A Study to Assess the Safety and Tolerability of E2730 After Multiple Dose and the Food Effect After Single Dose in Healthy Participants

Healthy Volunteers Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose and Single Dose Food Effect Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2730 in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04676685
• Other study ID #: E2730-A001-013
• Status: Completed
• Phase: Phase 1
• Start date: December 16, 2020
• Est. completion date: June 23, 2021

Study information

• Verified date: August 2021
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of E2730 of multiple ascending oral doses in healthy adult participants and to assess the differences in PK, safety, and tolerability of E2730 between healthy Japanese and non-Japanese participants following multiple doses. This study will also determine the effect of food on PK of E2730.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: June 23, 2021
• Est. primary completion date: June 23, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Non-smoking, healthy male or female, age greater than or equal to (>=) 18 years and <55 years old at the time of informed consent. To be considered non-smokers, Participants must have discontinued smoking for at least 4 weeks before dosing

2. Japanese Participants must have been born in Japan of Japanese parents and Japanese grandparents, must have lived no more than 5 years outside of Japan, and must not have changed their life style or habits, including diet, while living outside of Japan

3. Body mass index (BMI) >=18 and <30 kilograms per meter square (kg/m^2) at Screening

Exclusion Criteria:

1. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] test). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug

2. Females of childbearing potential who:

• Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:

• Total abstinence (if it is their preferred and usual lifestyle)

• An intrauterine device or intrauterine hormone-releasing system (IUS)

• A contraceptive implant

• An oral contraceptive (Participant must have been on a stable dose of the same oral contraceptive product for at least 28 days before dosing and must agree to stay on the same dose of the oral contraceptive throughout the study and for 28 days after study drug discontinuation)

• Have a vasectomized partner with confirmed azoospermia

• Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation

3. Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (that is, the female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation)

4. Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing

5. Evidence of disease that may influence the outcome of the study within 4 weeks before dosing; example, psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or participants who have a congenital abnormality in metabolism

6. Any history of gastrointestinal surgery that may affect PK profiles of E2730, example, hepatectomy, nephrectomy, and digestive organ resection

7. Any clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, ECG finding, or laboratory test results that require medical treatment at Screening

8. A prolonged QT interval of the ECG/Corrected QT interval (QT/QTc) (QTcF greater than [>] 450 milliseconds [ms]) demonstrated by a repeated ECG at Screening or Baseline (based on average of triplicate ECGs). A history of risk factors for torsade de pointes (example, heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolonged the QT/QTc interval

9. Persistent systolic BP >139 or <90 millimeter of mercury (mmHg) or diastolic BP >89 or <50 mmHg at Screening or Baseline

10. Heart rate <45 beats/minute or >100 beats/minute at Screening or Baseline

11. Any lifetime history of suicidal ideation or any lifetime history of suicidal behavior as indicated by the Columbia-Suicide Severity Rating Scale (C-SSRS) or equivalent scale or via interview with a psychiatrist

12. Any lifetime history of psychiatric disease (including but not limited to depression or other mood disorders, bipolar disorder, psychotic disorders, including schizophrenia, panic attacks, anxiety disorders ). The absence of a history of psychiatric disease should be documented by a checklist in the electronic case report form (eCRF)

13. Any current psychiatric symptoms as indicated by a standard screening tool

14. Any suicidal ideation with intent with or without a plan at Screening or within 6 months of Screening (that is, answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the C-SSRS)

15. Any lifetime suicidal behavior (per the Suicidal Behavior Section of the C-SSRS)

16. Known history of clinically significant drug allergy at Screening

17. Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening

18. Known to be human immunodeficiency virus (HIV) positive at Screening

19. Active viral hepatitis (A, B, or C) and syphilis as demonstrated by positive serology at Screening

20. History of drug or alcohol dependency or abuse, or those who have a positive drug test at Screening or Baseline

21. Exposure within the last 14 days to an individual with confirmed or probable corona virus disease 2019 (COVID-19) or symptoms within the last 14 days that are on the most recent Centers for Disease Control and Prevention (CDC) list of COVID symptoms or any other reason to consider the participants at potential risk for an acute COVID-19 infection

22. Currently enrolled in another clinical study or used any investigational drug or device within 28 days or 5 half-lives, whichever is longer, preceding informed consent

23. Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week of dosing

24. Any personal or family history of seizures (including febrile seizures) or epilepsy or episode of unexplained loss of consciousness

25. Any history of neurological or other medical conditions which in the opinion of the investigator has the potential to reduce seizure threshold (example, history of head concussion, traumatic brain injury, alcohol abuse, substance abuse, developmental abnormalities in the brain)

26. Any epileptiform discharges on resting EEG (including during hyperventilation and photo-stimulation)

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• E2730
E2730 capsules.
• E2730-matched placebo
E2730-matched placebo capsules.

