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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: AZD8848
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Placebo given once daily on 7 days | Drug: Placebo<br>* Placebo<br>|
| Experimental: 2<br>Active treatment at Day 1 and Day 7. Placebo on Day 2, 3, 4, 5 and 6 | Drug: AZD8848<br>* 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.<br>Drug: Placebo<br>* Placebo<br>|
| Experimental: 3<br>Active treatment at Day 1, 4 and 7. Placebo on Day 2, 3, 5 and 6. | Drug: AZD8848<br>* 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.<br>Drug: Placebo<br>* Placebo<br>|
| Experimental: 4<br>Active treatment at Day 1, 3, 5 and 7. Placebo on Day 2, 4 and 6. | Drug: AZD8848<br>* 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.<br>Drug: Placebo<br>* Placebo<br>|
| Experimental: 5<br>Active treatment once daily on 7 days | Drug: AZD8848<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intranasal, Biomarker, Healthy, Effect of different doses and dosing regimens of AZD8848 on biomarkers, Effect different doses and dosing frequency of AZD8848 on biomarkers