Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E6742 in Healthy Adult Subjects

Eisai

Status and phase: Completed; Phase 1

Conditions: Healthy Participants

Treatments: Drug: E6742; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03082235

E6742-A001-001

Details and patient eligibility

About

Study E6742-A001-001 is a randomized, double-blind, placebo-controlled, single ascending dose study conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending oral doses of E6742 in healthy adult participants.

Enrollment: 72 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Nonsmoking, male or female, age ≥18 years and ≤45 years old at the time of informed consent
• Body mass index (BMI) ≥18 and <32 kilograms per meters squared (kg/m2) at Screening

Exclusion criteria

• Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [β-hCG] or human chorionic gonadotropin [hCG] test with a minimum sensitivity of 25 International Units per Liter [IU/L] or equivalent units of β-hCG [or hCG]). 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.
• Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception throughout the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation). No sperm donation is allowed during the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation.
• Any history of gastrointestinal surgery that may affect pharmacokinetic (PK) profiles of E6742 (eg, hepatectomy, nephrectomy, digestive organ resection) at Screening
• A prolonged QTcF interval (QTcF >450 ms) demonstrated on ECG at Screening or Baseline
• Persistent systolic blood pressure >130 mmHg or diastolic blood pressure >85 mmHg diastolic at Screening or Baseline Heart rate less than 50 or more than 100 beats/min at Screening or Baseline
• Known history of prolonged QT/QTc interval
• Left bundle branch block
• Known history of myocardial infarction or active ischemic heart disease
• Known history of clinically significant arrhythmia or uncontrolled arrhythmia
• Known history of clinically significant drug allergy at Screening
• Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening
• Known to be human immunodeficiency virus (HIV) positive at Screening
• Active viral hepatitis (A, B, or C) as demonstrated by positive serology at Screening
• History of drug or alcohol dependency or abuse within the 2 years prior to Screening, or those who have a positive urine drug and alcohol test at Screening or Baseline
• Intake of herbal preparations containing St. John's Wort within 4 weeks before dosing
• Use of prescription drugs within 4 weeks before dosing
• Intake of over-the-counter (OTC) medications within 2 weeks before dosing
• Currently enrolled in another clinical study or used any investigational drug or device within 30 days (or 5 half-lives, whichever is longer) before informed consent
• Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week before dosing

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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72 participants in 14 patient groups, including a placebo group

Cohort 1: 10 mg E6742

Experimental group

Description:

Participants will receive 10 milligrams (mg) E6742 as a single oral dose in the fasted state.

Treatment:

Drug: E6742

Cohort 1: Matching placebo

Placebo Comparator group

Description:

Participants will receive a single oral dose of placebo matching E6742 in the fasted state.

Treatment:

Drug: Placebo

Cohort 2: 25 mg E6742

Experimental group

Description:

Participants will receive 25 mg E6742 as a single oral dose in the fasted state.

Treatment:

Drug: E6742

Cohort 2: Matching placebo

Placebo Comparator group

Description:

Participants will receive a single oral dose of placebo matching E6742 in the fasted state.

Treatment:

Drug: Placebo

Cohort 3: 50 mg E6742

Experimental group

Description:

Participants will receive 50 mg E6742 as a single oral dose in the fasted state.

Treatment:

Drug: E6742

Cohort 3: Matching placebo

Placebo Comparator group

Description:

Participants will receive a single oral dose of placebo matching E6742 in the fasted state.

Treatment:

Drug: Placebo

Cohort 4: 100 mg E6742

Experimental group

Description:

Participants will receive 100 mg E6742 as a single oral dose in the fasted state. Participants will then receive the same single oral dose of E6742 again in the fed state after a washout interval (at least 7 days or 5 half-lives of E6742, whichever is longer) for the evaluation of food effect.

Treatment:

Drug: E6742

Cohort 4: Matching placebo

Placebo Comparator group

Description:

Participants will receive a single oral dose of placebo matching E6742 in the fasted state. Participants will then receive the same single oral dose of placebo again in the fed state after a washout interval (at least 7 days ) for the evaluation of food effect.

Treatment:

Drug: Placebo

Cohort 5: 200 mg E6742

Experimental group

Description:

Participants will receive 200 mg E6742 as a single oral dose in the fasted state.

Treatment:

Drug: E6742

Cohort 5: Matching placebo

Placebo Comparator group

Description:

Participants will receive a single oral dose of placebo matching E6742 in the fasted state.

Treatment:

Drug: Placebo

Cohort 6: 400 mg E6742

Experimental group

Description:

Participants will receive 400 mg E6742 as a single oral dose in the fasted state.

Treatment:

Drug: E6742

Cohort 6: Matching placebo

Placebo Comparator group

Description:

Participants will receive a single oral dose of placebo matching E6742 in the fasted state.

Treatment:

Drug: Placebo

Cohort 7: 800 mg E6742

Experimental group

Description:

Participants will receive 800 mg E6742 as a single oral dose in the fasted state.

Treatment:

Drug: E6742

Cohort 7: Matching placebo

Placebo Comparator group

Description:

Participants will receive a single oral dose of placebo matching E6742 in the fasted state.

Treatment:

Drug: Placebo