A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ESN364 in Healthy Japanese Male and Pre- and Post-menopausal Female Subjects

NCT03436849 | Completed Phase 1

• 1 other identifier: 2693-CL-0020
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of single and multiple oral doses of ESN364 in healthy Japanese male and pre- and post-menopausal female subjects. This study will also evaluate the pharmacokinetics (PK) of ESN364 and its metabolite, and the pharmacodynamics (PD) of ESN364 after single and multiple oral doses administration in healthy Japanese male and pre- and post-menopausal female subjects.

Conditions

Healthy Subjects

Keywords

ASP2693; Pharmacodynamics; Pharmacokinetics; ESN364; Safety

Outcome Measures

Primary Outcomes (31)

• Safety assessed by incidence of adverse events (AEs) in Part 1

  AEs will be coded using Medical Dictionary for Regulatory Activities (MedDRA).

  Up to Day 12 in Part 1

• Safety assessed by incidence of AEs in Part 2

  AEs will be coded using MedDRA.

  Up to Day 24 in Part 2

• Safety assessed by vital signs: Body temperature in Part 1

  To assess vital signs as a criterion of safety variables.

  Up to day 12 in Part 1

• Safety assessed by vital signs: Body temperature in Part 2

  To assess vital signs as a criterion of safety variables.

  Up to Day 24 in Part 2

• Safety assessed by vital signs: Blood pressure in Part 1

  To assess vital signs as a criterion of safety variables.

  Up to Day 12 in Part 1

• Safety assessed by vital signs: Blood pressure in Part 2

  To assess vital signs as a criterion of safety variables.

  Up to Day 24 in Part 2

• Safety assessed by vital signs: Pulse rate in Part 1

  To assess vital signs as a criterion of safety variables.

  Up to Day 12 in Part 1

• Safety assessed by vital signs: Pulse rate in Part 2

  To assess vital signs as a criterion of safety variables.

  Up to Day 24 in Part 2

• Safety assessed by laboratory test: Hematology in Part 1

  To assess laboratory values as a criterion of safety variables. Potentially clinically significant laboratory values will be reported as AEs.

  Up to Day 12 in Part 1

• Safety assessed by laboratory test: Hematology in Part 2

  To assess laboratory values as a criterion of safety variables. Potentially clinically significant laboratory values will be reported as AEs.

  Up to Day 24 in Part 2

• Safety assessed by laboratory test: Biochemistry in Part 1

  To assess laboratory values as a criterion of safety variables. Potentially clinically significant laboratory values will be reported as AEs.

  Up to Day 12 in Part 1

• Safety assessed by laboratory test: Biochemistry in Part 2

  To assess laboratory values as a criterion of safety variables. Potentially clinically significant laboratory values will be reported as AEs.

  Up to Day 24 in Part 2

• Safety assessed by laboratory test: Urinalysis in Part 1

  To assess laboratory values as a criterion of safety variables. Potentially clinically significant laboratory values will be reported as AEs.

  Up to Day 12 in Part 1

• Safety assessed by laboratory test: Urinalysis in Part 2

  To assess laboratory values as a criterion of safety variables. Potentially clinically significant laboratory values will be reported as AEs.

  Up to Day 24 in Part 2

• Safety assessed by standard 12-lead electrocardiogram (ECG) in Part 1

  Subjects should keep rest for 5 minutes before evaluation. Any clinically significant adverse changes on the ECG will be reported as AEs.

  Up to Day 12 in Part 1

• Safety assessed by standard ECG in Part 2

  Subjects should keep rest for 5 minutes before evaluation. Any clinically significant adverse changes on the ECG will be reported as AEs.

  Up to Day 24 in Part 2

• Safety assessed by ECG parameters: Heart rate in Part 1

  To assess ECG parameters as a criterion of safety variables.

  Up to 24 hr after dosing in Part 1

• Safety assessed by ECG parameters: Heart rate in Part 2

  To assess ECG parameters as a criterion of safety variables.

