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

Overview

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).

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 2013

Detailed Description

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.

Interventions

  • Drug: Abiraterone
    • 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.
  • Drug: Prednisone
    • Prednisone will be administered as 5 mg oral tablet twice daily during Cycle 1 Day 8 to Cycle 1 Day 14.

Arms, Groups and Cohorts

  • Experimental: Abiraterone+prednisone (low-fat meal)
    • 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.
  • Experimental: Abiraterone+prednisone (high-fat meal)
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • 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
    • Time Frame: Postdose on Cycle 1 Day 8 to predose on Cycle 2 Day 1
    • 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.

Secondary Measures

  • Maximum Observed Plasma Concentration (Cmax) of Abiraterone
    • Time Frame: Day 7 and Day 14
    • The table below shows mean Cmax of Abiraterone. The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration.
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of Abiraterone
    • Time Frame: Day 7 and Day 14
    • The table below shows median Tmax of Abiraterone. The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
  • Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
    • Time Frame: Day 7 and Day 14
    • 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.

Participating in This Clinical Trial

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

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Janssen-Ortho Inc., Canada
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Janssen-Ortho, Canada Clinical Trial, Study Director, Janssen-Ortho Inc., Canada

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