A Study to Investigate the Impact of Dose and Dosing Frequency of AZD8848 on the Response on Biomarkers

A Single-blind, Randomized, Placebo Controlled, Parallel-group, Adaptive-design Study to Investigate the Impact of Dose and Dosing Frequency of AZD8848 Administered Intranasally for up to 7 Days, on the Biomarker

The study will investigate how the dose of AZD8848 and the dosing frequency will affect the immunological/inflammatory response by measuring the production of biomarkers in blood and nasal lavage.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy men or women aged 18 to 55 years (inclusive). Women must be of non-childbearing potential or must have been stable on a highly effective contraceptive method for at least 3 months prior to Visit 1 and be willing to continue on the chosen contraceptive method, with additional use of a condom by male partners, until 3 months after last dose.
• Female subjects should have a negative pregnancy test at Visit 2 and date of last menstruation consistent of non-pregnancy
• Ability to metabolise AZD8848 (an in vitro screening assay will determine metabolic activity in a blood sample taken at Visit 1 using a pre-defined limit)

Exclusion Criteria:

• Any clinically significant disease or disorder
• Any clinically relevant abnormal findings in physical examination
• Structural abnormalities of the nose or nasal disorder symptomatic enough to cause significant nasal obstruction
• Ongoing pregnancy or lactation
• Abnormal immune function

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1; Placebo given once daily on 7 days	Drug: Placebo; Placebo
Experimental: 2; Active treatment at Day 1 and Day 7. Placebo on Day 2, 3, 4, 5 and 6	Drug: Placebo; Placebo; Drug: AZD8848; The subjects are dosed with a range of intranasal doses of AZD8848 on 2, 3, 4 or 7 days of the 7 days treatment period. On the other days the subjects receive placebo.
Experimental: 3; Active treatment at Day 1, 4 and 7. Placebo on Day 2, 3, 5 and 6.	Drug: Placebo; Placebo; Drug: AZD8848; The subjects are dosed with a range of intranasal doses of AZD8848 on 2, 3, 4 or 7 days of the 7 days treatment period. On the other days the subjects receive placebo.
Experimental: 4; Active treatment at Day 1, 3, 5 and 7. Placebo on Day 2, 4 and 6.	Drug: Placebo; Placebo; Drug: AZD8848; The subjects are dosed with a range of intranasal doses of AZD8848 on 2, 3, 4 or 7 days of the 7 days treatment period. On the other days the subjects receive placebo.
Experimental: 5; Active treatment once daily on 7 days	Drug: AZD8848; The subjects are dosed with a range of intranasal doses of AZD8848 on 2, 3, 4 or 7 days of the 7 days treatment period. On the other days the subjects receive placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
CXCL 10 (IP-10) and mRNA expression of IFNα regulated genes in blood and nasal lavage	Samples collected pre-dose and 1 day after first dose.
CXCL 10 (IP-10) and mRNA expression of IFNα regulated genes in blood and nasal lavage	Samples collected pre-dose and 7 days after first dose.
CXCL 10 (IP-10) and mRNA expression of IFNα regulated genes in blood and nasal lavage	Samples collected pre-dose and 8 days after first dose.
CXCL 10 (IP-10) and mRNA expression of IFNα regulated genes in blood and nasal lavage	Samples collected pre-dose and 10 days after first dose.
CXCL 10 (IP-10) and mRNA expression of IFNα regulated genes in blood and nasal lavage	Samples collected pre-dose and 12-14 days after first dose.

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess safety and tolerability of intranasal administration of AZD8848 at different doses and dosing regimens	During the 7 days dosing period and at four follow-up visits up to 11-13 months after the last dose

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Leif T Eriksson, MD, PhD, AstraZeneca; Principal Investigator: Wolfgang Kuhn, MD, Quintiles, Inc.

Publications and helpful links

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: September 15, 2010
• First Submitted That Met QC Criteria: September 15, 2010
• First Posted (Estimate): September 16, 2010

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: Biomarker; Healthy; Intranasal; Effect of different doses and dosing regimens of AZD8848 on biomarkers; Effect different doses and dosing frequency of AZD8848 on biomarkers
• Other Study ID Numbers: D0540C00016; 2010-022574-14 (EudraCT Number)