To Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses AZD8848 in Healthy Subjects

August 13, 2015 updated by: AstraZeneca

A Phase 1, Single Centre, Double-blind, Randomised, Placebo-controlled, Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Administration of Multiple Ascending (MAD) Once Weekly Inhaled Doses of AZD8848 in Healthy Subjects

This study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of AZD8848 in healthy subjects.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A Phase 1, Single Centre, Double-blind, Randomised, Placebo-controlled, Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics after Administration of Multiple Ascending (MAD) Once Weekly Inhaled Doses of AZD8848 in Healthy Subjects

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy male and/or female subjects aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venipuncture
  • Women must be of non-childbearing potential or must have been stable on a highly effective contraceptive for at least 3 months prior to Screening and be willing to continue on the chosen contraceptive with additonal use of condom until 3 months postdose
  • Male subjects should be willing to use barrier contraception ie, condoms, from the first day of investigational product administration until 3 months after the last administration of investigational product
  • Have a body mass index (BMI) between 18 and 32 kg/m2 and weigh at least 50 kg and no more than 110 kg
  • Women must have a negative pregnancy test at screening and on admission to the study centre, must have a date of last menstruation, must not be lactating or must be of non-childbearing potential

Exclusion Criteria:

  • Abnormal vital signs, after 10 minutes supine rest, defined as any of the following: SBP >140 mmHg, Diastolic blood pressure (DBP) >90 mmHg, Heart rate <40 or >85 beats per minute
  • History of asthma or allergic rhinitis
  • Prolonged QTcF >450 ms or shortened QTcF <340 ms or family history of long QT syndrome
  • History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class as AZD8848 - Any clinically significant abnormalities in clinical chemistry.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AZD8848
Subjects will participate in 1 of 3 groups and receive multiple doses of AZD8848 or matching placebo In each group 6 subjects will receive AZD8848 and 2 subjects will receive matching placebo.
Drug: AZD8848
Multiple doses inhaled IMP via a nebulizer
Placebo Comparator: Placebo to match AZD8848
Subjects will participate in 1 of 3 groups and receive multiple doses of AZD8848 or matching placebo. In each group 6 subjects will receive AZD8848 and 2 subjects will receive matching placebo.
Drug: Placebo to match AZD8848
Multiple doses inhaled matching placebo via a nebulizer

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from baseline up to 77 days in safety variables (adverse events, vital signs, body temperature, physical exams, ECGs, clinical laboratory tests, pulse oximetry, spirometry).
Time Frame: From screening visit (Day -42) through the Treatment Follow Up visit (Day 35) at multiple timepoints up to 77 days.
From screening visit (Day -42) through the Treatment Follow Up visit (Day 35) at multiple timepoints up to 77 days.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Single dose pharmacokinetics profile for AZD8848 and its acid metabolite (AZ12432045) combined and, if possible, for AZD8848 alone in plasma and urine from healthy subjects
Time Frame: Plasma: From Days 1 and 22, pre-dose, 5, 10, 20, 30, 45, 60, 90 min, 2, 3, 4, 6, 8 and 24 hrs post dose. Urine: From days 1 and 22, pre-dose, 0 to 6, 6 to 12 and 12 to 24 hrs post dose
PK parameters: Cmax, tmax, area under the plasma concentration-time curve from zero to 24 hours postdose (AUC(0-24)), from zero to the time of the last quantifiable concentration (AUC(0-t)) and from zero to infinity (AUC), CL/F, Vz/F, CLR and Ae
Plasma: From Days 1 and 22, pre-dose, 5, 10, 20, 30, 45, 60, 90 min, 2, 3, 4, 6, 8 and 24 hrs post dose. Urine: From days 1 and 22, pre-dose, 0 to 6, 6 to 12 and 12 to 24 hrs post dose
Multiple dose pharmacokinetics profile for AZD8848 and its acid metabolite (AZ12432045) combined and, if possible, for AZD8848 alone in plasma
Time Frame: Plasma: From Days 1 and 22, pre-dose, 5, 10, 20, 30, 45, 60, 90 min, 2, 3, 4, 6, 8 and 24 hrs post dose
PK parameters: AUC accumulation ratio and Cmax accumulation ratio
Plasma: From Days 1 and 22, pre-dose, 5, 10, 20, 30, 45, 60, 90 min, 2, 3, 4, 6, 8 and 24 hrs post dose
Pharmacodynamic effect after multiple doses of inhaled AZD8848 by assessment of the CXCL10 biomarker concentration in plasma
Time Frame: From Days 1 and 22, pre-dose, 24 and 48 hrs post dose. One sample 7 to 13 days post last dose.
Pharmacodynamic effect: CXCL10 concentration and change-from-baseline ratios in plasma
From Days 1 and 22, pre-dose, 24 and 48 hrs post dose. One sample 7 to 13 days post last dose.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Investigators

  • Principal Investigator: Tim Mant, BSc, MB BS, MRCP, FRCP, FFPM, Quintiles Drug Research Unit at Guy's Hospital, 6 Newcomen Street London SE1 1YR UK
  • Study Chair: Aray Aggarwal, AstraZeneca Pharmaceuticals 35 Gathouse Drive, Waltham, Ma 02451 United States

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2014

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

March 18, 2013

First Submitted That Met QC Criteria

March 26, 2013

First Posted (Estimate)

March 27, 2013

Study Record Updates

Last Update Posted (Estimate)

August 14, 2015

Last Update Submitted That Met QC Criteria

August 13, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D0542C00002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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