Evaluation of Histamine H3 Receptor Radioligand [11C]AZ12807110 and Histamine H3 Receptor Occupancy of AZD5213 After Oral Administration

Study Overview
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Brief Summary
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The purpose of this study is to investigate features of radioligand [11C]AZ12807110 and how much AZD5213 displaces radioligand from histamine receptors when given together.

Official Title
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An Open-label Positron Emission Tomography Study to Evaluate Use of Histamine H3 Receptor Radioligand [11C]AZ12807110 and to Determine Histamine H3 Receptor Occupancy of AZD5213 After Oral Administration to Healthy Volunteers

Conditions
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Brain Distribution of [11C]AZ12807110 and AZD5213

Intervention / Treatment
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* Other: [11C]AZ12807110
* Drug: AZD5213


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female volunteers between 20 to 45 years with suitable veins for cannulation or repeated venipuncture (pilot panel) Female must be of non-child bearing potential (pilot panel) BMI between 18 to 30 30 kg/m2 Normal MRI scan Provision of signed, written and dated informed consent Exclusion Criteria: History of any clinically significant disease or disorder History or presence of gastrointestinal, hepatic or renal disease Prolonged QTcF >450 ms or shortened QTcF <340 ms or family history of long QT syndrome History of severe allergy or hypersensitivity or ongoing allergy or hypersensitivity Healthy volunteer suffers from claustrophobia

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

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: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pilot panel<br>[11C]AZ12807110 distribution and kinetics | Other: [11C]AZ12807110<br>* Radioligand<br>|
| Experimental: Main panel<br>Histamine receptor occupancy reached by AZD5213 | Other: [11C]AZ12807110<br>* Radioligand<br>Drug: AZD5213<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distribution volume (VT) |  | Venous blood samples for determination of concentrations of AZD5213 in plasma will be taken on many occasions from pre-dose until 48 h post-dose. Single PET measurement will take maximum 2 hours. | 
| Estimation of the plasma concentration resulting in 50% receptor occupancy (Ki, pl). | Each healthy volunteer in the main panel will complete 3 PET measurements using radioligand; one at baseline and 2 after treatment with AZD5213. | Venous blood samples for determination of concentrations of AZD5213 in plasma will be taken on many occasions from pre-dose until 48 h post-dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | Collected from Day 1 to follow-up | 
| Vital signs (body temperature, BP and pulse) |  | Measured at screening, study days -1 to day 3 and at follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Receptor binding, Histamine H3 receptor, binding, radioligand