Comparative Study of Abiraterone Acetate Tablets (I) or ZYTIGA® in Patients With Metastatic Castration-resistant Prostate Cancer

Study Overview
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Brief Summary
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To evaluate whether the efficacy of the abiraterone acetate tablets (I) is comparable to that of the ZYTIGA®) by comparing the serum testosterone concentrations on Day 9 and/or Day 10 after oral administration of the two formulations in patients with metastatic castration-resistant prostate cancer (mCRPC).

Official Title
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A Randomized, Open-Label, Multi-Center, Parallel Controlled Study Comparing the Serum Testosterone Levels in Patients With Metastatic Castration-Resistant Prostate Cancer After Oral Administration of Abiraterone Acetate Tablets (I) or ZYTIGA®

Conditions
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Metastatic Castration-resistant Prostate Cancer (mCRPC)

Intervention / Treatment
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* Drug: Abiraterone Acetate Tablets (I)
* Drug: ZYTIGA®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males, ≥ 18 years old; Histologically or cytologically diagnosed with prostate adenocarcinoma, without neuroendocrine or small cell characteristics, and having metastatic lesions with imaging evidence (such as positive bone scan or metastatic lesions on CT/MRI); Serum testosterone level < 50 ng/dL or 1.7 nmol/L at the screening; subjects who have not undergone bilateral orchidectomy must plan to continue medication throughout the study to maintain therapy with effective GnRH agonist or antagonist; Progression of prostate cancer as confirmed by diagnostic files, meeting one of the conditions for disease progression: 1) Biochemistry evidence of recurrence: continuous 3 rises of PSA (taken a minimum of 1 week apart) from a baseline measurement of at least 2 ng/mL, greater than 50% of the minimum value in 2 rises; 2) Radiographic progression: a clear evidence of new lesion; 2 or more new bone lesions appearing on bone scan; CT or MRI showing lesion progression (RECIST 1.1); ECOG performance status score of ≤ 1; Life expectancy of ≥ 6 months; Major organs are functioning well Exclusion Criteria: History of pituitary or adrenal dysfunction; Have used flutamide within 4 weeks before the first dose of study treatment, and bicalutamide or nilutamide within 6 weeks before the first dose of study treatment; Prior therapy with CYP17 inhibitors (such as abiraterone acetate, ketoconazole, TAK-700, etc.) or investigational drugs or marketed drugs of new androgen receptor antagonists (such as enzalutamide, apalutamide, SHR3680, ODM-201, and proxalutamide); Have received 5-reductase inhibitors (such as finasteride and dutasteride), estrogen, progesterone, any herbal products (such as saw palmetto) that may decrease PSA levels, and radiotherapy within 4 weeks prior to the start of study medication; Have previously received biotherapy or cytotoxic chemotherapy for mCRPC; patients who have completed docetaxel treatment for at least 1 year before enrollment can participate in screening; Prostate cancer with moderate to severe pain symptoms, with a score of > 3 for Question 3 (the worst pain in the last 24 hours, 0-1 point means asymptomatic, 2-3 points mean mild symptoms) of the Brief Pain Inventory-Short Form (BPI-SF); With contraindications to the use of glucocorticoids, such as uncontrolled persistent infections or other conditions; Chronic diseases that require systemic corticosteroid therapy (> 10 mg/day prednisone or equivalent). Patients who have discontinued the administration or reduced the dose to < 10 mg within 14 days prior to the start of study treatment are eligible; Presence of abdominal fistula, gastrointestinal perforation, abdominal abscess, or other abnormal gastrointestinal function within 6 months before the first dose of study treatment, which may affect drug absorption as judged by the investigator; Presence of active heart disease within 6 months prior to the first dose of study treatment, including: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, left ventricular ejection fraction < 50%, and severe arrhythmia requiring treatment or New York Heart Association (NYHA) Class III-IV heart failure; Inability to swallow the whole tablet; Other conditions that make the patient unsuitable for the study as judged by the investigator.

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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Abiraterone Acetate Tablets (I) compared with ZYTIGA®
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abiraterone Acetate Tablets (I)<br> | Drug: Abiraterone Acetate Tablets (I)<br>* Abiraterone Acetate Tablets (I)<br>|
| Active Comparator: ZYTIGA®.<br> | Drug: ZYTIGA®<br>* ZYTIGA®<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum testosterone concentration | Blood Sample tested for Serum Testosterone Levels | Day 9/Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA level | The serum total PSA level | Day 28, Day 56, and Day 84 | 
| PSA-50 response rate | The percentage of subjects with total serum PSA level decreased by 50% from the baseline value. | Day 28, Day 56, and Day 84 | 
| Absolute testosterone concentration | The actual measured serum testosterone concentration. | Day 9/10, Day 28, Day 56, and Day 84 | 
| Testosterone inhibition rate | The percentage of subjects with a serum testosterone concentration of ≤ 1 ng/dL | Day 9/10, Day 28, Day 56, and Day 84 | 
| Steady-state minimum concentration of abiraterone | Defined as the plasma concentration of abiraterone | Day 9/10, Day 28, Day 56, and Day 84 | 
| Cmax, ss | Defined as the steady-state maximum concentration | Day 9 | 
| AUC0-τ | Defined as the area under the curve within the dosing interval at steady state | Day 9 | 
| Cmin, ss | Defined as the steady-state minimum concentration | Day 9 | 
| Cav, ss | Defined as the mean blood drug concentration during the dosing interval at steady state | Day 9 |