A Study Evaluating Enzalutamide Pharmacokinetics and Pharmacodynamics, and Related Changes After Drug Switch
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: enzalutamide 160mg |
Drug: Enzalutamide
oral
|
| Experimental: HC-1119 To be determined |
Drug: HC1119
oral
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 [From the first dose of the study drug to 24 weeks after dose]
Safety measures
- Percentage of patients with > 50% decrease in prostate specific antigen (PSA) [From the first dose of the study drug to 12 weeks after dose]
Percentage of patients with > 50% decrease in PSA levels from baseline at weeks1,3,5 6, 8, 10, and 12.
Eligibility Criteria
Criteria
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;
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With histologically or cytologically confirmed prostate cancer, without neuroendocrine carcinoma or ductal adenocarcinoma;
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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;
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ECOG performance status ≤1;
-
Laboratory tests must meet the following criteria:
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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);
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Coagulation: INR < 1.5.
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Estimated life expectancy > 6 months.
Exclusion Criteria:
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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;
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Brain metastases;
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Subjects are excluded if any of the following conditions are met:
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Other malignancies within the last 5 years (except for curatively treated non-melanoma skin cancer);
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History of organ transplants;
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Past medical history of seizures, serious CNS diseases, or unexplained coma, family history of seizures, or history of traumatic brain injury;
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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);
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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;
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Other uncontrolled clinical diseases, including but not limited to: persistent or active infections.
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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;
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Treatment with 5α-reductase inhibitors (finasteride, dutasteride), estrogen, or cyproterone within 4 weeks prior to screening;
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Treatment with ketoconazole within 4 weeks prior to screening;
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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.
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Known hypersensitivity to any ingredient of the study drugs (enzalutamide and HC-1119) or similar drugs;
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HIV seropositive;
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History of medication or drug abuse;
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Other conditions that subject is determined by the investigator to be unsuitable for this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Medical Ethics Committee of Hunan Cancer Hospital | Changsha | China |
Sponsors and Collaborators
- Hinova Pharmaceuticals Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HC-1119-02