Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2609 in Healthy Adult Male Japanese and White Subjects

Healthy Subjects Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Single Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2609 in Healthy Adult Male Japanese and White Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02207790
• Other study ID #: E2609-A001-006
• Status: Completed
• Phase: Phase 1
• First received: July 31, 2014
• Last updated: November 2, 2015
• Start date: July 2014
• Est. completion date: October 2014

Study information

• Verified date: November 2015
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is primarily designed to bridge the pharmacokinetics (PK) and safety data for E2609 between Japanese subjects and non-Japanese (ie, white) subjects. To bridge these PK characteristics, the proposed study includes a cohort of white subjects treated for comparison with the cohort of Japanese subjects treated at the same dose. This comparison serves as a key PK bridge in assessing ethnic factors that may contribute to differences in plasma concentrations. Pharmacokinetic assessments in the proposed study will include confirmation of dose proportionality in Japanese subjects. This study will also evaluate safety and tolerability in Japanese subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: October 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 30 Years to 60 Years

Eligibility

Inclusion Criteria:

The subject must meet all of the following criteria in order to be included in the study.

Japanese Subjects Only:

1. Birth in Japan to Japanese parents and grandparents of Japanese descent

2. Have been living outside Japan for less than 5 years

3. Lifestyle, including diet, has not changed significantly since leaving Japan

White Subjects Only:

4. A person having origins in any of the original peoples of Europe, the Middle East, or North Africa based on documented subject self-report

All Subjects:

5. Healthy male, 30 to 60 years inclusive, at the time of informed consent

6. BMI of 18 to 32 kg/m2 inclusive at Screening

7. Subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must not be of childbearing potential or must be practicing highly effective contraception (i.e. condom plus spermicide, condom plus diaphragm with spermicide, intrauterine device starting for at least one menstrual cycle before starting study drug[s]) and throughout the study period and for 30 days after study drug discontinuation. No sperm donation is allowed during the study period and for 30 days after study drug discontinuation.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from this study:

1. Any history of seizures or epilepsy

2. Any medical condition which, in the opinion of the investigator has high risk of seizures

3. Any history of cerebrovascular disease

4. A history of prolonged QTc interval

5. Any other clinically significant ECG abnormalities

6. History of risk factors for torsade de pointes or the use of medications that prolonged the QT/QTc interval

7. Heart rate less than 50 or greater than 100 beats/min

8. History of ischemic heart disease

9. Persistent systolic blood pressure (BP) greater than 140 mmHg or less than 90 mmHg and diastolic BP greater than 90 mmHg or less than 60 mmHg

10. Left bundle branch block

11. Evidence of clinically significant disease

12. Any laboratory abnormalities considered clinically significant

13. Clinically significant illness which requires medical treatment

14. Any history of abdominal surgery that may affect study drugs

15. Hypersensitivity to the study drug

16. Known to be HIV positive

17. Active viral hepatitis

18. History of drug or alcohol dependency or abuse within approximately the last 2 years

19. Scheduled for surgery during the study

20. Engagement in strenuous exercise within 2 weeks before dosing (eg, marathon runners, weight lifters)

21. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days before informed consent

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• E2609

• Placebo
E2609 low-dose and placebo in healthy Japanese subjects, E2609 mid-dose and placebo in healthy Japanese subjects, E2609 high-dose and placebo in healthy Japanese subjects, E2609 mid-dose and placebo in healthy White subjects

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics of E2609: Cmax		Up to Day 10 (216 hours postdose)	No
Primary	Pharmacokinetics of E2609: tmax		Up to Day 10 (216 hours postdose)	No
Primary	Pharmacokinetics of E2609: AUC(0-24h)+D90		Up to Day 10 (216 hours postdose)	No
Primary	Pharmacokinetics of E2609: AUC(0-72h)		Up to Day 10 (216 hours postdose)	No
Primary	Pharmacokinetics of E2609: AUC(0-t)		Up to Day 10 (216 hours postdose)	No
Primary	Pharmacokinetics of E2609: AUC(0-inf)		Up to Day 10 (216 hours postdose)	No
Primary	Pharmacokinetics of E2609: AUC Metabolite Ratio		Up to Day 10 (216 hours postdose)	No
Primary	Pharmacokinetics of E2609: t1/2		Up to Day 10 (216 hours postdose)	No
Primary	Pharmacokinetics of E2609: CL/F		Up to Day 10 (216 hours postdose)	No
Primary	Pharmacokinetics of E2609: V/F		Up to Day 10 (216 hours postdose)	No
Primary	To evaluate the safety and tolerability of E2609	Safety will be assessed by monitoring and recording all adverse events (AEs), serious adverse events (SAEs), regular monitoring of hematology, blood chemistry, urine values, regular measurement of vital signs, ECGs and performance of physical examinations	Baseline and up to 30 days from last dosing of subject	Yes
Secondary	Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): Amax		Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10	No
Secondary	Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): T(Amax)		Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10	No
Secondary	Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): AUAC(-24h-0h)		Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10	No
Secondary	Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): AUAC(0-144h)		Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10	No
Secondary	Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): Change in AUAC		Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10	No
Secondary	Change from baseline in QTcF obtained from ECGs extracted from Holter recordings	Holter ECG measurements will start on Day -1, at a time equivalent to 24 hours predose, and will continue for 24 hours postdose of Day 1, with interruptions allowed to adjust equipment. ECGs will be extracted from Holter monitors.	Baseline, Day 1, and Day 2	No