An Abiraterone Acetate Plus Prednisone Drug-Drug Interaction Study With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer
Overview
- Phase
- Phase 1
- Intervention
- Abiraterone acetate
- Conditions
- Prostate Neoplasms
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 34
- Locations
- 3
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 13 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
Group A: abiraterone + prednisone + dextromethorphan
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.
Intervention: Abiraterone acetate
Group A: abiraterone + prednisone + dextromethorphan
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.
Intervention: Prednisone
Group A: abiraterone + prednisone + dextromethorphan
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.
Intervention: Dextromethorphan hydrobromide
Group B: abiraterone + prednisone + 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.
Intervention: Abiraterone acetate
Group B: abiraterone + prednisone + 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.
Intervention: Prednisone
Group B: abiraterone + prednisone + 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.
Intervention: Theophylline
Outcomes
Primary Outcomes
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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: Cycle 1 Day -8 and Day 8
Secondary Outcomes
- Number of participants reporting adverse events(Up to 30 days after the last dose of study drug)