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

NCT01818869 | Completed Phase 1

• 1 other identifier: D0542C00002
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Safety,; Tolerability,; Healthy Subjects

Keywords

Safety,; tolerability,; Phase I,; pharmacokinetic,; pharmacodynamic,; inhaled

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

• 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

• 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.

Study Arms (2)

AZD8848

EXPERIMENTAL

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

Placebo to match AZD8848

PLACEBO COMPARATOR

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

Interventions

AZD8848 DRUG

Multiple doses inhaled IMP via a nebulizer

AZD8848

Placebo to match AZD8848 DRUG

Multiple doses inhaled matching placebo via a nebulizer

Placebo to match AZD8848

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

London, United Kingdom

Location

Related Publications (1)

• Delaney S, Biffen M, Maltby J, Bell J, Asimus S, Aggarwal A, Kraan M, Keeling D. Tolerability in man following inhalation dosing of the selective TLR7 agonist, AZD8848. BMJ Open Respir Res. 2016 Feb 23;3(1):e000113. doi: 10.1136/bmjresp-2015-000113. eCollection 2016.

  PMID: 26933507 DERIVED

Related Links

• Study Synopsis

MeSH Terms

Conditions

Respiratory Aspiration

Interventions

AZD8848

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Tim Mant, BSc, MB BS, MRCP, FRCP, FFPM

  Quintiles Drug Research Unit at Guy's Hospital, 6 Newcomen Street London SE1 1YR UK

  PRINCIPAL INVESTIGATOR

• Aray Aggarwal

  AstraZeneca Pharmaceuticals 35 Gathouse Drive, Waltham, Ma 02451 United States

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: March 18, 2013
• First Posted: March 27, 2013
• Study Start: January 1, 2014
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: August 14, 2015

Record last verified: 2015-08

Locations

GB (1)