  Up to 24 hr after dosing on Day 10 in multiple dose (MD) of Part 2

• Safety assessed by ECG parameters: QT interval in Part 1

  To assess ECG parameters as a criterion of safety variables.

  Up to 24 hr after dosing in Part 1

• Safety assessed by ECG parameters: QT interval in Part 2

  To assess ECG parameters as a criterion of safety variables.

  Up to 24 hr after dosing on Day 10 in MD of Part 2

• Safety assessed by ECG parameters: RR interval in Part 1

  To assess ECG parameters as a criterion of safety variables.

  Up to 24 hr after dosing in Part 1

• Safety assessed by ECG parameters: RR interval in Part 2

  To assess ECG parameters as a criterion of safety variables.

  Up to 24 hr after dosing on Day 10 in MD of Part 2

• Safety assessed by ECG parameters: PR interval in Part 1

  To assess ECG parameters as a criterion of safety variables.

  Up to 24 hr after dosing in Part 1

• Safety assessed by ECG parameters: PR interval in Part 2

  To assess ECG parameters as a criterion of safety variables.

  Up to 24 hr after dosing on Day 10 in MD of Part 2

• Safety assessed by ECG parameters: QRS interval in Part 1

  To assess ECG parameters as a criterion of safety variables.

  Up to 24 hr after dosing in Part 1

• Safety assessed by ECG parameters: QRS interval in Part 2

  To assess ECG parameters as a criterion of safety variables.

  Up to 24 hr after dosing on Day 10 in MD of Part 2

• Safety assessed by ECG parameters: QTc interval corrected by Fridericia method (QTcF) in Part 1

  To assess ECG parameters as a criterion of safety variables.

  Up to 24 hr after dosing in Part 1

• Safety assessed by ECG parameters: QTcF in Part 2

  To assess ECG parameters as a criterion of safety variables.

  Up to 24 hr after dosing on Day 10 in MD of Part 2

• Safety assessed by body weight in Part 1

  To assess body weight as a criterion of safety variables

  Up to Day 3 in Part 1

• Safety assessed by body weight in Part 2

  To assess body weight as a criterion of safety variables

  Up to Day 15 in Part 2

• Safety assessed by menstrual cycle in pre-menopausal females

  To assess menstrual cycle as a criterion of safety variables

  Up to an average of two weeks after last dosing

Secondary Outcomes (71)

• Pharmacokinetics (PK) parameter for ESN364 and its metabolite: Area under the concentration-time curve (AUC) from the time of dosing to time 24 h (AUC24) in plasma

  Up to 48 hr after dosing in Part 1 and after first dosing in Part 2

• PK parameter for ESN364 and its metabolite: AUC from the time of dosing extrapolated to time infinity (AUCinf) in plasma

  Up to 48 hr after dosing in Part 1 and after first dosing in Part 2

• PK parameter for ESN364 and its metabolite: Percentage of AUCinf (AUCinf(%extrap)) in plasma

  Up to 48 hr after dosing in Part 1

• PK parameter for ESN364 and its metabolite: AUC from the time of dosing to the last measurable concentration (AUClast) in plasma

  Up to 48 hr after dosing in Part 1

• PK parameter for ESN364 and its metabolite: Maximum concentration (Cmax) in plasma

  Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2

Study Arms (9)

ESN364 dose-1 group in Part 1

EXPERIMENTAL

Healthy male subjects will receive a single dose of ESN364.

Drug: ESN364

ESN364 dose-2 group in Part 1

EXPERIMENTAL

Healthy male subjects will receive a single dose of ESN364.

Drug: ESN364

Placebo group in Part 1

PLACEBO COMPARATOR

Healthy male subjects will receive a single dose of Placebo.

Drug: Placebo

Male ESN364 group in Part 2

EXPERIMENTAL

Healthy male subjects will receive a single dose of ESN364 followed by washout period, then receive once daily dosing of ESN364 for 10 consecutive days at the same dose level.

