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

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02209766

Enrollment

Registered

2014-08-06

Start date

2014-08-31

Completion date

2014-11-30

Last updated

2016-05-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, D5884, Japanese, Caucasian

Brief summary

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

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.

Interventions

DRUGD5884

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

DRUGPlacebo

1. st cohort: Dose 1(2g) D5884(n=3) in Japanese 2. nd cohort: Dose 2(4g) D5884(n=3) in Japanese

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

MALE

Age

20 Years to 45 Years

Healthy volunteers

Yes

Inclusion criteria

1. Healthy adult male, 20 to 45 years of age (inclusive) 2. 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 3. 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 4. No habitual use of drug(s) and non-tobacco/nicotine-containing products for a minimum of 6 months prior to dosing 5. 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. 6. 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

1. Participation in another clinical study with an investigational product(IP) during the 4 months prior to enrolment 2. Past history of psychological or physical disorder which may affect the objectives of this study, in the opinion of the PI 3. 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) 4. A history or presence of significant cardiovascular, pulmonary, hepatic, renal, haematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease 5. 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.) 6. A positive test for syphilis, human immunodeficiency virus, hepatitis B surface antigen or hepatitis C virus antibodies. 7. Had used fish oil, other EPA- and/or DHA-containing supplements within 2 months of the planned time of admission 8. Current evidence, or a history of alcoholism or drug abuse within the 2 years prior to admission 9. A known sensitivity or allergy to soybeans, fish and/or shellfish 10. A hypersensitivity or idiosyncratic reaction to compounds related to EPA and/or DHA 11. Had used any prescription medication within 14 days prior to admission 12. 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 13. 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 14. 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 15. Had donated plasma within 7 days prior to admission 16. History of drug abuse or past history of alcohol abuse or habit of taking nicotine-containing product(s) on a daily basis 17. Those who have difficulty in giving blood during blood sampling via the peripheral vein 18. Any potential subjects who are considered as not eligible for the study in the opinion of the PI and/or the sub-investigator

Design outcomes

Primary

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

Secondary

Measure	Time frame
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 Eicosapentaenoic Acid (EPA), Single 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
Cmax in Plasma Baseline-adjusted Total DHA, Multiple Dose	Day1-3, 4, 7, 11, 14, 17-18 and 25

Countries

Japan

Participant flow

Recruitment details

86 male subjects were screened.

Pre-assignment details

Of the 86 subjects, 43 did not meet the inclusion/exclusion criteria, 14 decided not to participate in the study and 5 had other reasons for declining participation in the study.

Participants by arm

Arm	Count
2 g D5884 Japanese Single dose followed by once daily for 14 consecutive days	6
4 g D5884 Japanese Single dose followed by once daily for 14 consecutive days	6
4 g D5884 Caucasian Single dose followed by once daily for 14 consecutive days	6
Placebo Japanese Single dose followed by once daily for 14 consecutive days	6
Total	24

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Withdrawal by Subject	0	0	0	1	0

Baseline characteristics

Characteristic	Total	4 g D5884 Japanese	2 g D5884 Japanese	4 g D5884 Caucasian	Placebo Japanese
Age, Continuous	30.3 years STANDARD_DEVIATION 6.93	28.3 years STANDARD_DEVIATION 6.15	26.7 years STANDARD_DEVIATION 8.71	34.0 years STANDARD_DEVIATION 5.25	32.3 years STANDARD_DEVIATION 6.12
BMI	21.82 kg/m^2 STANDARD_DEVIATION 1.559	22.67 kg/m^2 STANDARD_DEVIATION 1.517	20.67 kg/m^2 STANDARD_DEVIATION 0.852	22.55 kg/m^2 STANDARD_DEVIATION 1.724	21.40 kg/m^2 STANDARD_DEVIATION 1.37
Race/Ethnicity, Customized Caucasian	6 Participants	0 Participants	0 Participants	6 Participants	0 Participants
Race/Ethnicity, Customized Japanese	18 Participants	6 Participants	6 Participants	0 Participants	6 Participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	24 Participants	6 Participants	6 Participants	6 Participants	6 Participants
Weight	66.26 kg STANDARD_DEVIATION 9.078	69.08 kg STANDARD_DEVIATION 7.059	60.42 kg STANDARD_DEVIATION 8.109	72.92 kg STANDARD_DEVIATION 10.169	62.63 kg STANDARD_DEVIATION 6.371

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	2 / 6	2 / 6	5 / 6	2 / 6
serious Total, serious adverse events	0 / 6	0 / 6	0 / 6	0 / 6

Outcome results

Primary

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)

Time frame: from first dosing (Day1) until follow-up (Day25)

Arm	Measure	Group	Value (NUMBER)
2g D5884 Japanese	Number of Patients With Treatment-emergent Adverse Events (TEAEs), by Treatment (Safety Analysis Set)	TEAEs	2 subjects
2g D5884 Japanese	Number of Patients With Treatment-emergent Adverse Events (TEAEs), by Treatment (Safety Analysis Set)	Serious TEAEs	0 subjects
2g D5884 Japanese	Number of Patients With Treatment-emergent Adverse Events (TEAEs), by Treatment (Safety Analysis Set)	TEAEs leading to discontinued	0 subjects
4g D5884 Japanese	Number of Patients With Treatment-emergent Adverse Events (TEAEs), by Treatment (Safety Analysis Set)	TEAEs	2 subjects
4g D5884 Japanese	Number of Patients With Treatment-emergent Adverse Events (TEAEs), by Treatment (Safety Analysis Set)	Serious TEAEs	0 subjects
4g D5884 Japanese	Number of Patients With Treatment-emergent Adverse Events (TEAEs), by Treatment (Safety Analysis Set)	TEAEs leading to discontinued	0 subjects
4g D5885 Caucasian	Number of Patients With Treatment-emergent Adverse Events (TEAEs), by Treatment (Safety Analysis Set)	TEAEs leading to discontinued	0 subjects
4g D5885 Caucasian	Number of Patients With Treatment-emergent Adverse Events (TEAEs), by Treatment (Safety Analysis Set)	TEAEs	5 subjects
4g D5885 Caucasian	Number of Patients With Treatment-emergent Adverse Events (TEAEs), by Treatment (Safety Analysis Set)	Serious TEAEs	0 subjects
Placebo Japanese	Number of Patients With Treatment-emergent Adverse Events (TEAEs), by Treatment (Safety Analysis Set)	TEAEs	2 subjects
Placebo Japanese	Number of Patients With Treatment-emergent Adverse Events (TEAEs), by Treatment (Safety Analysis Set)	Serious TEAEs	0 subjects
Placebo Japanese	Number of Patients With Treatment-emergent Adverse Events (TEAEs), by Treatment (Safety Analysis Set)	TEAEs leading to discontinued	0 subjects

Secondary