Locations

Country	Name	City	State
United States	Collaborative Neuroscience Research, LLC.	Long Beach	California

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Safety assessments will consist of monitoring and recording all adverse events (AEs); laboratory evaluation for hematology, clinical chemistry, and urinalysis; periodic measurement of vital signs, electrocardiograms (ECGs), electroencephalogram (EEGs), corrected QT (QTc) interval and blood pressure.	Screening up to Day 32 (approximately 60 days)
Primary	Part A, Cmax: Maximum Observed Plasma Concentration for E2730		Day 1: 0-24 hours; Day 18: 0-336 hours
Primary	Part A, Css,min: Minimum Observed Plasma Concentration at Steady State for E2730		Time Frame: Day 18: 0-24 hours
Primary	Part A, tmax: Time at Which the Highest Drug Plasma Concentration Occurs for E2730		Day 1: 0-24 hours; Day 18: 0-336 hours
Primary	Part A, Css,av: Average Steady State Plasma Concentration at Steady State for E2730		Time Frame: Day 18: 0-24 hours
Primary	Part A, AUC(0-24h): Area Under the Plasma Concentration-time Curve From Zero Time to 24 Hours After Dosing for E2730		Day 1: 0-24 hours; Day 18: 0-24 hours
Primary	Part A, t1/2: Terminal Elimination Phase Half-life Following Last day of Dosing for E2730		Day 18: 0-336 hours
Primary	Part A, PTF: Peak-trough Fluctuation for E2730		Day 18: 0-24 hours
Primary	Part A, Rac: Accumulation Ratio for Cmax and AUC for E2730		Day 1: 0-24 hours; Day 18: 0-24 hours
Primary	Part A, CLss/F: Apparent Total Clearance Following Extravascular Administration at Steady State for E2730		Day 18: 0-336 hours
Primary	Part A, Vz/F: Apparent Volume of Distribution at Terminal Phase		Day 18: 0-336 hours
Primary	Part B, Cmax: Maximum Observed Plasma Concentration for E2730		Day 1: 0-288 hours; Day 22: 0-288 hours
Primary	Part B, tmax: Time at Which the Highest Drug Plasma Concentration Occurs for E2730		Day 1: 0-288 hours; Day 22: 0-288 hours
Primary	Part B, AUC(0-24h): Area Under the Plasma Concentration-time Curve From Zero Time to 24 Hours After Dosing for E2730		Day 1: 0-24 hours; Day 22: 0-24 hours
Primary	Part B, AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to Time of Last Quantifiable Concentration for E2730		Day 1: 0-288 hours; Day 22: 0-288 hours
Primary	Part B, AUC(0-72h): Area Under the Plasma Concentration-time Curve From Zero Time to 72 Hours After Dosing for E2730		Day 1: 0-72 hours; Day 22: 0-72 hours
Primary	Part B, AUC(0-inf): Area Under the Plasma Concentration-time Curve From Zero Time Extrapolated to Infinite Time for E2730		Day 1: 0-288 hours; Day 22: 0-288 hours
Primary	Part B, t1/2: Terminal Elimination Phase Half-life for E2730		Day 1: 0-288 hours; Day 22: 0-288 hours
Primary	Part A: Geometric Mean Ratio of Cmax Between the Healthy Japanese and non-Japanese Participants for E2730		Day 1: 0-24 hours; Day 18: 0-336 hours
Primary	Part A: Geometric Mean Ratio of AUC(0-24) Between the Healthy Japanese and non-Japanese Participants for E2730		Day 1: 0-24 hours; Day 18: 0-24 hours
Primary	Part B: Geometric Mean Ratio of Cmax Between the Fasted and fed State for E2730		Day 1: 0-288 hours; Day 22: 0-288 hours
Primary	Part B: Geometric Mean Ratio of AUC(0-t) Between the Fasted and fed State for E2730		Day 1: 0-288 hours; Day 22: 0-288 hours
Primary	Part B: Geometric Mean Ratio of AUC(0-72h) Between the Fasted and fed State for E2730		Day 1: 0-72 hours; Day 22: 0-72 hours
Primary	Part B: Geometric Mean Ratio of AUC(0-inf) Between the Fasted and fed State for E2730		Day 1: 0-288 hours; Day 22: 0-288 hours
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)		Baseline, Day 32
Secondary	Change From Baseline in Heart Rate (HR)		Baseline, Day 32
Secondary	Placebo Corrected Change From Baseline in SBP and DBP		Baseline, Day 32
Secondary	Placebo Corrected Change From Baseline in HR		Baseline, Day 32
Secondary	Number of Participants With Categorical Outliers for SBP and DBP		Baseline up to Day 32
Secondary	Change From Baseline in QT Interval by Fridericia (QTcF)		Baseline, Day 32
Secondary	Change From Baseline in PR Interval of the ECG (PR), QRS Interval of the ECG (QRS)		Baseline, Day 32
Secondary	Placebo Corrected Change From Baseline in QTcF, PR and QRS		Baseline, Day 32
Secondary	Number of Participants With Categorical Outliers for QTcF, HR, PR, and QRS		Baseline, Day 32
Secondary	Number of Participants With T-wave Morphology Changes	The T-wave morphology categories includes the following: Normal T-wave (Any positive T-wave not meeting any criterion); Flat T-wave (T amplitude less than (<) 1 millimeter [mm] [either positive or negative] including flat isoelectric line); Notched T-wave (+) (Presence of notch(es) of at least 0.05 millivolt [mV] amplitude on ascending or descending arm of the positive T-wave); Biphasic (T-wave that contains a second component with an opposite phase that is at least 0.1 mV deep (both positive/negative and negative/positive and polyphasic T-waves included); Normal T-wave (-) (T amplitude that is negative, without biphasic T-wave or notches); Notched T-wave (-) (Presence of notch(es) of at least 0.05 mV amplitude on descending or ascending arm of the negative T-wave).	Baseline up to Day 32
Secondary	Number of Participants With Presence of Abnormal U-wave		Baseline up to Day 32