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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen-Ortho Inc., Canada
ClinicalTrials.gov Identifier:
NCT01424930
First received: August 26, 2011
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

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).


Condition Intervention Phase
Prostate Neoplasms
Prostate Cancer
Drug: Abiraterone acetate and prednisone; low-fat diet
Drug: Abiraterone acetate and prednisone; high-fat diet
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Janssen-Ortho Inc., Canada:

Primary Outcome Measures:
  • Toxicity related to dosing after low-fat or high-fat meals [ Time Frame: Cycle 1 Day 8 to Cycle 2 Day 1 pre-dose (food safety evaluation period) ] [ Designated as safety issue: Yes ]
    Grade 3 or higher AEs of special interest, including fluid retention/edema, hypokalemia, cardiac disorders, hepatotoxicity (liver function test [LFT] abnormalities), and hypertension; or Grade 3 or higher serious adverse events (SAEs) that occur during the food safety evaluation period.

  • Physical exams [ Time Frame: Cycle 1 Day 8 to Cycle 2 Day 1 pre-dose (food safety evaluation period) ] [ Designated as safety issue: Yes ]
    Grade 3 or higher AEs of fluid retention/edema, cardiac disorders, and hypertension

  • Vital sign measurements [ Time Frame: Cycle 1 Day 8 to Cycle 2 Day 1 pre-dose (food safety evaluation period) ] [ Designated as safety issue: Yes ]
    Grade 3 or higher cardiac disorders, and hypertension

  • Hematology and chemistry assessments [ Time Frame: Cycle 1 Day 8 to Cycle 2 Day 1 pre-dose (food safety evaluation period) ] [ Designated as safety issue: Yes ]
    Grade 3 or higher hypokalemia, hepatotoxicity (liver function test [LFT] abnormalities)


Secondary Outcome Measures:
  • Plasma levels of study agents [ Time Frame: Cycle 1 Day 7 through Cycle 1 Day 14 ] [ Designated as safety issue: No ]
    The metrics of abiraterone systemic exposure (Cmax and AUC) in the different prandial states


Enrollment: 25
Study Start Date: October 2011
Study Completion Date: May 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001 Drug: Abiraterone acetate and prednisone; low-fat diet

Abiraterone acetate: type=exact, unit=mg, number=1000, form=tablets, route=oral use, once daily. Prednisone: type=exact, unit=mg, number=5, form=tablets, route=oral use, twice daily. Standardized low-fat meal from Cycle 1 Days 8-14.

Treatments may be taken until progression of clinical disease.

Experimental: 002 Drug: Abiraterone acetate and prednisone; high-fat diet
Abiraterone acetate: type=exact, unit=mg, number=1000, form=tablets, route=oral use, once daily. Prednisone: type=exact, unit=mg, number=5, form=tablets, route=oral use, twice daily. Standardized high-fat meal from Cycle 1 Days 8-14. Treatments may be taken until progression of clinical disease.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01424930

Locations
Canada, Alberta
Edmonton, Alberta, Canada
Canada, British Columbia
Vancouver, British Columbia, Canada
Sponsors and Collaborators
Janssen-Ortho Inc., Canada
Investigators
Study Director: Janssen-Ortho, Canada Clinical Trial Janssen-Ortho Inc., Canada
  More Information

No publications provided

Responsible Party: Janssen-Ortho Inc., Canada
ClinicalTrials.gov Identifier: NCT01424930     History of Changes
Other Study ID Numbers: CR018715, 212082PCR2008
Study First Received: August 26, 2011
Last Updated: January 27, 2014
Health Authority: Canada: Health Canada

Keywords provided by Janssen-Ortho Inc., Canada:
Metastatic castration-resistant prostate cancer
CRPC
Abiraterone Acetate
Prednisone
Food Safety

Additional relevant MeSH terms:
Neoplasms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Prednisone
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 17, 2014