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

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT01818869

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

7.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Safety, Tolerability, Healthy Subjects	Drug: AZD8848 Drug: Placebo to match AZD8848	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

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 Start Date :

Jan 1, 2014

Actual Primary Completion Date :

Feb 1, 2014

Actual Study Completion Date :

Feb 1, 2014

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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). [From screening visit (Day -42) through the Treatment Follow Up visit (Day 35) at multiple timepoints up to 77 days.]

Secondary Outcome Measures

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 [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
Multiple dose pharmacokinetics profile for AZD8848 and its acid metabolite (AZ12432045) combined and, if possible, for AZD8848 alone in plasma [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
Pharmacodynamic effect after multiple doses of inhaled AZD8848 by assessment of the CXCL10 biomarker concentration in plasma [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	London		United Kingdom

Sponsors and Collaborators

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