A Study to Investigate the Effect of Food on Pharmacokinetics of Total EPA and Total DHA of AZD0585 in Healthy Male Japanese Subjects

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the effect of food timing on pharmacokinetics (PK) of AZD0585 and the effect of food timing on tolerability and safety of AZD0585 in healthy male Japanese subjects.

Detailed Description
-----------------
This study is an open-label, randomized, cross-over design with three single-dose treatment periods and a washout of at least 10 days in between each treatment visit. The study period consists of 5 visits to the study centre: Visit 1 (enrolment), Visit 2 (first single-dose treatment), Visit 3 (second single-dose treatment), Visit 4 (third single-dose treatment) and Visit 5 (follow-up). Target subject population is healthy male Japanese subjects aged 20-45 years. Following an overnight fast of at least 10 hours, a single dose of 4 g AZD0585 will be administered on 3 separate occasions (fasting, before meal, and after meal) in a randomized crossover fashion with different food restrictions.

Official Title
-----------------
A Phase I, Single Centre, Randomized, Open-Label, Three-Period Crossover Study to Investigate the Effect of Food on Pharmacokinetics of Total EPA and Total DHA With a Single 4 g Dose of AZD0585 in Healthy Male Japanese Subjects

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: AZD0585


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy Japanese male, 20 to 45 years of age (inclusive). Body mass index (BMI) ≥ 18.5 and ≤ 25 (kg/m2). Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical histories, ECGs, physical findings). Hemoglobin level must be ≥ the lower limit of study centre reference range. 12-Lead ECG with QT interval corrected for heart rate using Fridericia's formula (QTcF) should be > 340 msec and < 450 msec. No habitual use of drug(s) and tobacco/nicotine-containing products for a minimum of 3 months prior to first dosing. Subjects must be willing and able to give written informed consent by signing an Institutional Review Board (IRB)-approved Informed Consent Form prior to admission to this study and follow the restrictions and procedures outlined for the study. Exclusion Criteria: Past history of psychological or physical disorder which may affect the objectives of this study, in the opinion of the PI. An individual who has abnormal laboratory values (ie, suggesting hepatic, renal, cardiovascular or endocrine disorders or diabetes mellitus), or an inappropriate current or past medical history for participation based on the decision of the PI. A history or presence of significant cardiovascular, pulmonary, hepatic, renal, haematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease. Had used fish oil, other EPA- and/or DHA-containing supplements within 2 months prior to first admission day. Have serum (or plasma) EPA and/or DHA concentrations exceeding the upper limit of reference range for the fatty acids profile, four-fraction test, determined at Visit 1.

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

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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: Fasting<br>Each subject will receive a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose will be administered at the end of a 10-hour fast. | Drug: AZD0585<br>* Following an overnight fast of at least 10 hours, a single dose of 4 g AZD0585 will be administered on 3 separate occasions (fasting, before meal, and after meal) in a randomized crossover fashion with different food restrictions.<br>|
| Experimental: Before meal<br>Each subject will receive a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose will be administered before consumption of a low calorie, low-fat breakfast (within 30 minutes before starting food intake). | Drug: AZD0585<br>* Following an overnight fast of at least 10 hours, a single dose of 4 g AZD0585 will be administered on 3 separate occasions (fasting, before meal, and after meal) in a randomized crossover fashion with different food restrictions.<br>|
| Experimental: After meal<br>Each subject will receive a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose will be administered after consumption of a low calorie, low-fat breakfast (within 30 minutes after starting food intake). | Drug: AZD0585<br>* Following an overnight fast of at least 10 hours, a single dose of 4 g AZD0585 will be administered on 3 separate occasions (fasting, before meal, and after meal) in a randomized crossover fashion with different food restrictions.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Effect of Food Timing (Fasting, Before Meal, and After Meal) on Pharmacokinetics (PK; AUC) of AZD0585 in Healthy Male Japanese. | To investigate the effect of food timing on PK (area under the plasma concentration-time curve from time zero to infinity [AUC]) of single dose of 4 g AZD0585 in healthy male Japanese by assessing plasma concentrations of total eicosapentaenoic acid (EPA) and total docosahexaenoic acid (DHA), and PK parameters over time under the three proposed conditions (fasting, before meal, and after meal). | Blood samples were collected from pre-dose (Day -1) up to 72 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4). | 
| The Effect of Food Timing (Fasting, Before Meal, and After Meal) on PK (Cmax) of AZD0585 in Healthy Male Japanese. | To investigate the effect of food timing on PK (maximum plasma concentration [Cmax]) of single dose of 4 g AZD0585 in healthy male Japanese by assessing plasma concentrations of total EPA and total DHA, and PK parameters over time under the three proposed conditions (fasting, before meal, and after meal). Analyses of the outcome measures presented are for baseline-adjusted data for total EPA and DHA since the presence of endogenous levels of these fatty acids would likely contribute to intra-subject variability and affect the analyses and interpretation. The geometric mean was calculated as the exponential of the arithmetic mean calculated from data on a log scale. | Blood samples were collected from pre-dose (Day -1) up to 72 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4). | 
| The Effect of Food Timing (Fasting, Before Meal, and After Meal) on PK (AUC0-72) of AZD0585 in Healthy Male Japanese. | To investigate the effect of food timing on PK (area under the plasma concentration-time curve from time zero to 72 hours [AUC0-72]) of single dose of 4 g AZD0585 in healthy male Japanese by assessing plasma concentrations of total EPA and total DHA, and PK parameters over time under the three proposed conditions (fasting, before meal, and after meal). Analyses of the outcome measures presented are for baseline-adjusted data for total EPA and DHA since the presence of endogenous levels of these fatty acids would likely contribute to intra-subject variability and affect the analyses and interpretation. The geometric mean was calculated as the exponential of the arithmetic mean calculated from data on a log scale. | Blood samples were collected from pre-dose (Day -1) up to 72 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4). | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
the effect of food timing on PK, the effect of food timing on Safety and Tolerability, AZD0585, Japanese