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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02209766
• Other study ID #: D5881C00005
• Status: Completed
• Phase: Phase 1
• First received: August 1, 2014
• Last updated: November 7, 2014
• Start date: August 2014
• Est. completion date: November 2014

Study information

• Verified date: November 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 45 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy

Intervention

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

Locations

Country	Name	City	State
Japan	CPC Clinical Trial Hospital	Kagoshima

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Comparison of the PK and Pharmacodynamic(PD) of single and multiple doses of D5884 in healthy, male Japanese and Caucasian subjects.	All PK parameters except for tmax and PD variables such as Triglycerides(TG), High density lipoprotein(HDL) cholesterol, Low-density lipoprotein(LDL)-cholesterol, Very low density lipoprotein(VLDL)-cholesterol, Apolipoprotein A-I, Apolipoprotein B, Apolipoprotein C-III, Arachidonic acid(AA) and EPA/AA ratio will be summarised by dose and race descriptively.	Blood samples will be collected from pre-dose(Day 1) to Day 18 in visit 3.	No
Other	Potential relationship between PK and PD effects of total EPA and DHA by assessment of percent change in TG levels.	To display the relationship between PK and PD(TG) graphically.	Blood samples will be collected from pre-dose(Day 1) to Day 18 in visit 3.	No
Primary	Safety and tolerability profile of D5884 by assessing adverse events (AEs), laboratory tests, vital signs, physical examination findings and electrocardiograms (ECGs).	To investigate the safety and tolerability (adverse events (AEs), laboratory tests (clinical chemistry, haematology, urinalysis), vital signs (blood pressure, pulse, body temperature), physical examination findings and electrocardiograms (ECGs)) of D5884 following administration.	Adverse event will be collected from randomization to last visit(Day 25). Clinical chemistry, Vital Signs and pECG's will be collected to last visit(Day 25).	Yes
Secondary	Pharmacokinetics(PK) profile for D5884 by assessing the plasma concentration versus time profile of total Eicosapentaenoic acid(EPA) and total Docosahexaenoic acid(DHA), and PK parameters.	To determine the PK of single and multiple doses of D5884 in healthy male Japanese subjects by assessing the plasma concentration versus time profile of total Eicosapentaenoic acid(EPA) and total Docosahexaenoic acid(DHA), and PK parameters(Maximum plasma analyte concentration (Cmax) and Area under the plasma analyte concentration-time curve (AUC) ).	Blood samples will be collected from pre-dose(Day 1 in visit 3) to last visit(Day 25 in visit 4).	No