Prostate Cancer, Prostate Neoplasms
Conditions
Keywords
Metastatic castration-resistant prostate cancer, CRPC, Abiraterone Acetate, Prednisone, Food Safety
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.
Interventions
DRUGAbiraterone
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.
DRUGPrednisone
Prednisone will be administered as 5 mg oral tablet twice daily during Cycle 1 Day 8 to Cycle 1 Day 14.
Sponsors
Janssen-Ortho Inc., Canada
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
Canada
Participant flow
Recruitment details
The study was conducted from 29 September 2011 to 29 May 2013. Participants were recruited at 2 study centers in Canada.
Participants by arm
| Arm | Count |
|---|---|
| Abiraterone+Prednisone (Low-fat Meal) Participants received 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 was administered as 5 mg oral tablet twice daily during Cycle 1 Day 8 to Cycle 1 Day 14. | 7 |
| Abiraterone+Prednisone (High-fat Meal) Participants received 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 was administered as 5 mg oral tablet twice daily during Cycle 1 Day 8 to Cycle 1 Day 14 | 18 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Progressive Disease | 3 | 6 |
| Overall Study | Reason not specified | 0 | 6 |
| Overall Study | Screen Failure | 0 | 1 |
Baseline characteristics
| Characteristic | Abiraterone+Prednisone (Low-fat Meal) | Abiraterone+Prednisone (High-fat Meal) | Total |
|---|---|---|---|
| Age, Continuous | 75.1 years STANDARD_DEVIATION 11.01 | 69.1 years STANDARD_DEVIATION 7.26 | 70.8 years STANDARD_DEVIATION 8.67 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 18 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 18 / 18 |
| serious Total, serious adverse events | 4 / 7 | 4 / 18 |
Outcome results
Primary
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.
Time frame: Postdose on Cycle 1 Day 8 to predose on Cycle 2 Day 1
Population: Safety population: Participants who received at least 1 dose of study medication and contributed any safety data after the start of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abiraterone+Prednisone (Low-fat Meal) | 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 | 0 Participants |
| Abiraterone+Prednisone (High-fat Meal) | 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 | 0 Participants |
Secondary
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.
Time frame: Day 7 and Day 14
Population: Participants who received at least 1 dose of study medication and were included in the pharmacokinetics analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Abiraterone+Prednisone (Low-fat Meal) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) | Day 7 | 1271 ng*h/mL | Standard Deviation 1279 |
| Abiraterone+Prednisone (Low-fat Meal) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) | Day 14 | 1264 ng*h/mL | Standard Deviation 963 |
| Abiraterone+Prednisone (High-fat Meal) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) | Day 7 | 973 ng*h/mL | Standard Deviation 667 |
| Abiraterone+Prednisone (High-fat Meal) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) | Day 14 | 1992 ng*h/mL | Standard Deviation 720 |
Secondary
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.
Time frame: Day 7 and Day 14
Population: Participants who received at least 1 dose of study medication and were included in the pharmacokinetics analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Abiraterone+Prednisone (Low-fat Meal) | Maximum Observed Plasma Concentration (Cmax) of Abiraterone | Day 7 | 218 ng/mL | Standard Deviation 168 |
| Abiraterone+Prednisone (Low-fat Meal) | Maximum Observed Plasma Concentration (Cmax) of Abiraterone | Day 14 | 265 ng/mL | Standard Deviation 229 |
| Abiraterone+Prednisone (High-fat Meal) | Maximum Observed Plasma Concentration (Cmax) of Abiraterone | Day 7 | 196 ng/mL | Standard Deviation 234 |
| Abiraterone+Prednisone (High-fat Meal) | Maximum Observed Plasma Concentration (Cmax) of Abiraterone | Day 14 | 342 ng/mL | Standard Deviation 289 |
Secondary
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.
Time frame: Day 7 and Day 14
Population: Participants who received at least 1 dose of study medication and were included in the pharmacokinetics analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abiraterone+Prednisone (Low-fat Meal) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Abiraterone | Day 7 | 2 hours |
| Abiraterone+Prednisone (Low-fat Meal) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Abiraterone | Day 14 | 2.5 hours |
| Abiraterone+Prednisone (High-fat Meal) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Abiraterone | Day 7 | 2 hours |
| Abiraterone+Prednisone (High-fat Meal) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Abiraterone | Day 14 | 4.0 hours |