A Study Evaluating Enzalutamide Pharmacokinetics and Pharmacodynamics, and Related Changes After Drug Switch

Study Overview
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Brief Summary
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This is a study for evaluating enzalutamide pharmacokinetics and pharmacodynamics, and related changes after drug switch in Chinese patients with metastatic castration-resistant prostate cancer. The study primary objective is to evaluate the pharmacokinetic characteristics of enzalutamide in Chinese patients with mCRPC.

Official Title
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A Clinical Study for Evaluating Enzalutamide Pharmacokinetics and Pharmacodynamics, and Related Changes After Drug Switch in Chinese Patients With Metastatic Castration-Resistant Prostate Cancer

Conditions
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Metastatic Castration Resistant Prostate Cancer

Intervention / Treatment
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* Drug: Enzalutamide
* Drug: HC1119


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily participated in the study, with understanding of and will to comply with relevant study procedures and signed informed consent form; Chinese male, ≥ 18 years old; With histologically or cytologically confirmed prostate cancer, without neuroendocrine carcinoma or ductal adenocarcinoma; With evidence of metastatic lesions (such as bone scan and CT/MRI); Patients with relapsed, refractory, or progressive disease despite castration (surgery or chemical) or combined androgen deprivation therapy. (Progressive disease is defined as 1 or more of the following 3 criteria: PSA progression: A minimum of 3 rising PSA values with an interval of at least 1 week between determinations, resulting in a final value higher than 50% of the minimum, with a starting PSA value > 2 ng/ml; Soft tissue disease progression as defined by RECIST 1.1; Bone progression as defined by PCWG2 with 2 or more new lesions on bone scan); Castrate levels of testosterone (< 50 ng/dl) at screening; bilateral orchiectomy or ongoing androgen deprivation therapy with effective GnRH analogues; ECOG performance status ≤1; Laboratory tests must meet the following criteria: Routine Blood Test: hemoglobin (Hb) ≥ 90g/L (no blood transfusions within 14 days prior to screening); absolute neutrophil count (ANC) ≥ 1.5 x 109/L; Platelet Count (PLT) ≥ 80 x 109/L; Blood Biochemistry: creatinine (Cr) ≤ 2 x upper limit of normal (ULN), or Cr > 2 x ULN but the calculated CrCl ≥ 60 ml/min; bilirubin (BIL) ≤2 x ULN; alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤2.5 x ULN (or ≤ 5.0 x ULN for patients with liver metastases); Coagulation: INR < 1.5. Estimated life expectancy > 6 months. Exclusion Criteria: Participated in other clinical drug trials within 1 month prior to screening, or the occurrence of toxicity caused by previous treatments that has not been relieved to ≤ Grade 2 toxicity (according to CTCAE 4.03) prior to enrollment; Brain metastases; Subjects are excluded if any of the following conditions are met: Other malignancies within the last 5 years (except for curatively treated non-melanoma skin cancer); History of organ transplants; Past medical history of seizures, serious CNS diseases, or unexplained coma, family history of seizures, or history of traumatic brain injury; Uncontrolled hypertension (systolic ≥ 160 mmHg or diastolic ≥ 100 mmHg) or other serious cardiovascular diseases. (Patients with a history of hypertension is eligible if his blood pressure is controlled with antihypertensives); Significant GI dysfunction which may affect the intake, transport, or absorption of drug (such as inability to swallow, chronic diarrhea, and bowel obstruction, etc.), or patients with complete gastrectomy; Other uncontrolled clinical diseases, including but not limited to: persistent or active infections. Subjects are excluded if any of the following conditions regarding past or concomitant medication are met: Medications that lower the seizure threshold must be used during the trial; Treatment with 5α-reductase inhibitors (finasteride, dutasteride), estrogen, or cyproterone within 4 weeks prior to screening; Treatment with ketoconazole within 4 weeks prior to screening; Previously treated with investigational or approved medications that inhibit testosterone synthesis (such as abiraterone acetate, TAK-683, and TAK-448) or target testosterone receptors (such as SHR3680, proxalutamide, and ARN509), except for bicalutamide and flutamide. Known hypersensitivity to any ingredient of the study drugs (enzalutamide and HC-1119) or similar drugs; HIV seropositive; History of medication or drug abuse; Other conditions that subject is determined by the investigator to be unsuitable for this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: enzalutamide<br>160mg | Drug: Enzalutamide<br>* oral<br>|
| Experimental: HC-1119<br>To be determined | Drug: HC1119<br>* oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum drug concentration(Cmax) |  | From the first dose of the study drug to 12 weeks after dose | 
| Time of maximum drug concentration(Tmax) |  | From the first dose of the study drug to 12 weeks after dose | 
| Area under curve from time 0 to 24h (AUC0-24h) |  | From the first dose of the study drug to 12 weeks after dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum drug concentration(Cmax) |  | From 13 weeks to 24 weeks after dose | 
| Time of maximum drug concentration(Tmax) |  | From 13 weeks to 24 weeks after dose | 
| Area under curve from time 0 to 24h (AUC0-24h) |  | From 13 weeks to 24 weeks after dose | 
| Number of patients with adverse events | Safety measures | From the first dose of the study drug to 24 weeks after dose | 
| Percentage of patients with > 50% decrease in prostate specific antigen (PSA) | Percentage of patients with > 50% decrease in PSA levels from baseline at weeks1,3,5 6, 8, 10, and 12. | From the first dose of the study drug to 12 weeks after dose |