A Study to Assess the Bioavailability and to Compare the Pharmacokinetics of AZD7594 Inhaled Via Monodose Inhaler and Multiple-dose Dry Powder Inhalers (DPI) or Pressurized Metered-dose Inhaler (pMDI) in Healthy Male Subjects

NCT02648438 | Completed Phase 1 Results

• 1 other identifier: D3741C00004
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label,partially randomized, four-period study in healthy male subjects to assess the bioavailability and pharmacokinetics of a single dose of AZD7594 when administered intravenously, orally and inhaled via two different dry powder inhalers (DPIs) and a pressurized meter-dose inhaler (pMDI)

Conditions

Asthma; Chronic Obstructive Pulmonary Disease (COPD)

Keywords

AZD7594; Bioavailability; Healthy male subjects; Safety; Tolerability; Pharmacokinetics; Monodose inhaler; Multiple-dose dry powder inhaler

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics (PK) of AZD7594 Delivered by Monodose Inhaler and Multiple-dose DPI or pMDI in Terms of Pulmonary Bioavailability After Inhalation (Fpulmonary)

  For oral and inhalation administrations: pre-dose (0 hour) and post-dose at 15, 30 and 45 minutes and 1.0, 2.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, 36.0, 48.0, 72.0 and 96.0 hours following the administration of the investigational product AZD7594. For IV administration: pre-dose (0 hour) and post-dose at 5, 10, 15 (end of infusion), 30, 45, 60 and 90 minutes and 2.0, 4.0, 6.0, 8.0, 12.0, 16.0, 48.0, 72.0 and 96.0 hours following the start of the IV infusion of the investigational product AZD7594

  0-96 hours

Secondary Outcomes (6)

• PK of AZD7594 Following Oral Administration by Assessment of the Absolute Systemic Bioavailability After Oral Administration (Fpo)

  0-96 hours

• Observed Maximum Plasma Concentration (Cmax)

  0-96 hours

• Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t)

  0-96 hours

• Absolute Systemic Bioavailability After Inhalation (F Inhalation, Total)

  0-96 hours

• Oral Bioavailability After Inhaled Treatment (F Oral)

  0-96 hours

Study Arms (2)

Treatment sequence 1

EXPERIMENTAL

Treatment Period 1:AZD7594 Solution for infusion (150 μg intravenous formulation) Treatment Period 2:AZD7594 Inhalation powder (400 μg) by dry powder inhaler (DPI) Device 1 (monodose inhaler) Treatment Period 3:AZD7594 Inhalation powder (400 μg) by DPI device 2 (multiple-dose inhaler) Treatment Period 4:AZD7594 Oral suspension (1200 μg oral formulation)

Drug: AZD7594 Solution for infusion (150 μg intravenous formulation); Drug: AZD7594 Oral suspension (1200 μg oral formulation); Drug: AZD7594 Inhalation powder (400 μg) by DPI Device 1 (monodose inhaler); Drug: AZD7594 Inhalation powder (400 μg) by DPI device 2 (multiple-dose inhaler)

Treatment sequence 2

EXPERIMENTAL

Treatment Period 1:AZD7594 Solution for infusion (150 μg intravenous formulation) Treatment Period 2:AZD7594 Inhalation powder (400 μg) by dry powder inhaler (DPI) Device 1 (monodose inhaler) Treatment Period 3:AZD7594 Pressurized inhalation suspension (400 μg) by pressurized metered-dose inhaler (pMDI) Treatment Period 4:AZD7594 Oral suspension (1200 μg oral formulation)

Drug: AZD7594 Solution for infusion (150 μg intravenous formulation); Drug: AZD7594 Oral suspension (1200 μg oral formulation); Drug: AZD7594 Inhalation powder (400 μg) by DPI Device 1 (monodose inhaler); Drug: AZD7594 Pressurized inhalation suspension (400 μg) by pMDI

Interventions

AZD7594 Solution for infusion (150 μg intravenous formulation) DRUG

Solution for infusion 0.01 mg/ml; AZD7594 150 μg IV

Treatment sequence 1; Treatment sequence 2

AZD7594 Oral suspension (1200 μg oral formulation) DRUG

0.1 - 10 mg/g oral solution; AZD7594 1200 μg oral

Treatment sequence 1; Treatment sequence 2

AZD7594 Inhalation powder (400 μg) by DPI Device 1 (monodose inhaler) DRUG

Inhalation powder, hard capsules 400 μg Monodose inhaler; AZD7594 400 μg by dry powder inhaler (DPI) Device 1 (Monodose inhaler)

Treatment sequence 1; Treatment sequence 2

AZD7594 Inhalation powder (400 μg) by DPI device 2 (multiple-dose inhaler) DRUG

Inhalation powder, multiple-dose dry powder inhaler (DPI) 400 μg; AZD7594 400 μg by DPI Device 2 (multiple-dose DPI)

Treatment sequence 1

AZD7594 Pressurized inhalation suspension (400 μg) by pMDI DRUG

Inhalation suspension 200 μg; AZD7594 400 μg by pressurized metered-dose inhaler (pMDI); 2 puffs x 200 μg = 400 μg

Treatment sequence 2

Eligibility Criteria

• Age: 18 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 subjects aged 18 - 45 years with suitable veins for cannulation or repeated venipuncture.
• Have a body mass index (BMI) between 18 and 30 kg/m2, inclusive, and weigh at least 50 kg.
• 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 investigational product.
• Be able to inhale from the dry powder inhaler (DPI) devices and the pressurized metered-dose inhaler (pMDI) device according to given instructions.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, 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 (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically significant illness, major medical/surgical procedure, or trauma within 4 weeks of the first administration of Investigational medicinal product (IMP).
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results at screening and check-in, as judged by the investigator.
• Any clinically significant abnormal findings in vital signs after a 5 minute rest at screening and check-in, as judged by the investigator, defined as any of the following:
• Systolic blood pressure (BP) \> 140 mm Hg;
• Systolic BP \< 90 mm Hg;
• Diastolic BP \> 90 mm Hg;
• Diastolic BP \< 60 mm Hg; or
• Heart rate \< 40 or \> 85 beats per minute (bpm).
• Any clinically significant abnormities in physical examination or lung function, as judged by the investigator.
• Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) at screening and check-in, as judged by the investigator.
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc (QT interval corrected) interval changes. This includes subjects with any of the following:
• Clinically significant PR (PQ) (ECG interval measured from the onset of the P wave to the onset of the QRS complex) interval prolongation;
• Intermittent or persistent second or third degree AV block;

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Baltimore, Maryland, United States

Location

MeSH Terms

Conditions

Asthma; Pulmonary Disease, Chronic Obstructive

Interventions

Dosage Forms

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

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Results Point of Contact

• Title: Global Clinical Leader
• Organization: AstraZeneca AB

ClinicalTrialTransparency@astrazeneca.com

+46 31 7761000

Study Officials

• Ronald Goldwater, M.D

  Parexel

  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: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2015
• First Posted: January 7, 2016
• Study Start: January 12, 2016
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: June 15, 2017
• Results First Posted: June 15, 2017

Record last verified: 2017-03

Locations

US (1)