A Drug-Drug Interaction Study of Abiraterone Acetate Plus Prednisone With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer

• Status: Completed
• Trial end date: 2012-04-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Janssen Research & Development, LLC
• Treatments: Abiraterone Acetate; Dextromethorphan; Prednisone; Theophylline

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

• 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)