A Study to Investigate the Effect of Renal Impairment on the Safety and Tolerability of Fezolinetant Compared to Participants With Normal Renal Function

NCT04476849 | Completed Phase 1 FDA Drug

• 1 other identifier: 2693-CL-0008
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics of a single oral dose of fezolinetant and ES259564 (fezolinetant metabolite) in female participants with varying levels of renal impairment (mild, moderate and severe) compared to healthy female participants with normal renal function. This study will also evaluate the safety and tolerability of a single oral dose of fezolinetant in female participants with varying levels of renal impairment (mild, moderate and severe) and healthy female participants with normal renal function. Renal function will be measured by estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease (MDRD) formula: Mild (eGFR 60 to \< 90 mL/min per 1.73 m\^2) renal impairment; moderate (eGFR 30 to \< 60 mL/min per 1.73 m\^2) renal impairment, severe (eGFR \< 30 mL/min per 1.73 m\^2) renal impairment and not on hemodialysis and normal (eGFR ≥ 90 mL/min per 1.73 m\^2) renal function.

Conditions

Healthy Volunteers; Renal Impairment

Keywords

Healthy volunteers; Pharmacokinetics; ES259564; Renal impairment; fezolinetant

Outcome Measures

Primary Outcomes (7)

• Pharmacokinetics (PK) of Fezolinetant in Plasma: Area Under the Concentration-time Curve (AUC) From the Time of Dosing Extrapolated to Time Infinity (AUCinf)

  AUCinf will be recorded from the PK plasma samples collected.

  Up to 5 days

• PK of Fezolinetant in Plasma: AUC From the Time of Dosing to the Last Measurable Concentration (AUClast)

  AUClast will be recorded from the PK plasma samples collected.

  Up to 5 days

• PK of Fezolinetant in Plasma: Maximum Concentration (Cmax)

  Cmax will be recorded from the PK plasma samples collected.

  Up to 5 days

• PK of Fezolinetant in Plasma: Apparent Clearance (CL/F)

  CL/F will be recorded from the PK plasma samples collected.

  Up to 5 days

• PK of Fezolinetant Metabolite ES259564 in Plasma: AUCinf

  AUCinf will be recorded from the PK plasma samples collected.

  Up to 5 days

• PK of Fezolinetant Metabolite ES259564 in Plasma: AUClast

  AUClast will be recorded from the PK plasma samples collected.

  Up to 5 days

• PK of Fezolinetant Metabolite ES259564 in Plasma: Cmax

  Cmax will be recorded from the PK plasma samples collected.

  Up to 5 days

Secondary Outcomes (4)

• Number of Participants With Adverse Events (AEs)

  Up to 14 days

• Number of Participants With Laboratory Value Abnormalities and/or Adverse Events (AEs)

  Up to 14 days

• Number of Participants With Vital Sign Abnormalities and/or Adverse Events (AEs)

  Up to 14 days

• Number of Participants With 12-lead Electrocardiogram (ECG) Abnormalities and/or Adverse Events (AEs)

  Up to 14 days

Study Arms (4)

Fezolinetant: Mild renal impairment

EXPERIMENTAL

Participants will receive a single oral dose of fezolinetant under fasting conditions on Day 1.

Drug: fezolinetant

Fezolinetant: Moderate renal impairment

EXPERIMENTAL

Participants will receive a single oral dose of fezolinetant under fasting conditions on Day 1.

Drug: fezolinetant

Fezolinetant: Severe renal impairment

EXPERIMENTAL

Participants will receive a single oral dose of fezolinetant under fasting conditions on Day 1.

Drug: fezolinetant

Fezolinetant: Normal renal function

EXPERIMENTAL

Participants will receive a single oral dose of fezolinetant under fasting conditions on Day 1.

Drug: fezolinetant

Interventions

fezolinetant DRUG

Oral

Also known as: ESN364

Fezolinetant: Mild renal impairment; Fezolinetant: Moderate renal impairment; Fezolinetant: Normal renal function; Fezolinetant: Severe renal impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has a Body Mass Index (BMI) range of 18.5 to 40 kg/m\^2, inclusive and weighs at least 50 kg at screening.
• Female subject is not pregnant and at least one of the following conditions apply:
• Not a woman of childbearing potential (WOCBP)
• WOCBP who agrees to follow the contraceptive guidance for at least 30 days prior to day -1 through at least 30 days after final IP administration
• Female subject must agree not to breastfeed starting at screening and throughout the study period and for 30 days after final IP administration.
• Female subject must not donate ova starting from administration of IP and throughout the study period and for 30 days after final IP administration.
• Subject has normal renal function as defined by estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease (MDRD) formula ≥ 90 milliliters per minute (mL/min) per 1.73 m\^2 or subject has varying degrees of chronic kidney disease as defined by the National Kidney Foundation and by eGFR:
• to \< 90 mL/min per 1.73 m\^2 for subject with mild renal impairment
• to \< 60 mL/min per 1.73 m\^2 for subject with moderate renal impairment
• \< 30 mL/min per 1.73 m\^2 and not on hemodialysis for subject with severe renal impairment
• Subject has adequate venous access.
• Subject agrees not to participate in another interventional study while participating in the present study.

You may not qualify if:

• Subject has received any investigational therapy within 28 days or five half-lives, whichever is longer, prior to Day -1.
• Subject has any condition which makes the subject unsuitable for study participation.
• Female subject who has been pregnant within six months prior to screening or breastfeeding within 3 months prior to screening.
• Subject has a known or suspected hypersensitivity to fezolinetant or any components of the formulation used.
• Subject has had previous exposure with fezolinetant.
• Subject has any of the liver function tests (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], and total bilirubin \[TBL\]) ≥ 1.5 × the 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 IP administration.
• 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 smoked, used tobacco-containing products and nicotine or nicotine-containing products (e.g., electronic vapes) within six months prior to screening or the subject tests positive for cotinine at screening or on Day -1.
• Subject has a history of consuming \> 7 units of alcoholic beverages per week within six months prior to screening or has a history of alcoholism three months prior to screening or drug/chemical/ substance abuse within one year 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 inducer of cytochrome P450 (CYP) 1A2 in the three months prior or inhibitors of CYP 1A2 in the two weeks or five half-lives, 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 seven 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.
• Additional criteria for subjects with renal impairment:

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (7)

National Institute of Clinical Research

Garden Grove, California, 92844, United States

Location

Inland Empire Clinical Trials, LLC

Rialto, California, 92377, United States

Location

Clinical Research of West Florida, Inc.

Clearwater, Florida, 33765, United States

Location

Accel Research Sites - DeLand Clinical Research Unit

DeLand, Florida, 32720, United States

Location

Clinical Pharmacology of Miami, LLC

Miami, Florida, 33014-3616, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Prism research, LLC

Saint Paul, Minnesota, 55114, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

fezolinetant

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Executive Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2020
• First Posted: July 20, 2020
• Study Start: August 10, 2020
• Primary Completion: March 6, 2022
• Study Completion: March 11, 2022
• Last Updated: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)