Drug: ESN364

Pre-menopausal female ESN364 group in Part 2

EXPERIMENTAL

Healthy pre-menopausal female subjects will receive a single dose of ESN364 followed by washout period, then receive once daily dosing of ESN364 for 10 consecutive days at the same dose level.

Drug: ESN364

Post-menopausal female ESN364 group in Part 2

EXPERIMENTAL

Healthy post-menopausal female subjects will receive a single dose of ESN364 followed by washout period, then receive once daily dosing of ESN364 for 10 consecutive days at the same dose level.

Drug: ESN364

Male placebo group in Part 2

PLACEBO COMPARATOR

Healthy male subjects will receive a single dose of Placebo followed by washout period, then receive once daily dosing of Placebo for 10 consecutive days.

Drug: Placebo

Pre-menopausal female placebo group in Part 2

PLACEBO COMPARATOR

Healthy pre-menopausal female subjects will receive a single dose of Placebo followed by washout period, then receive once daily dosing of Placebo for 10 consecutive days.

Drug: Placebo

Post-menopausal female placebo group in Part 2

PLACEBO COMPARATOR

Healthy post-menopausal female subjects will receive a single dose of Placebo followed by washout period, then receive once daily dosing of Placebo for 10 consecutive days.

Drug: Placebo

Interventions

ESN364 DRUG

ESN364 will be administered orally.

ESN364 dose-1 group in Part 1; ESN364 dose-2 group in Part 1; Male ESN364 group in Part 2; Post-menopausal female ESN364 group in Part 2; Pre-menopausal female ESN364 group in Part 2

Placebo DRUG

Placebo will be administered orally.

Male placebo group in Part 2; Placebo group in Part 1; Post-menopausal female placebo group in Part 2; Pre-menopausal female placebo group in Part 2

Eligibility Criteria

• Age: 20 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male subject between 20 to \< 45 years of age, or female subject between 20 to \< 65 years of age.
• Body weight at screening: ≥ 50.0 kg and \< 80.0 kg for male, ≥ 40.0 kg and \< 70.0 kg for female.
• Body mass index (BMI) at screening: range of ≥ 17.6 kg/m2 and \< 26.4 kg/m2 \[BMI = Body weight (kg) ÷ {Body height (m)2}\].

You may not qualify if:

• Subjects who participated or are scheduled to participate in any clinical trials or post-marketing studies within 84 days prior to screening.
• Subject has had previous exposure with ESN364.
• Subject has any clinically significant history of allergic conditions prior to study drug administration.
• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy.
• Subject has contracted pyretic or symptomatic viral, bacterial, or fungal infection within 7 days prior to hospital admission.
• Any deviation from the normal range of blood pressure, pulse, body temperature, or routine 12-lead ECG at screening or on the day of hospital admission.
• Subjects who has any significantly abnormal results of laboratory tests at screening or on the day of hospital admission.
• Subjects who are positive for any of urinary drug abuse test or serology test at screening.
• Subject took a drug or underwent therapy within 2 weeks prior to hospital admission.
• Subjects used a drug or underwent therapy that affects sex hormones within 3 months prior to hospital admission.
• Subjects who had bilateral orchiectomy.
• Subject has used any inducer of metabolism in the 3 months prior to hospital admission.
• Subject has a history of smoking more than 10 cigarettes per day within 3 months prior to screening test.
• Subject consumes, on average, more than approximately 500 mg/day of caffeine
• Subject has a history of consuming more than 30 units of alcoholic beverages per week within 6 months prior to screening or has a history of alcoholism or drug/chemical/ substance abuse within past 2 years prior to screening.

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (1)

Site JP00001

Fukuoka, Japan

Location

MeSH Terms

Interventions

fezolinetant

Study Officials

• Medical Director

  Astellas Pharma Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2018
• First Posted: February 19, 2018
• Study Start: February 22, 2018
• Primary Completion: May 23, 2018
• Study Completion: May 23, 2018
• Last Updated: October 16, 2024

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)