A Study to Determine the Short-Term Safety of Continuous Dosing of Abiraterone Acetate and Prednisone in Modified Fasting and Fed States to Patients With Metastatic Castration-Resistant Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to establish the safety profile of oral (by mouth) abiraterone acetate and oral prednisone following short-term administration after standardized low-fat or high-fat meals to patients with metastatic (spreading) castration-resistant prostate cancer (mCRPC).

Detailed Description
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This is a multicenter, open-label study of 24 (up to a total of 28) men to assess the short-term safety of oral abiraterone acetate 1 g and oral prednisone 5 mg twice daily administered in the modified fasted state and after meals of various fat contents. All patients will take daily abiraterone acetate for the first 7 days in the modified fasted state (no food for 2 hours before and 1 hour after the dose). In Cohort 1, up to 6 evaluable patients will take abiraterone acetate daily for 7 days after a standardized low-fat meal from Cycle 1 Day 8 to Cycle 1 Day 14; or, in Cohort 2, up to 6 evaluable patients will take abiraterone acetate daily for 7 days after a standardized high-fat meal from Cycle 1 Day 8 to Cycle 1 Day 14. All patients will then continue to take abiraterone acetate daily in the modified fasted state starting on Cycle 1 Day 15 until disease progression. Toxicity related to dosing after the low-fat or high-fat meals is defined as Grade 3 or higher AEs of special interest; or Grade 3 or higher serious adverse events (SAEs) that occur during the food safety evaluation period. Cohort 2 may be expanded to a total of 18 evaluable patients if deemed to be safe. Decisions regarding the escalation of cohort or expansion of cohorts will be made by a study evaluation team. Pharmacokinetic evaluation for each cohort will be performed on Cycle 1 Days 7 and 14 at predose and multiple timepoints postdose over 24 hours; Cycle 1 Days 8 and 11 at 2 hours following abiraterone acetate dose administration. Abiraterone acetate, 1 g (four 250-mg tablets) orally (taken by mouth) once daily. Patients may take abiraterone acetate until progression of clinical disease. Prednisone, 5 mg, orally, twice a day.

Official Title
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An Open-Label Study to Determine the Short-Term Safety of Continuous Dosing of Abiraterone Acetate and Prednisone in Modified Fasting and Fed States to Subjects With Metastatic Castration-Resistant Prostate Cancer

Conditions
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Prostate Neoplasms, Prostate Cancer

Intervention / Treatment
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* Drug: Abiraterone
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adenocarcinoma of the prostate Metastatic disease documented by bone, computed tomography (CT) or magnetic resonance imaging (MRI) scan Surgical or medical castration with testosterone less than 50 ng/dL (< 2.0 nM) Prostate-specific antigen (PSA) or radiographic progression documented by assessments specified in study protocol Platelets >100,000/µl Hemoglobin >=9.0 g/dL Liver function tests (LFTs): Serum bilirubin < 1.5 x ULN; AST or ALT < 2.5 x ULN; Eastern Cooperative Oncology Group (ECOG) status score of <=2 Exclusion Criteria: Small cell carcinoma of the prostate Known brain metastasis, chronic liver disease with elevated LFTs Prior cytotoxic chemotherapy for metastatic prostate cancer Treatment of prostate cancer within 30 days of Day 1 Cycle 1 with surgery, radiation, chemotherapy or immunotherapy Use of investigational drug within 30 days of Day 1 Cycle 1 or current enrollment in an investigational drug or device study Recent history of ischemic heart disease, Electrocardiogram (ECG) abnormalities or atrial fibrillation Active infection or other medical condition that would make prednisone (corticosteroid) use contraindicated Chronic medical condition requiring a higher dose of corticosteroid than prednisone 5 mg twice daily

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abiraterone+prednisone (low-fat meal)<br>Participants will receive abiraterone acetate at a starting dose of 1,000 milligram (mg) once daily for 7 days post 30-minutes of a standardized low-fat meal from Cycle 1 Day 8 to Cycle 1 Day 14. Prednisone will be administered as 5 mg oral tablet twice daily during Cycle 1 Day 8 to Cycle 1 Day 14. | Drug: Abiraterone<br>* Participants will receive abiraterone acetate at a starting dose of 1,000 mg once daily for 7 days post 30-minutes of a standardized low-fat meal and high-fat meal from Cycle 1 Day 8 to Cycle 1 Day 14.<br>Drug: Prednisone<br>* Prednisone will be administered as 5 mg oral tablet twice daily during Cycle 1 Day 8 to Cycle 1 Day 14.<br>|
| Experimental: Abiraterone+prednisone (high-fat meal)<br>Participants will receive abiraterone acetate at a starting dose of 1,000 mg once daily for 7 days post 30-minutes of a standardized high-fat meal from Cycle 1 Day 8 to Cycle 1 Day 14. Prednisone will be administered as 5 mg oral tablet twice daily during Cycle 1 Day 8 to Cycle 1 Day 14. | Drug: Abiraterone<br>* Participants will receive abiraterone acetate at a starting dose of 1,000 mg once daily for 7 days post 30-minutes of a standardized low-fat meal and high-fat meal from Cycle 1 Day 8 to Cycle 1 Day 14.<br>Drug: Prednisone<br>* Prednisone will be administered as 5 mg oral tablet twice daily during Cycle 1 Day 8 to Cycle 1 Day 14.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Grade 3 or Higher Adverse Events (AEs) of Special Interest or Grade 3 or Higher Serious AEs Due to Study Medication | AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. | Postdose on Cycle 1 Day 8 to predose on Cycle 2 Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Abiraterone | The table below shows mean Cmax of Abiraterone. The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. | Day 7 and Day 14 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Abiraterone | The table below shows median Tmax of Abiraterone. The Tmax is defined as actual sampling time to reach maximum observed analyte concentration. | Day 7 and Day 14 | 
| Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) | The table below shows mean AUC24h. The Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. | Day 7 and Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Food Safety, Metastatic castration-resistant prostate cancer, CRPC, Abiraterone Acetate, Prednisone