A Ph1 Study in Healthy Male Japanese and Caucasian After Single and Multiple Doses of D5884(Omega-3-carboxylic Acids)

Study Overview
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Brief Summary
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The purpose of this study is to assess safety, tolerability and pharmacokinetics of D5884 following administration of single and multiple doses in healthy male Japanese subjects.

Detailed Description
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This is a Phase 1, single-centre study that plans to enrol 3 cohorts in 3 study arms (Study Arms A, B and C). Study Arms A and B will be comprised of cohorts of healthy male Japanese subjects in randomised, single-blind, placebo-controlled, single and multiple dose parallel studies and Study Arm C will be comprised of a cohort of healthy male Caucasian subjects in a single and multiple dose open-label study. Two dose levels, 2 and 4 g D5884, will be investigated in healthy male Japanese subjects. Up to 18 healthy male Japanese subjects aged 20 to 45 years, inclusive, will be enrolled in 2 cohorts (Study Arms A and B) and up to 6 healthy male Caucasian subjects will be enrolled in a 3rd cohort (Study Arm C). Each subject will participate in 1 cohort only. Following a screening period of a maximum of 42 days, subjects will reside at the study facility for 18 nights starting from the day before dosing (Day -1) to Day 18 (day of discharge). The follow-up period after dosing will be 8 (±2) days after last dose. Dose administration in all 3 study arms will be done in the following sequence: a single dose of D5884 or placebo will be administered; this will be followed by a 2-day washout period; after the washout period, multiple doses of D5884 or placebo will be administered, once daily for 14 consecutive days. The 1st cohort (Study Arm A) will receive 2 g D5884 (n=6) or placebo (n=3), the 2nd cohort (Study Arm B) will receive 4 g D5884 (n=6) or placebo (n=3) and the 3rd cohort (Study Arm C) will receive 4 g D5884 (n=6). The PK analysis included all evaluable PK data appropriate for the evaluation of interest (eg, with no major protocol deviations or violations thought to significantly affect the PK of the drug) from all subjects who received D5884.

Official Title
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A Phase 1 Study to Assess the Safety, Tolerability and Pharmacokinetics in Healthy Male Japanese (Single-blind, Randomized, Placebo-controlled) and Caucasian (Open-label) Subjects After Single and Once Daily Multiple Oral Doses of D5884

Conditions
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Healthy

Intervention / Treatment
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* Drug: D5884
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult male, 20 to 45 years of age (inclusive) Body mass index (BMI) ≥18.5 and ≤25 kg/m2 for Japanese subjects, ≥18.5 and ≤30 kg/m2 for Caucasian subjects. BMI calculations to be conducted on height and weight values obtained at Visit 1 Medically healthy with clinically insignificant screening results (eg, laboratory profile, medical history, ECGs, physical examination). Haemoglobin has to be ≥ the lower limit of the study site reference range, 12-lead ECG must have QT interval corrected for heart rate using Fridericia's formula(QTcF) >340 msec and <450 msec No habitual use of drug(s) and non-tobacco/nicotine-containing products for a minimum of 6 months prior to dosing Subjects must be willing and able to give written informed consent by signing an Institutional Review Board(IRB)-approved informed consent form (ICF) prior to admission to this study and follow the restrictions and procedures outlined for the study. Mean fasting Triglyceride(TG) at -4 and -2 weeks of <150 mg/dL, and %TG change of <30% between Weeks -4 and -2 Exclusion Criteria: Participation in another clinical study with an investigational product(IP) during the 4 months prior to enrolment 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 principal investigator(PI) A history or presence of significant cardiovascular, pulmonary, hepatic, renal, haematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease A positive urine drug/alcohol test at screening or admission (Visit 3, Day -1). (The drug test includes testing for phencyclidine, benzodiazepine, cocaine, amphetamines, cannabis, opiates, barbiturates and tricyclic anti-depressants. The alcohol test is an alcohol breath assessment.) A positive test for syphilis, human immunodeficiency virus, hepatitis B surface antigen or hepatitis C virus antibodies. Had used fish oil, other EPA- and/or DHA-containing supplements within 2 months of the planned time of admission Current evidence, or a history of alcoholism or drug abuse within the 2 years prior to admission A known sensitivity or allergy to soybeans, fish and/or shellfish A hypersensitivity or idiosyncratic reaction to compounds related to EPA and/or DHA Had used any prescription medication within 14 days prior to admission Had used any over-the-counter (OTC) medication, including herbal products (bromelains, danshen, dong quai [Angelica sinensis], garlic, ginko biloba, ginseng, and St. John's wort), within the 7 days prior to admission Had used any drugs known to significantly inhibit [strong or moderate] or induce liver enzymes involved in drug metabolism [cytochrome P450]) within 30 days prior to admission Had donated blood or had had significant blood loss in excess of 200 mL within 1 month prior to admission or in excess of 400 mL within 3 months prior to admission Had donated plasma within 7 days prior to admission History of drug abuse or past history of alcohol abuse or habit of taking nicotine-containing product(s) on a daily basis Those who have difficulty in giving blood during blood sampling via the peripheral vein Any potential subjects who are considered as not eligible for the study in the opinion of the PI and/or the sub-investigator

