A Study to Assess Bioequivalence of Fezolinetant Formulations in Healthy Female Participants

February 10, 2022 updated by: Astellas Pharma Global Development, Inc.

A Phase 1 Crossover Study to Assess the Bioequivalence of Fezolinetant Following a Single Dose of Fezolinetant (Test Formulation) Compared to a Single Dose of Fezolinetant Phase 3 Formulation (Reference Formulation) in Healthy Female Subjects

The purpose of this study is to assess the bioequivalence of a single dose of fezolinetant test formulation compared to a single dose of fezolinetant reference formulation under fasting conditions. This study will also evaluate the safety and tolerability of a single dose of fezolinetant test formulation and a single dose of fezolinetant reference formulation.

Study Overview

Detailed Description

Each participant will participate in 2 study periods separated by a washout of at least 5 days between investigational product (IP) administrations. Participants will be randomized to 1 of 2 sequences: either fezolinetant test formulation followed by fezolinetant reference formulation or fezolinetant reference formulation followed by fezolinetant test formulation. Participants will be admitted to the clinical unit on day -1 and will be residential for 2 study periods for a total of 10 days/9 nights. Premenopausal female participants will be admitted to the clinical unit during days 1 to 3 of their menstrual cycle. Participants will receive a single dose of test formulation or reference formulation under fasting conditions on day 1 of each period i.e., days 2 to 4 (period 1) and days 7 to 9 (period 2) of their menstrual cycle for premenopausal female participants. Participants are to remain semirecumbent and avoid lying on either the left or right side for 4 hours postdose. Pharmacokinetic samples will be collected predose on day 1 of each period and at multiple time points postdose. Standard safety and tolerability assessments will be conducted. Participants will be discharged from the clinical unit on day 4 of period 2 on the condition that all required assessments have been performed and that there are no medical reasons for a longer stay in the clinical unit.

The study will be completed with an end-of-study visit (ESV). The ESV will take place 5 to 9 days after discharge from period 2 or at early discontinuation from the study.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Baltimore, Maryland, United States, 21225
        • Parexel Early Phase Clinical Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Subject is a healthy female subject.
  • Subject has a body mass index (BMI) range of 18.5 to 34.0 kg/m^2, inclusive and weighs at least 50 kg at screening.
  • Postmenopausal female subjects only: Subject is postmenopausal according to 1 of the following criteria:

    • Spontaneous amenorrhea for ≥ 12 consecutive months
    • Spontaneous amenorrhea for ≥ 6 months with biochemical criteria of menopause (follicle-stimulating hormone [FSH] > 40 IU/L); or
    • Having had bilateral oophorectomy ≥ 6 weeks prior to the screening visit (with or without hysterectomy)
  • Subject agrees not to participate in another interventional study while participating in the present study.
  • Premenopausal female subjects only: Subject has had a regular menstrual cycle (from 25 to 31 days ± 3 days) for 3 months prior to starting the IP administration.
  • Premenopausal female subjects only: Subject is not pregnant and at least meets 1 of the following criteria:

    • If the subject is not of childbearing potential: Subject has lost fertility permanently by surgery excluding oophorectomy (e.g., hysterectomy, bilateral salpingectomy).
    • If the subject is a woman of childbearing potential (WOCBP): Subject agrees to follow the contraceptive guidance from the time of providing informed consent through at least 30 days after the final IP administration. However, if the subject's partner has lost fertility by surgery (vasectomy or bilateral orchiectomy) etc., confirmed with documentation of both the procedure and absence of sperm, it is not necessary to implement contraceptive methods.

Note: If absence of sperm cannot be confirmed in the subject's partner who received a vasectomy, an alternative contraceptive method must be used.

  • Premenopausal female subjects only: Subject agrees not to breastfeed or donate ova from the time of providing informed consent until 30 days after the last IP administration.

Exclusion Criteria:

