Prostate Cancer
Conditions
Keywords
Prostate Cancer, ESN364, fezolinetant, VEOZAH™, Pharmacokinetics, Healthy Volunteer
Brief summary
Hormone therapy, or androgen deprivation therapy (ADT) is a standard way to treat prostate cancer. It works by reducing the amount of testosterone in the body. One of the side effects of hormone therapy is hot flashes. There is an unmet medical need to treat hot flashes in men undergoing hormone therapy for prostate cancer. This study will help researchers understand if hormone therapy (enzalutamide, apalutamide or bicalutamide) affects the way fezolinetant is processed by the body in men with prostate cancer. The main aim of this study is checking levels of fezolinetant in the blood over time to learn how long it takes to get into the blood, spread through the body and be cleared from the body. Men with prostate cancer or healthy men can take part. The men with prostate cancer will have already been taking standard hormone therapy (enzalutamide, apalutamide or bicalutamide) for a few months. Men cannot take part if they have recently had major surgery, have had an infection, have a heart condition, or have gut problems. Men with prostate cancer cannot take part if they have other cancers, have recently had certain treatments for prostate cancer, have certain ongoing medical conditions or any chronic disease. This includes any liver problems. There will be 4 groups in this study: Group 1 - men with prostate cancer who are taking enzalutamide will be given fezolinetant. Group 2 - men with prostate cancer who are taking apalutamide will be given fezolinetant. Group 3 - men with prostate cancer who are taking bicalutamide will be given fezolinetant. Group 4 - healthy men will only be given fezolinetant. The men taking part in the study will stay in the clinic for a few days and nights. The men will have nothing to eat or drink for several hours before taking 1 tablet of fezolinetant. Blood samples will be taken and health checks done. During their stay, the men with prostate cancer will continue to be given the standard dose of their hormone therapy. All the men in the study will continue to have regular health checks and will be asked if they have any medical problems. After the men leave the clinic, they will return to the clinic about a week later for a final health check.
Interventions
DRUGfezolinetant
oral
DRUGenzalutamide
oral
DRUGapalutamide
oral
DRUGbicalutamide
oral
Per local product label
Sponsors
Astellas Pharma Global Development, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
50 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant is born male, inclusive of all gender ideologies. * Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 30 days after final fezolinetant administration. * Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 30 days after final study intervention administration. * Male participant must not donate sperm during the treatment period and for 30 days after final study intervention administration. * Participant agrees not to participate in another interventional study while participating in the present study. * Participant has a body mass index (BMI) range of 18.5 to 30.0 kg/m\^2 inclusive and weighs at least 50 kg at screening. Inclusion Criteria for Participants with Prostate Cancer: * Participant is diagnosed with histologically or cytologically confirmed adenocarcinoma of the prostate. * Participant must be receiving concurrent gonadotropin-releasing hormone (GnRH) agonist or antagonist therapy for a minimum of 3 months prior to study intervention on day 1 and be planning to continue on the therapy for the duration of the study. * Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at screening. * Participant is receiving concurrent and stable enzalutamide, apalutamide or bicalutamide for at least 3 months prior to study intervention on day 1, which must be continued throughout the study. * Participant has at least 6-month life expectancy. Inclusion Criteria for Healthy Participants: * Participant is healthy and has no clinically significant medical conditions based on the physical examination, electrocardiograms (ECGs) and protocol-defined clinical laboratory tests at screening or on day -1.
