A Study to Assess the Effect of Particle Size of AZD7594 on Pharmacokinetics (PK) After a Single Inhaled Dose When Administered Using the Dry Powder Inhaler in Healthy Volunteers

NCT02928354 | Completed Phase 1

• 1 other identifier: D3741C00006
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open label, randomized, three-way crossover study to assess the effect of particle size on the PK and safety of single inhaled doses of AZD7594 in healthy subjects (males aged 18 to 55 years \[inclusive\]). The study will be performed at a single study center.

Conditions

Asthma, Chronic Obstructive Pulmonary Disease (COPD)

Keywords

Asthma; Chronic obstructive pulmonary disease (COPD); Healthy volunteers; Pharmacokinetics (PK); Bioavailability; AZD7594; Safety; Tolerability

Outcome Measures

Primary Outcomes (3)

• Area under plasma concentration-time curve from time zero to infinity (AUC)

  Assessment of AUC in healthy male volunteers after the administration of single inhaled dose of AZD7594.

  Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose

• Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC last)

  Assessment of AUC last in healthy male volunteers after the administration of single inhaled dose of AZD7594.

  Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose

• Maximum observed plasma concentration (Cmax)

  Assessment of Cmax in healthy male volunteers after the administration of single inhaled dose of AZD7594.

  Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose

Secondary Outcomes (12)

• Time to reach maximum observed plasma concentration (tmax)

  Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose

• Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t ½,λz)

  Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose

• Mean residence time from zero to infinity (MRT)

  pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose

• Terminal elimination rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (λz)

  Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose

• Apparent total body clearance of drug from plasma after extravascular administration, estimated as dose divided by AUC (CL/F)

  pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose

Study Arms (3)

Treatment A - AZD7594

EXPERIMENTAL

Treatment A - AZD7594 inhalation powder Particle size Large

Drug: Treatment A - AZD7594

Treatment B - AZD7594

EXPERIMENTAL

Treatment B - AZD7594 inhalation powder Particle size Medium

Drug: Treatment B - AZD7594

Treatment C - AZD7594

EXPERIMENTAL

Treatment C - AZD7594 inhalation powder Particle size Small

Drug: Treatment C - AZD7594

Interventions

Treatment A - AZD7594 DRUG

Particle size Large as a single inhaled dose of 440 µg (nominal dose), administered via DPI

Treatment A - AZD7594

Treatment B - AZD7594 DRUG

Particle size Medium as a single inhaled dose of 440 µg (nominal dose), administered via DPI

Treatment B - AZD7594

Treatment C - AZD7594 DRUG

Particle size Small as a single inhaled dose of 440 µg (nominal dose), administered via DPI

Treatment C - AZD7594

Eligibility Criteria

• Age: 18 Years - 55 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 subjects aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
• Have a body mass index (BMI) between 18 and 29.9 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
• Subjects should be willing to follow reproductive restrictions to prevent pregnancy and drug exposure of a female partner and refrain from donating sperm or fathering a child from the first day of dosing until 3 months after the last dose of IMP.
• Be able to inhale from the DPI devices according to given instructions.
• Subjects must read, speak and understand German language.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
• History or presence of gastrointestinal, 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 IMP.
• Any clinically significant abnormalities in clinical chemistry, hematology or urinalysis results, at screening and first admission to the study unit as judged by the PI.
• Any clinically significant abnormal findings in vital signs at screening and first admission to the study unit, as judged by the PI. Abnormal vital signs, after 10 minutes supine rest, defined as any of the following: - Systolic BP (SBP) \< 90 mmHg or \> 140 mmHg - Diastolic BP (DBP) \< 50 mmHg or \> 90 mmHg - Heart rate \< 45 or \> 90 beats per minute.
• Any clinically significant abnormalities on 12-lead ECG at screening and first admission to the study unit, as judged by the PI.
• Any positive result on screening for serum hepatitis surface antigen or antiHBc antibody suggestive of hepatitis B infection, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
• Known or suspected history of drug abuse, as judged by the PI.
• Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to AZD7594.
• Current smokers or those who have smoked or used nicotine products within the 3 months prior to screening.
• Subjects who are not able to perform correct spirometry tests at screening.
• Subjects with forced expiratory volume at one second (FEV1) and forced vital capacity (FVC) \<80% predicted (calculated) values and FEV1/FVC ratio \<0.7 in pulmonary function test (spirometry) at Screening Visit.
• Positive screen for drugs of abuse or cotinine at screening or on each admission to the study center or positive screen for alcohol on each admission to the study center.
• Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Berlin, 14050, Germany

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

Study Officials

• Dr. Thomas Körnicke

  PAREXEL Early Phase Clinical Unit Berlin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2016
• First Posted: October 10, 2016
• Study Start: November 25, 2016
• Primary Completion: March 21, 2017
• Study Completion: March 21, 2017
• Last Updated: February 6, 2018

Record last verified: 2018-02

Locations

DE (1)