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

NCT02372344 | Completed Phase 1 Results

• 1 other identifier: D5884C00004
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

the effect of food timing on PK; the effect of food timing on Safety and Tolerability; AZD0585; Japanese

Outcome Measures

Primary Outcomes (3)

• 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).

Study Arms (3)

Fasting

EXPERIMENTAL

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

Before meal

EXPERIMENTAL

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

After meal

EXPERIMENTAL

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

Interventions

AZD0585 DRUG

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.

After meal; Before meal; Fasting

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Fukuoka, Japan

Location

Related Publications (1)

• Shimada H, Nilsson C, Noda Y, Kim H, Lundstrom T, Yajima T. Effects of Food on the Pharmacokinetics of Omega-3-Carboxylic Acids in Healthy Japanese Male Subjects: A Phase I, Randomized, Open-label, Three-period, Crossover Trial. J Atheroscler Thromb. 2017 Sep 1;24(9):980-987. doi: 10.5551/jat.38737. Epub 2017 Mar 24.

  PMID: 28344197 DERIVED

Limitations and Caveats

Statistical analysis is not provided for the treatment comparisons of AUC for the parameter total DHA (not possible to calculate in majority of subjects). Therefore, AUC(0-72) alone represents total plasma exposure in the bioavailability comparison.

Results Point of Contact

• Title: Stefan C Carlsson, MD, PhD, Global Clinical Lead
• Organization: AstraZeneca Pharmaceuticals

ClinicalTrialTransparency@astrazeneca.com

+46 31 7761000

Study Officials

• Kei Sakamoto, MD, PhD

  Sugioka Memorial Hospital, Medical Co. LTA

  PRINCIPAL INVESTIGATOR

• Torbjörn Lundström, MD

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2015
• First Posted: February 26, 2015
• Study Start: March 1, 2015
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: May 16, 2016
• Results First Posted: May 16, 2016

Record last verified: 2016-04

Locations

JP (1)