AZD8848 Single Ascending Dose Study

A Double-blind, Placebo-controlled, Randomised Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Inhaled Doses of AZD8848 in Healthy Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: AZD8848

Detailed Description

A Double-blind, Placebo-controlled, Randomised Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Inhaled Doses of AZD8848 in Healthy Subjects

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy men or women aged 18 to 45 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
• Women can be of childbearing potential and must have been stable on a highly effective contraceptive method for at least 3 months prior to Visit 1 (screening) and be willing to continue on the chosen contraceptive method
• Male subjects should be willing to use a condom (with spermicide) to prevent pregnancy and drug exposure of a female partner and refrain from donating sperm or fathering a child from the day of the investigational product administration until 3 months
• Have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg
• Ability to produce sputum of good enough quality for assessment of biomarkers

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)
• 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
• History of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalaemia, family history of Long QT syndrome, or sudden death)
• History of asthma or allergic rhinitis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Single dose, oral inhalation (nebuliser solution)
Experimental: AZD8848	Drug: AZD8848; Single dose, oral inhalation (nebuliser solution)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Summary of number of subjects who had at least one adverse event	Screening up to Day 13
Summary for Lymphocytes Laboratory Results		Baseline, Day 1, Day 2, Day 3, and Follow up (up to Day 13)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC (Nmol*h/L)		On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h
Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC(0-t) (Nmol*h/L)		On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h
Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - Cmax (Nmol/L)		On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h
Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma	Smmarizes the statistical assessment comparing active CXCL10 ratio to baseline to placebo at each dose level, sampling time, and matrix	Baseline, 24 Hours.
Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma	Smmarize the statistical assessment comparing active CXCL10 ratio to baseline to placebo at each dose level, sampling time, and matrix	Baseline, 48 Hours
Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum	Summarize the statistical assessment comparing active CXCL10 ratio to baseline to placebo at each dose level, sampling time, and matrix	Baseline, 24 Hours.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Ajay Aggarwal, AstraZeneca R&D, 35 Gatehouse Drive, MA 02451 USA; Principal Investigator: James Ritter, BA,MA D Phil,BM BCh,MRCP,FRCP, Quintile Drug Research Unit at Guy's Hospital Quintiles Ltd 6 Newcomen Street London SE1 1YR United Kingdom

Publications and helpful links

General Publications

• 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.

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: March 20, 2012
• First Submitted That Met QC Criteria: March 21, 2012
• First Posted (Estimate): March 22, 2012

Study Record Updates

• Last Update Posted (Estimate): June 6, 2016
• Last Update Submitted That Met QC Criteria: May 5, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Safety; tolerability; pharmacokinetic; healthy; pharmacodynamic; inhaled
• Other Study ID Numbers: D0542C00001; Eudract number 2011-005986-20