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

Completed · Phase 1

Conditions studied: Hepatic Impairment, Healthy Volunteers

In brief

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 mild and moderate hepatic impairment compared to healthy female participants with normal hepatic function. This study will also evaluate the safety and tolerability of a single oral dose of fezolinetant in female participants with mild and moderate hepatic impairment and healthy female participants with normal hepatic function.

Key facts

Study ID

NCT04482270

Run by

Astellas Pharma Global Development, Inc.

People needed

26

Starts

2020-09-02

Expected to finish

2021-03-22

Last updated by the study team

2024-10-17

Who can join

Age: 18 and older, up to 75. Sex: female. Healthy volunteers: accepted.

You may qualify if…

• Subject has a Body Mass Index (BMI) range of 18.5 to 36.0 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 IP administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period and for 30 days after IP administration.
• Female subject must not donate ova starting at first dose of IP and throughout the study period and for 30 days after IP administration.
• Subject agrees not to participate in another interventional study while participating in the present study.
• Additional Criterion for Subjects with Hepatic Impairment:
• Subject has mild (Child-Pugh classification Class A, score 5 or 6) or moderate (Child-Pugh classification Class B, score 7 to 9) hepatic impairment.

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 three 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 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 of the inhibitor, whichever is longer, prior to Day -1.
• 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 (excluding chronic hepatitis B and C), bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within one 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 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 is an employee of Astellas, the study-related contract research organizations (CROs) or the clinical unit.
• Subject has creatinine level outside normal limits on Day -1. In such a case, the assessment may be repeated once.
• Additional Criteria for Subjects with Hepatic Impairment:
• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, immunologic, metabolic, dermatologic, psychiatric, renal and/or other major disease or malignancy, not related to current disease state.
• Subject has a history of consuming > 7 units of alcoholic beverages per week within three months prior to screening or has a history of alcoholism 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 a mean pulse < 45 or > 90 beats per minute (bpm); mean systolic blood pressure (SBP) > 160 millimeters of mercury (mmHg); mean diastolic blood pressure (DBP) > 100 mmHg (measurements taken in triplicate after subject has been resting in the supine position for at least five minutes; pulse will be measured automatically) on Day -1. If the mean blood pressure exceeds the limits above, one additional triplicate may be taken.
• Subject has a mean corrected QT interval using Fridericia's formula (QTcF) of > 480 millisecond (msec) on Day -1. If the mean QTcF exceeds the limits above, one additional triplicate electrocardiogram (ECG) may be taken.
• Subject has used any drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and/or opiates) within three 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, unless the positive test is due to prescription drug use that is approved by the principal investigator and sponsor.
• Subject has a positive serology test for hepatitis A virus (HAV) antibodies (immunoglobulin M [IgM]) or antibodies to human immunodeficiency virus (HIV) type 1 and/or type 2 at screening.
• Subject has fluctuating or rapidly deteriorating hepatic function, as indicated by strongly varying or worsening of clinical and/or laboratory signs of hepatic impairment within the screening period (e.g., advanced ascites, infection of ascites, fever, active gastrointestinal bleeding).
• Subject who has had a change in dose regimen of medically required medication(s) in the two weeks prior to screening (permitted concomitant medications) and/or subject for whom dose changes are likely to occur during the study (minor dose changes are allowed in agreement with the sponsor) and/or subject has used nonpermitted concomitant medication(s) in the three weeks prior to admission to the clinical unit (nonpermitted concomitant medications include any known hepatic enzyme-altering agents or compounds known to restrict metabolism, vitamins, hormonal contraceptives, hormone replacement therapy [HRT] and natural and herbal remedies, e.g., St. John's Wort).
• Subject has a presence of a hepatocellular carcinoma, or an acute liver disease caused by an infection or drug toxicity.
• Subject has severe portal hypertension or surgical portosystemic shunts, including transjugular intrahepatic portosystemic shunt.
• Subject has biliary liver cirrhosis, biliary obstruction or other cause of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
• Subject has signs of significant hepatic encephalopathy (hepatic encephalopathy Grade ≥ 2).

Where it is running

• Clinical Research of West Florida, Inc. — Clearwater, Florida, United States
• Clinical Pharmacology of Miami, LLC — Miami, Florida, United States
• Orlando Clinical Research Center — Orlando, Florida, United States
• American Research Corporation — San Antonio, Texas, United States

Full record on ClinicalTrials.gov

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