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
Overview
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 22
- Locations
- 1
- Primary Endpoint
- Pharmacokinetics (PK) of fezolinetant in plasma: Area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf)
Overview
Brief Summary
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.
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
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).
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 -
- •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 -
- •Subject has any clinically significant abnormality following the physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or on day -
Arms & Interventions
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.
Intervention: fezolinetant - test formulation (Drug)
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.
Intervention: fezolinetant - reference formulation (Drug)
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.
Intervention: fezolinetant - test formulation (Drug)
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.
Intervention: fezolinetant - reference formulation (Drug)
Outcomes
Primary Outcomes
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
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
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
Secondary Outcomes
- Number of participants with vital sign abnormalities and/or adverse events (AEs)(Up to 19 days)
- Number of participants with laboratory value abnormalities and/or adverse events (AEs)(Up to 19 days)
- Number of participants with Adverse Events (AEs)(Up to 19 days)