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

Phase 2

Completed

• Conditions: Prostate Neoplasms; Prostate Cancer
• Interventions: Drug: Abiraterone; Drug: Prednisone

• Registration Number: NCT01424930
• Lead Sponsor: Janssen-Ortho Inc., Canada

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2011-08-26
• Study First Submitted QC: 2011-08-26
• Study First Posted: 2011-08-29
• Study Start: 2011-10
• Primary Completion: 2013-04
• Study Completion: 2013-05
• Results First Submitted: 2014-03-28
• Results First Submitted QC: 2014-03-28
• Results First Posted: 2014-04-30
• Status Verified: 2014-07
• Last Update Submitted: 2014-07-14
• Last Update Posted: 2014-07-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 25

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Abiraterone+prednisone (low-fat meal)	Abiraterone	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.
Abiraterone+prednisone (high-fat meal)	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 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.
Abiraterone+prednisone (low-fat meal)	Prednisone	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.
Abiraterone+prednisone (high-fat meal)	Prednisone	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.

Primary Outcome Measures

Name	Time	Method
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	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 Outcome Measures

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