Exclusion criteria
* Participant has had major surgery (e.g., requiring general anesthesia) within 90 days before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study or within 5 half-lives (approximately 2 days) after the last dose of study drug administration or end-of-study visit (ESV), whichever is longer. * Participant has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 28 days prior to day -1. * Participant has a history of drug or alcohol abuse according to Diagnostic and Statistical Manual (American Psychiatric Association), Fifth Edition (DSM-5) criteria within 2 years before screening. * Participant has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease or a family history of long QT syndrome. * Participant has a gastrointestinal disorder affecting absorption. * Participant has present exposure or history of participation in a study of the study intervention (fezolinetant) or previous exposure to fezolinetant within 28 days prior to day -1. * Participant has received any investigational therapy within 90 days or 5 half-lives, whichever is longer, prior to screening * Participant tests positive for alcohol at screening or on day -1. * Participant has a positive serology test for hepatitis A virus (HAV) antibodies (immunoglobulin M (IgM)), hepatitis B (HBc) antibodies, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies or antibodies to human immunodeficiency virus (HIV) type 1 and/or type 2 at screening. * Participant tests positive for drugs of abuse (e.g., amphetamines, barbiturates, benzodiazepines, cocaine, opiates and cannabinoids) at screening or on day -1. * Participant has a positive result for Severe Acute Respiratory Syndrome Coronavirus-2 (novel coronavirus causing COVID-19 disease) (SARS-CoV-2) test at screening or on day -1. * Participant has creatinine \> 1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m\^2 using the Modification of Diet in Renal Disease formula at the screening visit. * Participant has active liver disease, jaundice, or elevated liver aminotransferase (ATs) (alanine aminotransferase (ALT) or aspartate aminotransferase (AST)), elevated total bilirubin (TBL) or direct bilirubin (DBL), or elevated alkaline phosphatase (ALP) at screening. A participant with mildly elevated ALT or AST up to \< 1.5 x ULN can be enrolled if TBL and DBL are normal. Participant with mildly elevated ALP (up to \< 1.5 x ULN) can be enrolled if cholestatic liver disease is excluded and no cause other than fatty liver is diagnosed. Participant with Gilbert's syndrome with elevated TBL may be enrolled as long as DBL, hemoglobin and reticulocytes are normal. * Participant has any condition which makes the participant unsuitable for study participation. * Participant regularly consumes \> 200 mg of caffeine per day. * Participant has smoked, used tobacco-containing products or nicotine or nicotine-containing products (e.g., electronic vapes) within 6 months prior to screening or the participant tests positive for cotinine at screening or day -1. * Participant 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. * Participant has a history of consuming \> 10 units of alcoholic beverages per week within 3 months prior to screening (note: 1 unit = 350 mL of beer, 150 mL of wine, 45 mL of spirits/hard liquor). * Participant has used any drugs of abuse (e.g., amphetamines, barbiturates, benzodiazepines, cocaine, opiates and cannabinoids) within 3 months prior to day -1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of Fezolinetant in plasma: Maximum Concentration (Cmax) | Up to Day 3 | Cmax will be recorded from the PK plasma samples collected. |
| PK of Fezolinetant in plasma: Area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf) | Up to Day 3 | AUCinf will be recorded from the PK plasma samples collected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Adverse Events (AEs) | Up to Day 12 | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. 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 study intervention. This includes events related to the comparator, if applicable, and events related to the (study) procedures. |
| Number of participants with laboratory value abnormalities and/or adverse events (AEs) | Up to Day 12 | Number of participants with potentially clinically significant laboratory values. |
| Number of participants with vital sign abnormalities and/or adverse events (AEs) | Up to Day 12 | Number of participants with potentially clinically significant vital sign values. |
| Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs) | Up to Day 12 | Number of participants with potentially clinically significant ECG values. |
| PK of metabolite ES259564 in plasma: Cmax | Up to Day 3 | Cmax will be recorded from the PK plasma samples collected. |
| PK of metabolite ES259564 in plasma: AUCinf | Up to Day 3 | AUCinf will be recorded from the PK plasma samples collected. |
| Metabolite ES259564 to parent ratio for AUCinf | Up to Day 3 | Metabolite ES259564 AUCinf and Fezolinetant AUCinf will be recorded from the PK plasma samples collected. |
Contacts
CONTACTAstellas Pharma Global Development, Inc.
STUDY_DIRECTORMedical Monitor
Astellas Pharma Global Development, Inc.
Outcome results
None listed