  • Subject has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening.
  • Subject has any condition which makes the subject unsuitable for study participation.
  • Subject has a known or suspected hypersensitivity to fezolinetant or any components of the formulations used.
  • Subject has had previous exposure with fezolinetant.
  • Subject has any of the liver function tests (alkaline phosphatase [ALP], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and total bilirubin [TBL]) > 1.5 × upper limit of normal (ULN) on day -1. In such a case, the assessment may be repeated once.
  • Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to first investigational product (IP) 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/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to day -1.
  • Subject has any clinically significant abnormality following the physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or on day -1.
  • Subject has a mean pulse < 45 or > 90 bpm or hypertension as defined by a systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 80 mmHg based on the average of 3 readings on at least 2 different occasions during the screening period.
  • Subject has a mean corrected QT interval using Fridericia's formula (QTcF) of > 470 msec on day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG may be taken.
  • Subject has used any prescribed or nonprescribed drugs (including vitamins, contraception [oral, injectable, implantable or transdermal] and natural and herbal remedies, e.g., St. John's Wort) in the 2 weeks prior to first IP administration and for hormone replacement therapy (HRT) in the 8 weeks prior to first IP administration, except for occasional use of acetaminophen (up to 2 g/day) and topical dermatological products, including corticosteroid products.
  • Subject has smoked, used tobacco-containing products and nicotine or nicotine-containing products (e.g., electronic vapes) within 6 months prior to screening.
  • Subject has a history of consuming > 7 units of alcoholic beverages per week within 6 months prior to screening or has a history of alcoholism or drug/chemical/substance abuse within 2 years prior to screening (note: 1 unit = 12 ounces of beer, 4 ounces of wine, 1 ounce of spirits/hard liquor) or the subject tests positive for alcohol at screening or on day -1.
  • Subject has used any drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and/or opiates) within 3 months prior to day -1 or the subject tests positive for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates) at screening or on day -1.
  • Subject has used any inducer of cytochrome P450 (CYP) 1A2 in the 3 months prior or inhibitors of CYP 1A2 in the 2 weeks or 5 half-lives of the inhibitor, whichever is longer, prior to day -1.
  • Subject has had significant blood loss, donated ≥ 1 unit (450 mL) of whole blood or donated plasma within 7 days prior to day -1 and/or received a transfusion of any blood or blood products within 60 days.
  • Subject has a positive serology test for hepatitis A virus antibodies (immunoglobulin M), hepatitis B core antibodies, hepatitis B surface antigen, hepatitis C virus antibodies or antibodies to human immunodeficiency virus type 1 and/or type 2 at screening.
  • Subject is an employee of Astellas, the study-related contract research organizations (CROs) or the clinical unit.
  • Premenopausal female subjects only: Subject has been pregnant within 6 months or has been breastfeeding within 3 months prior to the screening visit.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fezolinetant: Test Formulation then Reference Formulation
Participants will receive a single oral dose of fezolinetant test formulation on day 1 of study period 1. After a washout of 5 days the participants will receive a single oral dose of fezolinetant reference formulation on day 1 of study period 2.
Administered orally
Other Names:
  • ESN364
Administered orally
Other Names:
  • ESN364
Experimental: Fezolinetant: Reference Formulation then Test Formulation
Participants will receive a single oral dose of fezolinetant reference formulation on day 1 of study period 1. After a washout of 5 days the participants will receive a single oral dose of fezolinetant test formulation on day 1 of study period 2.
Administered orally
Other Names:
  • ESN364
Administered orally
Other Names:
  • ESN364

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics (PK) of fezolinetant in plasma: Area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf)
Time Frame: Up to 72 hours postdose in each study period
AUCinf will be recorded from the pharmacokinetic (PK) plasma samples collected
Up to 72 hours postdose in each study period
Pharmacokinetics (PK) of fezolinetant in plasma: Area under the concentration-time curve (AUC) from the time of dosing to the last measurable concentration (AUClast)
Time Frame: Up to 72 hours postdose in each study period
AUClast will be recorded from the pharmacokinetic (PK) plasma samples collected
Up to 72 hours postdose in each study period
Pharmacokinetics (PK) of fezolinetant in plasma: Maximum concentration (Cmax)
Time Frame: Up to 72 hours postdose in each study period
Cmax will be recorded from the pharmacokinetic (PK) plasma samples collected
Up to 72 hours postdose in each study period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with Adverse Events (AEs)
Time Frame: Up to 19 days
An AE is any untoward medical occurrence in a subject administered an investigatonal product (IP), and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP whether or not considered related to the IP.
Up to 19 days
Number of participants with laboratory value abnormalities and/or adverse events (AEs)
Time Frame: Up to 19 days
Number of participants with potentially clinically significant laboratory values.
Up to 19 days
Number of participants with vital sign abnormalities and/or adverse events (AEs)
Time Frame: Up to 19 days
Number of participants with potentially clinically significant vital sign values.
Up to 19 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 20, 2020

Primary Completion (Actual)

February 21, 2021

Study Completion (Actual)

February 26, 2021

Study Registration Dates

First Submitted

February 18, 2020

First Submitted That Met QC Criteria

February 18, 2020

First Posted (Actual)

February 20, 2020

Study Record Updates

Last Update Posted (Actual)

February 23, 2022

Last Update Submitted That Met QC Criteria

February 10, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Other Study ID Numbers

  • 2693-CL-0010

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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