Pharmacokinetics of Extended-Release Test- and Reference Formulations of AZD0837

Study Overview
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Brief Summary
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The aims of this study are to evaluate the pharmacokinetics, safety and tolerability of the oral doses of the extended-release test- and reference formulations of AZD0837 in healthy volunteers both in fasting and fed conditions.

Official Title
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A Phase I, Single-Centre, Open, Randomized, Two-Way Crossover Study to Evaluate the Pharmacokinetics of the Extended-Release Test Formulation of AZD0837 Compared to the Extended-Release AZD0837 Reference Formulation After Repeated Dosing in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: AZD0837
* Drug: AZD0837


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subject aged between 18 to 45 years inclusive Body mass index (BMI) between 19 to 30 kg/m2 inclusive Body weight between 50 to 100 kg inclusive Women must be either post-menopausal, permanently sterilised or, if of childbearing potential, must have a negative pregnancy test before intake of study medication and use a reliable form of contraception before and during participation in the study. Exclusion Criteria: Significant illness (including ongoing or history of liver disease), trauma or surgical procedures from 2 weeks before the pre-entry visit until the first administration of Investigational Product Clinical significant abnormalities in clinical chemistry, haematology or urinalysis result including positive result on screening tests for serum hepatitis B surface antigen, hepatitis C antibody or HIV or positive F-Hb result pre-entry History of bleeding disturbance (including extensive menstrual bleedings) or thrombotic disorder Clinically significant medical history, as judged by the investigator, including psychiatric disorders or severe allergies.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HAB<br>AZD0837 test- (in session 1) and reference- (in session 2) formulation with heavy breakfast | Drug: AZD0837<br>* Extended-release tablets, test formulation. 2 tablets given in the morning for 6 days<br>|
| Experimental: HBA<br>AZD0837 reference- (in session 1) and test- (in session 2) formulation with heavy breakfast | Drug: AZD0837<br>* Extended-release tablets, reference formulation. 2 tablets given in the morning for 6 days<br>|
| Experimental: LAB<br>AZD0837 test- (in session 1) and reference- (in session 2) formulation with light breakfast | Drug: AZD0837<br>* Extended-release tablets, test formulation. 2 tablets given in the morning for 6 days<br>|
| Experimental: LBA<br>AZD0837 reference- (in session 1) and test- (in session 2) formulation with light breakfast | Drug: AZD0837<br>* Extended-release tablets, reference formulation. 2 tablets given in the morning for 6 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the pharmacokinetics of AZD0837 and the active metabolite AR-H067637XX for the extended-release test formulation of AZD0837 compared to the ER reference formulation. |  | Intense PK-sampling during 5 pre- defined study days for PK profiling. In 2 of the study days the subjects will have a breakfast before intake of the Investigational Product. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the PK of the intermediate metabolite AR-H069927XX |  | Since the metbolite will be evaluated from the AZD0837-samples the time frame is the same as above. | 
| Safety variables (ECG, pulse, blood pressure, safety lab, physical examination, adverse events) |  | ECG & physical examination at start and end of study. Pulse and blood pressure predose day 1 and every day 2 h post dose. Adverse events collected during the whole study. Safety lab at a few timepoints but APTT will be checked on 4 h post dose on day 1. | 
| Measurement of plasma concentrations of 4 beta-hydroxycholesterol to investigate whether AZD0837 affects the level of CYP3A4 |  | Once predose on day 1, session 1 and once predose on day 5, session 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy volunteers