A Drug-Drug Interaction Study of Abiraterone Acetate Plus Prednisone With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer
Phase 1
Completed
- Conditions
- Prostate Neoplasms
- Interventions
- Registration Number
- NCT01017939
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to evaluate the effects of multiple doses of abiraterone acetate plus prednisone on the pharmacokinetics (study of what the body does to a drug) of single doses of dextromethorphan hydrobromide and theophylline in patients with castration resistant prostate cancer.
- Detailed Description
This is an open-label (identity of assigned study drug will be known) study of abiraterone acetate plus prednisone in male patients with metastatic castration-resistant prostate cancer. This study will consist of screening, treatment, and follow-up periods, and will have 2 study groups. Patients in Group A and B will receive daily abiraterone acetate (1000 mg) plus prednisone (5 mg) twice daily beginning on Cycle 1 Day 1 until disease progression. Patients in Group A will take dextromethorphan hydrobromide 30 mg administered orally once daily on Day -8 and Day 8 of Cycle 1. Patients in Group B will take theophylline 100 mg administered orally once daily on Day -8 and Day 8 of Cycle 1. Serial pharmacokinetic samples will be collected and safety will be monitored throughout the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 34
Inclusion Criteria
- Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology
- Documented metastatic disease
- Documented prostate specific antigen (PSA) progression according to Prostate Cancer Working Group 2 criteria, with PSA value >=2 ng/mL despite medical or surgical castration, or prostate cancer progression documented by radiographic progression according to Response Evaluation Criteria In Solid Tumors criteria
- Surgically or medically castrated with testosterone levels of <50 ng/dL
- Eastern Cooperative Oncology Group (ECOG) Performance Status of <=2
- Group A only: genomic testing at screening indicating CYP2D6 extensive metabolizer status
- Protocol-defined laboratory values
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Exclusion Criteria
- Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection
- Group A only: genomic testing at screening indicating CYP2D6 non-extensive metabolizer status, or prior treatment with dextromethorphan-containing medication or any medication that is a strong inhibitor or inducer of CYP2D6 within 5 half-lives of that drug or 7 days, whichever is longer, prior to Cycle 1 Day -8
- Group B only: prior treatment with theophylline or any medication that is a strong inhibitor or inducer of CYP1A2 within 5 half-lives of that drug or 7 days, whichever is longer, prior to Cycle 1 Day -8
- Abnormal liver function
- Uncontrolled hypertension (repeated systolic blood pressure >=160 mmHg, or diastolic blood pressure >=95 mmHg)
- Active or symptomatic viral hepatitis or chronic liver disease
- Known brain metastasis
- History of pituitary or adrenal dysfunction
- Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association Class III or IV heart disease or cardiac ejection fraction measurement of <50% at baseline
- History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
- Surgery or local prostatic intervention within 28 days of the first dose, and any clinically relevant sequelae from the surgery must have resolved prior to Cycle 1 Day 1
- Radiotherapy or immunotherapy within 28 days, or single fraction of palliative radiotherapy within 14 days of administration of Cycle 1 Day 1
- Any acute toxicities due to prior therapy that have not resolved
- Current enrollment in an investigational drug or device study or participation in such a study within 28 days of Cycle 1 Day 1
- Previous abiraterone acetate or other investigational CYP17 inhibitor (eg, TAK-700)
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A: abiraterone + prednisone + dextromethorphan Prednisone Group A will assess the effect of multiple doses of abiraterone acetate plus prednisone on CYP2D6 using 2 single doses of dextromethorphan hydrobromide as a probe drug. Group B: abiraterone + prednisone + theophylline Abiraterone acetate Group B will assess the effect of multiple doses of abiraterone acetate plus prednisone on CYP1A2 using 2 single doses of theophylline as a probe drug. Group A: abiraterone + prednisone + dextromethorphan Abiraterone acetate Group A will assess the effect of multiple doses of abiraterone acetate plus prednisone on CYP2D6 using 2 single doses of dextromethorphan hydrobromide as a probe drug. Group B: abiraterone + prednisone + theophylline Theophylline Group B will assess the effect of multiple doses of abiraterone acetate plus prednisone on CYP1A2 using 2 single doses of theophylline as a probe drug. Group A: abiraterone + prednisone + dextromethorphan Dextromethorphan hydrobromide Group A will assess the effect of multiple doses of abiraterone acetate plus prednisone on CYP2D6 using 2 single doses of dextromethorphan hydrobromide as a probe drug. Group B: abiraterone + prednisone + theophylline Prednisone Group B will assess the effect of multiple doses of abiraterone acetate plus prednisone on CYP1A2 using 2 single doses of theophylline as a probe drug.
- Primary Outcome Measures
Name Time Method Ratio of the mean area under the concentration curve (AUC) of dextromethorphan, dextrorphan, and parent/metabolite, with and without co-administration of abiraterone acetate and prednisone Cycle 1 Day -8 and Day 8 Ratio of the mean maximum plasma concentration (Cmax) of dextromethorphan, dextrorphan, and parent/metabolite, with and without co-administration of abiraterone acetate and prednisone Cycle 1 Day -8 and Day 8 Ratio of the mean area under the concentration curve (AUC) of theophylline with and without co-administration of abiraterone acetate and prednisone Cycle 1 Day -8 and Day 8 Ratio of the mean maximum plasma concentration (Cmax) of theophylline with and without co-administration of abiraterone acetate and prednisone Cycle 1 Day -8 and Day 8
- Secondary Outcome Measures
Name Time Method Number of participants reporting adverse events Up to 30 days after the last dose of study drug
Trial Locations
- Locations (3)
START - South Texas Accelerated Research Therapeutics, LLC
🇺🇸San Antonio, Texas, United States
Tower Cancer Research Foundation
🇺🇸Beverly Hills, California, United States
BC Cancer Agency
🇨🇦Vancouver, British Columbia, Canada