A Drug-Drug Interaction Study of Abiraterone Acetate Plus Prednisone With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer
Information source: Janssen Research & Development, LLC
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Prostate Neoplasms
Intervention: Abiraterone acetate (Drug); Prednisone (Drug); Dextromethorphan hydrobromide (Drug); Theophylline (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Janssen Research & Development, LLC Official(s) and/or principal investigator(s): Janssen Research & Development, LLC Clinical Trial, Study Director, Affiliation: Janssen Research & Development, LLC
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.
Clinical Details
Official title: An Abiraterone Acetate Plus Prednisone Drug-Drug Interaction Study With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: 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 prednisoneRatio of the mean maximum plasma concentration (Cmax) of dextromethorphan, dextrorphan, and parent/metabolite, with and without co-administration of abiraterone acetate and prednisone Ratio of the mean area under the concentration curve (AUC) of theophylline with and without co-administration of abiraterone acetate and prednisone Ratio of the mean maximum plasma concentration (Cmax) of theophylline with and without co-administration of abiraterone acetate and prednisone
Secondary outcome: Number of participants reporting adverse events
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Male.
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)
Locations and Contacts
Vancouver, British Columbia, Canada
BC Cancer Agency, Vancouver, British Columbia V5Z 4E6, Canada
Beverly Hills, California, United States
Tower Cancer Research Foundation, Beverly Hills, California 90211, United States
San Antonio, Texas, United States
START - South Texas Accelerated Research Therapeutics, LLC, San Antonio, Texas 78229, United States
Additional Information
An Abiraterone Acetate Plus Prednisone Drug-Drug Interaction Study with Dextromethorphan and Theophylline in Patients with Metastatic Castration-Resistant Prostate Cancer
Starting date: January 2010
Last updated: April 11, 2013
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