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

Prostate Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01017939
• Other study ID #: CR017128
• Secondary ID: COU-AA-015
• Status: Completed
• Phase: Phase 1
• First received: November 19, 2009
• Last updated: April 11, 2013
• Start date: January 2010
• Est. completion date: April 2012

Study information

• Verified date: April 2013
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: April 2012
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Neoplasms
• Prostatic Neoplasms

Intervention

Drug:
• Abiraterone acetate
Abiraterone acetate 1000 mg tablets administered orally once daily beginning on Cycle 1 Day 1 up to the time of disease progression
• Prednisone
Prednisone 5mg tablets administered orally twice daily beginning on Cycle 1 Day 1 up to the time of disease progression
• Dextromethorphan hydrobromide
Dextromethorphan hydrobromide 30 mg capsules administered orally on Cycle 1 Day -8 and Cycle 1 Day 8 under fasting conditions
• Theophylline
Theophylline 100 mg tablets administered orally on Cycle 1 Day -8 and Cycle 1 Day 8 under fasting conditions

Locations

Country	Name	City	State
Canada	BC Cancer Agency	Vancouver	British Columbia
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	START - South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	Number of participants reporting adverse events		Up to 30 days after the last dose of study drug	Yes

External Links

•   An Abiraterone Acetate Plus Prednisone Drug-Drug Interaction Study with Dextromethorphan and Theophylline in Patients with Metastatic Castration-Resistant Prostate Cancer