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

Sexes Eligible for Study
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Male

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D5884<br>D5884 capsule, Per oral(po) | Drug: D5884<br>* 1st cohort: Dose 1(2g) D5884(n=6) in Japanese 2nd cohort: Dose 2(4g) D5884(n=6) in Japanese 3rd cohort: Dose 2(4g) D5884(n=6) in Caucasian<br>|
| Placebo Comparator: Placebo<br>Placebo capsule, po | Drug: Placebo<br>* st cohort: Dose 1(2g) D5884(n=3) in Japanese nd cohort: Dose 2(4g) D5884(n=3) in Japanese<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Treatment-emergent Adverse Events (TEAEs), by Treatment (Safety Analysis Set) | Number of patients with treatment-emergent adverse events (TEAEs), by treatment (Safety Analysis Set) | from first dosing (Day1) until follow-up (Day25) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax in Plasma Baseline-adjusted Total Eicosapentaenoic Acid (EPA), Single Dose |  | Day1-3, 4, 7, 11, 14, 17-18 and 25 | 
| Tmax in Plasma Baseline-adjusted Total EPA, Single Dose |  | Day1-3, 4, 7, 11, 14, 17-18 and 25 | 
| Cmax in Plasma Baseline-adjusted Total Docosahexaenoic Acid (DHA), Single Dose |  | Day1-3, 4, 7, 11, 14, 17-18 and 25 | 
| Tmax in Plasma Baseline-adjusted Total DHA, Single Dose |  | Day1-3, 4, 7, 11, 14, 17-18 and 25 | 
| Cmax in Plasma Baseline-adjusted Total EPA, Multiple Dose |  | Day1-3, 4, 7, 11, 14, 17-18 and 25 | 
| Tmax in Plasma Baseline-adjusted Total EPA, Multiple Dose |  | Day1-3, 4, 7, 11, 14, 17-18 and 25 | 
| Cmax in Plasma Baseline-adjusted Total DHA, Multiple Dose |  | Day1-3, 4, 7, 11, 14, 17-18 and 25 | 
| Tmax in Plasma Baseline-adjusted Total DHA, Multiple Dose |  | Day1-3, 4, 7, 11, 14, 17-18 and 25 | 
| AUC(0-tau) in Plasma Baseline-adjusted Total DHA, Multiple Dose |  | Day1-3, 4, 7, 11, 14, 17-18 and 25 | 
| AUC(0-tau) in Plasma Baseline-adjusted Total EPA, Multiple Dose |  | Day1-3, 4, 7, 11, 14, 17-18 and 25 | 
| AUC(0-tau) in Plasma Baseline-adjusted Total Docosahexaenoic Acid (DHA), Single Dose |  | Day1-3, 4, 7, 11, 14, 17-18 and 25 | 
| AUC(0-tau) in Plasma Baseline-adjusted Total Eicosapentaenoic Acid (EPA), Single Dose |  | Day1-3, 4, 7, 11, 14, 17-18 and 25 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, D5884, Japanese, Caucasian