A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD7594 Inhaled Formulation in Healthy Japanese Men

NCT02645253 | Completed Phase 1 Results

• 1 other identifier: D3741C00005
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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)

Conditions

Asthma; Chronic Obstructive Pulmonary Disease COPD

Keywords

Safety; Pharmacokinetics; Pharmacodynamics; Glucocorticoid receptor modulator; Healthy male subjects

Outcome Measures

Primary Outcomes (1)

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

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

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

Secondary Outcomes (34)

• 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 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 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 (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 (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

Study Arms (4)

Cohort 1

EXPERIMENTAL

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

Drug: AZD7594 inhalation powder (200 μg); Drug: AZD7594 placebo inhalation powder

Cohort 2

EXPERIMENTAL

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

Drug: AZD7594 inhalation powder (400 μg); Drug: AZD7594 placebo inhalation powder

Cohort 3

EXPERIMENTAL

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

Drug: AZD7594 inhalation powder (400 μg); Drug: AZD7594 placebo inhalation powder

Cohort 4

EXPERIMENTAL

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

Drug: AZD7594 pressurized inhalation suspension (200 μg); Drug: AZD7594 placebo pressurized inhalation suspension

Interventions

AZD7594 inhalation powder (200 μg) DRUG

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

Cohort 1

AZD7594 inhalation powder (400 μg) DRUG

Cohort 2: 400 μg AZD7594 inhalation powder via multi-dose DPI Cohort 3: 1600 μg (4 x 400 μg inhalations) AZD7594 inhalation powder via multi-dose DPI

Cohort 2; Cohort 3

AZD7594 pressurized inhalation suspension (200 μg) DRUG

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

Cohort 4

AZD7594 placebo inhalation powder DRUG

AZD7594 placebo inhalation powder via multi-dose DPI

Cohort 1; Cohort 2; Cohort 3

AZD7594 placebo pressurized inhalation suspension DRUG

AZD7594 placebo pressurized inhalation suspension via pressurized metered dose inhaler (pMDI)

Cohort 4

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Abnormal vital signs, after 10 minutes supine rest, defined as any of the following:
• Systolic blood pressure (BP) \< 90mmHg or \> 140 mmHg
• Diastolic BP \< 60mmHg or \> 90 mmHg
• Pulse rate \< 40 or \> 85 beats per minute (bpm)
• Any clinically significant abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically significant abnormalities in the 12-lead ECG, as considered by the investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Glendale, California, 91206, United States

Location

MeSH Terms

Conditions

Asthma; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: AZD7594 Global Clinical Leader
• Organization: AstraZeneca AB

ClinicalTrialTransparency@astrazeneca.com

+46317761000

Study Officials

• Esther Yoon, M.D

  California Clinical Trials Medical Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: December 23, 2015
• First Posted: January 1, 2016
• Study Start: January 12, 2016
• Primary Completion: April 17, 2016
• Study Completion: April 17, 2016
• Last Updated: February 19, 2018
• Results First Posted: February 19, 2018

Record last verified: 2017-08

Locations

US (1)