg AZD7594 inhalation powder (4 x 400 μg) or AZD7594 placebo inhalation powder via multi-dose dry powder inhaler (DPI)

Intervention: AZD7594 placebo inhalation powder

Cohort 4

400 μg AZD7594 pressurized inhalation suspension (2 x 200 μg inhalations) or placebo pressurized inhalation suspension via pressurized metered dose inhaler (pMDI)

Intervention: AZD7594 pressurized inhalation suspension (200 μg)

Cohort 4

400 μg AZD7594 pressurized inhalation suspension (2 x 200 μg inhalations) or placebo pressurized inhalation suspension via pressurized metered dose inhaler (pMDI)

Intervention: AZD7594 placebo pressurized inhalation suspension

Outcomes

Primary Outcomes

Safety and Tolerability of AZD7594 by Assessment of the Number of Participants With Adverse Events

Time Frame: At screening (Day -28, Day -02 and Day -1), Treatment period (Days 1 to 20) and Follow-up (Day 29).

To assess the safety and tolerability of single and multiple doses of AZD7594

Secondary Outcomes

Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the AUC From Time Zero Extrapolated to Infinity (AUC).(Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose)
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of Last Quantifiable Analyte Concentration (AUC [0-last])(Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose)
Rate and Extent of Absorption of AZD7594 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration, Estimated by Dividing CL/F by Lamda z (Vz/F)(Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Cmin at Steady State (Cmin, ss)(Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Time to Reach Maximum Plasma Concentration (Tmax)(Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Cmax at Steady State (Css,Max).(Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose)
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Tmax at Steady State (Tss,Max).(Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 by Assessment of the AUC(0-last)(Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 by Assessment of Lamda z (λz)(Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 by Assessment of the Peak Trough Fluctuation (%Fluctuation).(Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Pharmacodynamic Analysis of AZD7594 by Assessment of Plasma Concentration of Osteocalcin(Day 1 (predose) and Day 16 (24 hours postdose))
Rate and Extent of Absorption of AZD7594 by Assessment of the Terminal Elimination Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve(Lamda z or λz).(Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose)
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Half-life Associated With the Terminal Slope of a Semi-logarithmic Concentration-time Curve (t1/2λz).(Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose)
Rate and Extent of Absorption of AZD7594 by Assessment of the AUC Divided by the Dose Administered (AUC/D).(Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Average Concentration Over One Dosing Interval (Cav)(Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 by Assessment of AUC(0-24)(Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 by Assessment AUC(0-24)/D.(Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 by Assessment of the Accumulation Ratio Calculated as AUC(0-24) on Day 16/AUC (0-24) on Day 1 (RAC).(Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Observed Maximum Plasma Concentration (Cmax)(Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the AUC From Time Zero to 24 Hours After Dosing (AUC [0-24]).(Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose)
Rate and Extent of Absorption of AZD7594 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (AZD7594) (CL/F).(Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 by Assessment of the Temporal Change Parameter (TCP)(Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 by Assessment of the Amount of AZD7594 Excreted Into the Urine From Time t1 to t2 (Ae [t1-t2])(Day 1 predose spot-collection and interval collection up to 96 hours postdose)
Pharmacodynamic Analysis of AZD7594 by Assessment of the Area Under the Effect Curve for Plasma Cortisol From Time Zero to 24 Hours After Dosing (AUEC [0-24]).(Day -1 (- 24 hours predose) up to 24 hours postdose; Day 1 and Day 16)
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Mean Residence Time From Time Zero Extrapolated to Infinity (MRT).(Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose)
Rate and Extent of Absorption of AZD7594 by Assessment of the Cmax Divided by the Dose Administered (Cmax/D).(Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose)
Rate and Extent of Absorption of AZD7594 by Assessment of the AUC(0-24) Divided by the Dose Administered (AUC(0-24)/D)(Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 by Assessment of the Observed Minimum Plasma Concentration (Cmin)(Days 5 to 15: Pre-dose)
Rate and Extent of Absorption of AZD7594 by Assessment of the Css,Max Divided by the Dose Administered (Css,Max/D).(Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.)
Rate and Extent of Absorption of AZD7594 by Assessment of t1/2λz.(Day 16: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose)
Rate and Extent of Absorption of AZD7594 by Assessment of the Renal Clearance, Estimated by Dividing Ae(0-96) by AUC(0-96) (CLR)(Day 1 predose spot-collection and interval collection up to 96 hours postdose)
Rate and Extent of Absorption of AZD7594 by Assessment of the Percentage of Dose Excreted Unchanged Into the Urine From Time Zero to the Last Measured Time Point for an AZD7594, Estimated by Dividing Ae(0-last) by Dose (fe(0-last)%)(Day 1 predose spot-collection and interval collection up to 96 hours postdose)
Pharmacodynamic Analysis of AZD7594 by Assessment of Plasma Concentration of Dehydroepiandrosterone Sulphate (DHEAS)(Day 1 (predose) and Day 16 (24 hours postdose))
Rate and Extent of Absorption of AZD7594 by Assessment of the Cumulative Amount of AZD7594 Excreted From Time Zero to the Last Sampling Interval (Ae [0-last])(Day 1 predose spot-collection and interval collection up to 96 hours postdose)