Clinical trial NCT01818869: To Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses AZD8848 in Healthy Subjects
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Safety,
Tolerability,
Healthy Subjects
Keywords: Safety,
tolerability,
Phase I,
pharmacokinetic,
pharmacodynamic,
inhaled
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-03-27
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

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

Eligibility criteria: 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.

Primary outcomes:
measure: 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).
timeFrame: From screening visit (Day -42) through the Treatment Follow Up visit (Day 35) at multiple timepoints up to 77 days.
Secondary outcomes:
measure: 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
timeFrame: 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
measure: Multiple dose pharmacokinetics profile for AZD8848 and its acid metabolite (AZ12432045) combined and, if possible, for AZD8848 alone in plasma
timeFrame: 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
measure: Pharmacodynamic effect after multiple doses of inhaled AZD8848 by assessment of the CXCL10 biomarker concentration in plasma
timeFrame: From Days 1 and 22, pre-dose, 24 and 48 hrs post dose. One sample 7 to 13 days post last dose.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Quintiles Drug Research Unit at Guy's Hospital, 6 Newcomen Street London SE1 1YR UK
name: Tim Mant, BSc, MB BS, MRCP, FRCP, FFPM
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca Pharmaceuticals 35 Gathouse Drive, Waltham, Ma 02451 United States
name: Aray Aggarwal
role: STUDY_CHAIR
References:
citation: 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.